Introduction

There have been incident reports of cardiac-related adverse events (CrAE) from immune checkpoint inhibitors (ICPI); however, the true incidence and subsequent management of these potential side effects have not been defined. It is therefore important to study ICPI related cardiac dysfunction to assist in monitoring and surveillance of these patients.

Methods

63 patients who received nivolumab and pembrolizumab at Stratton VAMC Albany between January 2015 to December 2018 were studied. Retrospective chart review was done to identify the CrAE up to two-year post-therapy completion or discontinuation. Naranjo score was used to assess drug-related side effect. IRB approval was obtained.

Results 

CrAE were defined as new onset arrythmia identified on electrocardiogram, evidence of cardiomyopathy on echocardiogram, an acute coronary event, and hospitalizations from primary cardiac disorder following ICPI administration. Of the 63 patients, 6 patients developed CrAE. Our review showed 3 patients developed new arrythmias including 1 with atrial fibrillation, and 2 with atrial flutter. There was 1 case each of new heart failure with reduced ejection fraction and pericarditis with pericardial tamponade. 1 patient developed acute coronary syndrome in addition to complete heart block. Of the 6 patients, 2 had elevated brain natriuretic peptide (BNP) prior to onset of CrAE. Elevated markers including BNP and troponin-I were also seen in 13 patients with preexisting heart conditions without CrAE. Duration of therapy was variable for all patients with CrAE. Therapy was continued for 3 patients without recurrence of CrAE. Therapy was permanently discontinued in the patient who developed pericardial effusion (grade IV toxicity). The remaining 2 patients had additional concurrent immune-related toxicities that required discontinuation of therapy. Our analysis showed 25/63 patients with pre-existing cardiac conditions (including arrhythmia, heart failure or coronary artery disease) who did not develop new CrAE; however 6 of these patients required hospitalization for exacerbation related to these pre-existing conditions.

Conclusions

CrAE can occur with ICPIs, and vigilance is required in high-risk patient including those with pre-existing cardiac comorbidity. Further studies are required to establish if baseline screening EKG and echocardiogram should be obtained for all patients starting ICPI.

Introduction

There have been incident reports of cardiac-related adverse events (CrAE) from immune checkpoint inhibitors (ICPI); however, the true incidence and subsequent management of these potential side effects have not been defined. It is therefore important to study ICPI related cardiac dysfunction to assist in monitoring and surveillance of these patients.

Methods

63 patients who received nivolumab and pembrolizumab at Stratton VAMC Albany between January 2015 to December 2018 were studied. Retrospective chart review was done to identify the CrAE up to two-year post-therapy completion or discontinuation. Naranjo score was used to assess drug-related side effect. IRB approval was obtained.

Results 

CrAE were defined as new onset arrythmia identified on electrocardiogram, evidence of cardiomyopathy on echocardiogram, an acute coronary event, and hospitalizations from primary cardiac disorder following ICPI administration. Of the 63 patients, 6 patients developed CrAE. Our review showed 3 patients developed new arrythmias including 1 with atrial fibrillation, and 2 with atrial flutter. There was 1 case each of new heart failure with reduced ejection fraction and pericarditis with pericardial tamponade. 1 patient developed acute coronary syndrome in addition to complete heart block. Of the 6 patients, 2 had elevated brain natriuretic peptide (BNP) prior to onset of CrAE. Elevated markers including BNP and troponin-I were also seen in 13 patients with preexisting heart conditions without CrAE. Duration of therapy was variable for all patients with CrAE. Therapy was continued for 3 patients without recurrence of CrAE. Therapy was permanently discontinued in the patient who developed pericardial effusion (grade IV toxicity). The remaining 2 patients had additional concurrent immune-related toxicities that required discontinuation of therapy. Our analysis showed 25/63 patients with pre-existing cardiac conditions (including arrhythmia, heart failure or coronary artery disease) who did not develop new CrAE; however 6 of these patients required hospitalization for exacerbation related to these pre-existing conditions.

Conclusions

CrAE can occur with ICPIs, and vigilance is required in high-risk patient including those with pre-existing cardiac comorbidity. Further studies are required to establish if baseline screening EKG and echocardiogram should be obtained for all patients starting ICPI.

Introduction

There have been incident reports of cardiac-related adverse events (CrAE) from immune checkpoint inhibitors (ICPI); however, the true incidence and subsequent management of these potential side effects have not been defined. It is therefore important to study ICPI related cardiac dysfunction to assist in monitoring and surveillance of these patients.

Methods

63 patients who received nivolumab and pembrolizumab at Stratton VAMC Albany between January 2015 to December 2018 were studied. Retrospective chart review was done to identify the CrAE up to two-year post-therapy completion or discontinuation. Naranjo score was used to assess drug-related side effect. IRB approval was obtained.

Results 

CrAE were defined as new onset arrythmia identified on electrocardiogram, evidence of cardiomyopathy on echocardiogram, an acute coronary event, and hospitalizations from primary cardiac disorder following ICPI administration. Of the 63 patients, 6 patients developed CrAE. Our review showed 3 patients developed new arrythmias including 1 with atrial fibrillation, and 2 with atrial flutter. There was 1 case each of new heart failure with reduced ejection fraction and pericarditis with pericardial tamponade. 1 patient developed acute coronary syndrome in addition to complete heart block. Of the 6 patients, 2 had elevated brain natriuretic peptide (BNP) prior to onset of CrAE. Elevated markers including BNP and troponin-I were also seen in 13 patients with preexisting heart conditions without CrAE. Duration of therapy was variable for all patients with CrAE. Therapy was continued for 3 patients without recurrence of CrAE. Therapy was permanently discontinued in the patient who developed pericardial effusion (grade IV toxicity). The remaining 2 patients had additional concurrent immune-related toxicities that required discontinuation of therapy. Our analysis showed 25/63 patients with pre-existing cardiac conditions (including arrhythmia, heart failure or coronary artery disease) who did not develop new CrAE; however 6 of these patients required hospitalization for exacerbation related to these pre-existing conditions.

Conclusions

CrAE can occur with ICPIs, and vigilance is required in high-risk patient including those with pre-existing cardiac comorbidity. Further studies are required to establish if baseline screening EKG and echocardiogram should be obtained for all patients starting ICPI.

On April 1, Houston Methodist Hospital in Houston, Texas, announced a new policy that all of its staff would need to be vaccinated against COVID-19 by June 7 in order to hold onto their jobs. Most responded positively but an estimated 150 staff members who did not comply either resigned or were terminated. A lawsuit by employees opposed to the vaccine mandate was dismissed by Federal District Court Judge Lynn Hughes in June, although a subsequent lawsuit was filed Aug. 16.

Vaccines have been shown to dramatically reduce both the incidence and the severity of COVID infections. Vaccinations of health care workers, especially those who have direct contact with patients, are demonstrated to be effective strategies to significantly reduce, although not eliminate, the possibility of viral transmissions to patients – or to health care workers themselves – thus saving lives.

Hospitalists, in their central role in the care of hospitalized patients, and often with primary responsibility for managing their hospital’s COVID-19 caseloads, may find themselves encountering conversations about the vaccine, its safety, effectiveness, and mandates with their peers, other hospital staff, patients, and families, and their communities. They can play key roles in advocating for the vaccine, answering questions, clarifying the science, and dispelling misinformation – for those who are willing to listen.

Becker’s Hospital Review, which has kept an ongoing tally of announced vaccine mandate policies in hospitals, health systems, and health departments nationwide, reported on Aug. 13 that 1,850 or 30% of U.S. hospitals, had announced vaccine mandates.¹ Often exceptions can be made, such as for medical or religious reasons, or with other declarations or opt-out provisions. But in many settings, mandating COVID vaccinations won’t be easy.

Amith Skandhan, MD, SFHM, FACP, a hospitalist at Southeast Health Medical Center in Dothan, Ala., and a core faculty member in the internal medicine residency program at Alabama College of Osteopathic Medicine, said that implementing vaccine mandates will be more difficult in smaller health systems, in rural communities, and in states with lower vaccination rates and greater vaccine controversy.

Alabama has the lowest vaccination rates in the country, reflected in the recent rise in COVID cases and hospitalizations, even higher than during the surge of late 2020, Dr. Skandhan said. “In June we had one COVID patient in this hospital.” By late August the number was 119 COVID patients and climbing.

But where he works, in a health system where staffing is already spread thin, a vaccine mandate would be challenging. “What if our staff started leaving? It’s only 10 minutes from here to the Florida or Georgia border,” Dr. Skandhan said. Health care workers opposed to vaccinations would have the option of easily seeking work elsewhere.

When contacted for this article, he had been off work for several days but was mentally preparing himself to go back. “I’m not even following the [COVID-19] numbers but I am prepared for the worst. I know it will be mostly COVID. People just don’t realize what goes into this work.”

Dr. Skandhan, who said he was the third or fourth person in Alabama to receive the COVID vaccine, often finds himself feeling frustrated and angry – in the midst of a surge in cases that could have been prevented – that such a beneficial medical advance for bringing the pandemic under control became so politicized. “It is imperative that we find out why this mistrust exists and work to address it. It has to be done.”

Protecting health care professionals

On July 26, the Society of Hospital Medicine joined 50 other health care organizations including the American Medical Association, American Nurses Association, and American Academy of Pediatrics in advocating for all health care employers to require their employees to be vaccinated against COVID, in order to protect the safety of all patients and residents of health care facilities.²

“As an organization, we support vaccinating health care workers, including hospitalists, to help stop the spread of COVID-19 and the increasingly dominant Delta variant,” said SHM’s chief executive officer Eric E. Howell, MD, MHM, in a prepared statement. “We aim to uphold the highest standards among hospitalists and other health care providers to help protect our fellow health care professionals, our patients, and our communities.”

To that end, Dr. Skandhan has started conversations with hospital staff who he knows are not vaccinated. “For some, we’re not able to have a civil conversation, but in most cases I can help to persuade people.” The reasons people give for not getting vaccinated are not based in science, he said. “I am worried about the safety of our hospitalists and staff nurses.” But unvaccinated frontline workers are also putting their patients at risk. “Can we say why they’re hesitating? Can we have an honest discourse? If we can’t do that with our colleagues, how can we blame the patients?”

Dr. Skandhan encourages hospitalists to start simply in their own hospitals, trying to influence their own departments and colleagues. “If you can convince one or two more every week, you can start a chain reaction. Have that conversation. Use your trust.” For some hospitalized patients, the vaccination conversation comes too late, after their infection, but even some of them might consider obtaining it down the road or trying to persuade family members to get vaccinated.

Adult hospitalists, however, may not have received training in how to effectively address vaccine fears and misconceptions among their patients, he said. Because the patients they see in the hospital are already very sick, they don’t get a lot of practice talking about vaccines except, perhaps, for the influenza vaccine.

Pediatric hospitalists have more experience with such conversations involving their patients’ parents, Dr. Skandhan said. “It comes more naturally to them. We need to learn quickly from them about how to talk about vaccines with our patients.”

Pediatric training and experience

Anika Kumar, MD, FHM, FAAP, a pediatric hospitalist at the Cleveland Clinic and the pediatric editor of The Hospitalist, agrees that pediatricians and pediatric hospitalists often have received more training in how to lead vaccination conversations. She often talks about vaccines with the parents of hospitalized children relative to chicken pox, measles, and other diseases of childhood.

Pediatric hospitalists may also ask to administer the hepatitis B vaccine to newborn babies, along with other preventive treatments such as eye drops and vitamin K shots. “I often encourage the influenza vaccine prior to the patient’s hospital discharge, especially for kids with chronic conditions, asthma, diabetes, or premature birth. We talk about how the influenza vaccine isn’t perfect, but it helps to prevent more serious disease,” she said.

“A lot of vaccine hesitancy comes from misunderstandings about the role of vaccines,” she said. People forget that for years children have been getting vaccines before starting school. “Misinformation and opinions about vaccines have existed for decades. What’s new today is the abundance of sources for obtaining these opinions. My job is to inform families of scientific facts and to address their concerns.”

It has become more common recently for parents to say they don’t want their kids to get vaccinated, Dr. Kumar said. Another group is better described as vaccine hesitant and just needs more information. “I may not, by the time they leave the hospital, convince them to allow me to administer the vaccine. But in the discharge summary, I document that I had this conversation. I’ve done my due diligence and tried to start a larger dialogue. I say: ‘I encourage you to continue this discussion with the pediatrician you trust.’ I also communicate with the outpatient team,” she said.

“But it’s our responsibility, because we’re the ones seeing these patients, to do whatever we can to keep our patients from getting sick. A lot of challenging conversations we have with families are just trying to find out where they’re at with the issue – which can lead to productive dialogue.”

Ariel Carpenter, MD, a 4th-year resident in internal medicine and pediatrics at the University of Louisville (Ky.), and a future pediatric hospitalist, agreed that her combined training in med-peds has been helpful preparation for the vaccine conversation. That training has included techniques of motivational interviewing. In pediatrics, she explained, the communication is a little softer. “I try to approach my patients in a family-centered way.”

Dr. Carpenter recently wrote a personal essay for Louisville Medicine magazine from the perspective of growing up homeschooled by a mother who didn’t believe in vaccines.³ As a teenager, she independently obtained the complete childhood vaccine series so that she could do medical shadowing and volunteering. In medical school she became a passionate vaccine advocate, eventually persuading her mother to change her mind on the subject in time for the COVID vaccine.

“There’s not one answer to the vaccination dilemma,” she said. “Different approaches are required because there are so many different reasons for it. Based on my own life experience, I try to approach patients where they are – not from a place of data and science. What worked in my own family, and works with my patients, is first to establish trust. If they trust you, they’re more likely to listen. Simply ask their worries and concerns,” Dr. Carpenter said.

“A lot of them haven’t had the opportunity before to sit down with a physician they trust and have their worries listened to. They don’t feel heard in our medical system. So I remind myself that I need to understand my patients first – before inserting myself into the conversation.”

Many patients she sees are in an information bubble, with a very different understanding of the issue than their doctors. “A lot of well-meaning people feel they are making the safer choice. Very few truly don’t care about protecting others. But they don’t feel the urgency about that and see the vaccine as the scarier option right now.”

Frontline vaccine advocates

Hospitalists are the frontline advocates within their hospital system, in a position to lead, so they need to make vaccines a priority, Dr. Carpenter said. They should also make sure that their hospitals have ready access to the vaccine, so patients who agree to receive it are able to get it quickly. “In our hospital they can get the shot within a few hours if the opportunity arises. We stocked the Johnson & Johnson vaccine so that they wouldn’t have to connect with another health care provider in order to get a second dose.”

Hospitals should also invest in access to vaccine counseling training and personnel. “Fund a nurse clinician who can screen and counsel hospitalized patients for vaccination. If they meet resistance, they can then refer to the dedicated physician of the day to have the conversation,” she said. “But if we don’t mention it, patients will assume we don’t feel strongly about it.”

Because hospitalists are front and center in treating COVID, they need to be the experts and the people offering guidance, said Shyam Odeti, MD, SFHM, FAAFP, section chief for hospital medicine at the Carilion Clinic in Roanoke, Va. “What we’re trying to do is spread awareness. We educated physician groups, learners, and clinical teams during the initial phase, and now mostly patients and their families.” COVID vaccine reluctance is hard to overcome, Dr. Odeti said. People feel the vaccine was developed very quickly. But there are different ways to present it.

“Like most doctors, I thought people would jump on a vaccine to get past the pandemic. I was surprised and then disappointed. Right now, the pandemic is among the unvaccinated. So we face these encounters, and we’re doing our best to overcome the misinformation. My organization is 100% supportive. We talk about these issues every day.”

Carilion, effective Oct. 1, has required unvaccinated employees to get weekly COVID tests and wear an N95 mask while working, and has developed Facebook pages, other social media, and an Internet presence to address these issues. “We’ve gone to the local African-American community with physician leaders active in that community. We had a Spanish language roundtable,” Dr. Odeti said.

Dr. Skandhan reported that the Wiregrass regional chapter of SHM recently organized a successful statewide community educational event aimed at empowering community leaders to address vaccine misinformation and mistrust. “We surveyed religious leaders and pastors regarding the causes of vaccine hesitancy and reached out to physicians active in community awareness.” Based on that input, a presentation by the faith leaders was developed. Legislators from the Alabama State Senate’s Healthcare Policy Committee were also invited to the presentation and discussion.
 

Trying to stay positive

It’s important to try to stay positive, Dr. Odeti said. “We have to be empathetic with every patient. We have to keep working at this, since there’s no way out of the pandemic except through vaccinations. But it all creates stress for hospitalists. Our job is made significantly more difficult by the vaccine controversy.”

Jennifer Cowart, MD, a hospitalist at Mayo Clinic in Jacksonville, Fla., has been outspoken in her community about vaccination and masking issues, talking to reporters, attending rallies and press conferences, posting on social media, and speaking in favor of mask policies at a local school board meeting. She is part of an informal local group called Doctors Fighting COVID, which meets online to strategize how to share its expertise, including writing a recent letter about masks to Jacksonville’s mayor.

“In July, when we saw the Delta variant surging locally, we held a webinar via local media, taking calls about the vaccine from the community. I’m trying not to make this a political issue, but we are health officials.” Dr. Cowart said she also tries not to raise her voice when speaking with vaccine opponents and tries to remain empathetic. “Even though inwardly I’m screaming, I try to stay calm. The misinformation is real. People are afraid and feeling pressure. I do my best, but I’m human, too.”

Hospitalists need to pull whatever levers they can to help advance understanding of vaccines, Dr. Cowart said. “In the hospital, our biggest issue is time. We often don’t have it, with a long list of patients to see. But every patient encounter is an opportunity to talk to patients, whether they have COVID or something else.” Sometimes, she might go back to a patient’s room after rounds to resume the conversation.

Hospital nurses have been trained and entrusted to do tobacco abatement counseling, she said, so why not mobilize them for vaccine education? “Or respiratory therapists, who do inhaler training, could talk about what it’s like to care for COVID patients. There’s a whole bunch of staff in the hospital who could be mobilized,” she said.

“I feel passionate about vaccines, as a hospitalist, as a medical educator, as a daughter, as a responsible member of society,” said Eileen Barrett, MD, MPH, SFHM, MACP, director of continuing medical education at the University of New Mexico, Albuquerque. “I see this as a personal and societal responsibility. When I speak about the vaccine among groups of doctors, I say we need to stay in our lane regarding our skills at interpreting the science and not undermining it.”

Some health care worker hesitancy is from distrust of pharmaceutical companies, or of federal agencies, she said. “Our research has highlighted to me the widespread inequity issues in our health care system. We should also take a long, hard look at how we teach the scientific method to health professionals. That will be part of a pandemic retrospective.”

Sometimes with people who are vaccine deliberative, whether health care workers or patients, there is a small window of opportunity. “We need to hear people and respond to them as people. Then, if they are willing to get vaccinated, we need to accomplish that as quickly and easily as possible,” Dr. Barrett said. “I see them make a face and say, ‘Well, okay, I’ll do it.’ We need to get the vaccine to them that same day. We should be able to accomplish that.”
 

References

1. Gamble M. 30% of US hospitals mandate vaccination for employment. Becker’s Hospital Review. 2021 Aug 13. www.beckershospitalreview.com/workforce/covid-19-vaccination-needed-to-work-at-30-of-us-hospitals.html .

2. Society of Hospital Medicine signs on to joint statement in support of health worker COVID-19 vaccine mandates. Press release. 2021 Jul 26. www.hospitalmedicine.org/news-publications/press-releases/society-of-hospital-medicine-signs-on-to-joint-statement-of-support-of-health-worker-covid-19-vaccine-mandates/.

3. Carpenter A. A physician’s lessons from an unvaccinated childhood. Louisville Medicine. 2021 July;69(2):26-7. https://viewer.joomag.com/louisville-medicine-volume-69-issue-2/0045988001624974172?short&.

