MDedge Endocrinology

As an increasing number of health systems implement “hospital-at-home” (HaH) programs to increase their traditional hospital capacity, the Centers for Medicare & Medicaid Services has given the movement a boost by changing its regulations to allow acute care to be provided in a patient’s home under certain conditions.

The CMS announced Nov. 25 that it was launching its Acute Hospital Care at Home program “to increase the capacity of the American health care system” during the COVID-19 pandemic.

At the same time, the agency announced it was giving more flexibility to ambulatory surgery centers (ASCs) to provide hospital-level care.

The CMS said its new HaH program is an expansion of the Hospitals Without Walls initiative that was unveiled last March. Hospitals Without Walls is a set of “temporary new rules” that provide flexibility for hospitals to provide acute care outside of inpatient settings. Under those rules, hospitals are able to transfer patients to outside facilities, such as ASCs, inpatient rehabilitation hospitals, hotels, and dormitories, while still receiving Medicare hospital payments.

Under CMS’ new Acute Hospital Care at Home, which is not described as temporary, patients can be transferred from emergency departments or inpatient wards to hospital-level care at home. The CMS said the HaH program is designed for people with conditions such as the acute phases of asthma, heart failure, pneumonia, and chronic obstructive pulmonary disease. Altogether, the agency said, more than 60 acute conditions can be treated safely at home.

However, the agency didn’t say that facilities can’t admit COVID-19 patients to the hospital at home. Rami Karjian, MBA, cofounder and CEO of Medically Home, a firm that supplies health systems with technical services and software for HaH programs, said in an interview that several Medically Home clients plan to treat both COVID-19 and non-COVID-19 patients at home when they begin to participate in the CMS program in the near future.

The CMS said it consulted extensively with academic and private industry leaders in building its HaH program. Before rolling out the initiative, the agency noted, it conducted successful pilot programs in leading hospitals and health systems. The results of some of these pilots have been reported in academic journals.

Participating hospitals will be required to have specified screening protocols in place before beginning acute care at home, the CMS announced. An in-person physician evaluation will be required before starting care at home. A nurse will evaluate each patient once daily in person or remotely, and either nurses or paramedics will visit the patient in person twice a day.

In contrast, Medicare regulations require nursing staff to be available around the clock in traditional hospitals. So the CMS has to grant waivers to hospitals for HaH programs.

While not going into detail on the telemonitoring capabilities that will be required in the acute hospital care at home, the release said, “Today’s announcement builds upon the critical work by CMS to expand telehealth coverage to keep beneficiaries safe and prevent the spread of COVID-19.”
 

More flexibility for ASCs

The agency is also giving ASCs the flexibility to provide 24-hour nursing services only when one or more patients are receiving care on site. This flexibility will be available to any of the 5,700 ASCs that wish to participate, and will be immediately effective for the 85 ASCs currently participating in the Hospital Without Walls initiative, the CMS said.

The new ASC regulations, the CMS said, are aimed at allowing communities “to maintain surgical capacity and other life-saving non-COVID-19 [care], like cancer surgeries.” Patients who need such procedures will be able to receive them in ASCs without being exposed to known COVID-19 cases.

Similarly, the CMS said patients and families not diagnosed with COVID-19 may prefer to receive acute care at home if local hospitals are full of COVID-19 patients. In addition, the CMS said it anticipates patients may value the ability to be treated at home without the visitation restrictions of hospitals.
 

Early HaH participants

Six health systems with extensive experience in providing acute hospital care at home have been approved for the new HaH waivers from Medicare rules. They include Brigham and Women’s Hospital (Massachusetts); Huntsman Cancer Institute (Utah); Massachusetts General Hospital (Massachusetts); Mount Sinai Health System (New York City); Presbyterian Healthcare Services (New Mexico); and UnityPoint Health (Iowa).

The CMS said that it’s in discussions with other health care systems and expects new applications to be submitted soon.

To support these efforts, the CMS has launched an online portal to streamline the waiver request process. The agency said it will closely monitor the program to safeguard beneficiaries and will require participating hospitals to report quality and safety data on a regular basis.
 

Support from hospitals

The first health systems participating in the CMS HaH appear to be supportive of the program, with some hospital leaders submitting comments to the CMS about their view of the initiative.

“The CMS has taken an extraordinary step today, facilitating the rapid expansion of Hospitalization at Home, an innovative care model with proven results,” said Kenneth L. Davis, MD, president and CEO of the Mount Sinai Health System in New York City. “This important and timely move will enable hospitals across the country to use effective tools to safely care for patients during this pandemic.”

David Levine, MD, assistant professor of medicine and medical director of strategy and innovation for Brigham Health Home Hospital in Boston, was similarly laudatory: “Our research at Brigham Health Home has shown that we can deliver hospital-level care in our patients’ homes with lower readmission rates, more physical mobility, and a positive patient experience,” he said. “During these challenging times, a focus on the home is critical. We are so encouraged that CMS is taking this important step, which will allow hospitals across the country to increase their capacity while delivering the care all patients deserve.”
 

Scaling up quickly

If other hospitals and health systems recognize the value of HaH, how long might it take them to develop and implement these programs in the midst of a pandemic?

Atrium Health, a large health system in the Southeast, ramped up a hospital-at-home initiative last spring for its 10 hospitals in the Charlotte, N.C., area, in just 2 weeks. However, it had been working on the project for some time before the pandemic struck. Focusing mostly on COVID-19 patients, the initiative reduced the COVID-19 patient load by 20%-25% in Atrium’s hospitals.

Medically Home, the HaH infrastructure company, said in a news release that it “enables health systems to establish new hospital-at-home services in as little as 30 days.” Medically Home has partnered in this venture with Huron Consulting Group, which has about 200 HaH-trained consultants, and Cardinal Health, a large global medical supplies distributor.

Mr. Karjian said in an interview that he expects private insurers to follow CMS’ example, as they often do. “We think this decision will cause not only CMS but private insurers to cover hospital at home after the pandemic, if it becomes the standard of care, because patients have better outcomes when treated at home,” he said.

Asked for his view on why the CMS specified that patients could be admitted to an HaH only from emergency departments or inpatient settings, Mr. Karjian said that the CMS wants to make sure that patients have access to brick-and-mortar hospital care if that’s what they need. Also, he noted, this model is new to most hospitals, so the CMS wants to make sure it starts “with all the safety guardrails” in place.

Overall, Mr. Karjian said, “This is an exciting development for patients across the country. What CMS has done is terrific in terms of letting patients get the care they want, where they want it, and get the benefit of better outcomes while the nation is going through this capacity crunch for hospital beds.”

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

As an increasing number of health systems implement “hospital-at-home” (HaH) programs to increase their traditional hospital capacity, the Centers for Medicare & Medicaid Services has given the movement a boost by changing its regulations to allow acute care to be provided in a patient’s home under certain conditions.

The CMS announced Nov. 25 that it was launching its Acute Hospital Care at Home program “to increase the capacity of the American health care system” during the COVID-19 pandemic.

At the same time, the agency announced it was giving more flexibility to ambulatory surgery centers (ASCs) to provide hospital-level care.

The CMS said its new HaH program is an expansion of the Hospitals Without Walls initiative that was unveiled last March. Hospitals Without Walls is a set of “temporary new rules” that provide flexibility for hospitals to provide acute care outside of inpatient settings. Under those rules, hospitals are able to transfer patients to outside facilities, such as ASCs, inpatient rehabilitation hospitals, hotels, and dormitories, while still receiving Medicare hospital payments.

Under CMS’ new Acute Hospital Care at Home, which is not described as temporary, patients can be transferred from emergency departments or inpatient wards to hospital-level care at home. The CMS said the HaH program is designed for people with conditions such as the acute phases of asthma, heart failure, pneumonia, and chronic obstructive pulmonary disease. Altogether, the agency said, more than 60 acute conditions can be treated safely at home.

However, the agency didn’t say that facilities can’t admit COVID-19 patients to the hospital at home. Rami Karjian, MBA, cofounder and CEO of Medically Home, a firm that supplies health systems with technical services and software for HaH programs, said in an interview that several Medically Home clients plan to treat both COVID-19 and non-COVID-19 patients at home when they begin to participate in the CMS program in the near future.