Lessons for hospitalists from the vaccination controversy

1. Remain up-to-date on information about the COVID infection, its treatment, and vaccination efficacy data.

2. Hospitalists should take advantage of their positions to lead conversations in their facilities about the importance of COVID vaccinations.

3. Other professionals in the hospital, with some additional training and support, could take on the role of providing vaccine education and support – with a physician to back them up on difficult cases.

4. It’s important to listen to people’s concerns, try to build trust, and establish dialogue before starting to convey a lot of information. People need to feel heard.

5. If you are successful in persuading someone to take the vaccine, a shot should be promptly and easily accessible to them.

6. Pediatric hospitalists may have more experience and skill with vaccine discussions, which they should share with their peers who treat adults.

On April 1, Houston Methodist Hospital in Houston, Texas, announced a new policy that all of its staff would need to be vaccinated against COVID-19 by June 7 in order to hold onto their jobs. Most responded positively but an estimated 150 staff members who did not comply either resigned or were terminated. A lawsuit by employees opposed to the vaccine mandate was dismissed by Federal District Court Judge Lynn Hughes in June, although a subsequent lawsuit was filed Aug. 16.

Vaccines have been shown to dramatically reduce both the incidence and the severity of COVID infections. Vaccinations of health care workers, especially those who have direct contact with patients, are demonstrated to be effective strategies to significantly reduce, although not eliminate, the possibility of viral transmissions to patients – or to health care workers themselves – thus saving lives.

Hospitalists, in their central role in the care of hospitalized patients, and often with primary responsibility for managing their hospital’s COVID-19 caseloads, may find themselves encountering conversations about the vaccine, its safety, effectiveness, and mandates with their peers, other hospital staff, patients, and families, and their communities. They can play key roles in advocating for the vaccine, answering questions, clarifying the science, and dispelling misinformation – for those who are willing to listen.

Becker’s Hospital Review, which has kept an ongoing tally of announced vaccine mandate policies in hospitals, health systems, and health departments nationwide, reported on Aug. 13 that 1,850 or 30% of U.S. hospitals, had announced vaccine mandates.¹ Often exceptions can be made, such as for medical or religious reasons, or with other declarations or opt-out provisions. But in many settings, mandating COVID vaccinations won’t be easy.

Amith Skandhan, MD, SFHM, FACP, a hospitalist at Southeast Health Medical Center in Dothan, Ala., and a core faculty member in the internal medicine residency program at Alabama College of Osteopathic Medicine, said that implementing vaccine mandates will be more difficult in smaller health systems, in rural communities, and in states with lower vaccination rates and greater vaccine controversy.

Alabama has the lowest vaccination rates in the country, reflected in the recent rise in COVID cases and hospitalizations, even higher than during the surge of late 2020, Dr. Skandhan said. “In June we had one COVID patient in this hospital.” By late August the number was 119 COVID patients and climbing.

But where he works, in a health system where staffing is already spread thin, a vaccine mandate would be challenging. “What if our staff started leaving? It’s only 10 minutes from here to the Florida or Georgia border,” Dr. Skandhan said. Health care workers opposed to vaccinations would have the option of easily seeking work elsewhere.

When contacted for this article, he had been off work for several days but was mentally preparing himself to go back. “I’m not even following the [COVID-19] numbers but I am prepared for the worst. I know it will be mostly COVID. People just don’t realize what goes into this work.”

Dr. Skandhan, who said he was the third or fourth person in Alabama to receive the COVID vaccine, often finds himself feeling frustrated and angry – in the midst of a surge in cases that could have been prevented – that such a beneficial medical advance for bringing the pandemic under control became so politicized. “It is imperative that we find out why this mistrust exists and work to address it. It has to be done.”

Protecting health care professionals

On July 26, the Society of Hospital Medicine joined 50 other health care organizations including the American Medical Association, American Nurses Association, and American Academy of Pediatrics in advocating for all health care employers to require their employees to be vaccinated against COVID, in order to protect the safety of all patients and residents of health care facilities.²

“As an organization, we support vaccinating health care workers, including hospitalists, to help stop the spread of COVID-19 and the increasingly dominant Delta variant,” said SHM’s chief executive officer Eric E. Howell, MD, MHM, in a prepared statement. “We aim to uphold the highest standards among hospitalists and other health care providers to help protect our fellow health care professionals, our patients, and our communities.”

To that end, Dr. Skandhan has started conversations with hospital staff who he knows are not vaccinated. “For some, we’re not able to have a civil conversation, but in most cases I can help to persuade people.” The reasons people give for not getting vaccinated are not based in science, he said. “I am worried about the safety of our hospitalists and staff nurses.” But unvaccinated frontline workers are also putting their patients at risk. “Can we say why they’re hesitating? Can we have an honest discourse? If we can’t do that with our colleagues, how can we blame the patients?”

Dr. Skandhan encourages hospitalists to start simply in their own hospitals, trying to influence their own departments and colleagues. “If you can convince one or two more every week, you can start a chain reaction. Have that conversation. Use your trust.” For some hospitalized patients, the vaccination conversation comes too late, after their infection, but even some of them might consider obtaining it down the road or trying to persuade family members to get vaccinated.

Adult hospitalists, however, may not have received training in how to effectively address vaccine fears and misconceptions among their patients, he said. Because the patients they see in the hospital are already very sick, they don’t get a lot of practice talking about vaccines except, perhaps, for the influenza vaccine.

Pediatric hospitalists have more experience with such conversations involving their patients’ parents, Dr. Skandhan said. “It comes more naturally to them. We need to learn quickly from them about how to talk about vaccines with our patients.”

Pediatric training and experience

Anika Kumar, MD, FHM, FAAP, a pediatric hospitalist at the Cleveland Clinic and the pediatric editor of The Hospitalist, agrees that pediatricians and pediatric hospitalists often have received more training in how to lead vaccination conversations. She often talks about vaccines with the parents of hospitalized children relative to chicken pox, measles, and other diseases of childhood.

Pediatric hospitalists may also ask to administer the hepatitis B vaccine to newborn babies, along with other preventive treatments such as eye drops and vitamin K shots. “I often encourage the influenza vaccine prior to the patient’s hospital discharge, especially for kids with chronic conditions, asthma, diabetes, or premature birth. We talk about how the influenza vaccine isn’t perfect, but it helps to prevent more serious disease,” she said.

“A lot of vaccine hesitancy comes from misunderstandings about the role of vaccines,” she said. People forget that for years children have been getting vaccines before starting school. “Misinformation and opinions about vaccines have existed for decades. What’s new today is the abundance of sources for obtaining these opinions. My job is to inform families of scientific facts and to address their concerns.”

It has become more common recently for parents to say they don’t want their kids to get vaccinated, Dr. Kumar said. Another group is better described as vaccine hesitant and just needs more information. “I may not, by the time they leave the hospital, convince them to allow me to administer the vaccine. But in the discharge summary, I document that I had this conversation. I’ve done my due diligence and tried to start a larger dialogue. I say: ‘I encourage you to continue this discussion with the pediatrician you trust.’ I also communicate with the outpatient team,” she said.

“But it’s our responsibility, because we’re the ones seeing these patients, to do whatever we can to keep our patients from getting sick. A lot of challenging conversations we have with families are just trying to find out where they’re at with the issue – which can lead to productive dialogue.”

Ariel Carpenter, MD, a 4th-year resident in internal medicine and pediatrics at the University of Louisville (Ky.), and a future pediatric hospitalist, agreed that her combined training in med-peds has been helpful preparation for the vaccine conversation. That training has included techniques of motivational interviewing. In pediatrics, she explained, the communication is a little softer. “I try to approach my patients in a family-centered way.”

Dr. Carpenter recently wrote a personal essay for Louisville Medicine magazine from the perspective of growing up homeschooled by a mother who didn’t believe in vaccines.³ As a teenager, she independently obtained the complete childhood vaccine series so that she could do medical shadowing and volunteering. In medical school she became a passionate vaccine advocate, eventually persuading her mother to change her mind on the subject in time for the COVID vaccine.

“There’s not one answer to the vaccination dilemma,” she said. “Different approaches are required because there are so many different reasons for it. Based on my own life experience, I try to approach patients where they are – not from a place of data and science. What worked in my own family, and works with my patients, is first to establish trust. If they trust you, they’re more likely to listen. Simply ask their worries and concerns,” Dr. Carpenter said.

“A lot of them haven’t had the opportunity before to sit down with a physician they trust and have their worries listened to. They don’t feel heard in our medical system. So I remind myself that I need to understand my patients first – before inserting myself into the conversation.”

Many patients she sees are in an information bubble, with a very different understanding of the issue than their doctors. “A lot of well-meaning people feel they are making the safer choice. Very few truly don’t care about protecting others. But they don’t feel the urgency about that and see the vaccine as the scarier option right now.”

Frontline vaccine advocates

Hospitalists are the frontline advocates within their hospital system, in a position to lead, so they need to make vaccines a priority, Dr. Carpenter said. They should also make sure that their hospitals have ready access to the vaccine, so patients who agree to receive it are able to get it quickly. “In our hospital they can get the shot within a few hours if the opportunity arises. We stocked the Johnson & Johnson vaccine so that they wouldn’t have to connect with another health care provider in order to get a second dose.”

Hospitals should also invest in access to vaccine counseling training and personnel. “Fund a nurse clinician who can screen and counsel hospitalized patients for vaccination. If they meet resistance, they can then refer to the dedicated physician of the day to have the conversation,” she said. “But if we don’t mention it, patients will assume we don’t feel strongly about it.”

Because hospitalists are front and center in treating COVID, they need to be the experts and the people offering guidance, said Shyam Odeti, MD, SFHM, FAAFP, section chief for hospital medicine at the Carilion Clinic in Roanoke, Va. “What we’re trying to do is spread awareness. We educated physician groups, learners, and clinical teams during the initial phase, and now mostly patients and their families.” COVID vaccine reluctance is hard to overcome, Dr. Odeti said. People feel the vaccine was developed very quickly. But there are different ways to present it.

“Like most doctors, I thought people would jump on a vaccine to get past the pandemic. I was surprised and then disappointed. Right now, the pandemic is among the unvaccinated. So we face these encounters, and we’re doing our best to overcome the misinformation. My organization is 100% supportive. We talk about these issues every day.”

Carilion, effective Oct. 1, has required unvaccinated employees to get weekly COVID tests and wear an N95 mask while working, and has developed Facebook pages, other social media, and an Internet presence to address these issues. “We’ve gone to the local African-American community with physician leaders active in that community. We had a Spanish language roundtable,” Dr. Odeti said.

Dr. Skandhan reported that the Wiregrass regional chapter of SHM recently organized a successful statewide community educational event aimed at empowering community leaders to address vaccine misinformation and mistrust. “We surveyed religious leaders and pastors regarding the causes of vaccine hesitancy and reached out to physicians active in community awareness.” Based on that input, a presentation by the faith leaders was developed. Legislators from the Alabama State Senate’s Healthcare Policy Committee were also invited to the presentation and discussion.
 

Trying to stay positive

It’s important to try to stay positive, Dr. Odeti said. “We have to be empathetic with every patient. We have to keep working at this, since there’s no way out of the pandemic except through vaccinations. But it all creates stress for hospitalists. Our job is made significantly more difficult by the vaccine controversy.”

Jennifer Cowart, MD, a hospitalist at Mayo Clinic in Jacksonville, Fla., has been outspoken in her community about vaccination and masking issues, talking to reporters, attending rallies and press conferences, posting on social media, and speaking in favor of mask policies at a local school board meeting. She is part of an informal local group called Doctors Fighting COVID, which meets online to strategize how to share its expertise, including writing a recent letter about masks to Jacksonville’s mayor.

“In July, when we saw the Delta variant surging locally, we held a webinar via local media, taking calls about the vaccine from the community. I’m trying not to make this a political issue, but we are health officials.” Dr. Cowart said she also tries not to raise her voice when speaking with vaccine opponents and tries to remain empathetic. “Even though inwardly I’m screaming, I try to stay calm. The misinformation is real. People are afraid and feeling pressure. I do my best, but I’m human, too.”

Hospitalists need to pull whatever levers they can to help advance understanding of vaccines, Dr. Cowart said. “In the hospital, our biggest issue is time. We often don’t have it, with a long list of patients to see. But every patient encounter is an opportunity to talk to patients, whether they have COVID or something else.” Sometimes, she might go back to a patient’s room after rounds to resume the conversation.

Hospital nurses have been trained and entrusted to do tobacco abatement counseling, she said, so why not mobilize them for vaccine education? “Or respiratory therapists, who do inhaler training, could talk about what it’s like to care for COVID patients. There’s a whole bunch of staff in the hospital who could be mobilized,” she said.

“I feel passionate about vaccines, as a hospitalist, as a medical educator, as a daughter, as a responsible member of society,” said Eileen Barrett, MD, MPH, SFHM, MACP, director of continuing medical education at the University of New Mexico, Albuquerque. “I see this as a personal and societal responsibility. When I speak about the vaccine among groups of doctors, I say we need to stay in our lane regarding our skills at interpreting the science and not undermining it.”

Some health care worker hesitancy is from distrust of pharmaceutical companies, or of federal agencies, she said. “Our research has highlighted to me the widespread inequity issues in our health care system. We should also take a long, hard look at how we teach the scientific method to health professionals. That will be part of a pandemic retrospective.”

Sometimes with people who are vaccine deliberative, whether health care workers or patients, there is a small window of opportunity. “We need to hear people and respond to them as people. Then, if they are willing to get vaccinated, we need to accomplish that as quickly and easily as possible,” Dr. Barrett said. “I see them make a face and say, ‘Well, okay, I’ll do it.’ We need to get the vaccine to them that same day. We should be able to accomplish that.”
 

References

1. Gamble M. 30% of US hospitals mandate vaccination for employment. Becker’s Hospital Review. 2021 Aug 13. www.beckershospitalreview.com/workforce/covid-19-vaccination-needed-to-work-at-30-of-us-hospitals.html .

2. Society of Hospital Medicine signs on to joint statement in support of health worker COVID-19 vaccine mandates. Press release. 2021 Jul 26. www.hospitalmedicine.org/news-publications/press-releases/society-of-hospital-medicine-signs-on-to-joint-statement-of-support-of-health-worker-covid-19-vaccine-mandates/.

3. Carpenter A. A physician’s lessons from an unvaccinated childhood. Louisville Medicine. 2021 July;69(2):26-7. https://viewer.joomag.com/louisville-medicine-volume-69-issue-2/0045988001624974172?short&.

Lessons for hospitalists from the vaccination controversy

1. Remain up-to-date on information about the COVID infection, its treatment, and vaccination efficacy data.

2. Hospitalists should take advantage of their positions to lead conversations in their facilities about the importance of COVID vaccinations.

3. Other professionals in the hospital, with some additional training and support, could take on the role of providing vaccine education and support – with a physician to back them up on difficult cases.

4. It’s important to listen to people’s concerns, try to build trust, and establish dialogue before starting to convey a lot of information. People need to feel heard.

5. If you are successful in persuading someone to take the vaccine, a shot should be promptly and easily accessible to them.

6. Pediatric hospitalists may have more experience and skill with vaccine discussions, which they should share with their peers who treat adults.

On April 1, Houston Methodist Hospital in Houston, Texas, announced a new policy that all of its staff would need to be vaccinated against COVID-19 by June 7 in order to hold onto their jobs. Most responded positively but an estimated 150 staff members who did not comply either resigned or were terminated. A lawsuit by employees opposed to the vaccine mandate was dismissed by Federal District Court Judge Lynn Hughes in June, although a subsequent lawsuit was filed Aug. 16.

Vaccines have been shown to dramatically reduce both the incidence and the severity of COVID infections. Vaccinations of health care workers, especially those who have direct contact with patients, are demonstrated to be effective strategies to significantly reduce, although not eliminate, the possibility of viral transmissions to patients – or to health care workers themselves – thus saving lives.

Hospitalists, in their central role in the care of hospitalized patients, and often with primary responsibility for managing their hospital’s COVID-19 caseloads, may find themselves encountering conversations about the vaccine, its safety, effectiveness, and mandates with their peers, other hospital staff, patients, and families, and their communities. They can play key roles in advocating for the vaccine, answering questions, clarifying the science, and dispelling misinformation – for those who are willing to listen.

Becker’s Hospital Review, which has kept an ongoing tally of announced vaccine mandate policies in hospitals, health systems, and health departments nationwide, reported on Aug. 13 that 1,850 or 30% of U.S. hospitals, had announced vaccine mandates.¹ Often exceptions can be made, such as for medical or religious reasons, or with other declarations or opt-out provisions. But in many settings, mandating COVID vaccinations won’t be easy.

Amith Skandhan, MD, SFHM, FACP, a hospitalist at Southeast Health Medical Center in Dothan, Ala., and a core faculty member in the internal medicine residency program at Alabama College of Osteopathic Medicine, said that implementing vaccine mandates will be more difficult in smaller health systems, in rural communities, and in states with lower vaccination rates and greater vaccine controversy.

Alabama has the lowest vaccination rates in the country, reflected in the recent rise in COVID cases and hospitalizations, even higher than during the surge of late 2020, Dr. Skandhan said. “In June we had one COVID patient in this hospital.” By late August the number was 119 COVID patients and climbing.

But where he works, in a health system where staffing is already spread thin, a vaccine mandate would be challenging. “What if our staff started leaving? It’s only 10 minutes from here to the Florida or Georgia border,” Dr. Skandhan said. Health care workers opposed to vaccinations would have the option of easily seeking work elsewhere.

When contacted for this article, he had been off work for several days but was mentally preparing himself to go back. “I’m not even following the [COVID-19] numbers but I am prepared for the worst. I know it will be mostly COVID. People just don’t realize what goes into this work.”

Dr. Skandhan, who said he was the third or fourth person in Alabama to receive the COVID vaccine, often finds himself feeling frustrated and angry – in the midst of a surge in cases that could have been prevented – that such a beneficial medical advance for bringing the pandemic under control became so politicized. “It is imperative that we find out why this mistrust exists and work to address it. It has to be done.”

Protecting health care professionals

On July 26, the Society of Hospital Medicine joined 50 other health care organizations including the American Medical Association, American Nurses Association, and American Academy of Pediatrics in advocating for all health care employers to require their employees to be vaccinated against COVID, in order to protect the safety of all patients and residents of health care facilities.²

“As an organization, we support vaccinating health care workers, including hospitalists, to help stop the spread of COVID-19 and the increasingly dominant Delta variant,” said SHM’s chief executive officer Eric E. Howell, MD, MHM, in a prepared statement. “We aim to uphold the highest standards among hospitalists and other health care providers to help protect our fellow health care professionals, our patients, and our communities.”

To that end, Dr. Skandhan has started conversations with hospital staff who he knows are not vaccinated. “For some, we’re not able to have a civil conversation, but in most cases I can help to persuade people.” The reasons people give for not getting vaccinated are not based in science, he said. “I am worried about the safety of our hospitalists and staff nurses.” But unvaccinated frontline workers are also putting their patients at risk. “Can we say why they’re hesitating? Can we have an honest discourse? If we can’t do that with our colleagues, how can we blame the patients?”

Dr. Skandhan encourages hospitalists to start simply in their own hospitals, trying to influence their own departments and colleagues. “If you can convince one or two more every week, you can start a chain reaction. Have that conversation. Use your trust.” For some hospitalized patients, the vaccination conversation comes too late, after their infection, but even some of them might consider obtaining it down the road or trying to persuade family members to get vaccinated.

Adult hospitalists, however, may not have received training in how to effectively address vaccine fears and misconceptions among their patients, he said. Because the patients they see in the hospital are already very sick, they don’t get a lot of practice talking about vaccines except, perhaps, for the influenza vaccine.

Pediatric hospitalists have more experience with such conversations involving their patients’ parents, Dr. Skandhan said. “It comes more naturally to them. We need to learn quickly from them about how to talk about vaccines with our patients.”