The CMS said it consulted extensively with academic and private industry leaders in building its HaH program. Before rolling out the initiative, the agency noted, it conducted successful pilot programs in leading hospitals and health systems. The results of some of these pilots have been reported in academic journals.

Participating hospitals will be required to have specified screening protocols in place before beginning acute care at home, the CMS announced. An in-person physician evaluation will be required before starting care at home. A nurse will evaluate each patient once daily in person or remotely, and either nurses or paramedics will visit the patient in person twice a day.

In contrast, Medicare regulations require nursing staff to be available around the clock in traditional hospitals. So the CMS has to grant waivers to hospitals for HaH programs.

While not going into detail on the telemonitoring capabilities that will be required in the acute hospital care at home, the release said, “Today’s announcement builds upon the critical work by CMS to expand telehealth coverage to keep beneficiaries safe and prevent the spread of COVID-19.”
 

More flexibility for ASCs

The agency is also giving ASCs the flexibility to provide 24-hour nursing services only when one or more patients are receiving care on site. This flexibility will be available to any of the 5,700 ASCs that wish to participate, and will be immediately effective for the 85 ASCs currently participating in the Hospital Without Walls initiative, the CMS said.

The new ASC regulations, the CMS said, are aimed at allowing communities “to maintain surgical capacity and other life-saving non-COVID-19 [care], like cancer surgeries.” Patients who need such procedures will be able to receive them in ASCs without being exposed to known COVID-19 cases.

Similarly, the CMS said patients and families not diagnosed with COVID-19 may prefer to receive acute care at home if local hospitals are full of COVID-19 patients. In addition, the CMS said it anticipates patients may value the ability to be treated at home without the visitation restrictions of hospitals.
 

Early HaH participants

Six health systems with extensive experience in providing acute hospital care at home have been approved for the new HaH waivers from Medicare rules. They include Brigham and Women’s Hospital (Massachusetts); Huntsman Cancer Institute (Utah); Massachusetts General Hospital (Massachusetts); Mount Sinai Health System (New York City); Presbyterian Healthcare Services (New Mexico); and UnityPoint Health (Iowa).

The CMS said that it’s in discussions with other health care systems and expects new applications to be submitted soon.

To support these efforts, the CMS has launched an online portal to streamline the waiver request process. The agency said it will closely monitor the program to safeguard beneficiaries and will require participating hospitals to report quality and safety data on a regular basis.
 

Support from hospitals

The first health systems participating in the CMS HaH appear to be supportive of the program, with some hospital leaders submitting comments to the CMS about their view of the initiative.

“The CMS has taken an extraordinary step today, facilitating the rapid expansion of Hospitalization at Home, an innovative care model with proven results,” said Kenneth L. Davis, MD, president and CEO of the Mount Sinai Health System in New York City. “This important and timely move will enable hospitals across the country to use effective tools to safely care for patients during this pandemic.”

David Levine, MD, assistant professor of medicine and medical director of strategy and innovation for Brigham Health Home Hospital in Boston, was similarly laudatory: “Our research at Brigham Health Home has shown that we can deliver hospital-level care in our patients’ homes with lower readmission rates, more physical mobility, and a positive patient experience,” he said. “During these challenging times, a focus on the home is critical. We are so encouraged that CMS is taking this important step, which will allow hospitals across the country to increase their capacity while delivering the care all patients deserve.”
 

Scaling up quickly

If other hospitals and health systems recognize the value of HaH, how long might it take them to develop and implement these programs in the midst of a pandemic?

Atrium Health, a large health system in the Southeast, ramped up a hospital-at-home initiative last spring for its 10 hospitals in the Charlotte, N.C., area, in just 2 weeks. However, it had been working on the project for some time before the pandemic struck. Focusing mostly on COVID-19 patients, the initiative reduced the COVID-19 patient load by 20%-25% in Atrium’s hospitals.

Medically Home, the HaH infrastructure company, said in a news release that it “enables health systems to establish new hospital-at-home services in as little as 30 days.” Medically Home has partnered in this venture with Huron Consulting Group, which has about 200 HaH-trained consultants, and Cardinal Health, a large global medical supplies distributor.

Mr. Karjian said in an interview that he expects private insurers to follow CMS’ example, as they often do. “We think this decision will cause not only CMS but private insurers to cover hospital at home after the pandemic, if it becomes the standard of care, because patients have better outcomes when treated at home,” he said.

Asked for his view on why the CMS specified that patients could be admitted to an HaH only from emergency departments or inpatient settings, Mr. Karjian said that the CMS wants to make sure that patients have access to brick-and-mortar hospital care if that’s what they need. Also, he noted, this model is new to most hospitals, so the CMS wants to make sure it starts “with all the safety guardrails” in place.

Overall, Mr. Karjian said, “This is an exciting development for patients across the country. What CMS has done is terrific in terms of letting patients get the care they want, where they want it, and get the benefit of better outcomes while the nation is going through this capacity crunch for hospital beds.”

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

As an increasing number of health systems implement “hospital-at-home” (HaH) programs to increase their traditional hospital capacity, the Centers for Medicare & Medicaid Services has given the movement a boost by changing its regulations to allow acute care to be provided in a patient’s home under certain conditions.

The CMS announced Nov. 25 that it was launching its Acute Hospital Care at Home program “to increase the capacity of the American health care system” during the COVID-19 pandemic.

At the same time, the agency announced it was giving more flexibility to ambulatory surgery centers (ASCs) to provide hospital-level care.

The CMS said its new HaH program is an expansion of the Hospitals Without Walls initiative that was unveiled last March. Hospitals Without Walls is a set of “temporary new rules” that provide flexibility for hospitals to provide acute care outside of inpatient settings. Under those rules, hospitals are able to transfer patients to outside facilities, such as ASCs, inpatient rehabilitation hospitals, hotels, and dormitories, while still receiving Medicare hospital payments.

Under CMS’ new Acute Hospital Care at Home, which is not described as temporary, patients can be transferred from emergency departments or inpatient wards to hospital-level care at home. The CMS said the HaH program is designed for people with conditions such as the acute phases of asthma, heart failure, pneumonia, and chronic obstructive pulmonary disease. Altogether, the agency said, more than 60 acute conditions can be treated safely at home.

However, the agency didn’t say that facilities can’t admit COVID-19 patients to the hospital at home. Rami Karjian, MBA, cofounder and CEO of Medically Home, a firm that supplies health systems with technical services and software for HaH programs, said in an interview that several Medically Home clients plan to treat both COVID-19 and non-COVID-19 patients at home when they begin to participate in the CMS program in the near future.

The CMS said it consulted extensively with academic and private industry leaders in building its HaH program. Before rolling out the initiative, the agency noted, it conducted successful pilot programs in leading hospitals and health systems. The results of some of these pilots have been reported in academic journals.

Participating hospitals will be required to have specified screening protocols in place before beginning acute care at home, the CMS announced. An in-person physician evaluation will be required before starting care at home. A nurse will evaluate each patient once daily in person or remotely, and either nurses or paramedics will visit the patient in person twice a day.

In contrast, Medicare regulations require nursing staff to be available around the clock in traditional hospitals. So the CMS has to grant waivers to hospitals for HaH programs.

While not going into detail on the telemonitoring capabilities that will be required in the acute hospital care at home, the release said, “Today’s announcement builds upon the critical work by CMS to expand telehealth coverage to keep beneficiaries safe and prevent the spread of COVID-19.”
 

More flexibility for ASCs

The agency is also giving ASCs the flexibility to provide 24-hour nursing services only when one or more patients are receiving care on site. This flexibility will be available to any of the 5,700 ASCs that wish to participate, and will be immediately effective for the 85 ASCs currently participating in the Hospital Without Walls initiative, the CMS said.

The new ASC regulations, the CMS said, are aimed at allowing communities “to maintain surgical capacity and other life-saving non-COVID-19 [care], like cancer surgeries.” Patients who need such procedures will be able to receive them in ASCs without being exposed to known COVID-19 cases.

Similarly, the CMS said patients and families not diagnosed with COVID-19 may prefer to receive acute care at home if local hospitals are full of COVID-19 patients. In addition, the CMS said it anticipates patients may value the ability to be treated at home without the visitation restrictions of hospitals.
 

Early HaH participants

Six health systems with extensive experience in providing acute hospital care at home have been approved for the new HaH waivers from Medicare rules. They include Brigham and Women’s Hospital (Massachusetts); Huntsman Cancer Institute (Utah); Massachusetts General Hospital (Massachusetts); Mount Sinai Health System (New York City); Presbyterian Healthcare Services (New Mexico); and UnityPoint Health (Iowa).

The CMS said that it’s in discussions with other health care systems and expects new applications to be submitted soon.

To support these efforts, the CMS has launched an online portal to streamline the waiver request process. The agency said it will closely monitor the program to safeguard beneficiaries and will require participating hospitals to report quality and safety data on a regular basis.
 

Support from hospitals

The first health systems participating in the CMS HaH appear to be supportive of the program, with some hospital leaders submitting comments to the CMS about their view of the initiative.

“The CMS has taken an extraordinary step today, facilitating the rapid expansion of Hospitalization at Home, an innovative care model with proven results,” said Kenneth L. Davis, MD, president and CEO of the Mount Sinai Health System in New York City. “This important and timely move will enable hospitals across the country to use effective tools to safely care for patients during this pandemic.”

David Levine, MD, assistant professor of medicine and medical director of strategy and innovation for Brigham Health Home Hospital in Boston, was similarly laudatory: “Our research at Brigham Health Home has shown that we can deliver hospital-level care in our patients’ homes with lower readmission rates, more physical mobility, and a positive patient experience,” he said. “During these challenging times, a focus on the home is critical. We are so encouraged that CMS is taking this important step, which will allow hospitals across the country to increase their capacity while delivering the care all patients deserve.”
 

Scaling up quickly

If other hospitals and health systems recognize the value of HaH, how long might it take them to develop and implement these programs in the midst of a pandemic?

Atrium Health, a large health system in the Southeast, ramped up a hospital-at-home initiative last spring for its 10 hospitals in the Charlotte, N.C., area, in just 2 weeks. However, it had been working on the project for some time before the pandemic struck. Focusing mostly on COVID-19 patients, the initiative reduced the COVID-19 patient load by 20%-25% in Atrium’s hospitals.

Medically Home, the HaH infrastructure company, said in a news release that it “enables health systems to establish new hospital-at-home services in as little as 30 days.” Medically Home has partnered in this venture with Huron Consulting Group, which has about 200 HaH-trained consultants, and Cardinal Health, a large global medical supplies distributor.

Mr. Karjian said in an interview that he expects private insurers to follow CMS’ example, as they often do. “We think this decision will cause not only CMS but private insurers to cover hospital at home after the pandemic, if it becomes the standard of care, because patients have better outcomes when treated at home,” he said.

Asked for his view on why the CMS specified that patients could be admitted to an HaH only from emergency departments or inpatient settings, Mr. Karjian said that the CMS wants to make sure that patients have access to brick-and-mortar hospital care if that’s what they need. Also, he noted, this model is new to most hospitals, so the CMS wants to make sure it starts “with all the safety guardrails” in place.

Overall, Mr. Karjian said, “This is an exciting development for patients across the country. What CMS has done is terrific in terms of letting patients get the care they want, where they want it, and get the benefit of better outcomes while the nation is going through this capacity crunch for hospital beds.”

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

For mid-career oncologist Tanya Wildes, MD, the pandemic was the last straw. In late September, she tweeted: “I have done the academically unfathomable: I am resigning my faculty position without another job lined up.”

She wasn’t burned out, she insisted. She loved her patients and her research. But she was also “100% confident” in her decision and “also 100% sad. This did not have to happen,” she lamented, asking not to disclose her workplace for fear of retribution.

Being a woman in medicine “is a hard life to start with,” Dr. Wildes said in an interview. “We all have that tenuous balance going on and the pandemic made everything just a little bit harder.”

She describes her prepandemic work-life balance as a “Jenga tower, with everything only just in place.” But she realized that the balance had tipped, when after a difficult clinic she felt emotionally wrung out. Her 11-year-old son had asked her to help him fly his model airplane. “I told him, ‘Honey, I can’t do it because if it crashes or gets stuck in a tree ... you’re going to be devastated and I have nothing left for you.’ “

This was a eureka moment, as “I realized, this is not who I want to be,” she said, holding back tears. “Seventy years from now my son is going to tell his grandchildren about the pandemic and I don’t want his memory of his mom to be that she couldn’t be there for him because she was too spent.”

When Dr. Wildes shared her story on Twitter, other female oncologists and physicians responded that they too have felt they’re under increased pressure this year, with the extra stress of the pandemic leading others to quit as well.

The trend of doctors leaving medicine has been noticeable. A July survey from the Physicians Foundation found that roughly 16,000 medical practices had already closed during the pandemic, with another 8,000 predicted to close within the next year.

“Similar patterns” were evident in another analysis by the Larry A. Green Center and the Primary Care Collaborative, as reported in The New York Times. In that survey, nearly one-fifth of primary care clinicians said “someone in their practice plans to retire early or has already retired because of COVID-19,” and 15% say “someone has left or plans to leave the practice.” About half said their mental exhaustion was at an all-time high, the survey found.

“COVID-19 is a burden, and that added burden has tipped people over the edge of many things,” said Monica Bertagnolli, MD, chief of the division of surgical oncology at Brigham and Women’s Hospital, Boston, and former president of the American Society of Clinical Oncology.

“It has illustrated that we do have a lot of people who are working kind of on the edge of not being able to handle everything,” she said.

While many in medicine are struggling, the pandemic seems to be pushing more women to leave, highlighting longtime gender disparities and increased caregiving burdens. And their absence may be felt for years to come.

Firm numbers are hard to come by, said Julie Silver, MD, associate professor, associate chair, and director of cancer rehabilitation in the department of physical medicine and rehabilitation at Harvard Medical School, Boston, and an expert in gender equity in medicine. But she sees some troubling trends.

“There are many indications that women are leaving medicine in disproportionately high numbers,” Dr. Silver said in an interview. “A lack of fair pay and promotion opportunities that were present before COVID-19 are now combined with a host of pandemic-related challenges.”

A survey of 1,809 women conducted in mid-April with the Physician Moms Facebook Group and accepted for online publication by the American Journal of Psychiatry found that 41% scored over the cutoff points for moderate or severe anxiety, with 46% meeting these criteria among front-line workers.

“It’s really important for society to recognize the extraordinary impact this pandemic is having on physician mothers, as there will be profound ripple effects on the ability of this key segment of the health care workforce to serve others if we do not address this problem urgently,” co-senior author Reshma Jagsi, MD, DPhil, a radiation oncologist at the University of Michigan, Ann Arbor, said in an interview.

Women weighed in on Twitter, in response to Dr. Silver’s tweet to #WomenInMedicine: “If you are thinking of leaving #medicine & need a reason to stay: we value you & need you.”

In reply, Emmy Betz, MD, MPH, associate professor of emergency medicine at the University of Colorado at Denver, Aurora, said via Twitter, “I’ve had lots of conversations with women considering leaving medicine.”

“I have thought about leaving many times. I love what I do, but medicine can be an unkind world at times,” responded Valerie Fitzhugh MD, associate professor and pathologist at New Jersey Medical School, Newark.

“Too late. Left at the end of July and it was the best decision ever,” wrote Michelle Gordon, DO, who was previously a board-certified general surgeon at Northern Westchester Surgical Associates in Putnam Valley, N.Y.


 

Prepandemic disparities accentuated

The pandemic “has merely accentuated – or made more apparent – some of the longstanding issues and struggles of women in oncology, women in medicine, women in academia,” said Sarah Holstein, MD, PhD, another mid-career oncologist and associate professor at the University of Nebraska Medical Center, Omaha.

“There are disparities in first-author/last-author publications, disparities in being asked to give speaking engagements, disparities in leadership,” Dr. Holstein said in an interview. “And then ... put on top of that the various surges with the pandemic where you are being asked to do clinical responsibilities you don’t normally do, perhaps some things you haven’t done since your training 10 or 20 years ago.”

This is backed up with data: There is already a “robust” body of prepandemic literature demonstrating pay gaps for female physicians and scientists, noted Dr. Silver, who founded the Her Time Is Now campaign for gender equity in medicine and runs a women’s leadership course at Harvard.