Pediatric training and experience

Anika Kumar, MD, FHM, FAAP, a pediatric hospitalist at the Cleveland Clinic and the pediatric editor of The Hospitalist, agrees that pediatricians and pediatric hospitalists often have received more training in how to lead vaccination conversations. She often talks about vaccines with the parents of hospitalized children relative to chicken pox, measles, and other diseases of childhood.

Pediatric hospitalists may also ask to administer the hepatitis B vaccine to newborn babies, along with other preventive treatments such as eye drops and vitamin K shots. “I often encourage the influenza vaccine prior to the patient’s hospital discharge, especially for kids with chronic conditions, asthma, diabetes, or premature birth. We talk about how the influenza vaccine isn’t perfect, but it helps to prevent more serious disease,” she said.

“A lot of vaccine hesitancy comes from misunderstandings about the role of vaccines,” she said. People forget that for years children have been getting vaccines before starting school. “Misinformation and opinions about vaccines have existed for decades. What’s new today is the abundance of sources for obtaining these opinions. My job is to inform families of scientific facts and to address their concerns.”

It has become more common recently for parents to say they don’t want their kids to get vaccinated, Dr. Kumar said. Another group is better described as vaccine hesitant and just needs more information. “I may not, by the time they leave the hospital, convince them to allow me to administer the vaccine. But in the discharge summary, I document that I had this conversation. I’ve done my due diligence and tried to start a larger dialogue. I say: ‘I encourage you to continue this discussion with the pediatrician you trust.’ I also communicate with the outpatient team,” she said.

“But it’s our responsibility, because we’re the ones seeing these patients, to do whatever we can to keep our patients from getting sick. A lot of challenging conversations we have with families are just trying to find out where they’re at with the issue – which can lead to productive dialogue.”

Ariel Carpenter, MD, a 4th-year resident in internal medicine and pediatrics at the University of Louisville (Ky.), and a future pediatric hospitalist, agreed that her combined training in med-peds has been helpful preparation for the vaccine conversation. That training has included techniques of motivational interviewing. In pediatrics, she explained, the communication is a little softer. “I try to approach my patients in a family-centered way.”

Dr. Carpenter recently wrote a personal essay for Louisville Medicine magazine from the perspective of growing up homeschooled by a mother who didn’t believe in vaccines.³ As a teenager, she independently obtained the complete childhood vaccine series so that she could do medical shadowing and volunteering. In medical school she became a passionate vaccine advocate, eventually persuading her mother to change her mind on the subject in time for the COVID vaccine.

“There’s not one answer to the vaccination dilemma,” she said. “Different approaches are required because there are so many different reasons for it. Based on my own life experience, I try to approach patients where they are – not from a place of data and science. What worked in my own family, and works with my patients, is first to establish trust. If they trust you, they’re more likely to listen. Simply ask their worries and concerns,” Dr. Carpenter said.

“A lot of them haven’t had the opportunity before to sit down with a physician they trust and have their worries listened to. They don’t feel heard in our medical system. So I remind myself that I need to understand my patients first – before inserting myself into the conversation.”

Many patients she sees are in an information bubble, with a very different understanding of the issue than their doctors. “A lot of well-meaning people feel they are making the safer choice. Very few truly don’t care about protecting others. But they don’t feel the urgency about that and see the vaccine as the scarier option right now.”

Frontline vaccine advocates

Hospitalists are the frontline advocates within their hospital system, in a position to lead, so they need to make vaccines a priority, Dr. Carpenter said. They should also make sure that their hospitals have ready access to the vaccine, so patients who agree to receive it are able to get it quickly. “In our hospital they can get the shot within a few hours if the opportunity arises. We stocked the Johnson & Johnson vaccine so that they wouldn’t have to connect with another health care provider in order to get a second dose.”

Hospitals should also invest in access to vaccine counseling training and personnel. “Fund a nurse clinician who can screen and counsel hospitalized patients for vaccination. If they meet resistance, they can then refer to the dedicated physician of the day to have the conversation,” she said. “But if we don’t mention it, patients will assume we don’t feel strongly about it.”

Because hospitalists are front and center in treating COVID, they need to be the experts and the people offering guidance, said Shyam Odeti, MD, SFHM, FAAFP, section chief for hospital medicine at the Carilion Clinic in Roanoke, Va. “What we’re trying to do is spread awareness. We educated physician groups, learners, and clinical teams during the initial phase, and now mostly patients and their families.” COVID vaccine reluctance is hard to overcome, Dr. Odeti said. People feel the vaccine was developed very quickly. But there are different ways to present it.

“Like most doctors, I thought people would jump on a vaccine to get past the pandemic. I was surprised and then disappointed. Right now, the pandemic is among the unvaccinated. So we face these encounters, and we’re doing our best to overcome the misinformation. My organization is 100% supportive. We talk about these issues every day.”

Carilion, effective Oct. 1, has required unvaccinated employees to get weekly COVID tests and wear an N95 mask while working, and has developed Facebook pages, other social media, and an Internet presence to address these issues. “We’ve gone to the local African-American community with physician leaders active in that community. We had a Spanish language roundtable,” Dr. Odeti said.

Dr. Skandhan reported that the Wiregrass regional chapter of SHM recently organized a successful statewide community educational event aimed at empowering community leaders to address vaccine misinformation and mistrust. “We surveyed religious leaders and pastors regarding the causes of vaccine hesitancy and reached out to physicians active in community awareness.” Based on that input, a presentation by the faith leaders was developed. Legislators from the Alabama State Senate’s Healthcare Policy Committee were also invited to the presentation and discussion.
 

Trying to stay positive

It’s important to try to stay positive, Dr. Odeti said. “We have to be empathetic with every patient. We have to keep working at this, since there’s no way out of the pandemic except through vaccinations. But it all creates stress for hospitalists. Our job is made significantly more difficult by the vaccine controversy.”

Jennifer Cowart, MD, a hospitalist at Mayo Clinic in Jacksonville, Fla., has been outspoken in her community about vaccination and masking issues, talking to reporters, attending rallies and press conferences, posting on social media, and speaking in favor of mask policies at a local school board meeting. She is part of an informal local group called Doctors Fighting COVID, which meets online to strategize how to share its expertise, including writing a recent letter about masks to Jacksonville’s mayor.

“In July, when we saw the Delta variant surging locally, we held a webinar via local media, taking calls about the vaccine from the community. I’m trying not to make this a political issue, but we are health officials.” Dr. Cowart said she also tries not to raise her voice when speaking with vaccine opponents and tries to remain empathetic. “Even though inwardly I’m screaming, I try to stay calm. The misinformation is real. People are afraid and feeling pressure. I do my best, but I’m human, too.”

Hospitalists need to pull whatever levers they can to help advance understanding of vaccines, Dr. Cowart said. “In the hospital, our biggest issue is time. We often don’t have it, with a long list of patients to see. But every patient encounter is an opportunity to talk to patients, whether they have COVID or something else.” Sometimes, she might go back to a patient’s room after rounds to resume the conversation.

Hospital nurses have been trained and entrusted to do tobacco abatement counseling, she said, so why not mobilize them for vaccine education? “Or respiratory therapists, who do inhaler training, could talk about what it’s like to care for COVID patients. There’s a whole bunch of staff in the hospital who could be mobilized,” she said.

“I feel passionate about vaccines, as a hospitalist, as a medical educator, as a daughter, as a responsible member of society,” said Eileen Barrett, MD, MPH, SFHM, MACP, director of continuing medical education at the University of New Mexico, Albuquerque. “I see this as a personal and societal responsibility. When I speak about the vaccine among groups of doctors, I say we need to stay in our lane regarding our skills at interpreting the science and not undermining it.”

Some health care worker hesitancy is from distrust of pharmaceutical companies, or of federal agencies, she said. “Our research has highlighted to me the widespread inequity issues in our health care system. We should also take a long, hard look at how we teach the scientific method to health professionals. That will be part of a pandemic retrospective.”

Sometimes with people who are vaccine deliberative, whether health care workers or patients, there is a small window of opportunity. “We need to hear people and respond to them as people. Then, if they are willing to get vaccinated, we need to accomplish that as quickly and easily as possible,” Dr. Barrett said. “I see them make a face and say, ‘Well, okay, I’ll do it.’ We need to get the vaccine to them that same day. We should be able to accomplish that.”
 

References

1. Gamble M. 30% of US hospitals mandate vaccination for employment. Becker’s Hospital Review. 2021 Aug 13. www.beckershospitalreview.com/workforce/covid-19-vaccination-needed-to-work-at-30-of-us-hospitals.html .

2. Society of Hospital Medicine signs on to joint statement in support of health worker COVID-19 vaccine mandates. Press release. 2021 Jul 26. www.hospitalmedicine.org/news-publications/press-releases/society-of-hospital-medicine-signs-on-to-joint-statement-of-support-of-health-worker-covid-19-vaccine-mandates/.

3. Carpenter A. A physician’s lessons from an unvaccinated childhood. Louisville Medicine. 2021 July;69(2):26-7. https://viewer.joomag.com/louisville-medicine-volume-69-issue-2/0045988001624974172?short&.

Lessons for hospitalists from the vaccination controversy

1. Remain up-to-date on information about the COVID infection, its treatment, and vaccination efficacy data.

2. Hospitalists should take advantage of their positions to lead conversations in their facilities about the importance of COVID vaccinations.

3. Other professionals in the hospital, with some additional training and support, could take on the role of providing vaccine education and support – with a physician to back them up on difficult cases.

4. It’s important to listen to people’s concerns, try to build trust, and establish dialogue before starting to convey a lot of information. People need to feel heard.

5. If you are successful in persuading someone to take the vaccine, a shot should be promptly and easily accessible to them.

6. Pediatric hospitalists may have more experience and skill with vaccine discussions, which they should share with their peers who treat adults.

A novel virus engineered to target malignant gliomas, which are particularly aggressive brain tumors, may prolong survival, according to a recent phase 1 study.

The findings, published June 29 in The Lancet Oncology, show early promise in targeting malignant gliomas, which have been notoriously difficult to treat. Only 1 in 4 patients are alive 2 years after diagnosis. The median overall survival from diagnosis is 14.6-16.7 months.

In a study of a novel therapy called NSC-CRAd-S-pk7 – an oncolytic adenovirus delivered across the blood-brain barrier by neural stem cells – overall survival improved by several months for patients with malignant gliomas.

“To my knowledge, this is the first time neural stem cells have been used as a delivery strategy for an oncolytic virus,” said Terence Burns, MD, PhD, associate professor of neurosurgery at the Mayo Clinic, Rochester, Minn., who was not involved in the research.

In this open-label, dose-escalation trial, researchers enrolled 12 patients with newly diagnosed malignant gliomas between April 2017 and November 2019. After neurosurgical tumor resection, patients were placed in one of three cohorts distinguished by dose of NSC-CRAd-S-pk7. Three patients received the lowest dose of 6.25×1010 viral particles administered by 5.00×10⁷ neural stem cells (NSCs), three received a more moderate dose of 1.25×10 viral particles administered by 1.00×108 NSCs, and the remaining six patients received a dose of 1.875×1011 viral particles administered by 1.50×108 NSCs. Within 10-14 days, the investigators also initiated treatment with temozolomide and radiotherapy.

The investigators report that after a median 18-month follow-up period, median progression-free survival was 9.1 months, and median overall survival of 18.4 months. In a subgroup of patients with unmethylated MGMT promoters – DNA repair enzymes that make tumor cells more resistant to treatment – median progression-free survival was 8.8 months, and median overall survival was 18.0 months.

There was no dose-limiting toxicity, and there were no treatment-related deaths. One patient developed viral meningitis, owing to the inadvertent ventricular injection of NSC-CRAd-S-pk7, and fully recovered after hospitalization.

Patients tolerated the treatment well, which is critical because “drugs that could fight gliomas might also have serious adverse effects,” first author Jawad Fares, MD, a postdoctoral fellow in neurological surgery at Northwestern University, Chicago, said in an interview.
 

A novel approach

A significant challenge to delivering drugs to the site of malignant gliomas is the blood-brain barrier, which blocks entry of many chemotherapeutic drugs.

“Because of this barrier, physicians often employ other strategies, such as direct injection in the brain cavity, but even with an injection, it is problematic to disseminate the drug so that the medication spreads throughout the tumor mass,” said Dr. Fares. “Our innovative approach, which employs the use of neural stem cells as shuttles to deliver viruses, seeks to address this problem. Neural stem cells tend to travel within hours to areas of injury, areas of stroke or brain tumors, and could disperse the oncolytic virus.”

Gliomas create an immunosuppressive tumor microenvironment, which uses tissue cells, blood vessels, immune cells, and other parts of the body to blunt antitumor immune responses. Using NSCs to deliver NSC-CRAd-S-pk7 directly to the tumor has the advantage of “giving the virus more time to replicate and kill tumor cells,” said Marta Alonso Roldán, MD, Clinica Universidad de Navarra, in Spain, in an interview.

Although NSC-CRAd-S-pk7 appeared to improve survival in this cohort by a few months, follow-up trials with larger sample sizes and control groups are necessary to demonstrate efficacy.

Moreover, patients in this trial may not be representative of the average patient, said Dr. Burns. “For instance, three of the patients had relatively small tumors in nicely operable areas with a high likelihood of getting a gross total resection. These things do stack your odds in favor of having a longer survival.”

Moving forward, “this trial sets the stage for a phase 2/3 study in which the efficacy of NSC-CRAd-S-pk7 in eliciting an antiglioma immune response and prolonging survival in a larger cohort of patients with controlled conditions can be explored,” Dr. Fares said.

The study was funded by the U.S. National Institutes of Health. Dr. Fares, Dr. Burns, and Dr. Roldán have disclosed no relevant financial relationships.

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

A novel virus engineered to target malignant gliomas, which are particularly aggressive brain tumors, may prolong survival, according to a recent phase 1 study.

The findings, published June 29 in The Lancet Oncology, show early promise in targeting malignant gliomas, which have been notoriously difficult to treat. Only 1 in 4 patients are alive 2 years after diagnosis. The median overall survival from diagnosis is 14.6-16.7 months.

In a study of a novel therapy called NSC-CRAd-S-pk7 – an oncolytic adenovirus delivered across the blood-brain barrier by neural stem cells – overall survival improved by several months for patients with malignant gliomas.

“To my knowledge, this is the first time neural stem cells have been used as a delivery strategy for an oncolytic virus,” said Terence Burns, MD, PhD, associate professor of neurosurgery at the Mayo Clinic, Rochester, Minn., who was not involved in the research.

In this open-label, dose-escalation trial, researchers enrolled 12 patients with newly diagnosed malignant gliomas between April 2017 and November 2019. After neurosurgical tumor resection, patients were placed in one of three cohorts distinguished by dose of NSC-CRAd-S-pk7. Three patients received the lowest dose of 6.25×1010 viral particles administered by 5.00×10⁷ neural stem cells (NSCs), three received a more moderate dose of 1.25×10 viral particles administered by 1.00×108 NSCs, and the remaining six patients received a dose of 1.875×1011 viral particles administered by 1.50×108 NSCs. Within 10-14 days, the investigators also initiated treatment with temozolomide and radiotherapy.

The investigators report that after a median 18-month follow-up period, median progression-free survival was 9.1 months, and median overall survival of 18.4 months. In a subgroup of patients with unmethylated MGMT promoters – DNA repair enzymes that make tumor cells more resistant to treatment – median progression-free survival was 8.8 months, and median overall survival was 18.0 months.

There was no dose-limiting toxicity, and there were no treatment-related deaths. One patient developed viral meningitis, owing to the inadvertent ventricular injection of NSC-CRAd-S-pk7, and fully recovered after hospitalization.

Patients tolerated the treatment well, which is critical because “drugs that could fight gliomas might also have serious adverse effects,” first author Jawad Fares, MD, a postdoctoral fellow in neurological surgery at Northwestern University, Chicago, said in an interview.
 

A novel approach

A significant challenge to delivering drugs to the site of malignant gliomas is the blood-brain barrier, which blocks entry of many chemotherapeutic drugs.

“Because of this barrier, physicians often employ other strategies, such as direct injection in the brain cavity, but even with an injection, it is problematic to disseminate the drug so that the medication spreads throughout the tumor mass,” said Dr. Fares. “Our innovative approach, which employs the use of neural stem cells as shuttles to deliver viruses, seeks to address this problem. Neural stem cells tend to travel within hours to areas of injury, areas of stroke or brain tumors, and could disperse the oncolytic virus.”

Gliomas create an immunosuppressive tumor microenvironment, which uses tissue cells, blood vessels, immune cells, and other parts of the body to blunt antitumor immune responses. Using NSCs to deliver NSC-CRAd-S-pk7 directly to the tumor has the advantage of “giving the virus more time to replicate and kill tumor cells,” said Marta Alonso Roldán, MD, Clinica Universidad de Navarra, in Spain, in an interview.

Although NSC-CRAd-S-pk7 appeared to improve survival in this cohort by a few months, follow-up trials with larger sample sizes and control groups are necessary to demonstrate efficacy.

Moreover, patients in this trial may not be representative of the average patient, said Dr. Burns. “For instance, three of the patients had relatively small tumors in nicely operable areas with a high likelihood of getting a gross total resection. These things do stack your odds in favor of having a longer survival.”

Moving forward, “this trial sets the stage for a phase 2/3 study in which the efficacy of NSC-CRAd-S-pk7 in eliciting an antiglioma immune response and prolonging survival in a larger cohort of patients with controlled conditions can be explored,” Dr. Fares said.

The study was funded by the U.S. National Institutes of Health. Dr. Fares, Dr. Burns, and Dr. Roldán have disclosed no relevant financial relationships.

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

A novel virus engineered to target malignant gliomas, which are particularly aggressive brain tumors, may prolong survival, according to a recent phase 1 study.

The findings, published June 29 in The Lancet Oncology, show early promise in targeting malignant gliomas, which have been notoriously difficult to treat. Only 1 in 4 patients are alive 2 years after diagnosis. The median overall survival from diagnosis is 14.6-16.7 months.

In a study of a novel therapy called NSC-CRAd-S-pk7 – an oncolytic adenovirus delivered across the blood-brain barrier by neural stem cells – overall survival improved by several months for patients with malignant gliomas.

“To my knowledge, this is the first time neural stem cells have been used as a delivery strategy for an oncolytic virus,” said Terence Burns, MD, PhD, associate professor of neurosurgery at the Mayo Clinic, Rochester, Minn., who was not involved in the research.

In this open-label, dose-escalation trial, researchers enrolled 12 patients with newly diagnosed malignant gliomas between April 2017 and November 2019. After neurosurgical tumor resection, patients were placed in one of three cohorts distinguished by dose of NSC-CRAd-S-pk7. Three patients received the lowest dose of 6.25×1010 viral particles administered by 5.00×10⁷ neural stem cells (NSCs), three received a more moderate dose of 1.25×10 viral particles administered by 1.00×108 NSCs, and the remaining six patients received a dose of 1.875×1011 viral particles administered by 1.50×108 NSCs. Within 10-14 days, the investigators also initiated treatment with temozolomide and radiotherapy.

The investigators report that after a median 18-month follow-up period, median progression-free survival was 9.1 months, and median overall survival of 18.4 months. In a subgroup of patients with unmethylated MGMT promoters – DNA repair enzymes that make tumor cells more resistant to treatment – median progression-free survival was 8.8 months, and median overall survival was 18.0 months.

There was no dose-limiting toxicity, and there were no treatment-related deaths. One patient developed viral meningitis, owing to the inadvertent ventricular injection of NSC-CRAd-S-pk7, and fully recovered after hospitalization.

Patients tolerated the treatment well, which is critical because “drugs that could fight gliomas might also have serious adverse effects,” first author Jawad Fares, MD, a postdoctoral fellow in neurological surgery at Northwestern University, Chicago, said in an interview.
 

A novel approach

A significant challenge to delivering drugs to the site of malignant gliomas is the blood-brain barrier, which blocks entry of many chemotherapeutic drugs.