In addition, female physicians are more likely to be involved in “nonpromotable” work, group projects and educator roles that are often underappreciated and undercompensated, she said.

Writing recently in a blog post for the BMJ, Dr. Silver and colleagues predict that as a result of the pandemic, female physicians will “face disadvantages from unconscious bias in decisions about whose pay should be cut, whose operating schedules should take priority when resources are limited, and whose contributions merit retention ... The ground that women lose now will likely have a profound effect for many years to come, perhaps putting them at a disadvantage for the rest of their careers.”

There is already evidence of reduced publishing by female scientists during the pandemic, something that “could undermine the careers of an entire generation of women scholars,” noted Caitlyn Collins, PhD, assistant professor of sociology at Washington University in St. Louis.

“Science needs to address the culture of overwork,” Dr. Collins said in an interview. “Parents and other caregivers deserve support. The stress and ‘overwhelm’ they feel is not inevitable. A more fair, just, and humane approach to combining work and family is possible – what we need is the political will to pass better policies and a massive shift in our cultural understandings about how work should fit into family life, not the other way around.”

Lack of support for “vulnerable scientists,” particularly “junior scientists who are parents, women, or minorities” could lead to “severe attrition in cancer research in the coming years,” Cullen Taniguchi, MD, PhD, a radiation oncologist and associate professor at the University of Texas MD Anderson Cancer Center, Houston, and colleagues, warned in a recent letter to the journal Cancer Cell.

“The biggest worries of attrition will come from young faculty who started just before or after the pandemic,” Dr. Taniguchi said in an interview. “The first year in an academic setting is incredibly challenging but also important for establishing research efforts and building networks of colleagues to collaborate with. While completely necessary, the restrictions put in place during the pandemic made doing these things even more difficult.”
 

Another stressor: Caregiving at home

Another reason female physicians may be marginalized during the pandemic is that they are more often the primary caregivers at home.

“Anyone who is a caregiver, be it to kids, parents, or spouses, can relate to the challenges brought [on] by the pandemic,” said Ishwaria Subbiah, MD, a palliative care physician and medical oncologist at MD Anderson.

“Most of us work toward meeting our responsibilities by engaging a network of support, whether it’s home care workers, center-based or at-home child care, schools, or activities outside of school. The pandemic led to a level of disruption that brought most (if not all) of those responsibilities onto the caregivers themselves,” she said in an interview.

As the mother of an adult son with severe epilepsy, Dr. Bertagnolli has certainly experienced the challenges of parenting during the pandemic. “Our son is now 24 but he is handicapped, and lives with us. The care issues we have to deal with as professionals have been enormously magnified by COVID,” she said.

But she cautions against making gender distinctions when it comes to caregiving. “Has it fallen on the women? Well, this kind of stuff generally falls on the women, but I am certain it has fallen on an awful lot of men as well, because I think the world is changing that way, so it’s fallen on all of us.”

There is no question that female oncologists are bearing the brunt, both at work and at home, contended Dr. Taniguchi. “Absolutely. I have seen this first-hand,” he said.

“If it was difficult for women, underrepresented minorities, and junior faculty to find a voice in the room prepandemic, I think it can be harder in the times of virtual meetings when it is difficult to engage audiences,” he said. 

Dr. Holstein said she is lucky to be well-supported at her institution, with both a female chief of hematology/oncology and a female chair of internal medicine, but still, she worries about the long-term consequences of the pandemic on the gender landscape of medicine.

“If you’re having to put aside research projects because you have extra responsibilities – again because women just tend to have a lot of other things going on – that might not be a big deal for 3 months, 6 months, but this is going to be a year or 2 years before ‘normal’ comes back,” she says. “One to two years of underpublishing or not getting the grants could be career killers for women in academic oncology.”
 

Cancer COVID-19 combo

As Dr. Wildes completed her final weeks of seeing cancer patients, she received an outpouring of support, which she says convinced her of the shared experience of all doctors, and especially female doctors, during the pandemic. But even more specifically, she feels that she has tapped into the unique burden shouldered by oncologists during this time.

“It’s intimidating being an oncologist; we are literally giving people poison for a living. Then throw into it a pandemic where early in March we had so little data. I was helping my patients make decisions about their cancer care based on a case series of four patients in China. The burden of those conversations is something I never want to have to live through again,” she said.

“Oncology is a particularly intense subspecialty within medicine,” agreed Dr. Subbiah. “The people we care for have received a life-altering and potentially life-limiting diagnosis. Coupled with that, the COVID-19 pandemic has brought an unprecedented cloud of uncertainty ... Whether the patients can see it overtly or not, oncologists carry the weight of this worry with them for not just one but all of their patients.”

Dr. Wildes said she plans to return to academic medicine and clinical care “in time,” but for now, the gap that she and others like her leave is troubling to those who have stayed on.

“We need these women in medicine,” said Dr. Holstein. “We have data suggesting that women take more time with their patients than men, that patient outcomes are better if they have a female physician. But also for the generations coming up, we need the mid-career and senior women to be in place to mentor and guide and make sure we continue to increase women in leadership.”

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

For mid-career oncologist Tanya Wildes, MD, the pandemic was the last straw. In late September, she tweeted: “I have done the academically unfathomable: I am resigning my faculty position without another job lined up.”

She wasn’t burned out, she insisted. She loved her patients and her research. But she was also “100% confident” in her decision and “also 100% sad. This did not have to happen,” she lamented, asking not to disclose her workplace for fear of retribution.

Being a woman in medicine “is a hard life to start with,” Dr. Wildes said in an interview. “We all have that tenuous balance going on and the pandemic made everything just a little bit harder.”

She describes her prepandemic work-life balance as a “Jenga tower, with everything only just in place.” But she realized that the balance had tipped, when after a difficult clinic she felt emotionally wrung out. Her 11-year-old son had asked her to help him fly his model airplane. “I told him, ‘Honey, I can’t do it because if it crashes or gets stuck in a tree ... you’re going to be devastated and I have nothing left for you.’ “

This was a eureka moment, as “I realized, this is not who I want to be,” she said, holding back tears. “Seventy years from now my son is going to tell his grandchildren about the pandemic and I don’t want his memory of his mom to be that she couldn’t be there for him because she was too spent.”

When Dr. Wildes shared her story on Twitter, other female oncologists and physicians responded that they too have felt they’re under increased pressure this year, with the extra stress of the pandemic leading others to quit as well.

The trend of doctors leaving medicine has been noticeable. A July survey from the Physicians Foundation found that roughly 16,000 medical practices had already closed during the pandemic, with another 8,000 predicted to close within the next year.

“Similar patterns” were evident in another analysis by the Larry A. Green Center and the Primary Care Collaborative, as reported in The New York Times. In that survey, nearly one-fifth of primary care clinicians said “someone in their practice plans to retire early or has already retired because of COVID-19,” and 15% say “someone has left or plans to leave the practice.” About half said their mental exhaustion was at an all-time high, the survey found.

“COVID-19 is a burden, and that added burden has tipped people over the edge of many things,” said Monica Bertagnolli, MD, chief of the division of surgical oncology at Brigham and Women’s Hospital, Boston, and former president of the American Society of Clinical Oncology.

“It has illustrated that we do have a lot of people who are working kind of on the edge of not being able to handle everything,” she said.

While many in medicine are struggling, the pandemic seems to be pushing more women to leave, highlighting longtime gender disparities and increased caregiving burdens. And their absence may be felt for years to come.

Firm numbers are hard to come by, said Julie Silver, MD, associate professor, associate chair, and director of cancer rehabilitation in the department of physical medicine and rehabilitation at Harvard Medical School, Boston, and an expert in gender equity in medicine. But she sees some troubling trends.

“There are many indications that women are leaving medicine in disproportionately high numbers,” Dr. Silver said in an interview. “A lack of fair pay and promotion opportunities that were present before COVID-19 are now combined with a host of pandemic-related challenges.”

A survey of 1,809 women conducted in mid-April with the Physician Moms Facebook Group and accepted for online publication by the American Journal of Psychiatry found that 41% scored over the cutoff points for moderate or severe anxiety, with 46% meeting these criteria among front-line workers.

“It’s really important for society to recognize the extraordinary impact this pandemic is having on physician mothers, as there will be profound ripple effects on the ability of this key segment of the health care workforce to serve others if we do not address this problem urgently,” co-senior author Reshma Jagsi, MD, DPhil, a radiation oncologist at the University of Michigan, Ann Arbor, said in an interview.

Women weighed in on Twitter, in response to Dr. Silver’s tweet to #WomenInMedicine: “If you are thinking of leaving #medicine & need a reason to stay: we value you & need you.”

In reply, Emmy Betz, MD, MPH, associate professor of emergency medicine at the University of Colorado at Denver, Aurora, said via Twitter, “I’ve had lots of conversations with women considering leaving medicine.”

“I have thought about leaving many times. I love what I do, but medicine can be an unkind world at times,” responded Valerie Fitzhugh MD, associate professor and pathologist at New Jersey Medical School, Newark.

“Too late. Left at the end of July and it was the best decision ever,” wrote Michelle Gordon, DO, who was previously a board-certified general surgeon at Northern Westchester Surgical Associates in Putnam Valley, N.Y.


 

Prepandemic disparities accentuated

The pandemic “has merely accentuated – or made more apparent – some of the longstanding issues and struggles of women in oncology, women in medicine, women in academia,” said Sarah Holstein, MD, PhD, another mid-career oncologist and associate professor at the University of Nebraska Medical Center, Omaha.

“There are disparities in first-author/last-author publications, disparities in being asked to give speaking engagements, disparities in leadership,” Dr. Holstein said in an interview. “And then ... put on top of that the various surges with the pandemic where you are being asked to do clinical responsibilities you don’t normally do, perhaps some things you haven’t done since your training 10 or 20 years ago.”

This is backed up with data: There is already a “robust” body of prepandemic literature demonstrating pay gaps for female physicians and scientists, noted Dr. Silver, who founded the Her Time Is Now campaign for gender equity in medicine and runs a women’s leadership course at Harvard.

In addition, female physicians are more likely to be involved in “nonpromotable” work, group projects and educator roles that are often underappreciated and undercompensated, she said.

Writing recently in a blog post for the BMJ, Dr. Silver and colleagues predict that as a result of the pandemic, female physicians will “face disadvantages from unconscious bias in decisions about whose pay should be cut, whose operating schedules should take priority when resources are limited, and whose contributions merit retention ... The ground that women lose now will likely have a profound effect for many years to come, perhaps putting them at a disadvantage for the rest of their careers.”

There is already evidence of reduced publishing by female scientists during the pandemic, something that “could undermine the careers of an entire generation of women scholars,” noted Caitlyn Collins, PhD, assistant professor of sociology at Washington University in St. Louis.

“Science needs to address the culture of overwork,” Dr. Collins said in an interview. “Parents and other caregivers deserve support. The stress and ‘overwhelm’ they feel is not inevitable. A more fair, just, and humane approach to combining work and family is possible – what we need is the political will to pass better policies and a massive shift in our cultural understandings about how work should fit into family life, not the other way around.”

Lack of support for “vulnerable scientists,” particularly “junior scientists who are parents, women, or minorities” could lead to “severe attrition in cancer research in the coming years,” Cullen Taniguchi, MD, PhD, a radiation oncologist and associate professor at the University of Texas MD Anderson Cancer Center, Houston, and colleagues, warned in a recent letter to the journal Cancer Cell.

“The biggest worries of attrition will come from young faculty who started just before or after the pandemic,” Dr. Taniguchi said in an interview. “The first year in an academic setting is incredibly challenging but also important for establishing research efforts and building networks of colleagues to collaborate with. While completely necessary, the restrictions put in place during the pandemic made doing these things even more difficult.”
 

Another stressor: Caregiving at home

Another reason female physicians may be marginalized during the pandemic is that they are more often the primary caregivers at home.

“Anyone who is a caregiver, be it to kids, parents, or spouses, can relate to the challenges brought [on] by the pandemic,” said Ishwaria Subbiah, MD, a palliative care physician and medical oncologist at MD Anderson.

“Most of us work toward meeting our responsibilities by engaging a network of support, whether it’s home care workers, center-based or at-home child care, schools, or activities outside of school. The pandemic led to a level of disruption that brought most (if not all) of those responsibilities onto the caregivers themselves,” she said in an interview.

As the mother of an adult son with severe epilepsy, Dr. Bertagnolli has certainly experienced the challenges of parenting during the pandemic. “Our son is now 24 but he is handicapped, and lives with us. The care issues we have to deal with as professionals have been enormously magnified by COVID,” she said.

But she cautions against making gender distinctions when it comes to caregiving. “Has it fallen on the women? Well, this kind of stuff generally falls on the women, but I am certain it has fallen on an awful lot of men as well, because I think the world is changing that way, so it’s fallen on all of us.”

There is no question that female oncologists are bearing the brunt, both at work and at home, contended Dr. Taniguchi. “Absolutely. I have seen this first-hand,” he said.

“If it was difficult for women, underrepresented minorities, and junior faculty to find a voice in the room prepandemic, I think it can be harder in the times of virtual meetings when it is difficult to engage audiences,” he said. 

Dr. Holstein said she is lucky to be well-supported at her institution, with both a female chief of hematology/oncology and a female chair of internal medicine, but still, she worries about the long-term consequences of the pandemic on the gender landscape of medicine.

“If you’re having to put aside research projects because you have extra responsibilities – again because women just tend to have a lot of other things going on – that might not be a big deal for 3 months, 6 months, but this is going to be a year or 2 years before ‘normal’ comes back,” she says. “One to two years of underpublishing or not getting the grants could be career killers for women in academic oncology.”
 

Cancer COVID-19 combo

As Dr. Wildes completed her final weeks of seeing cancer patients, she received an outpouring of support, which she says convinced her of the shared experience of all doctors, and especially female doctors, during the pandemic. But even more specifically, she feels that she has tapped into the unique burden shouldered by oncologists during this time.

“It’s intimidating being an oncologist; we are literally giving people poison for a living. Then throw into it a pandemic where early in March we had so little data. I was helping my patients make decisions about their cancer care based on a case series of four patients in China. The burden of those conversations is something I never want to have to live through again,” she said.

“Oncology is a particularly intense subspecialty within medicine,” agreed Dr. Subbiah. “The people we care for have received a life-altering and potentially life-limiting diagnosis. Coupled with that, the COVID-19 pandemic has brought an unprecedented cloud of uncertainty ... Whether the patients can see it overtly or not, oncologists carry the weight of this worry with them for not just one but all of their patients.”

Dr. Wildes said she plans to return to academic medicine and clinical care “in time,” but for now, the gap that she and others like her leave is troubling to those who have stayed on.

“We need these women in medicine,” said Dr. Holstein. “We have data suggesting that women take more time with their patients than men, that patient outcomes are better if they have a female physician. But also for the generations coming up, we need the mid-career and senior women to be in place to mentor and guide and make sure we continue to increase women in leadership.”

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

For mid-career oncologist Tanya Wildes, MD, the pandemic was the last straw. In late September, she tweeted: “I have done the academically unfathomable: I am resigning my faculty position without another job lined up.”

She wasn’t burned out, she insisted. She loved her patients and her research. But she was also “100% confident” in her decision and “also 100% sad. This did not have to happen,” she lamented, asking not to disclose her workplace for fear of retribution.

Being a woman in medicine “is a hard life to start with,” Dr. Wildes said in an interview. “We all have that tenuous balance going on and the pandemic made everything just a little bit harder.”

She describes her prepandemic work-life balance as a “Jenga tower, with everything only just in place.” But she realized that the balance had tipped, when after a difficult clinic she felt emotionally wrung out. Her 11-year-old son had asked her to help him fly his model airplane. “I told him, ‘Honey, I can’t do it because if it crashes or gets stuck in a tree ... you’re going to be devastated and I have nothing left for you.’ “

This was a eureka moment, as “I realized, this is not who I want to be,” she said, holding back tears. “Seventy years from now my son is going to tell his grandchildren about the pandemic and I don’t want his memory of his mom to be that she couldn’t be there for him because she was too spent.”

When Dr. Wildes shared her story on Twitter, other female oncologists and physicians responded that they too have felt they’re under increased pressure this year, with the extra stress of the pandemic leading others to quit as well.