“Because of this barrier, physicians often employ other strategies, such as direct injection in the brain cavity, but even with an injection, it is problematic to disseminate the drug so that the medication spreads throughout the tumor mass,” said Dr. Fares. “Our innovative approach, which employs the use of neural stem cells as shuttles to deliver viruses, seeks to address this problem. Neural stem cells tend to travel within hours to areas of injury, areas of stroke or brain tumors, and could disperse the oncolytic virus.”

Gliomas create an immunosuppressive tumor microenvironment, which uses tissue cells, blood vessels, immune cells, and other parts of the body to blunt antitumor immune responses. Using NSCs to deliver NSC-CRAd-S-pk7 directly to the tumor has the advantage of “giving the virus more time to replicate and kill tumor cells,” said Marta Alonso Roldán, MD, Clinica Universidad de Navarra, in Spain, in an interview.

Although NSC-CRAd-S-pk7 appeared to improve survival in this cohort by a few months, follow-up trials with larger sample sizes and control groups are necessary to demonstrate efficacy.

Moreover, patients in this trial may not be representative of the average patient, said Dr. Burns. “For instance, three of the patients had relatively small tumors in nicely operable areas with a high likelihood of getting a gross total resection. These things do stack your odds in favor of having a longer survival.”

Moving forward, “this trial sets the stage for a phase 2/3 study in which the efficacy of NSC-CRAd-S-pk7 in eliciting an antiglioma immune response and prolonging survival in a larger cohort of patients with controlled conditions can be explored,” Dr. Fares said.

The study was funded by the U.S. National Institutes of Health. Dr. Fares, Dr. Burns, and Dr. Roldán have disclosed no relevant financial relationships.

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

The number of U.S. adults who are at least partially vaccinated rose five percentage points to 72% in August, a slightly faster increase than in previous months, according to the latest monthly COVID-19 Vaccine Monitor report of the Kaiser Family Foundation (KFF).

The largest increases in vaccine uptake between July and September were among Hispanic adults and people aged 18-29 years. Roughly equal shares of adults now report being vaccinated across racial and ethnic groups: 71% of White adults, 70% of Black adults, and 73% of Hispanic adults.

Overall, the big takeaway of the latest Kaiser COVID-19 survey is that the partisan divide on all aspects of the pandemic, from vaccination status to attitudes toward vaccination and mask mandates, remains as wide as ever.

The only thing that Republicans, Democrats, and Independents mostly agree on is that COVID-19 will probably become an endemic disease like influenza. Seventy-nine percent of respondents agreed with that statement; 14% predicted that COVID-19 would probably be largely eliminated in future years, like polio.
 

Delta motivated many

The most important factor that recently led people toward being vaccinated against COVID-19 was the surge in cases, hospitalizations, and deaths due to the Delta variant, KFF reports.

Full approval of the Pfizer vaccine by the Food and Drug Administration and the increasing prevalence of vaccine mandates played secondary roles in the vaccination uptick.

Specifically, 10% of the recently vaccinated said the main reason they got shots was the increase in COVID-19 cases due to the Delta variant. Concern about reports of local hospitals and intensive care units filling up with COVID-19 patients was the main motivator for 12% of those who just got shots. Fourteen percent of the recently vaccinated got inoculated mainly because someone they knew had become seriously ill or had died from COVID-19.

The role of the Delta threat is also evident with regard to where those who were recently vaccinated live. Twenty-four percent of those who received their first dose of vaccine after June 1, 2021, reside in counties with a high COVID-19 case rate; 15% of them live in counties with a relatively low case rate.

Despite the recent surge in vaccinations, however, 7% of adults are still taking a wait-and-see approach; 4% said they’d get a shot only if required; and 12% said they definitely wouldn’t get vaccinated. The latter figure has barely budged since January of this year.

Ninety percent of Democrats said they had received at least one dose of the COVID-19 vaccine, vs. 68% of Independents, and 58% of Republicans.

Wealthier, better educated, urban, and older people were more likely to be vaccinated, with one exception: Sixty-eight percent of those aged 18-29 were vaccinated, vs. 66% of those aged 30-49. The group least likely to be vaccinated were uninsured people younger than 65, suggesting that some of them were unaware that the shot is free.
 

Partisan affiliation

Attitudes toward vaccine booster shots – which are now recommended for people older than 65, the immunocompromised, and certain frontline workers – largely fell along party lines and/or reflected whether respondents had been vaccinated.

Discussion of the boosters, KFF said, “appears to be a net positive for people who are already vaccinated, but a net negative for the unvaccinated. While a larger share of vaccinated adults say the information they have seen about boosters has been helpful (54%) than find it confusing (35%), among the unvaccinated almost twice as many find the information confusing as find it helpful (45% vs. 24%).”

Among fully vaccinated adults, 68% of Democrats say they’d definitely get a booster, and 20% say they probably would. Among Republicans, those percentages are 36% and 33%, respectively. Independents fall in between the other groups.

Although 82% of Democrats say the boosters show that scientists are continuing to make vaccines more effective, 52% of Republicans say that it shows that the vaccines are not working as well as promised.

Similarly, partisan attitudes emerged in questions about breakthrough infections. The fact that COVID-19 cases are fairly mild when they occur among persons who have been vaccinated indicates that the vaccines are working, said 87% of Democrats, but only 55% of Republicans agreed with that assessment.

In contrast, just 10% of Democrats but 39% of Republicans said that breakthrough infections mean the vaccines are not working.
 

Vaccine requirements

The public is more evenly divided on vaccine requirements. About 6 in 10 respondents said that vaccines should be required for health care workers (62%) and schoolteachers (58%). Slim majorities supported mandates for federal government employees (55%), college students (55%), and state and local government employees (54%).

On the question of whether employers in general should require their workers to be vaccinated, 48% of respondents said they should, and 50% said they should not.

Similarly, 52% said that all schools should mandate vaccines for eligible students; 46% didn’t approve of such requirements.

Three in four Democrats supported employer vaccine mandates, compared to 45% of Independents and just 20% of Republicans. Large partisan gaps were also seen for government, school, and health care vaccine mandates.

In contrast, 78% of the public favored requiring large employers to give their workers paid time off to get vaccinated and to recover from any side effects.
 

Twenty percent of workers under mandates

One in five workers said their employers require COVID-19 vaccination. Twenty-eight percent of employed people want their employers to require vaccination, and 50% don’t.

Again, the responses broke down along party lines, with 52% of Democrats, 21% of Independents, and 10% of Republicans favoring a vaccine mandate by their employers.

Most unvaccinated people didn’t support an employer mandate. A third of unvaccinated workers said they’d be likely to get vaccinated if their companies required it, but most of them said they would choose weekly testing if offered the option.

Being unable to use gyms, restaurants, or indoor entertainment venues that require vaccination was cited by 13% of the recently vaccinated as the main reason why they got shots.

The public was evenly divided on whether states or local governments should require such businesses to mandate that staff and customers show proof of vaccination. Although the views of the public were tied on this issue overall, 79% of Democrats, 43% of Independents, and 21% of Republicans supported having these kinds of businesses require proof of vaccination.

On school mask mandates, 56% of the respondents supported requiring all students and staff to wear masks. Favoring this kind of mandate were 83% of Democrats, 53% of Independents, and 29% of Republicans.

Partisanship also defined how Democrats and Republicans viewed the current high number of COVID-19 cases. Most Democrats blamed people who don’t wear masks and those who don’t get vaccinated, whereas Republicans were more likely to blame immigrants and tourists bringing COVID-19 into the United States.

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

The number of U.S. adults who are at least partially vaccinated rose five percentage points to 72% in August, a slightly faster increase than in previous months, according to the latest monthly COVID-19 Vaccine Monitor report of the Kaiser Family Foundation (KFF).

The largest increases in vaccine uptake between July and September were among Hispanic adults and people aged 18-29 years. Roughly equal shares of adults now report being vaccinated across racial and ethnic groups: 71% of White adults, 70% of Black adults, and 73% of Hispanic adults.

Overall, the big takeaway of the latest Kaiser COVID-19 survey is that the partisan divide on all aspects of the pandemic, from vaccination status to attitudes toward vaccination and mask mandates, remains as wide as ever.

The only thing that Republicans, Democrats, and Independents mostly agree on is that COVID-19 will probably become an endemic disease like influenza. Seventy-nine percent of respondents agreed with that statement; 14% predicted that COVID-19 would probably be largely eliminated in future years, like polio.
 

Delta motivated many

The most important factor that recently led people toward being vaccinated against COVID-19 was the surge in cases, hospitalizations, and deaths due to the Delta variant, KFF reports.

Full approval of the Pfizer vaccine by the Food and Drug Administration and the increasing prevalence of vaccine mandates played secondary roles in the vaccination uptick.

Specifically, 10% of the recently vaccinated said the main reason they got shots was the increase in COVID-19 cases due to the Delta variant. Concern about reports of local hospitals and intensive care units filling up with COVID-19 patients was the main motivator for 12% of those who just got shots. Fourteen percent of the recently vaccinated got inoculated mainly because someone they knew had become seriously ill or had died from COVID-19.

The role of the Delta threat is also evident with regard to where those who were recently vaccinated live. Twenty-four percent of those who received their first dose of vaccine after June 1, 2021, reside in counties with a high COVID-19 case rate; 15% of them live in counties with a relatively low case rate.

Despite the recent surge in vaccinations, however, 7% of adults are still taking a wait-and-see approach; 4% said they’d get a shot only if required; and 12% said they definitely wouldn’t get vaccinated. The latter figure has barely budged since January of this year.

Ninety percent of Democrats said they had received at least one dose of the COVID-19 vaccine, vs. 68% of Independents, and 58% of Republicans.

Wealthier, better educated, urban, and older people were more likely to be vaccinated, with one exception: Sixty-eight percent of those aged 18-29 were vaccinated, vs. 66% of those aged 30-49. The group least likely to be vaccinated were uninsured people younger than 65, suggesting that some of them were unaware that the shot is free.
 

Partisan affiliation

Attitudes toward vaccine booster shots – which are now recommended for people older than 65, the immunocompromised, and certain frontline workers – largely fell along party lines and/or reflected whether respondents had been vaccinated.

Discussion of the boosters, KFF said, “appears to be a net positive for people who are already vaccinated, but a net negative for the unvaccinated. While a larger share of vaccinated adults say the information they have seen about boosters has been helpful (54%) than find it confusing (35%), among the unvaccinated almost twice as many find the information confusing as find it helpful (45% vs. 24%).”

Among fully vaccinated adults, 68% of Democrats say they’d definitely get a booster, and 20% say they probably would. Among Republicans, those percentages are 36% and 33%, respectively. Independents fall in between the other groups.

Although 82% of Democrats say the boosters show that scientists are continuing to make vaccines more effective, 52% of Republicans say that it shows that the vaccines are not working as well as promised.

Similarly, partisan attitudes emerged in questions about breakthrough infections. The fact that COVID-19 cases are fairly mild when they occur among persons who have been vaccinated indicates that the vaccines are working, said 87% of Democrats, but only 55% of Republicans agreed with that assessment.

In contrast, just 10% of Democrats but 39% of Republicans said that breakthrough infections mean the vaccines are not working.
 

Vaccine requirements

The public is more evenly divided on vaccine requirements. About 6 in 10 respondents said that vaccines should be required for health care workers (62%) and schoolteachers (58%). Slim majorities supported mandates for federal government employees (55%), college students (55%), and state and local government employees (54%).

On the question of whether employers in general should require their workers to be vaccinated, 48% of respondents said they should, and 50% said they should not.

Similarly, 52% said that all schools should mandate vaccines for eligible students; 46% didn’t approve of such requirements.

Three in four Democrats supported employer vaccine mandates, compared to 45% of Independents and just 20% of Republicans. Large partisan gaps were also seen for government, school, and health care vaccine mandates.

In contrast, 78% of the public favored requiring large employers to give their workers paid time off to get vaccinated and to recover from any side effects.
 

Twenty percent of workers under mandates

One in five workers said their employers require COVID-19 vaccination. Twenty-eight percent of employed people want their employers to require vaccination, and 50% don’t.

Again, the responses broke down along party lines, with 52% of Democrats, 21% of Independents, and 10% of Republicans favoring a vaccine mandate by their employers.

Most unvaccinated people didn’t support an employer mandate. A third of unvaccinated workers said they’d be likely to get vaccinated if their companies required it, but most of them said they would choose weekly testing if offered the option.

Being unable to use gyms, restaurants, or indoor entertainment venues that require vaccination was cited by 13% of the recently vaccinated as the main reason why they got shots.

The public was evenly divided on whether states or local governments should require such businesses to mandate that staff and customers show proof of vaccination. Although the views of the public were tied on this issue overall, 79% of Democrats, 43% of Independents, and 21% of Republicans supported having these kinds of businesses require proof of vaccination.

On school mask mandates, 56% of the respondents supported requiring all students and staff to wear masks. Favoring this kind of mandate were 83% of Democrats, 53% of Independents, and 29% of Republicans.

Partisanship also defined how Democrats and Republicans viewed the current high number of COVID-19 cases. Most Democrats blamed people who don’t wear masks and those who don’t get vaccinated, whereas Republicans were more likely to blame immigrants and tourists bringing COVID-19 into the United States.

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

The number of U.S. adults who are at least partially vaccinated rose five percentage points to 72% in August, a slightly faster increase than in previous months, according to the latest monthly COVID-19 Vaccine Monitor report of the Kaiser Family Foundation (KFF).

The largest increases in vaccine uptake between July and September were among Hispanic adults and people aged 18-29 years. Roughly equal shares of adults now report being vaccinated across racial and ethnic groups: 71% of White adults, 70% of Black adults, and 73% of Hispanic adults.

Overall, the big takeaway of the latest Kaiser COVID-19 survey is that the partisan divide on all aspects of the pandemic, from vaccination status to attitudes toward vaccination and mask mandates, remains as wide as ever.

The only thing that Republicans, Democrats, and Independents mostly agree on is that COVID-19 will probably become an endemic disease like influenza. Seventy-nine percent of respondents agreed with that statement; 14% predicted that COVID-19 would probably be largely eliminated in future years, like polio.
 

Delta motivated many

The most important factor that recently led people toward being vaccinated against COVID-19 was the surge in cases, hospitalizations, and deaths due to the Delta variant, KFF reports.

Full approval of the Pfizer vaccine by the Food and Drug Administration and the increasing prevalence of vaccine mandates played secondary roles in the vaccination uptick.

Specifically, 10% of the recently vaccinated said the main reason they got shots was the increase in COVID-19 cases due to the Delta variant. Concern about reports of local hospitals and intensive care units filling up with COVID-19 patients was the main motivator for 12% of those who just got shots. Fourteen percent of the recently vaccinated got inoculated mainly because someone they knew had become seriously ill or had died from COVID-19.

The role of the Delta threat is also evident with regard to where those who were recently vaccinated live. Twenty-four percent of those who received their first dose of vaccine after June 1, 2021, reside in counties with a high COVID-19 case rate; 15% of them live in counties with a relatively low case rate.

Despite the recent surge in vaccinations, however, 7% of adults are still taking a wait-and-see approach; 4% said they’d get a shot only if required; and 12% said they definitely wouldn’t get vaccinated. The latter figure has barely budged since January of this year.

Ninety percent of Democrats said they had received at least one dose of the COVID-19 vaccine, vs. 68% of Independents, and 58% of Republicans.

Wealthier, better educated, urban, and older people were more likely to be vaccinated, with one exception: Sixty-eight percent of those aged 18-29 were vaccinated, vs. 66% of those aged 30-49. The group least likely to be vaccinated were uninsured people younger than 65, suggesting that some of them were unaware that the shot is free.
 

Partisan affiliation

Attitudes toward vaccine booster shots – which are now recommended for people older than 65, the immunocompromised, and certain frontline workers – largely fell along party lines and/or reflected whether respondents had been vaccinated.

Discussion of the boosters, KFF said, “appears to be a net positive for people who are already vaccinated, but a net negative for the unvaccinated. While a larger share of vaccinated adults say the information they have seen about boosters has been helpful (54%) than find it confusing (35%), among the unvaccinated almost twice as many find the information confusing as find it helpful (45% vs. 24%).”

Among fully vaccinated adults, 68% of Democrats say they’d definitely get a booster, and 20% say they probably would. Among Republicans, those percentages are 36% and 33%, respectively. Independents fall in between the other groups.

Although 82% of Democrats say the boosters show that scientists are continuing to make vaccines more effective, 52% of Republicans say that it shows that the vaccines are not working as well as promised.

Similarly, partisan attitudes emerged in questions about breakthrough infections. The fact that COVID-19 cases are fairly mild when they occur among persons who have been vaccinated indicates that the vaccines are working, said 87% of Democrats, but only 55% of Republicans agreed with that assessment.

In contrast, just 10% of Democrats but 39% of Republicans said that breakthrough infections mean the vaccines are not working.
 

Vaccine requirements

The public is more evenly divided on vaccine requirements. About 6 in 10 respondents said that vaccines should be required for health care workers (62%) and schoolteachers (58%). Slim majorities supported mandates for federal government employees (55%), college students (55%), and state and local government employees (54%).

On the question of whether employers in general should require their workers to be vaccinated, 48% of respondents said they should, and 50% said they should not.

Similarly, 52% said that all schools should mandate vaccines for eligible students; 46% didn’t approve of such requirements.

Three in four Democrats supported employer vaccine mandates, compared to 45% of Independents and just 20% of Republicans. Large partisan gaps were also seen for government, school, and health care vaccine mandates.

In contrast, 78% of the public favored requiring large employers to give their workers paid time off to get vaccinated and to recover from any side effects.
 

Twenty percent of workers under mandates

One in five workers said their employers require COVID-19 vaccination. Twenty-eight percent of employed people want their employers to require vaccination, and 50% don’t.

Again, the responses broke down along party lines, with 52% of Democrats, 21% of Independents, and 10% of Republicans favoring a vaccine mandate by their employers.

Most unvaccinated people didn’t support an employer mandate. A third of unvaccinated workers said they’d be likely to get vaccinated if their companies required it, but most of them said they would choose weekly testing if offered the option.

Being unable to use gyms, restaurants, or indoor entertainment venues that require vaccination was cited by 13% of the recently vaccinated as the main reason why they got shots.

The public was evenly divided on whether states or local governments should require such businesses to mandate that staff and customers show proof of vaccination. Although the views of the public were tied on this issue overall, 79% of Democrats, 43% of Independents, and 21% of Republicans supported having these kinds of businesses require proof of vaccination.

On school mask mandates, 56% of the respondents supported requiring all students and staff to wear masks. Favoring this kind of mandate were 83% of Democrats, 53% of Independents, and 29% of Republicans.

Partisanship also defined how Democrats and Republicans viewed the current high number of COVID-19 cases. Most Democrats blamed people who don’t wear masks and those who don’t get vaccinated, whereas Republicans were more likely to blame immigrants and tourists bringing COVID-19 into the United States.

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

Juvenile xanthogranuloma (JXG) is a benign disorder presenting as firm, yellow-red skin papules or nodules, usually in infancy or early childhood. It derives its name based on its yellowish color and the histologic finding of lipid-filled histiocytes. In fact, it is a form of non-Langerhans’ cell histiocytosis. It most commonly presents on the head, neck, and trunk, but can arise anywhere on the body as demonstrated by this case. While often pink to reddish early on, the characteristic yellow or orange, brown appearance over time is common, occasionally with overlying telangiectasia, and ranging in size from 1 mm to 2 cm. While typically asymptomatic, it is possible for lesions to itch. JXG is usually self-limiting, and spontaneously resolves over several years. On dermoscopy (with polarized light), it has a characteristic “setting sun” appearance because of its central yellow area surrounded by a reddish periphery.

David Schairer, MD

JXGs have been associated with neurofibromatosis-1 and a “triple association” of NF-1, JXG, and juvenile myelomonocytic leukemia (JMML) has been debated. Many cases are diagnosed on clinical grounds without histologic confirmation, so while the absolute incidence is unknown, they are not uncommon.
 

What is on the differential?

Spitz nevus is a melanocytic lesion which typically presents as a sharply circumscribed, dome-shaped, pink-red or brown papule or nodule, and is composed of large epithelioid and/or spindled cells. These nevi can present with a spectrum of morphology and biologic activity; commonly with benign melanocytic proliferations and a symmetric appearance or, rarely, with atypical tumors or lesions, characterized as Spitzoid melanomas. The yellowish color of JXG is distinct from the appearance of Spitz tumors.

Molluscum contagiosum is a common pox viral infection seen in children that presents with round, flat-topped firm papules on the skin and distinctive whitish centers with or without umbilication. Like JXG, molluscum contagiosum papules may grow over time and cause pruritus. However, this diagnosis is less likely given the absence of other lesions on the skin, lack of known contacts with similar lesions, and yellowish color without a more typical appearance of molluscum.

Dermatofibromas occur in people of all ages, although more commonly between the ages of 20 and 40 and in those with a history of trauma at the lesion. Like JXGs, dermatofibromas tend to be firm, solitary papules or nodules. They usually are hyperpigmented, and classically “dimple when pinched” as they are fixed to the subcutaneous tissue. However, this patient’s age, lack of trauma, and the lesion morphology are not consistent with dermatofibromas.

Like XJGs, mastocytomas commonly present in the first 2 years of life with maculopapular or nodular lesions that itch. However, the history of new-onset itch in recent months as the lesion grew larger and the yellow color on dermoscopy are more consistent with JXG.

Eruptive xanthomas typically appear suddenly as multiple erythematous yellow, dome-shaped papules on the extensor surfaces of the extremities, buttocks, and hands. They are usually present with hypertriglyceridemia and are very rare in young children. The presence of a solitary lesion in a 6-month-old patient without a history of lipid abnormalities favors the diagnosis of XJG.
 

Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Ms. Kleinman is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital. Dr. Eichenfield and Ms. Kleinman have no relevant financial disclosures.

References

Hernandez-Martin A et al. J Am Acad Dermatol. 1997 Mar;36(3 Pt 1):355-67.

Prendiville J. Lumps, bumps and hamartomas in “Neonatal and Infant Dermatology,” 3rd ed. (Philadelphia: Elsevier, 2015).

Püttgen KB. Juvenile xanthogranuloma. UpToDate, 2021.

Schaffer JV. Am J Clin Dermatol. 2021 Mar;22(2):205-20.

Juvenile xanthogranuloma (JXG) is a benign disorder presenting as firm, yellow-red skin papules or nodules, usually in infancy or early childhood. It derives its name based on its yellowish color and the histologic finding of lipid-filled histiocytes. In fact, it is a form of non-Langerhans’ cell histiocytosis. It most commonly presents on the head, neck, and trunk, but can arise anywhere on the body as demonstrated by this case. While often pink to reddish early on, the characteristic yellow or orange, brown appearance over time is common, occasionally with overlying telangiectasia, and ranging in size from 1 mm to 2 cm. While typically asymptomatic, it is possible for lesions to itch. JXG is usually self-limiting, and spontaneously resolves over several years. On dermoscopy (with polarized light), it has a characteristic “setting sun” appearance because of its central yellow area surrounded by a reddish periphery.

David Schairer, MD

JXGs have been associated with neurofibromatosis-1 and a “triple association” of NF-1, JXG, and juvenile myelomonocytic leukemia (JMML) has been debated. Many cases are diagnosed on clinical grounds without histologic confirmation, so while the absolute incidence is unknown, they are not uncommon.
 

What is on the differential?

Spitz nevus is a melanocytic lesion which typically presents as a sharply circumscribed, dome-shaped, pink-red or brown papule or nodule, and is composed of large epithelioid and/or spindled cells. These nevi can present with a spectrum of morphology and biologic activity; commonly with benign melanocytic proliferations and a symmetric appearance or, rarely, with atypical tumors or lesions, characterized as Spitzoid melanomas. The yellowish color of JXG is distinct from the appearance of Spitz tumors.

Molluscum contagiosum is a common pox viral infection seen in children that presents with round, flat-topped firm papules on the skin and distinctive whitish centers with or without umbilication. Like JXG, molluscum contagiosum papules may grow over time and cause pruritus. However, this diagnosis is less likely given the absence of other lesions on the skin, lack of known contacts with similar lesions, and yellowish color without a more typical appearance of molluscum.

Dermatofibromas occur in people of all ages, although more commonly between the ages of 20 and 40 and in those with a history of trauma at the lesion. Like JXGs, dermatofibromas tend to be firm, solitary papules or nodules. They usually are hyperpigmented, and classically “dimple when pinched” as they are fixed to the subcutaneous tissue. However, this patient’s age, lack of trauma, and the lesion morphology are not consistent with dermatofibromas.

Like XJGs, mastocytomas commonly present in the first 2 years of life with maculopapular or nodular lesions that itch. However, the history of new-onset itch in recent months as the lesion grew larger and the yellow color on dermoscopy are more consistent with JXG.

Eruptive xanthomas typically appear suddenly as multiple erythematous yellow, dome-shaped papules on the extensor surfaces of the extremities, buttocks, and hands. They are usually present with hypertriglyceridemia and are very rare in young children. The presence of a solitary lesion in a 6-month-old patient without a history of lipid abnormalities favors the diagnosis of XJG.
 

Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Ms. Kleinman is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital. Dr. Eichenfield and Ms. Kleinman have no relevant financial disclosures.

References

Hernandez-Martin A et al. J Am Acad Dermatol. 1997 Mar;36(3 Pt 1):355-67.

Prendiville J. Lumps, bumps and hamartomas in “Neonatal and Infant Dermatology,” 3rd ed. (Philadelphia: Elsevier, 2015).

Püttgen KB. Juvenile xanthogranuloma. UpToDate, 2021.

Schaffer JV. Am J Clin Dermatol. 2021 Mar;22(2):205-20.

Juvenile xanthogranuloma (JXG) is a benign disorder presenting as firm, yellow-red skin papules or nodules, usually in infancy or early childhood. It derives its name based on its yellowish color and the histologic finding of lipid-filled histiocytes. In fact, it is a form of non-Langerhans’ cell histiocytosis. It most commonly presents on the head, neck, and trunk, but can arise anywhere on the body as demonstrated by this case. While often pink to reddish early on, the characteristic yellow or orange, brown appearance over time is common, occasionally with overlying telangiectasia, and ranging in size from 1 mm to 2 cm. While typically asymptomatic, it is possible for lesions to itch. JXG is usually self-limiting, and spontaneously resolves over several years. On dermoscopy (with polarized light), it has a characteristic “setting sun” appearance because of its central yellow area surrounded by a reddish periphery.

David Schairer, MD

JXGs have been associated with neurofibromatosis-1 and a “triple association” of NF-1, JXG, and juvenile myelomonocytic leukemia (JMML) has been debated. Many cases are diagnosed on clinical grounds without histologic confirmation, so while the absolute incidence is unknown, they are not uncommon.
 

What is on the differential?

Spitz nevus is a melanocytic lesion which typically presents as a sharply circumscribed, dome-shaped, pink-red or brown papule or nodule, and is composed of large epithelioid and/or spindled cells. These nevi can present with a spectrum of morphology and biologic activity; commonly with benign melanocytic proliferations and a symmetric appearance or, rarely, with atypical tumors or lesions, characterized as Spitzoid melanomas. The yellowish color of JXG is distinct from the appearance of Spitz tumors.

Molluscum contagiosum is a common pox viral infection seen in children that presents with round, flat-topped firm papules on the skin and distinctive whitish centers with or without umbilication. Like JXG, molluscum contagiosum papules may grow over time and cause pruritus. However, this diagnosis is less likely given the absence of other lesions on the skin, lack of known contacts with similar lesions, and yellowish color without a more typical appearance of molluscum.

Dermatofibromas occur in people of all ages, although more commonly between the ages of 20 and 40 and in those with a history of trauma at the lesion. Like JXGs, dermatofibromas tend to be firm, solitary papules or nodules. They usually are hyperpigmented, and classically “dimple when pinched” as they are fixed to the subcutaneous tissue. However, this patient’s age, lack of trauma, and the lesion morphology are not consistent with dermatofibromas.

Like XJGs, mastocytomas commonly present in the first 2 years of life with maculopapular or nodular lesions that itch. However, the history of new-onset itch in recent months as the lesion grew larger and the yellow color on dermoscopy are more consistent with JXG.

Eruptive xanthomas typically appear suddenly as multiple erythematous yellow, dome-shaped papules on the extensor surfaces of the extremities, buttocks, and hands. They are usually present with hypertriglyceridemia and are very rare in young children. The presence of a solitary lesion in a 6-month-old patient without a history of lipid abnormalities favors the diagnosis of XJG.
 

Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Ms. Kleinman is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital. Dr. Eichenfield and Ms. Kleinman have no relevant financial disclosures.

References

Hernandez-Martin A et al. J Am Acad Dermatol. 1997 Mar;36(3 Pt 1):355-67.

Prendiville J. Lumps, bumps and hamartomas in “Neonatal and Infant Dermatology,” 3rd ed. (Philadelphia: Elsevier, 2015).

Püttgen KB. Juvenile xanthogranuloma. UpToDate, 2021.

Schaffer JV. Am J Clin Dermatol. 2021 Mar;22(2):205-20.

The U.S. Department of Veteran Affairs (VA) has been unable to provide genetic counseling to veterans at the same level as the civilian community, and other gaps exist, a genetic counselor told oncologist and hematologist colleagues. The good news is that telemedicine is turning out to be a valuable and proven way to reach veterans who need this kind of care, she said, although certain patients are being left behind.

“To me, telehealth is no doubt the way to go. But it is really important that we continue to look into these disparities, what's causing them, and how we can find a path forward,” said

Deborah Hartzfeld, MS, CGC, of the Genomic Medicine Service based in Salt Lake City, Utah. She spoke in a presentation at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) that was held virtually and in person in Denver, Colorado, from September 24 to September 26, 2021.

As Harzfeld explained, the genetic counselor workforce is expanding along with the number of indications for genetic testing, especially in cancer, “where the need for germline genetic testing for inherited cancer genes becomes broader every year.”

Genetic counselors are a homogenous group, she said, as revealed by a 2021 survey of most of the nation’s 5,629 certified generic counselors. The North American survey, by the National Society of Genetic Counselors, found that 94% of respondents identified themselves as female, and 90% were white/non-Hispanic.  

The survey report also noted that “the genetic counseling profession has grown by over 100% in the last 10 years and is expected to grow another 100% over the next 10 years. By 2025 there should be nearly 7,500 certified genetic counselors, and by 2030 there are likely to be over 10,000.”

Genetic counseling within the VA has also grown rapidly. In 2010, Harzfeld said, about 737 veterans were referred for the service. In 2020, the number was about 10,000, with about half referred for personal or family history of cancer.

The VA has 18 genetic counselors, not all of whom are actively seeing patients or working full time, she said. “Per the National Society of Genetic Counselors, there's one clinical genetic counselor per 100,000 people in the general population,” she said. “It's one for about 474,000 in the VA.”

Wait times for genetic counseling within the VA exceed Mission Act standards outside of urgent referrals in matters such as surgical or medical management, she said. “We usually see those patients within a week, but other folks have to wait or are referred into the community. It remains unclear how many of our patients could access care easily in the community or what the wait times at any individual VA will be.”

Fortunately, she said, telemedicine has increased access to genetic counseling within the general population and the VA, Harzfeld said. “A recent systematic evidence review found providing genetic counseling via video or telephone is comparable to in-person care, it increases access and it's likely feasible and acceptable to major stakeholders. It's worth noting that the data in this evidence review was collected prior to COVID-19 when fewer programs were using telehealth.”

Genetic counseling works especially well via telehealth because counselors don’t perform physical examinations, she said. “Prior to COVID, service probably saw maybe 4 VVC [VA Video Connect] appointments per month for genetic counseling. Now, VVC makes up about 70% of our new patient encounters. About 25% are telephone and about 5% are clinical video telehealth where the veteran goes into their clinic to be seated in front of the machine.”

Research has suggested that non-White patients are 40 to 50% less likely to be referred to telehealth for genetic counseling vs. in-person encounters, she said, although women in general (including black women) are more likely to be referred.

Harzfeld highlighted several challenges facing genetic counseling in the VA. She notes that contracted laboratories aren’t “really set up to be experts in germline genetic testing, so they’re not as nimble, and their test catalogs are not most likely going to be as comprehensive enough for what is needed.” Also, she said, “test ordering can be quite burdensome.”

“We need to continue working with various partners to increase access and the ease of ordering genetic testing,” she said.

Hartzfeld reports no disclosures.

The U.S. Department of Veteran Affairs (VA) has been unable to provide genetic counseling to veterans at the same level as the civilian community, and other gaps exist, a genetic counselor told oncologist and hematologist colleagues. The good news is that telemedicine is turning out to be a valuable and proven way to reach veterans who need this kind of care, she said, although certain patients are being left behind.

“To me, telehealth is no doubt the way to go. But it is really important that we continue to look into these disparities, what's causing them, and how we can find a path forward,” said

Deborah Hartzfeld, MS, CGC, of the Genomic Medicine Service based in Salt Lake City, Utah. She spoke in a presentation at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) that was held virtually and in person in Denver, Colorado, from September 24 to September 26, 2021.

As Harzfeld explained, the genetic counselor workforce is expanding along with the number of indications for genetic testing, especially in cancer, “where the need for germline genetic testing for inherited cancer genes becomes broader every year.”

Genetic counselors are a homogenous group, she said, as revealed by a 2021 survey of most of the nation’s 5,629 certified generic counselors. The North American survey, by the National Society of Genetic Counselors, found that 94% of respondents identified themselves as female, and 90% were white/non-Hispanic.  

The survey report also noted that “the genetic counseling profession has grown by over 100% in the last 10 years and is expected to grow another 100% over the next 10 years. By 2025 there should be nearly 7,500 certified genetic counselors, and by 2030 there are likely to be over 10,000.”

Genetic counseling within the VA has also grown rapidly. In 2010, Harzfeld said, about 737 veterans were referred for the service. In 2020, the number was about 10,000, with about half referred for personal or family history of cancer.

The VA has 18 genetic counselors, not all of whom are actively seeing patients or working full time, she said. “Per the National Society of Genetic Counselors, there's one clinical genetic counselor per 100,000 people in the general population,” she said. “It's one for about 474,000 in the VA.”

Wait times for genetic counseling within the VA exceed Mission Act standards outside of urgent referrals in matters such as surgical or medical management, she said. “We usually see those patients within a week, but other folks have to wait or are referred into the community. It remains unclear how many of our patients could access care easily in the community or what the wait times at any individual VA will be.”

Fortunately, she said, telemedicine has increased access to genetic counseling within the general population and the VA, Harzfeld said. “A recent systematic evidence review found providing genetic counseling via video or telephone is comparable to in-person care, it increases access and it's likely feasible and acceptable to major stakeholders. It's worth noting that the data in this evidence review was collected prior to COVID-19 when fewer programs were using telehealth.”

Genetic counseling works especially well via telehealth because counselors don’t perform physical examinations, she said. “Prior to COVID, service probably saw maybe 4 VVC [VA Video Connect] appointments per month for genetic counseling. Now, VVC makes up about 70% of our new patient encounters. About 25% are telephone and about 5% are clinical video telehealth where the veteran goes into their clinic to be seated in front of the machine.”

Research has suggested that non-White patients are 40 to 50% less likely to be referred to telehealth for genetic counseling vs. in-person encounters, she said, although women in general (including black women) are more likely to be referred.

Harzfeld highlighted several challenges facing genetic counseling in the VA. She notes that contracted laboratories aren’t “really set up to be experts in germline genetic testing, so they’re not as nimble, and their test catalogs are not most likely going to be as comprehensive enough for what is needed.” Also, she said, “test ordering can be quite burdensome.”

“We need to continue working with various partners to increase access and the ease of ordering genetic testing,” she said.

Hartzfeld reports no disclosures.

The U.S. Department of Veteran Affairs (VA) has been unable to provide genetic counseling to veterans at the same level as the civilian community, and other gaps exist, a genetic counselor told oncologist and hematologist colleagues. The good news is that telemedicine is turning out to be a valuable and proven way to reach veterans who need this kind of care, she said, although certain patients are being left behind.

“To me, telehealth is no doubt the way to go. But it is really important that we continue to look into these disparities, what's causing them, and how we can find a path forward,” said

Deborah Hartzfeld, MS, CGC, of the Genomic Medicine Service based in Salt Lake City, Utah. She spoke in a presentation at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) that was held virtually and in person in Denver, Colorado, from September 24 to September 26, 2021.

As Harzfeld explained, the genetic counselor workforce is expanding along with the number of indications for genetic testing, especially in cancer, “where the need for germline genetic testing for inherited cancer genes becomes broader every year.”

Genetic counselors are a homogenous group, she said, as revealed by a 2021 survey of most of the nation’s 5,629 certified generic counselors. The North American survey, by the National Society of Genetic Counselors, found that 94% of respondents identified themselves as female, and 90% were white/non-Hispanic.  

The survey report also noted that “the genetic counseling profession has grown by over 100% in the last 10 years and is expected to grow another 100% over the next 10 years. By 2025 there should be nearly 7,500 certified genetic counselors, and by 2030 there are likely to be over 10,000.”

Genetic counseling within the VA has also grown rapidly. In 2010, Harzfeld said, about 737 veterans were referred for the service. In 2020, the number was about 10,000, with about half referred for personal or family history of cancer.

The VA has 18 genetic counselors, not all of whom are actively seeing patients or working full time, she said. “Per the National Society of Genetic Counselors, there's one clinical genetic counselor per 100,000 people in the general population,” she said. “It's one for about 474,000 in the VA.”

Wait times for genetic counseling within the VA exceed Mission Act standards outside of urgent referrals in matters such as surgical or medical management, she said. “We usually see those patients within a week, but other folks have to wait or are referred into the community. It remains unclear how many of our patients could access care easily in the community or what the wait times at any individual VA will be.”

Fortunately, she said, telemedicine has increased access to genetic counseling within the general population and the VA, Harzfeld said. “A recent systematic evidence review found providing genetic counseling via video or telephone is comparable to in-person care, it increases access and it's likely feasible and acceptable to major stakeholders. It's worth noting that the data in this evidence review was collected prior to COVID-19 when fewer programs were using telehealth.”

Genetic counseling works especially well via telehealth because counselors don’t perform physical examinations, she said. “Prior to COVID, service probably saw maybe 4 VVC [VA Video Connect] appointments per month for genetic counseling. Now, VVC makes up about 70% of our new patient encounters. About 25% are telephone and about 5% are clinical video telehealth where the veteran goes into their clinic to be seated in front of the machine.”

Research has suggested that non-White patients are 40 to 50% less likely to be referred to telehealth for genetic counseling vs. in-person encounters, she said, although women in general (including black women) are more likely to be referred.

Harzfeld highlighted several challenges facing genetic counseling in the VA. She notes that contracted laboratories aren’t “really set up to be experts in germline genetic testing, so they’re not as nimble, and their test catalogs are not most likely going to be as comprehensive enough for what is needed.” Also, she said, “test ordering can be quite burdensome.”

“We need to continue working with various partners to increase access and the ease of ordering genetic testing,” she said.

Hartzfeld reports no disclosures.

A monoclonal antibody combination of casirivimab and imdevimab (REGEN-COV) significantly reduced the risk of COVID-19–related hospitalizations and death from any cause in the phase 3 portion of an adaptive trial of outpatients.

Researchers, led by David Weinreich, MD, MBA, executive vice president of the drug cocktail’s manufacturer Regeneron, found in the randomized trial that the combination also resolved symptoms and reduced the SARS-CoV-2 viral load more quickly, compared with placebo.

Findings were published in the New England Journal of Medicine. 

COVID-related hospitalization or death from any cause occurred in 18 of 1,355 patients (1.3%) in the group getting 2,400 mg infusions of the study drug, compared with 62 (4.6%) of 1,341 in the matching placebo group, indicating a relative risk reduction of 71.3%; P < .001.