The trend of doctors leaving medicine has been noticeable. A July survey from the Physicians Foundation found that roughly 16,000 medical practices had already closed during the pandemic, with another 8,000 predicted to close within the next year.

“Similar patterns” were evident in another analysis by the Larry A. Green Center and the Primary Care Collaborative, as reported in The New York Times. In that survey, nearly one-fifth of primary care clinicians said “someone in their practice plans to retire early or has already retired because of COVID-19,” and 15% say “someone has left or plans to leave the practice.” About half said their mental exhaustion was at an all-time high, the survey found.

“COVID-19 is a burden, and that added burden has tipped people over the edge of many things,” said Monica Bertagnolli, MD, chief of the division of surgical oncology at Brigham and Women’s Hospital, Boston, and former president of the American Society of Clinical Oncology.

“It has illustrated that we do have a lot of people who are working kind of on the edge of not being able to handle everything,” she said.

While many in medicine are struggling, the pandemic seems to be pushing more women to leave, highlighting longtime gender disparities and increased caregiving burdens. And their absence may be felt for years to come.

Firm numbers are hard to come by, said Julie Silver, MD, associate professor, associate chair, and director of cancer rehabilitation in the department of physical medicine and rehabilitation at Harvard Medical School, Boston, and an expert in gender equity in medicine. But she sees some troubling trends.

“There are many indications that women are leaving medicine in disproportionately high numbers,” Dr. Silver said in an interview. “A lack of fair pay and promotion opportunities that were present before COVID-19 are now combined with a host of pandemic-related challenges.”

A survey of 1,809 women conducted in mid-April with the Physician Moms Facebook Group and accepted for online publication by the American Journal of Psychiatry found that 41% scored over the cutoff points for moderate or severe anxiety, with 46% meeting these criteria among front-line workers.

“It’s really important for society to recognize the extraordinary impact this pandemic is having on physician mothers, as there will be profound ripple effects on the ability of this key segment of the health care workforce to serve others if we do not address this problem urgently,” co-senior author Reshma Jagsi, MD, DPhil, a radiation oncologist at the University of Michigan, Ann Arbor, said in an interview.

Women weighed in on Twitter, in response to Dr. Silver’s tweet to #WomenInMedicine: “If you are thinking of leaving #medicine & need a reason to stay: we value you & need you.”

In reply, Emmy Betz, MD, MPH, associate professor of emergency medicine at the University of Colorado at Denver, Aurora, said via Twitter, “I’ve had lots of conversations with women considering leaving medicine.”

“I have thought about leaving many times. I love what I do, but medicine can be an unkind world at times,” responded Valerie Fitzhugh MD, associate professor and pathologist at New Jersey Medical School, Newark.

“Too late. Left at the end of July and it was the best decision ever,” wrote Michelle Gordon, DO, who was previously a board-certified general surgeon at Northern Westchester Surgical Associates in Putnam Valley, N.Y.


 

Prepandemic disparities accentuated

The pandemic “has merely accentuated – or made more apparent – some of the longstanding issues and struggles of women in oncology, women in medicine, women in academia,” said Sarah Holstein, MD, PhD, another mid-career oncologist and associate professor at the University of Nebraska Medical Center, Omaha.

“There are disparities in first-author/last-author publications, disparities in being asked to give speaking engagements, disparities in leadership,” Dr. Holstein said in an interview. “And then ... put on top of that the various surges with the pandemic where you are being asked to do clinical responsibilities you don’t normally do, perhaps some things you haven’t done since your training 10 or 20 years ago.”

This is backed up with data: There is already a “robust” body of prepandemic literature demonstrating pay gaps for female physicians and scientists, noted Dr. Silver, who founded the Her Time Is Now campaign for gender equity in medicine and runs a women’s leadership course at Harvard.

In addition, female physicians are more likely to be involved in “nonpromotable” work, group projects and educator roles that are often underappreciated and undercompensated, she said.

Writing recently in a blog post for the BMJ, Dr. Silver and colleagues predict that as a result of the pandemic, female physicians will “face disadvantages from unconscious bias in decisions about whose pay should be cut, whose operating schedules should take priority when resources are limited, and whose contributions merit retention ... The ground that women lose now will likely have a profound effect for many years to come, perhaps putting them at a disadvantage for the rest of their careers.”

There is already evidence of reduced publishing by female scientists during the pandemic, something that “could undermine the careers of an entire generation of women scholars,” noted Caitlyn Collins, PhD, assistant professor of sociology at Washington University in St. Louis.

“Science needs to address the culture of overwork,” Dr. Collins said in an interview. “Parents and other caregivers deserve support. The stress and ‘overwhelm’ they feel is not inevitable. A more fair, just, and humane approach to combining work and family is possible – what we need is the political will to pass better policies and a massive shift in our cultural understandings about how work should fit into family life, not the other way around.”

Lack of support for “vulnerable scientists,” particularly “junior scientists who are parents, women, or minorities” could lead to “severe attrition in cancer research in the coming years,” Cullen Taniguchi, MD, PhD, a radiation oncologist and associate professor at the University of Texas MD Anderson Cancer Center, Houston, and colleagues, warned in a recent letter to the journal Cancer Cell.

“The biggest worries of attrition will come from young faculty who started just before or after the pandemic,” Dr. Taniguchi said in an interview. “The first year in an academic setting is incredibly challenging but also important for establishing research efforts and building networks of colleagues to collaborate with. While completely necessary, the restrictions put in place during the pandemic made doing these things even more difficult.”
 

Another stressor: Caregiving at home

Another reason female physicians may be marginalized during the pandemic is that they are more often the primary caregivers at home.

“Anyone who is a caregiver, be it to kids, parents, or spouses, can relate to the challenges brought [on] by the pandemic,” said Ishwaria Subbiah, MD, a palliative care physician and medical oncologist at MD Anderson.

“Most of us work toward meeting our responsibilities by engaging a network of support, whether it’s home care workers, center-based or at-home child care, schools, or activities outside of school. The pandemic led to a level of disruption that brought most (if not all) of those responsibilities onto the caregivers themselves,” she said in an interview.

As the mother of an adult son with severe epilepsy, Dr. Bertagnolli has certainly experienced the challenges of parenting during the pandemic. “Our son is now 24 but he is handicapped, and lives with us. The care issues we have to deal with as professionals have been enormously magnified by COVID,” she said.

But she cautions against making gender distinctions when it comes to caregiving. “Has it fallen on the women? Well, this kind of stuff generally falls on the women, but I am certain it has fallen on an awful lot of men as well, because I think the world is changing that way, so it’s fallen on all of us.”

There is no question that female oncologists are bearing the brunt, both at work and at home, contended Dr. Taniguchi. “Absolutely. I have seen this first-hand,” he said.

“If it was difficult for women, underrepresented minorities, and junior faculty to find a voice in the room prepandemic, I think it can be harder in the times of virtual meetings when it is difficult to engage audiences,” he said. 

Dr. Holstein said she is lucky to be well-supported at her institution, with both a female chief of hematology/oncology and a female chair of internal medicine, but still, she worries about the long-term consequences of the pandemic on the gender landscape of medicine.

“If you’re having to put aside research projects because you have extra responsibilities – again because women just tend to have a lot of other things going on – that might not be a big deal for 3 months, 6 months, but this is going to be a year or 2 years before ‘normal’ comes back,” she says. “One to two years of underpublishing or not getting the grants could be career killers for women in academic oncology.”
 

Cancer COVID-19 combo

As Dr. Wildes completed her final weeks of seeing cancer patients, she received an outpouring of support, which she says convinced her of the shared experience of all doctors, and especially female doctors, during the pandemic. But even more specifically, she feels that she has tapped into the unique burden shouldered by oncologists during this time.

“It’s intimidating being an oncologist; we are literally giving people poison for a living. Then throw into it a pandemic where early in March we had so little data. I was helping my patients make decisions about their cancer care based on a case series of four patients in China. The burden of those conversations is something I never want to have to live through again,” she said.

“Oncology is a particularly intense subspecialty within medicine,” agreed Dr. Subbiah. “The people we care for have received a life-altering and potentially life-limiting diagnosis. Coupled with that, the COVID-19 pandemic has brought an unprecedented cloud of uncertainty ... Whether the patients can see it overtly or not, oncologists carry the weight of this worry with them for not just one but all of their patients.”