Sunil Joshi, MD, president of the Duval County Medical Society Foundation and an immunologist in Jacksonville, Fla., said in an interview that these findings confirm benefits of REGEN-COV and are very good news for a patient group that includes those age 65 and older with high blood pressure, diabetes, or obesity; and for people not vaccinated, who are all at high risk of hospitalization or death if they get COVID-19.

“Vaccines are critically important,” he said, “but if you were to be infected and know that there’s a way to keep yourself out of the hospital, this is very good news.”
 

Researchers seek lowest doses

This trial found that the effect was similar when researchers cut the doses in half. These outcomes occurred in 7 of 736 (1%) of patients given 1,200 mg of REGEN-COV and in 24 (3.2%) of 748 in the matching placebo group (relative risk reduction, 70.4%; P = .002).

Symptoms were resolved on average 4 days earlier with each REGEN-COV dose than with placebo (10 days vs. 14 days; P < .001 for both comparisons).

Dr. Weinreich said in an interview that trials will continue to find the lowest effective doses that can stand up to all evolving variants.

“This is one of those settings where you don’t want to underdose. You’ve got one shot at this,” he said. “We’d love to do lower doses. It would be more convenient and we could treat more patients, but if it generates more clinical failures or doesn’t work with certain variants, then you’ve done a huge disservice to the world.”

Also new in this study is that researchers tested not only seronegative patients, but patients at high risk regardless of blood antibody status, he said.

“It’s the first suggestion of data that if you’re breaking through a vaccine and you’re at high risk, the use of the cocktail is something to strongly consider because treatment early is better than treatment later,” Dr. Weinreich said.

In addition to efficacy, the phase 3 trial demonstrated the cocktail had a good safety profile. Serious adverse events occurred more often in the placebo group (4%) than in the 1,200-mg group (1.1%) and the 2,400-mg group (1.3%). Infusion reactions (grade 2 or higher) occurred in less than 0.3% of patients in all groups. 

William Fales, MD, state medical director for the Michigan Department of Health and Human Services, said the results confirm the promise of REGEN-COV for reducing hospitalizations and death in a peer-reviewed publication.
 

COVID-19 a moving target

However, Dr. Fales noted that COVID-19 is a moving target with emerging variants. The criteria for populations at high risk have also broadened since the start of the study, he said.

“A great example is pregnancy is now included as high risk, and that would have likely been a specific contraindication of patients in this clinical trial,” he said.

Dr. Fales said Michigan has been using both REGEN-COV and the Eli Lilly combination of bamlanivimab and etesevimab, which also has an emergency use authorization (EUA) from the Food and Drug Administration, with positive results.

REGEN-COV has an EUA to treat people who are at high risk of serious consequences from COVID-19, including those who are already infected (nonhospitalized) or those in certain postexposure prophylaxis settings.

“We’re seeing very low hospitalization rates and few deaths in a state that is predominately Delta,” Dr. Fales said. “So, this makes us feel that we’re doing the right thing and supports the current efforts around the country to make monoclonal antibody therapy available to high-risk patients.”  

Dr. Joshi noted that trial results have been emerging from other monoclonal antibody cocktails with different COVID-19 patient groups.

However, he said in an interview, “how much more effective they would be than this is something we’d have to look at, as 71% effectiveness in keeping people out of the hospital is pretty good for any treatment.”

“These are great numbers, but vaccination itself keeps you from getting the disease in the first place and not just for a short time period. This treatment is just that – a treatment. It gets you through that episode but it doesn’t mean you won’t get sick again. You don’t develop an immune response as you do with the vaccine,” he said.

Dr. Weinreich agreed: “This is not a substitute for a vaccine except for the small group who get the vaccine and their bodies can’t respond to it because they’re significantly immunocompromised.”

The results from this paper “are one piece of a large, multistudy, phase 3 program that basically spans from prophylaxis all the way to hospitalization and pretty much the gamut – all of them – have worked. All of these studies have shown dramatic improvement in whatever the definitive regulatory endpoint is,” Dr. Weinreich said.

He said discussions are ongoing for full regulatory approval in the United States and for expanding the EUA for other populations, including pre-exposure prophylaxis, “which the [United Kingdom’s] authority has already granted us but the FDA has not.”

The study is funded by Regeneron and the Department of Health & Human Services. Dr. Weinreich is a vice president of Regeneron. Dr. Joshi reported no relevant financial relationships. Dr. Fales holds stock in Eli Lilly.

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

A monoclonal antibody combination of casirivimab and imdevimab (REGEN-COV) significantly reduced the risk of COVID-19–related hospitalizations and death from any cause in the phase 3 portion of an adaptive trial of outpatients.

Researchers, led by David Weinreich, MD, MBA, executive vice president of the drug cocktail’s manufacturer Regeneron, found in the randomized trial that the combination also resolved symptoms and reduced the SARS-CoV-2 viral load more quickly, compared with placebo.

Findings were published in the New England Journal of Medicine. 

COVID-related hospitalization or death from any cause occurred in 18 of 1,355 patients (1.3%) in the group getting 2,400 mg infusions of the study drug, compared with 62 (4.6%) of 1,341 in the matching placebo group, indicating a relative risk reduction of 71.3%; P < .001.

Sunil Joshi, MD, president of the Duval County Medical Society Foundation and an immunologist in Jacksonville, Fla., said in an interview that these findings confirm benefits of REGEN-COV and are very good news for a patient group that includes those age 65 and older with high blood pressure, diabetes, or obesity; and for people not vaccinated, who are all at high risk of hospitalization or death if they get COVID-19.

“Vaccines are critically important,” he said, “but if you were to be infected and know that there’s a way to keep yourself out of the hospital, this is very good news.”
 

Researchers seek lowest doses

This trial found that the effect was similar when researchers cut the doses in half. These outcomes occurred in 7 of 736 (1%) of patients given 1,200 mg of REGEN-COV and in 24 (3.2%) of 748 in the matching placebo group (relative risk reduction, 70.4%; P = .002).

Symptoms were resolved on average 4 days earlier with each REGEN-COV dose than with placebo (10 days vs. 14 days; P < .001 for both comparisons).

Dr. Weinreich said in an interview that trials will continue to find the lowest effective doses that can stand up to all evolving variants.

“This is one of those settings where you don’t want to underdose. You’ve got one shot at this,” he said. “We’d love to do lower doses. It would be more convenient and we could treat more patients, but if it generates more clinical failures or doesn’t work with certain variants, then you’ve done a huge disservice to the world.”

Also new in this study is that researchers tested not only seronegative patients, but patients at high risk regardless of blood antibody status, he said.

“It’s the first suggestion of data that if you’re breaking through a vaccine and you’re at high risk, the use of the cocktail is something to strongly consider because treatment early is better than treatment later,” Dr. Weinreich said.

In addition to efficacy, the phase 3 trial demonstrated the cocktail had a good safety profile. Serious adverse events occurred more often in the placebo group (4%) than in the 1,200-mg group (1.1%) and the 2,400-mg group (1.3%). Infusion reactions (grade 2 or higher) occurred in less than 0.3% of patients in all groups. 

William Fales, MD, state medical director for the Michigan Department of Health and Human Services, said the results confirm the promise of REGEN-COV for reducing hospitalizations and death in a peer-reviewed publication.
 

COVID-19 a moving target

However, Dr. Fales noted that COVID-19 is a moving target with emerging variants. The criteria for populations at high risk have also broadened since the start of the study, he said.

“A great example is pregnancy is now included as high risk, and that would have likely been a specific contraindication of patients in this clinical trial,” he said.

Dr. Fales said Michigan has been using both REGEN-COV and the Eli Lilly combination of bamlanivimab and etesevimab, which also has an emergency use authorization (EUA) from the Food and Drug Administration, with positive results.

REGEN-COV has an EUA to treat people who are at high risk of serious consequences from COVID-19, including those who are already infected (nonhospitalized) or those in certain postexposure prophylaxis settings.

“We’re seeing very low hospitalization rates and few deaths in a state that is predominately Delta,” Dr. Fales said. “So, this makes us feel that we’re doing the right thing and supports the current efforts around the country to make monoclonal antibody therapy available to high-risk patients.”  

Dr. Joshi noted that trial results have been emerging from other monoclonal antibody cocktails with different COVID-19 patient groups.

However, he said in an interview, “how much more effective they would be than this is something we’d have to look at, as 71% effectiveness in keeping people out of the hospital is pretty good for any treatment.”

“These are great numbers, but vaccination itself keeps you from getting the disease in the first place and not just for a short time period. This treatment is just that – a treatment. It gets you through that episode but it doesn’t mean you won’t get sick again. You don’t develop an immune response as you do with the vaccine,” he said.

Dr. Weinreich agreed: “This is not a substitute for a vaccine except for the small group who get the vaccine and their bodies can’t respond to it because they’re significantly immunocompromised.”

The results from this paper “are one piece of a large, multistudy, phase 3 program that basically spans from prophylaxis all the way to hospitalization and pretty much the gamut – all of them – have worked. All of these studies have shown dramatic improvement in whatever the definitive regulatory endpoint is,” Dr. Weinreich said.

He said discussions are ongoing for full regulatory approval in the United States and for expanding the EUA for other populations, including pre-exposure prophylaxis, “which the [United Kingdom’s] authority has already granted us but the FDA has not.”

The study is funded by Regeneron and the Department of Health & Human Services. Dr. Weinreich is a vice president of Regeneron. Dr. Joshi reported no relevant financial relationships. Dr. Fales holds stock in Eli Lilly.

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

A monoclonal antibody combination of casirivimab and imdevimab (REGEN-COV) significantly reduced the risk of COVID-19–related hospitalizations and death from any cause in the phase 3 portion of an adaptive trial of outpatients.

Researchers, led by David Weinreich, MD, MBA, executive vice president of the drug cocktail’s manufacturer Regeneron, found in the randomized trial that the combination also resolved symptoms and reduced the SARS-CoV-2 viral load more quickly, compared with placebo.

Findings were published in the New England Journal of Medicine. 

COVID-related hospitalization or death from any cause occurred in 18 of 1,355 patients (1.3%) in the group getting 2,400 mg infusions of the study drug, compared with 62 (4.6%) of 1,341 in the matching placebo group, indicating a relative risk reduction of 71.3%; P < .001.

Sunil Joshi, MD, president of the Duval County Medical Society Foundation and an immunologist in Jacksonville, Fla., said in an interview that these findings confirm benefits of REGEN-COV and are very good news for a patient group that includes those age 65 and older with high blood pressure, diabetes, or obesity; and for people not vaccinated, who are all at high risk of hospitalization or death if they get COVID-19.

“Vaccines are critically important,” he said, “but if you were to be infected and know that there’s a way to keep yourself out of the hospital, this is very good news.”
 

Researchers seek lowest doses

This trial found that the effect was similar when researchers cut the doses in half. These outcomes occurred in 7 of 736 (1%) of patients given 1,200 mg of REGEN-COV and in 24 (3.2%) of 748 in the matching placebo group (relative risk reduction, 70.4%; P = .002).

Symptoms were resolved on average 4 days earlier with each REGEN-COV dose than with placebo (10 days vs. 14 days; P < .001 for both comparisons).

Dr. Weinreich said in an interview that trials will continue to find the lowest effective doses that can stand up to all evolving variants.

“This is one of those settings where you don’t want to underdose. You’ve got one shot at this,” he said. “We’d love to do lower doses. It would be more convenient and we could treat more patients, but if it generates more clinical failures or doesn’t work with certain variants, then you’ve done a huge disservice to the world.”

Also new in this study is that researchers tested not only seronegative patients, but patients at high risk regardless of blood antibody status, he said.

“It’s the first suggestion of data that if you’re breaking through a vaccine and you’re at high risk, the use of the cocktail is something to strongly consider because treatment early is better than treatment later,” Dr. Weinreich said.

In addition to efficacy, the phase 3 trial demonstrated the cocktail had a good safety profile. Serious adverse events occurred more often in the placebo group (4%) than in the 1,200-mg group (1.1%) and the 2,400-mg group (1.3%). Infusion reactions (grade 2 or higher) occurred in less than 0.3% of patients in all groups. 

William Fales, MD, state medical director for the Michigan Department of Health and Human Services, said the results confirm the promise of REGEN-COV for reducing hospitalizations and death in a peer-reviewed publication.
 

COVID-19 a moving target

However, Dr. Fales noted that COVID-19 is a moving target with emerging variants. The criteria for populations at high risk have also broadened since the start of the study, he said.

“A great example is pregnancy is now included as high risk, and that would have likely been a specific contraindication of patients in this clinical trial,” he said.

Dr. Fales said Michigan has been using both REGEN-COV and the Eli Lilly combination of bamlanivimab and etesevimab, which also has an emergency use authorization (EUA) from the Food and Drug Administration, with positive results.

REGEN-COV has an EUA to treat people who are at high risk of serious consequences from COVID-19, including those who are already infected (nonhospitalized) or those in certain postexposure prophylaxis settings.

“We’re seeing very low hospitalization rates and few deaths in a state that is predominately Delta,” Dr. Fales said. “So, this makes us feel that we’re doing the right thing and supports the current efforts around the country to make monoclonal antibody therapy available to high-risk patients.”  

Dr. Joshi noted that trial results have been emerging from other monoclonal antibody cocktails with different COVID-19 patient groups.

However, he said in an interview, “how much more effective they would be than this is something we’d have to look at, as 71% effectiveness in keeping people out of the hospital is pretty good for any treatment.”

“These are great numbers, but vaccination itself keeps you from getting the disease in the first place and not just for a short time period. This treatment is just that – a treatment. It gets you through that episode but it doesn’t mean you won’t get sick again. You don’t develop an immune response as you do with the vaccine,” he said.

Dr. Weinreich agreed: “This is not a substitute for a vaccine except for the small group who get the vaccine and their bodies can’t respond to it because they’re significantly immunocompromised.”

The results from this paper “are one piece of a large, multistudy, phase 3 program that basically spans from prophylaxis all the way to hospitalization and pretty much the gamut – all of them – have worked. All of these studies have shown dramatic improvement in whatever the definitive regulatory endpoint is,” Dr. Weinreich said.

He said discussions are ongoing for full regulatory approval in the United States and for expanding the EUA for other populations, including pre-exposure prophylaxis, “which the [United Kingdom’s] authority has already granted us but the FDA has not.”

The study is funded by Regeneron and the Department of Health & Human Services. Dr. Weinreich is a vice president of Regeneron. Dr. Joshi reported no relevant financial relationships. Dr. Fales holds stock in Eli Lilly.

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

Linked-color imaging (LCI) significantly increases the detection of adenomas in screening colonoscopies compared to white-light imaging (WLI) and blue-laser imaging (BLI)–bright, according to data from 205 adults who underwent screening colonoscopies.

LCI is a relatively new image-enhancement method designed to better identify adenomatous lesions by increasing the contrast of the mucosal surface, wrote Carlos E.O. dos Santos, MD, of Pontifícia Universidade Católica do Rio Grande do Sul in Porto Alegre, Brazil, and colleagues. Their report is in the Journal of Clinical Gastroenterology. With LCI, the lesions are more vascularized, and thus become reddish due to color contrast of hemoglobin present in capillary vessels, whereas the surrounding mucosa becomes whitish. Until this new study, the potential of LCI to detect adenomas compared with other imaging had not been evaluated.

The researchers randomized 205 patients with a total of 296 colorectal lesions to WLI, BLI-bright, or LCI; 70 patients were examined by WLI, 66 by BLI-bright, and 69 by LCI. The average age of the patients was 59 years, and 52% were women. The primary outcome measures were adenoma detection rate (ADR), mean number of adenomas per patient, and withdrawal time.

A total of 251 adenomas were detected, with an overall ADR of 62%. The total number of adenomas detected by each method were 112 by LCI, 71 by WLI, and 68 by BLI-bright.

The ADR was significantly higher for patients in the LCI group compared with those in the WLI group (71% vs. 52.9%, P = .04). ADR for LCI was greater than the ADR for BLI-bright, but the difference was not significant (71% vs. 62.1%, P = .28). No significant differences in ADR were noted between the WLI and BLI-bright groups.

The mean number of adenomas identified per patient was 1.17 overall, but significantly higher in the LCI group compared to the WLI and BLI-bright groups (1.62, 1.01, and 1.03, respectively, P = .02). Mean withdrawal times were not significantly different among the three groups and ranged from approximately 10 to 11 minutes. An analysis of secondary outcomes showed no differences among the groups in terms of size and morphology of the adenomas, or in the detection of sessile serrated adenomas or polyps.

The researchers noted that the study findings were limited by several factors including the use of data from a single center with a high level of experience in image-enhanced endoscopy and by the relatively small sample size.

Nevertheless, concluded the researchers, “It is evident that better visibility of the mucosa is a key factor for the detection of neoplastic lesions,” and the results support the potential of LCI given the demonstrated superiority of LCI over WLI for colorectal adenoma detection and the mean number of adenomas detected per patient.

The researchers said that further single and multicenter randomized studies are needed to validate the results and to confirm whether one image-enhancement system is superior to the other for increasing the ADR.
 

Door is open for better detection tools

In an interview, Atsushi Sakuraba, MD, of the University of Chicago, who was not involved with the study, said that colonoscopy is considered the best method for colorectal cancer screening and prevention, but is associated with a certain risk of missing adenomas, so new methods and technologies to improve detection rate are needed. “Linked-color imaging provides an increased contrast of the mucosal surface and enhances the findings of adenomatous lesions in comparison to white-light endoscopy and has been shown to be effective in detecting adenomas, so the findings of the present study are not surprising,” said Dr. Sakuraba.

LCI provides clearer and brighter images by enhancing the differences in color contrast, and therefore does not cause the impaired visibility that can occur with narrow band imaging or BLI images, Dr. Sakuraba said. However, he noted, not all endoscopy centers carry the scopes equipped with LCI, which is a barrier to widespread use.

Dr. Sakuraba said that multicenter studies need to be undertaken to confirm the generalizability of the results of the present study.

“There is now convincing evidence that increasing adenoma detection rate is associated with fewer missed cancers and lower mortality from colorectal cancer,” said Ziad F. Gellad, MD, of Duke University, Durham, N.C., who was also not involved with the study. “As such, utilizing tools that enhance ADR may improve our ability to prevent colorectal cancer. ... Understanding the relative benefits and drawbacks of available tools and technologies in the market can help practicing gastroenterologists decide where to invest their time and resources to improve care.”

Dr. Gellad said he was not surprised by the enhanced detection using LCI, as the study is not the first to evaluate this technology. “However, I was surprised by how high the ADR was in the screening population (62%),” said Dr. Gellad, observing that this exceeds benchmarks set by the society. “We don’t have a full understanding of the demographic characteristics of this screening population. ... Nonetheless, I think this paper adds to accumulating data that current benchmarks may be too low.”

Dr. Gellad said he didn’t think the findings of the study are strong enough to change practice, but the results are a “valuable contribution to the literature and will empower future larger studies as well as meta-analyses.” He called for larger studies in nonspecialized centers to relate the findings from this small study to general practice.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Sakuraba disclosed collaborative research relationships with Fuji, the manufacturer of the imaging equipment used in the study. Dr. Gellad had no financial conflicts to disclose but serves on the editorial board of GI & Hepatology News.

Linked-color imaging (LCI) significantly increases the detection of adenomas in screening colonoscopies compared to white-light imaging (WLI) and blue-laser imaging (BLI)–bright, according to data from 205 adults who underwent screening colonoscopies.

LCI is a relatively new image-enhancement method designed to better identify adenomatous lesions by increasing the contrast of the mucosal surface, wrote Carlos E.O. dos Santos, MD, of Pontifícia Universidade Católica do Rio Grande do Sul in Porto Alegre, Brazil, and colleagues. Their report is in the Journal of Clinical Gastroenterology. With LCI, the lesions are more vascularized, and thus become reddish due to color contrast of hemoglobin present in capillary vessels, whereas the surrounding mucosa becomes whitish. Until this new study, the potential of LCI to detect adenomas compared with other imaging had not been evaluated.