Dr. Wildes said she plans to return to academic medicine and clinical care “in time,” but for now, the gap that she and others like her leave is troubling to those who have stayed on.

“We need these women in medicine,” said Dr. Holstein. “We have data suggesting that women take more time with their patients than men, that patient outcomes are better if they have a female physician. But also for the generations coming up, we need the mid-career and senior women to be in place to mentor and guide and make sure we continue to increase women in leadership.”

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

Delayed health care brought on by the pandemic is taking its toll on patients, a survey of primary care doctors shows. 

More than half (56%) of responding clinicians reported seeing a decline in patient health because of delayed or inaccessible care amid the pandemic, according to the results of the latest survey by the Larry A. Green Center and the Primary Care Collaborative. The survey was conducted in mid-October and the results were published online Nov. 17.  

In addition, 37% of respondents said their patients with chronic conditions showed “noticeably worse health resulting from the pandemic.” And a resounding 85% said patient mental health had worsened. 

“I think it’s worse than we thought,” said Rebecca Etz, PhD, codirector of the Larry Green Center. “It’s the outcome of not sufficiently sending resources to primary care either before or during the pandemic.” According to Dr. Etz, survey respondents noted substantial increases in patient weight gain as well as weight loss, anxiety and depression, sleep issues, domestic abuse, and poor oral and eye health, among others.

One clinician from Pennsylvania wrote: “Patients are becoming sicker during the pandemic. I’m seeing more uncontrolled [diabetes]and new [patients with diabetes]. They prefer telehealth yet [have] no access to glucose monitoring or a blood pressure cuff. I am concerned about patients’ isolation and mental health. People are delaying care.”

Now, with COVID numbers peaking across much of the country, many clinicians are trying to close the gap in care with telehealth – something they’re more prepared to do now than they were in March. Over two-thirds of practices are using telehealth for visits to keep up with patients who have stable chronic conditions, according to the survey.

Over 60% of physicians report using telehealth for mental health visits. But a much smaller number – only 16% of respondents – said their practice had added staff to help manage the rising number of behavioral and mental health cases. About one-third (35%) of practices say they’re not financially able to take on new staff.

“We’ve been looking for more ways for patients to do self-support. A big part of chronic disease is health behaviors,” Alex Krist, MD, MPH, a family doctor in Fairfax, Va., and chairperson of the U.S. Preventive Services Task Force, said in an interview. And unfortunately, on top of limited access to basic care, healthy habits that are essential to managing many chronic conditions have become more difficult and less consistent during the pandemic. 

The survey – the 22nd iteration in a series of surveys the Green Center and the Primary Care Collaborative have conducted – received 580 respondents from 47 states and Guam. Over two-thirds of respondents were primary care physicians (MDs and DOs). Over half were owners, partners, or employees of a private practice, 66% of which were family medicine practices. And one fifth of respondents provided care in a rural area.

Funding and support for primary care has been wildly insufficient, Dr. Etz said in an interview. If that doesn’t change, patient health, clinic staffing, and public health strategies amid the pandemic will continue to suffer.

“When you think of the COVID vaccine, who do you think is going to be sending that out?” Dr. Etz asked. “If we don’t bolster primary care now how are they going to handle that.”
 

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

Delayed health care brought on by the pandemic is taking its toll on patients, a survey of primary care doctors shows. 

More than half (56%) of responding clinicians reported seeing a decline in patient health because of delayed or inaccessible care amid the pandemic, according to the results of the latest survey by the Larry A. Green Center and the Primary Care Collaborative. The survey was conducted in mid-October and the results were published online Nov. 17.  

In addition, 37% of respondents said their patients with chronic conditions showed “noticeably worse health resulting from the pandemic.” And a resounding 85% said patient mental health had worsened. 

“I think it’s worse than we thought,” said Rebecca Etz, PhD, codirector of the Larry Green Center. “It’s the outcome of not sufficiently sending resources to primary care either before or during the pandemic.” According to Dr. Etz, survey respondents noted substantial increases in patient weight gain as well as weight loss, anxiety and depression, sleep issues, domestic abuse, and poor oral and eye health, among others.

One clinician from Pennsylvania wrote: “Patients are becoming sicker during the pandemic. I’m seeing more uncontrolled [diabetes]and new [patients with diabetes]. They prefer telehealth yet [have] no access to glucose monitoring or a blood pressure cuff. I am concerned about patients’ isolation and mental health. People are delaying care.”

Now, with COVID numbers peaking across much of the country, many clinicians are trying to close the gap in care with telehealth – something they’re more prepared to do now than they were in March. Over two-thirds of practices are using telehealth for visits to keep up with patients who have stable chronic conditions, according to the survey.

Over 60% of physicians report using telehealth for mental health visits. But a much smaller number – only 16% of respondents – said their practice had added staff to help manage the rising number of behavioral and mental health cases. About one-third (35%) of practices say they’re not financially able to take on new staff.

“We’ve been looking for more ways for patients to do self-support. A big part of chronic disease is health behaviors,” Alex Krist, MD, MPH, a family doctor in Fairfax, Va., and chairperson of the U.S. Preventive Services Task Force, said in an interview. And unfortunately, on top of limited access to basic care, healthy habits that are essential to managing many chronic conditions have become more difficult and less consistent during the pandemic. 

The survey – the 22nd iteration in a series of surveys the Green Center and the Primary Care Collaborative have conducted – received 580 respondents from 47 states and Guam. Over two-thirds of respondents were primary care physicians (MDs and DOs). Over half were owners, partners, or employees of a private practice, 66% of which were family medicine practices. And one fifth of respondents provided care in a rural area.

Funding and support for primary care has been wildly insufficient, Dr. Etz said in an interview. If that doesn’t change, patient health, clinic staffing, and public health strategies amid the pandemic will continue to suffer.

“When you think of the COVID vaccine, who do you think is going to be sending that out?” Dr. Etz asked. “If we don’t bolster primary care now how are they going to handle that.”
 

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

Delayed health care brought on by the pandemic is taking its toll on patients, a survey of primary care doctors shows. 

More than half (56%) of responding clinicians reported seeing a decline in patient health because of delayed or inaccessible care amid the pandemic, according to the results of the latest survey by the Larry A. Green Center and the Primary Care Collaborative. The survey was conducted in mid-October and the results were published online Nov. 17.  

In addition, 37% of respondents said their patients with chronic conditions showed “noticeably worse health resulting from the pandemic.” And a resounding 85% said patient mental health had worsened. 

“I think it’s worse than we thought,” said Rebecca Etz, PhD, codirector of the Larry Green Center. “It’s the outcome of not sufficiently sending resources to primary care either before or during the pandemic.” According to Dr. Etz, survey respondents noted substantial increases in patient weight gain as well as weight loss, anxiety and depression, sleep issues, domestic abuse, and poor oral and eye health, among others.

One clinician from Pennsylvania wrote: “Patients are becoming sicker during the pandemic. I’m seeing more uncontrolled [diabetes]and new [patients with diabetes]. They prefer telehealth yet [have] no access to glucose monitoring or a blood pressure cuff. I am concerned about patients’ isolation and mental health. People are delaying care.”

Now, with COVID numbers peaking across much of the country, many clinicians are trying to close the gap in care with telehealth – something they’re more prepared to do now than they were in March. Over two-thirds of practices are using telehealth for visits to keep up with patients who have stable chronic conditions, according to the survey.

Over 60% of physicians report using telehealth for mental health visits. But a much smaller number – only 16% of respondents – said their practice had added staff to help manage the rising number of behavioral and mental health cases. About one-third (35%) of practices say they’re not financially able to take on new staff.

“We’ve been looking for more ways for patients to do self-support. A big part of chronic disease is health behaviors,” Alex Krist, MD, MPH, a family doctor in Fairfax, Va., and chairperson of the U.S. Preventive Services Task Force, said in an interview. And unfortunately, on top of limited access to basic care, healthy habits that are essential to managing many chronic conditions have become more difficult and less consistent during the pandemic. 

The survey – the 22nd iteration in a series of surveys the Green Center and the Primary Care Collaborative have conducted – received 580 respondents from 47 states and Guam. Over two-thirds of respondents were primary care physicians (MDs and DOs). Over half were owners, partners, or employees of a private practice, 66% of which were family medicine practices. And one fifth of respondents provided care in a rural area.