The researchers randomized 205 patients with a total of 296 colorectal lesions to WLI, BLI-bright, or LCI; 70 patients were examined by WLI, 66 by BLI-bright, and 69 by LCI. The average age of the patients was 59 years, and 52% were women. The primary outcome measures were adenoma detection rate (ADR), mean number of adenomas per patient, and withdrawal time.

A total of 251 adenomas were detected, with an overall ADR of 62%. The total number of adenomas detected by each method were 112 by LCI, 71 by WLI, and 68 by BLI-bright.

The ADR was significantly higher for patients in the LCI group compared with those in the WLI group (71% vs. 52.9%, P = .04). ADR for LCI was greater than the ADR for BLI-bright, but the difference was not significant (71% vs. 62.1%, P = .28). No significant differences in ADR were noted between the WLI and BLI-bright groups.

The mean number of adenomas identified per patient was 1.17 overall, but significantly higher in the LCI group compared to the WLI and BLI-bright groups (1.62, 1.01, and 1.03, respectively, P = .02). Mean withdrawal times were not significantly different among the three groups and ranged from approximately 10 to 11 minutes. An analysis of secondary outcomes showed no differences among the groups in terms of size and morphology of the adenomas, or in the detection of sessile serrated adenomas or polyps.

The researchers noted that the study findings were limited by several factors including the use of data from a single center with a high level of experience in image-enhanced endoscopy and by the relatively small sample size.

Nevertheless, concluded the researchers, “It is evident that better visibility of the mucosa is a key factor for the detection of neoplastic lesions,” and the results support the potential of LCI given the demonstrated superiority of LCI over WLI for colorectal adenoma detection and the mean number of adenomas detected per patient.

The researchers said that further single and multicenter randomized studies are needed to validate the results and to confirm whether one image-enhancement system is superior to the other for increasing the ADR.
 

Door is open for better detection tools

In an interview, Atsushi Sakuraba, MD, of the University of Chicago, who was not involved with the study, said that colonoscopy is considered the best method for colorectal cancer screening and prevention, but is associated with a certain risk of missing adenomas, so new methods and technologies to improve detection rate are needed. “Linked-color imaging provides an increased contrast of the mucosal surface and enhances the findings of adenomatous lesions in comparison to white-light endoscopy and has been shown to be effective in detecting adenomas, so the findings of the present study are not surprising,” said Dr. Sakuraba.

LCI provides clearer and brighter images by enhancing the differences in color contrast, and therefore does not cause the impaired visibility that can occur with narrow band imaging or BLI images, Dr. Sakuraba said. However, he noted, not all endoscopy centers carry the scopes equipped with LCI, which is a barrier to widespread use.

Dr. Sakuraba said that multicenter studies need to be undertaken to confirm the generalizability of the results of the present study.

“There is now convincing evidence that increasing adenoma detection rate is associated with fewer missed cancers and lower mortality from colorectal cancer,” said Ziad F. Gellad, MD, of Duke University, Durham, N.C., who was also not involved with the study. “As such, utilizing tools that enhance ADR may improve our ability to prevent colorectal cancer. ... Understanding the relative benefits and drawbacks of available tools and technologies in the market can help practicing gastroenterologists decide where to invest their time and resources to improve care.”

Dr. Gellad said he was not surprised by the enhanced detection using LCI, as the study is not the first to evaluate this technology. “However, I was surprised by how high the ADR was in the screening population (62%),” said Dr. Gellad, observing that this exceeds benchmarks set by the society. “We don’t have a full understanding of the demographic characteristics of this screening population. ... Nonetheless, I think this paper adds to accumulating data that current benchmarks may be too low.”

Dr. Gellad said he didn’t think the findings of the study are strong enough to change practice, but the results are a “valuable contribution to the literature and will empower future larger studies as well as meta-analyses.” He called for larger studies in nonspecialized centers to relate the findings from this small study to general practice.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Sakuraba disclosed collaborative research relationships with Fuji, the manufacturer of the imaging equipment used in the study. Dr. Gellad had no financial conflicts to disclose but serves on the editorial board of GI & Hepatology News.

Linked-color imaging (LCI) significantly increases the detection of adenomas in screening colonoscopies compared to white-light imaging (WLI) and blue-laser imaging (BLI)–bright, according to data from 205 adults who underwent screening colonoscopies.

LCI is a relatively new image-enhancement method designed to better identify adenomatous lesions by increasing the contrast of the mucosal surface, wrote Carlos E.O. dos Santos, MD, of Pontifícia Universidade Católica do Rio Grande do Sul in Porto Alegre, Brazil, and colleagues. Their report is in the Journal of Clinical Gastroenterology. With LCI, the lesions are more vascularized, and thus become reddish due to color contrast of hemoglobin present in capillary vessels, whereas the surrounding mucosa becomes whitish. Until this new study, the potential of LCI to detect adenomas compared with other imaging had not been evaluated.

The researchers randomized 205 patients with a total of 296 colorectal lesions to WLI, BLI-bright, or LCI; 70 patients were examined by WLI, 66 by BLI-bright, and 69 by LCI. The average age of the patients was 59 years, and 52% were women. The primary outcome measures were adenoma detection rate (ADR), mean number of adenomas per patient, and withdrawal time.

A total of 251 adenomas were detected, with an overall ADR of 62%. The total number of adenomas detected by each method were 112 by LCI, 71 by WLI, and 68 by BLI-bright.

The ADR was significantly higher for patients in the LCI group compared with those in the WLI group (71% vs. 52.9%, P = .04). ADR for LCI was greater than the ADR for BLI-bright, but the difference was not significant (71% vs. 62.1%, P = .28). No significant differences in ADR were noted between the WLI and BLI-bright groups.

The mean number of adenomas identified per patient was 1.17 overall, but significantly higher in the LCI group compared to the WLI and BLI-bright groups (1.62, 1.01, and 1.03, respectively, P = .02). Mean withdrawal times were not significantly different among the three groups and ranged from approximately 10 to 11 minutes. An analysis of secondary outcomes showed no differences among the groups in terms of size and morphology of the adenomas, or in the detection of sessile serrated adenomas or polyps.

The researchers noted that the study findings were limited by several factors including the use of data from a single center with a high level of experience in image-enhanced endoscopy and by the relatively small sample size.

Nevertheless, concluded the researchers, “It is evident that better visibility of the mucosa is a key factor for the detection of neoplastic lesions,” and the results support the potential of LCI given the demonstrated superiority of LCI over WLI for colorectal adenoma detection and the mean number of adenomas detected per patient.

The researchers said that further single and multicenter randomized studies are needed to validate the results and to confirm whether one image-enhancement system is superior to the other for increasing the ADR.
 

Door is open for better detection tools

In an interview, Atsushi Sakuraba, MD, of the University of Chicago, who was not involved with the study, said that colonoscopy is considered the best method for colorectal cancer screening and prevention, but is associated with a certain risk of missing adenomas, so new methods and technologies to improve detection rate are needed. “Linked-color imaging provides an increased contrast of the mucosal surface and enhances the findings of adenomatous lesions in comparison to white-light endoscopy and has been shown to be effective in detecting adenomas, so the findings of the present study are not surprising,” said Dr. Sakuraba.

LCI provides clearer and brighter images by enhancing the differences in color contrast, and therefore does not cause the impaired visibility that can occur with narrow band imaging or BLI images, Dr. Sakuraba said. However, he noted, not all endoscopy centers carry the scopes equipped with LCI, which is a barrier to widespread use.

Dr. Sakuraba said that multicenter studies need to be undertaken to confirm the generalizability of the results of the present study.

“There is now convincing evidence that increasing adenoma detection rate is associated with fewer missed cancers and lower mortality from colorectal cancer,” said Ziad F. Gellad, MD, of Duke University, Durham, N.C., who was also not involved with the study. “As such, utilizing tools that enhance ADR may improve our ability to prevent colorectal cancer. ... Understanding the relative benefits and drawbacks of available tools and technologies in the market can help practicing gastroenterologists decide where to invest their time and resources to improve care.”

Dr. Gellad said he was not surprised by the enhanced detection using LCI, as the study is not the first to evaluate this technology. “However, I was surprised by how high the ADR was in the screening population (62%),” said Dr. Gellad, observing that this exceeds benchmarks set by the society. “We don’t have a full understanding of the demographic characteristics of this screening population. ... Nonetheless, I think this paper adds to accumulating data that current benchmarks may be too low.”

Dr. Gellad said he didn’t think the findings of the study are strong enough to change practice, but the results are a “valuable contribution to the literature and will empower future larger studies as well as meta-analyses.” He called for larger studies in nonspecialized centers to relate the findings from this small study to general practice.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Sakuraba disclosed collaborative research relationships with Fuji, the manufacturer of the imaging equipment used in the study. Dr. Gellad had no financial conflicts to disclose but serves on the editorial board of GI & Hepatology News.

With the Delta variant of COVID-19 still raging in the United States and ICUs in parts of the country filled with patients with the coronavirus, experts are voicing concern about the added risk of a difficult flu season.

Two mathematical models are predicting a big rebound in the number and severity of flu cases in the 2021-22 season after 2020-2021’s flu season failed to show up when public health measures brought in to control COVID-19 seemed to have the added benefit of stopping the flu.

But both analyses, posted to the medRxiv preprint server and not yet peer reviewed by other experts, have come to the same conclusion: The flu could make a comeback this year.

In the worst-case scenario, the United States could see an extra 300,000-400,000 hospitalizations from the flu – almost double the usual number – according to senior study author Mark Roberts, MD, director of the Public Health Dynamics Laboratory at the University of Pittsburgh. These numbers could be a disaster in areas where hospitals are already filled with COVID-19 patients.

Waning natural immunity in the public because of 2020-2021’s missing flu season could make people, especially young children, more likely to get the virus.

“Usually, a combination of natural immunity and vaccination helps tamp down seasonal influenza,” said Dr. Roberts. “If we don’t have the first part, we’ll have to rely more on the vaccine.”

In a typical year, about half of Americans get the flu shot. The new mathematical models predict that the vaccination rate would need to rise to about 75% to avoid the extra hospitalizations. But even a 10% increase in vaccination rates could reduce hospitalizations by 6%-46%, depending on what strains are dominant.

Usually, the Southern Hemisphere flu season, from February to August, helps show what the Northern Hemisphere can expect over the coming winter. But with strict COVID-19 measures and limits on international travel still in place in countries like Australia and New Zealand and much of South America, it has been another record-low year for flu infections, said Ian Barr, PhD, deputy director of the World Health Organization’s Collaborating Center for Reference and Research on Influenza in Melbourne.

Australia detected only around 500 cases in 2021, compared with about 300,000 in a normal year, and recorded no hospitalizations or deaths from the flu. New Zealand recorded just two cases.

“I’ve never seen anything like this,” Dr. Barr said.

In Australia, the mild flu season led to fewer people getting their flu shot than usual. The rate fell from around 50% to just 33%, said Dr. Barr. “If that happens in the U.S., the population will be even more vulnerable because there has been almost no flu for more than 12 months,” he said.

Both Dr. Roberts and Dr. Barr say it is vital that as many people as possible get vaccinated during the upcoming flu season, especially children who will have almost no natural immunity to the virus.

“The vaccine is our best weapon against the flu, especially for the most at-risk groups,” said Dr. Barr.

Other parts of the world had mixed results. India saw a high number of flu cases, while neighboring Sri Lanka had very few. West Africa also saw quite a high level of circulating virus. Overall, the flu was detected in 45 countries during the Southern Hemisphere season, less than half of what might be expected in a normal year, said Dr. Barr.

Despite the overall low numbers, the WHO saw enough in the data to make two changes to 2022’s Southern Hemisphere vaccine formulation at its meeting on Sept. 24, after changing just one of the strains for the Northern Hemisphere vaccine at its meeting in February.

The CDC recommends that everyone 6 months or older get the flu shot, with few exceptions.

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

With the Delta variant of COVID-19 still raging in the United States and ICUs in parts of the country filled with patients with the coronavirus, experts are voicing concern about the added risk of a difficult flu season.

Two mathematical models are predicting a big rebound in the number and severity of flu cases in the 2021-22 season after 2020-2021’s flu season failed to show up when public health measures brought in to control COVID-19 seemed to have the added benefit of stopping the flu.

But both analyses, posted to the medRxiv preprint server and not yet peer reviewed by other experts, have come to the same conclusion: The flu could make a comeback this year.

In the worst-case scenario, the United States could see an extra 300,000-400,000 hospitalizations from the flu – almost double the usual number – according to senior study author Mark Roberts, MD, director of the Public Health Dynamics Laboratory at the University of Pittsburgh. These numbers could be a disaster in areas where hospitals are already filled with COVID-19 patients.

Waning natural immunity in the public because of 2020-2021’s missing flu season could make people, especially young children, more likely to get the virus.

“Usually, a combination of natural immunity and vaccination helps tamp down seasonal influenza,” said Dr. Roberts. “If we don’t have the first part, we’ll have to rely more on the vaccine.”

In a typical year, about half of Americans get the flu shot. The new mathematical models predict that the vaccination rate would need to rise to about 75% to avoid the extra hospitalizations. But even a 10% increase in vaccination rates could reduce hospitalizations by 6%-46%, depending on what strains are dominant.

Usually, the Southern Hemisphere flu season, from February to August, helps show what the Northern Hemisphere can expect over the coming winter. But with strict COVID-19 measures and limits on international travel still in place in countries like Australia and New Zealand and much of South America, it has been another record-low year for flu infections, said Ian Barr, PhD, deputy director of the World Health Organization’s Collaborating Center for Reference and Research on Influenza in Melbourne.

Australia detected only around 500 cases in 2021, compared with about 300,000 in a normal year, and recorded no hospitalizations or deaths from the flu. New Zealand recorded just two cases.

“I’ve never seen anything like this,” Dr. Barr said.

In Australia, the mild flu season led to fewer people getting their flu shot than usual. The rate fell from around 50% to just 33%, said Dr. Barr. “If that happens in the U.S., the population will be even more vulnerable because there has been almost no flu for more than 12 months,” he said.

Both Dr. Roberts and Dr. Barr say it is vital that as many people as possible get vaccinated during the upcoming flu season, especially children who will have almost no natural immunity to the virus.

“The vaccine is our best weapon against the flu, especially for the most at-risk groups,” said Dr. Barr.

Other parts of the world had mixed results. India saw a high number of flu cases, while neighboring Sri Lanka had very few. West Africa also saw quite a high level of circulating virus. Overall, the flu was detected in 45 countries during the Southern Hemisphere season, less than half of what might be expected in a normal year, said Dr. Barr.

Despite the overall low numbers, the WHO saw enough in the data to make two changes to 2022’s Southern Hemisphere vaccine formulation at its meeting on Sept. 24, after changing just one of the strains for the Northern Hemisphere vaccine at its meeting in February.

The CDC recommends that everyone 6 months or older get the flu shot, with few exceptions.

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

With the Delta variant of COVID-19 still raging in the United States and ICUs in parts of the country filled with patients with the coronavirus, experts are voicing concern about the added risk of a difficult flu season.

Two mathematical models are predicting a big rebound in the number and severity of flu cases in the 2021-22 season after 2020-2021’s flu season failed to show up when public health measures brought in to control COVID-19 seemed to have the added benefit of stopping the flu.

But both analyses, posted to the medRxiv preprint server and not yet peer reviewed by other experts, have come to the same conclusion: The flu could make a comeback this year.

In the worst-case scenario, the United States could see an extra 300,000-400,000 hospitalizations from the flu – almost double the usual number – according to senior study author Mark Roberts, MD, director of the Public Health Dynamics Laboratory at the University of Pittsburgh. These numbers could be a disaster in areas where hospitals are already filled with COVID-19 patients.

Waning natural immunity in the public because of 2020-2021’s missing flu season could make people, especially young children, more likely to get the virus.

“Usually, a combination of natural immunity and vaccination helps tamp down seasonal influenza,” said Dr. Roberts. “If we don’t have the first part, we’ll have to rely more on the vaccine.”

In a typical year, about half of Americans get the flu shot. The new mathematical models predict that the vaccination rate would need to rise to about 75% to avoid the extra hospitalizations. But even a 10% increase in vaccination rates could reduce hospitalizations by 6%-46%, depending on what strains are dominant.

Usually, the Southern Hemisphere flu season, from February to August, helps show what the Northern Hemisphere can expect over the coming winter. But with strict COVID-19 measures and limits on international travel still in place in countries like Australia and New Zealand and much of South America, it has been another record-low year for flu infections, said Ian Barr, PhD, deputy director of the World Health Organization’s Collaborating Center for Reference and Research on Influenza in Melbourne.

Australia detected only around 500 cases in 2021, compared with about 300,000 in a normal year, and recorded no hospitalizations or deaths from the flu. New Zealand recorded just two cases.

“I’ve never seen anything like this,” Dr. Barr said.

In Australia, the mild flu season led to fewer people getting their flu shot than usual. The rate fell from around 50% to just 33%, said Dr. Barr. “If that happens in the U.S., the population will be even more vulnerable because there has been almost no flu for more than 12 months,” he said.

Both Dr. Roberts and Dr. Barr say it is vital that as many people as possible get vaccinated during the upcoming flu season, especially children who will have almost no natural immunity to the virus.

“The vaccine is our best weapon against the flu, especially for the most at-risk groups,” said Dr. Barr.

Other parts of the world had mixed results. India saw a high number of flu cases, while neighboring Sri Lanka had very few. West Africa also saw quite a high level of circulating virus. Overall, the flu was detected in 45 countries during the Southern Hemisphere season, less than half of what might be expected in a normal year, said Dr. Barr.

Despite the overall low numbers, the WHO saw enough in the data to make two changes to 2022’s Southern Hemisphere vaccine formulation at its meeting on Sept. 24, after changing just one of the strains for the Northern Hemisphere vaccine at its meeting in February.

The CDC recommends that everyone 6 months or older get the flu shot, with few exceptions.

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

After many years at the University of California, San Francisco, Lindsey A. Criswell, MD, MPH, DSc, began a new chapter in February 2021 as the director of the National Institute of Arthritis and Musculoskeletal and Skin Disease, part of the National Institutes of Health. NIH Director Francis S. Collins, MD, PhD, selected her for the post.

“Dr. Criswell has rich experience as a clinician, researcher, and administrator,” Dr. Collins said in a prepared statement. “Her ability to oversee the research program of one of the country’s top research-intensive medical schools, and her expertise in autoimmune diseases, including rheumatoid arthritis and lupus, make her well positioned to direct NIAMS.” Dr. Criswell, a rheumatologist, was named a full professor of medicine at UCSF in 2007 and had served as vice chancellor of research at the university since 2017. She has authored more than 250 peer-reviewed scientific papers, and her efforts have contributed to the identification of more than 30 genes linked to autoimmune disorders. In her first media interview, Dr. Criswell opens up about her mentors, operational challenges posed by the COVID-19 pandemic, and highlights many NIAMS research projects underway.

Who inspired you most early in your career as a physician scientist? I have had great opportunities to work with fabulous mentors. Wallace (Wally) Epstein, MD, was my mentor when I was a rheumatology fellow and junior faculty member at UCSF. He was broadly admired for the breadth of his experience as a clinician and a researcher, and he was noteworthy at that time for his strong support for women and students of color. One of the many things I appreciated about him was his diverse range of interests outside of work, which included cello playing and woodworking.

Another mentor was Ephraim (Eph) Engleman, MD, the first academic rheumatologist in California. Eph continued to see patients beyond the age of 100. Perhaps his most important contributions were his efforts towards advocacy for funding for research and education in rheumatology. A prodigy violinist, he too had a broad range of personal interests.

What research into the genetics and epidemiology of human autoimmune disease that you have been a part of has most surprised you, in term of its ultimate clinical impact? Some of my most rewarding and impactful work has focused on the shared genetic basis of autoimmune diseases. We’ve identified dozens of genes that contribute to the risk and outcome of rheumatoid arthritis, lupus, and other autoimmune disorders. These discoveries regarding shared genes and pathways among such a diverse set of conditions have helped to inform optimal therapeutic target and treatment strategies across multiple diseases. For example, exploration of RA genes and pathways has revealed that approved agents for other conditions, such as cancer, may be appropriately repurposed for the treatment of RA. These are critical observations that have the potential to dramatically accelerate progress in developing new therapies for autoimmune diseases, such as RA.

Did you have much interaction with Stephen I. Katz, MD, PhD, your longtime predecessor who passed away unexpectedly in 2018? If so, what do you remember most about him? I regret that I had very little interaction with Steve, but I am well aware of the impact he had on NIAMS, NIH, and the research enterprise overall. He inspired so many people in a personal way, and I am energized by the legacy that he left behind.

What are your goals for the early part of your tenure as the new director of NIAMS? An important goal is getting to know the NIAMS community and expanding my knowledge of the Institute’s musculoskeletal and skin portfolios. I am also conducting outreach to Institute/Center directors and other NIH leadership to increase opportunities for input and advice. In doing this, I am identifying shared research interests, best practices, and potential partners for possible future collaborations. Another important goal is to increase NIAMS’ visibility within and beyond NIH. Ultimately, I want to contribute to the great work of the Institute and improve the lives of people with rheumatic, musculoskeletal, and skin diseases.

How would you characterize your management style? I like to lead with a flat hierarchy and work collectively to address opportunities and challenges. I value team building and tend to tap a variety of perspectives and expertise at all levels to achieve consensus, where possible.

The Accelerating Medicines Partnership (AMP) program was launched in 2014, with projects in three disease areas including the autoimmune disorders RA and lupus. What are some recent highlights from this program with respect to RA and lupus? AMP RA/SLE was dedicated to identifying promising therapeutic targets for RA and systemic lupus erythematosus. AMP-funded researchers have applied cutting-edge technologies to study cells from the synovial tissues of the joints of people with RA, and from the kidneys of people with lupus nephritis. In 2014, studying tissues in patients where the disease is active was a novel approach, since most research was conducted in mouse models or human blood samples.

The AMP RA/SLE Network developed a rich dataset that is available to the research community. Investigators are now using the data to facilitate RA and lupus research. For example, using AMP data, NIAMS-supported researchers identified potential biomarkers that could help predict an imminent RA flare. Work from another NIAMS-supported group suggests that targeting the regulatory transcription factor HIF-1, which drives inflammation and tissue damage, might be an effective approach for treating renal injury in lupus.

The data generated are accessible to the scientific community through two NIH websites: the database of Genotypes and Phenotypes (dbGaP) and the Immunology Database and Analysis Portal (IMMPORT).

Given the success of AMP RA/SLE, NIH plans to launch an “AMP 2.0” later in 2021. The AMP Autoimmune and Immune-Mediated Diseases (AMP AIM) program will provide an opportunity to leverage the accomplishments of AMP RA/SLE to new conditions, including psoriatic spectrum diseases and Sjögren’s syndrome.

What are some recent highlights from NIAMS-supported research in skin diseases? NIAMS-supported investigators continue to make significant strides in our understanding of skin biology and disease. For example, researchers recently demonstrated that imiquimod, a drug used to treat precancerous skin lesions, can help mouse ear wounds heal without scarring.

Another team addressed the safety and potential benefit of Staphylococcus hominis A9, a bacterium isolated from healthy human skin, as a topical therapy for atopic dermatitis.

Moving forward, AMP AIM will refine and extend the single-cell analysis of tissues to additional diseases, including psoriasis, setting the stage for the discovery of new therapeutic targets for the disease.

How has the COVID-19 pandemic changed the landscape of research, at least for the short term? This is a once-in-a-century pandemic that none of us were fully prepared for. We understand that it has been particularly challenging for women scientists, scientists with young children, and trainees and junior faculty who are at critically important and vulnerable stages of their careers. There isn’t a lab or clinical setting that hasn’t been negatively impacted in some way.

During the pandemic, the NIH instituted administrative flexibilities to support the grantee community, including extensions in time. In addition, the agency has issued several funding opportunities specific to COVID-19, some of which involve NIAMS participation.

What is NIAMS doing to help early/young investigators as well as female investigators and those from minority groups? Structural racism in biomedical research is a heightened concern. Earlier this year, Dr. Collins established the UNITE initiative to address structural racism and promote racial equity and inclusion at the NIH and within the larger biomedical community that we support. NIAMS is fully committed to this effort. One example is the Diversity Supplement Program, which is designed to attract and encourage eligible individuals from underrepresented populations to research careers.

Early-stage investigators are another top priority. In a tribute to the beloved former NIAMS director, NIH recently established the Stephen I. Katz Early Stage Investigator Research Grant Program. The R01 award provides support for a project unrelated to an early investigator’s area of postdoctoral study. (No preliminary data are allowed.) This award mechanism is a unique opportunity for early-stage investigators to take their research in a completely new direction.

Managing work and family life is an important concern, particularly for female investigators. Many NIH grant awards allow for reimbursement of actual, allowable costs incurred for childcare and parental leave. The NIH is exploring initiatives to promote research continuity and retention of eligible investigators facing major life events, such as pregnancy, childbirth, and adoption, at vulnerable career stages.

Who inspires you most in your work today? I am inspired by the ongoing struggles of our patients, junior investigators, and by the committed staff members on my team.

[email protected]

After many years at the University of California, San Francisco, Lindsey A. Criswell, MD, MPH, DSc, began a new chapter in February 2021 as the director of the National Institute of Arthritis and Musculoskeletal and Skin Disease, part of the National Institutes of Health. NIH Director Francis S. Collins, MD, PhD, selected her for the post.

“Dr. Criswell has rich experience as a clinician, researcher, and administrator,” Dr. Collins said in a prepared statement. “Her ability to oversee the research program of one of the country’s top research-intensive medical schools, and her expertise in autoimmune diseases, including rheumatoid arthritis and lupus, make her well positioned to direct NIAMS.” Dr. Criswell, a rheumatologist, was named a full professor of medicine at UCSF in 2007 and had served as vice chancellor of research at the university since 2017. She has authored more than 250 peer-reviewed scientific papers, and her efforts have contributed to the identification of more than 30 genes linked to autoimmune disorders. In her first media interview, Dr. Criswell opens up about her mentors, operational challenges posed by the COVID-19 pandemic, and highlights many NIAMS research projects underway.

Who inspired you most early in your career as a physician scientist? I have had great opportunities to work with fabulous mentors. Wallace (Wally) Epstein, MD, was my mentor when I was a rheumatology fellow and junior faculty member at UCSF. He was broadly admired for the breadth of his experience as a clinician and a researcher, and he was noteworthy at that time for his strong support for women and students of color. One of the many things I appreciated about him was his diverse range of interests outside of work, which included cello playing and woodworking.

Another mentor was Ephraim (Eph) Engleman, MD, the first academic rheumatologist in California. Eph continued to see patients beyond the age of 100. Perhaps his most important contributions were his efforts towards advocacy for funding for research and education in rheumatology. A prodigy violinist, he too had a broad range of personal interests.

What research into the genetics and epidemiology of human autoimmune disease that you have been a part of has most surprised you, in term of its ultimate clinical impact? Some of my most rewarding and impactful work has focused on the shared genetic basis of autoimmune diseases. We’ve identified dozens of genes that contribute to the risk and outcome of rheumatoid arthritis, lupus, and other autoimmune disorders. These discoveries regarding shared genes and pathways among such a diverse set of conditions have helped to inform optimal therapeutic target and treatment strategies across multiple diseases. For example, exploration of RA genes and pathways has revealed that approved agents for other conditions, such as cancer, may be appropriately repurposed for the treatment of RA. These are critical observations that have the potential to dramatically accelerate progress in developing new therapies for autoimmune diseases, such as RA.

Did you have much interaction with Stephen I. Katz, MD, PhD, your longtime predecessor who passed away unexpectedly in 2018? If so, what do you remember most about him? I regret that I had very little interaction with Steve, but I am well aware of the impact he had on NIAMS, NIH, and the research enterprise overall. He inspired so many people in a personal way, and I am energized by the legacy that he left behind.

What are your goals for the early part of your tenure as the new director of NIAMS? An important goal is getting to know the NIAMS community and expanding my knowledge of the Institute’s musculoskeletal and skin portfolios. I am also conducting outreach to Institute/Center directors and other NIH leadership to increase opportunities for input and advice. In doing this, I am identifying shared research interests, best practices, and potential partners for possible future collaborations. Another important goal is to increase NIAMS’ visibility within and beyond NIH. Ultimately, I want to contribute to the great work of the Institute and improve the lives of people with rheumatic, musculoskeletal, and skin diseases.

How would you characterize your management style? I like to lead with a flat hierarchy and work collectively to address opportunities and challenges. I value team building and tend to tap a variety of perspectives and expertise at all levels to achieve consensus, where possible.

The Accelerating Medicines Partnership (AMP) program was launched in 2014, with projects in three disease areas including the autoimmune disorders RA and lupus. What are some recent highlights from this program with respect to RA and lupus? AMP RA/SLE was dedicated to identifying promising therapeutic targets for RA and systemic lupus erythematosus. AMP-funded researchers have applied cutting-edge technologies to study cells from the synovial tissues of the joints of people with RA, and from the kidneys of people with lupus nephritis. In 2014, studying tissues in patients where the disease is active was a novel approach, since most research was conducted in mouse models or human blood samples.

The AMP RA/SLE Network developed a rich dataset that is available to the research community. Investigators are now using the data to facilitate RA and lupus research. For example, using AMP data, NIAMS-supported researchers identified potential biomarkers that could help predict an imminent RA flare. Work from another NIAMS-supported group suggests that targeting the regulatory transcription factor HIF-1, which drives inflammation and tissue damage, might be an effective approach for treating renal injury in lupus.

The data generated are accessible to the scientific community through two NIH websites: the database of Genotypes and Phenotypes (dbGaP) and the Immunology Database and Analysis Portal (IMMPORT).

Given the success of AMP RA/SLE, NIH plans to launch an “AMP 2.0” later in 2021. The AMP Autoimmune and Immune-Mediated Diseases (AMP AIM) program will provide an opportunity to leverage the accomplishments of AMP RA/SLE to new conditions, including psoriatic spectrum diseases and Sjögren’s syndrome.

What are some recent highlights from NIAMS-supported research in skin diseases? NIAMS-supported investigators continue to make significant strides in our understanding of skin biology and disease. For example, researchers recently demonstrated that imiquimod, a drug used to treat precancerous skin lesions, can help mouse ear wounds heal without scarring.

Another team addressed the safety and potential benefit of Staphylococcus hominis A9, a bacterium isolated from healthy human skin, as a topical therapy for atopic dermatitis.

Moving forward, AMP AIM will refine and extend the single-cell analysis of tissues to additional diseases, including psoriasis, setting the stage for the discovery of new therapeutic targets for the disease.

How has the COVID-19 pandemic changed the landscape of research, at least for the short term? This is a once-in-a-century pandemic that none of us were fully prepared for. We understand that it has been particularly challenging for women scientists, scientists with young children, and trainees and junior faculty who are at critically important and vulnerable stages of their careers. There isn’t a lab or clinical setting that hasn’t been negatively impacted in some way.

During the pandemic, the NIH instituted administrative flexibilities to support the grantee community, including extensions in time. In addition, the agency has issued several funding opportunities specific to COVID-19, some of which involve NIAMS participation.

What is NIAMS doing to help early/young investigators as well as female investigators and those from minority groups? Structural racism in biomedical research is a heightened concern. Earlier this year, Dr. Collins established the UNITE initiative to address structural racism and promote racial equity and inclusion at the NIH and within the larger biomedical community that we support. NIAMS is fully committed to this effort. One example is the Diversity Supplement Program, which is designed to attract and encourage eligible individuals from underrepresented populations to research careers.

Early-stage investigators are another top priority. In a tribute to the beloved former NIAMS director, NIH recently established the Stephen I. Katz Early Stage Investigator Research Grant Program. The R01 award provides support for a project unrelated to an early investigator’s area of postdoctoral study. (No preliminary data are allowed.) This award mechanism is a unique opportunity for early-stage investigators to take their research in a completely new direction.

Managing work and family life is an important concern, particularly for female investigators. Many NIH grant awards allow for reimbursement of actual, allowable costs incurred for childcare and parental leave. The NIH is exploring initiatives to promote research continuity and retention of eligible investigators facing major life events, such as pregnancy, childbirth, and adoption, at vulnerable career stages.

Who inspires you most in your work today? I am inspired by the ongoing struggles of our patients, junior investigators, and by the committed staff members on my team.

[email protected]

After many years at the University of California, San Francisco, Lindsey A. Criswell, MD, MPH, DSc, began a new chapter in February 2021 as the director of the National Institute of Arthritis and Musculoskeletal and Skin Disease, part of the National Institutes of Health. NIH Director Francis S. Collins, MD, PhD, selected her for the post.

“Dr. Criswell has rich experience as a clinician, researcher, and administrator,” Dr. Collins said in a prepared statement. “Her ability to oversee the research program of one of the country’s top research-intensive medical schools, and her expertise in autoimmune diseases, including rheumatoid arthritis and lupus, make her well positioned to direct NIAMS.” Dr. Criswell, a rheumatologist, was named a full professor of medicine at UCSF in 2007 and had served as vice chancellor of research at the university since 2017. She has authored more than 250 peer-reviewed scientific papers, and her efforts have contributed to the identification of more than 30 genes linked to autoimmune disorders. In her first media interview, Dr. Criswell opens up about her mentors, operational challenges posed by the COVID-19 pandemic, and highlights many NIAMS research projects underway.

Who inspired you most early in your career as a physician scientist? I have had great opportunities to work with fabulous mentors. Wallace (Wally) Epstein, MD, was my mentor when I was a rheumatology fellow and junior faculty member at UCSF. He was broadly admired for the breadth of his experience as a clinician and a researcher, and he was noteworthy at that time for his strong support for women and students of color. One of the many things I appreciated about him was his diverse range of interests outside of work, which included cello playing and woodworking.

Another mentor was Ephraim (Eph) Engleman, MD, the first academic rheumatologist in California. Eph continued to see patients beyond the age of 100. Perhaps his most important contributions were his efforts towards advocacy for funding for research and education in rheumatology. A prodigy violinist, he too had a broad range of personal interests.

What research into the genetics and epidemiology of human autoimmune disease that you have been a part of has most surprised you, in term of its ultimate clinical impact? Some of my most rewarding and impactful work has focused on the shared genetic basis of autoimmune diseases. We’ve identified dozens of genes that contribute to the risk and outcome of rheumatoid arthritis, lupus, and other autoimmune disorders. These discoveries regarding shared genes and pathways among such a diverse set of conditions have helped to inform optimal therapeutic target and treatment strategies across multiple diseases. For example, exploration of RA genes and pathways has revealed that approved agents for other conditions, such as cancer, may be appropriately repurposed for the treatment of RA. These are critical observations that have the potential to dramatically accelerate progress in developing new therapies for autoimmune diseases, such as RA.

Did you have much interaction with Stephen I. Katz, MD, PhD, your longtime predecessor who passed away unexpectedly in 2018? If so, what do you remember most about him? I regret that I had very little interaction with Steve, but I am well aware of the impact he had on NIAMS, NIH, and the research enterprise overall. He inspired so many people in a personal way, and I am energized by the legacy that he left behind.

What are your goals for the early part of your tenure as the new director of NIAMS? An important goal is getting to know the NIAMS community and expanding my knowledge of the Institute’s musculoskeletal and skin portfolios. I am also conducting outreach to Institute/Center directors and other NIH leadership to increase opportunities for input and advice. In doing this, I am identifying shared research interests, best practices, and potential partners for possible future collaborations. Another important goal is to increase NIAMS’ visibility within and beyond NIH. Ultimately, I want to contribute to the great work of the Institute and improve the lives of people with rheumatic, musculoskeletal, and skin diseases.

How would you characterize your management style? I like to lead with a flat hierarchy and work collectively to address opportunities and challenges. I value team building and tend to tap a variety of perspectives and expertise at all levels to achieve consensus, where possible.

The Accelerating Medicines Partnership (AMP) program was launched in 2014, with projects in three disease areas including the autoimmune disorders RA and lupus. What are some recent highlights from this program with respect to RA and lupus? AMP RA/SLE was dedicated to identifying promising therapeutic targets for RA and systemic lupus erythematosus. AMP-funded researchers have applied cutting-edge technologies to study cells from the synovial tissues of the joints of people with RA, and from the kidneys of people with lupus nephritis. In 2014, studying tissues in patients where the disease is active was a novel approach, since most research was conducted in mouse models or human blood samples.

The AMP RA/SLE Network developed a rich dataset that is available to the research community. Investigators are now using the data to facilitate RA and lupus research. For example, using AMP data, NIAMS-supported researchers identified potential biomarkers that could help predict an imminent RA flare. Work from another NIAMS-supported group suggests that targeting the regulatory transcription factor HIF-1, which drives inflammation and tissue damage, might be an effective approach for treating renal injury in lupus.

The data generated are accessible to the scientific community through two NIH websites: the database of Genotypes and Phenotypes (dbGaP) and the Immunology Database and Analysis Portal (IMMPORT).

Given the success of AMP RA/SLE, NIH plans to launch an “AMP 2.0” later in 2021. The AMP Autoimmune and Immune-Mediated Diseases (AMP AIM) program will provide an opportunity to leverage the accomplishments of AMP RA/SLE to new conditions, including psoriatic spectrum diseases and Sjögren’s syndrome.

What are some recent highlights from NIAMS-supported research in skin diseases? NIAMS-supported investigators continue to make significant strides in our understanding of skin biology and disease. For example, researchers recently demonstrated that imiquimod, a drug used to treat precancerous skin lesions, can help mouse ear wounds heal without scarring.

Another team addressed the safety and potential benefit of Staphylococcus hominis A9, a bacterium isolated from healthy human skin, as a topical therapy for atopic dermatitis.

Moving forward, AMP AIM will refine and extend the single-cell analysis of tissues to additional diseases, including psoriasis, setting the stage for the discovery of new therapeutic targets for the disease.

How has the COVID-19 pandemic changed the landscape of research, at least for the short term? This is a once-in-a-century pandemic that none of us were fully prepared for. We understand that it has been particularly challenging for women scientists, scientists with young children, and trainees and junior faculty who are at critically important and vulnerable stages of their careers. There isn’t a lab or clinical setting that hasn’t been negatively impacted in some way.

During the pandemic, the NIH instituted administrative flexibilities to support the grantee community, including extensions in time. In addition, the agency has issued several funding opportunities specific to COVID-19, some of which involve NIAMS participation.

What is NIAMS doing to help early/young investigators as well as female investigators and those from minority groups? Structural racism in biomedical research is a heightened concern. Earlier this year, Dr. Collins established the UNITE initiative to address structural racism and promote racial equity and inclusion at the NIH and within the larger biomedical community that we support. NIAMS is fully committed to this effort. One example is the Diversity Supplement Program, which is designed to attract and encourage eligible individuals from underrepresented populations to research careers.

Early-stage investigators are another top priority. In a tribute to the beloved former NIAMS director, NIH recently established the Stephen I. Katz Early Stage Investigator Research Grant Program. The R01 award provides support for a project unrelated to an early investigator’s area of postdoctoral study. (No preliminary data are allowed.) This award mechanism is a unique opportunity for early-stage investigators to take their research in a completely new direction.

Managing work and family life is an important concern, particularly for female investigators. Many NIH grant awards allow for reimbursement of actual, allowable costs incurred for childcare and parental leave. The NIH is exploring initiatives to promote research continuity and retention of eligible investigators facing major life events, such as pregnancy, childbirth, and adoption, at vulnerable career stages.

Who inspires you most in your work today? I am inspired by the ongoing struggles of our patients, junior investigators, and by the committed staff members on my team.

[email protected]