Funding and support for primary care has been wildly insufficient, Dr. Etz said in an interview. If that doesn’t change, patient health, clinic staffing, and public health strategies amid the pandemic will continue to suffer.

“When you think of the COVID vaccine, who do you think is going to be sending that out?” Dr. Etz asked. “If we don’t bolster primary care now how are they going to handle that.”
 

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

The Moderna COVID-19 vaccine in development was 94.1% effective in the final analysis of its 30,000-participant phase 3 study. Bolstered by the new findings, the company plans to file for an emergency use authorization (EUA) from the Food and Drug Administration (FDA) today, according to a company release.

A total of 11 people in the mRNA-1273 vaccinated group later tested positive for COVID-19, compared with 185 participants given two placebo injections, resulting in a point estimate of 94.1% efficacy. This finding aligns with the 94.5% efficacy in interim trial results announced on November 16, as reported by Medscape Medical News.

Furthermore, Moderna announced that the vaccine prevented serious cases of infection. All 30 severe infections occurred among those people randomly assigned to placebo.

The FDA plans to review the Moderna vaccine safety and efficacy data at the next Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting scheduled for December 17. If and when approved, healthcare providers can use the new 91301 CPT code specific to mRNA-1273 vaccination.

“This positive primary analysis confirms the ability of our vaccine to prevent COVID-19 disease with 94.1% efficacy and, importantly, the ability to prevent severe COVID-19 disease,” said Stéphane Bancel, MBA, MEng, chief executive officer of Moderna, in the news release. “We believe that our vaccine will provide a new and powerful tool that may change the course of this pandemic and help prevent severe disease, hospitalizations, and death.”

Vaccine efficacy remained consistent across different groups analyzed by age, race/ethnicity, and gender. The 196 COVID-19 cases in the trial included 33 adults older than 65 years and 42 people from diverse communities, including 29 Hispanic or Latinx, six Black or African Americans, four Asian Americans, and three multiracial participants, the company reported.
 

No serious vaccine-related safety issues

The mRNA-1273 vaccine was generally well tolerated and no serious safety concerns with the vaccine have been identified to date, the company reported. 

Injection site pain, fatigue, myalgia, arthralgia, headache, and erythema/redness at the injection site were the most common solicited adverse events in a prior analysis. The company noted that these solicited adverse reactions increased in frequency and severity after the second vaccine dose. A continuous review of safety data is ongoing.

One COVID-19-related death in the study occurred in the placebo group.
 

Ready to start shipping

Moderna expects to have approximately 20 million doses of mRNA-1273 available in the United States by the end of this year. The company reports that it’s on track to manufacture 500 million to 1 billion doses globally in 2021.

The company also is seeking approval from nations and organizations worldwide, including a conditional approval from the European Medicines Agency (EMA). The  study is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the US Department of Health and Human Services.

Moderna will be the second company to file an EUA with the FDA for a COVID vaccine, after Pfizer requested one for its mRNA vaccine earlier this month.

This article first appeared on Medscape.com.

The Moderna COVID-19 vaccine in development was 94.1% effective in the final analysis of its 30,000-participant phase 3 study. Bolstered by the new findings, the company plans to file for an emergency use authorization (EUA) from the Food and Drug Administration (FDA) today, according to a company release.

A total of 11 people in the mRNA-1273 vaccinated group later tested positive for COVID-19, compared with 185 participants given two placebo injections, resulting in a point estimate of 94.1% efficacy. This finding aligns with the 94.5% efficacy in interim trial results announced on November 16, as reported by Medscape Medical News.

Furthermore, Moderna announced that the vaccine prevented serious cases of infection. All 30 severe infections occurred among those people randomly assigned to placebo.

The FDA plans to review the Moderna vaccine safety and efficacy data at the next Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting scheduled for December 17. If and when approved, healthcare providers can use the new 91301 CPT code specific to mRNA-1273 vaccination.

“This positive primary analysis confirms the ability of our vaccine to prevent COVID-19 disease with 94.1% efficacy and, importantly, the ability to prevent severe COVID-19 disease,” said Stéphane Bancel, MBA, MEng, chief executive officer of Moderna, in the news release. “We believe that our vaccine will provide a new and powerful tool that may change the course of this pandemic and help prevent severe disease, hospitalizations, and death.”

Vaccine efficacy remained consistent across different groups analyzed by age, race/ethnicity, and gender. The 196 COVID-19 cases in the trial included 33 adults older than 65 years and 42 people from diverse communities, including 29 Hispanic or Latinx, six Black or African Americans, four Asian Americans, and three multiracial participants, the company reported.
 

No serious vaccine-related safety issues

The mRNA-1273 vaccine was generally well tolerated and no serious safety concerns with the vaccine have been identified to date, the company reported. 

Injection site pain, fatigue, myalgia, arthralgia, headache, and erythema/redness at the injection site were the most common solicited adverse events in a prior analysis. The company noted that these solicited adverse reactions increased in frequency and severity after the second vaccine dose. A continuous review of safety data is ongoing.

One COVID-19-related death in the study occurred in the placebo group.
 

Ready to start shipping

Moderna expects to have approximately 20 million doses of mRNA-1273 available in the United States by the end of this year. The company reports that it’s on track to manufacture 500 million to 1 billion doses globally in 2021.

The company also is seeking approval from nations and organizations worldwide, including a conditional approval from the European Medicines Agency (EMA). The  study is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the US Department of Health and Human Services.

Moderna will be the second company to file an EUA with the FDA for a COVID vaccine, after Pfizer requested one for its mRNA vaccine earlier this month.

This article first appeared on Medscape.com.

The Moderna COVID-19 vaccine in development was 94.1% effective in the final analysis of its 30,000-participant phase 3 study. Bolstered by the new findings, the company plans to file for an emergency use authorization (EUA) from the Food and Drug Administration (FDA) today, according to a company release.

A total of 11 people in the mRNA-1273 vaccinated group later tested positive for COVID-19, compared with 185 participants given two placebo injections, resulting in a point estimate of 94.1% efficacy. This finding aligns with the 94.5% efficacy in interim trial results announced on November 16, as reported by Medscape Medical News.

Furthermore, Moderna announced that the vaccine prevented serious cases of infection. All 30 severe infections occurred among those people randomly assigned to placebo.

The FDA plans to review the Moderna vaccine safety and efficacy data at the next Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting scheduled for December 17. If and when approved, healthcare providers can use the new 91301 CPT code specific to mRNA-1273 vaccination.

“This positive primary analysis confirms the ability of our vaccine to prevent COVID-19 disease with 94.1% efficacy and, importantly, the ability to prevent severe COVID-19 disease,” said Stéphane Bancel, MBA, MEng, chief executive officer of Moderna, in the news release. “We believe that our vaccine will provide a new and powerful tool that may change the course of this pandemic and help prevent severe disease, hospitalizations, and death.”

Vaccine efficacy remained consistent across different groups analyzed by age, race/ethnicity, and gender. The 196 COVID-19 cases in the trial included 33 adults older than 65 years and 42 people from diverse communities, including 29 Hispanic or Latinx, six Black or African Americans, four Asian Americans, and three multiracial participants, the company reported.
 

No serious vaccine-related safety issues

The mRNA-1273 vaccine was generally well tolerated and no serious safety concerns with the vaccine have been identified to date, the company reported. 

Injection site pain, fatigue, myalgia, arthralgia, headache, and erythema/redness at the injection site were the most common solicited adverse events in a prior analysis. The company noted that these solicited adverse reactions increased in frequency and severity after the second vaccine dose. A continuous review of safety data is ongoing.

One COVID-19-related death in the study occurred in the placebo group.
 

Ready to start shipping

Moderna expects to have approximately 20 million doses of mRNA-1273 available in the United States by the end of this year. The company reports that it’s on track to manufacture 500 million to 1 billion doses globally in 2021.

The company also is seeking approval from nations and organizations worldwide, including a conditional approval from the European Medicines Agency (EMA). The  study is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the US Department of Health and Human Services.

Moderna will be the second company to file an EUA with the FDA for a COVID vaccine, after Pfizer requested one for its mRNA vaccine earlier this month.

This article first appeared on Medscape.com.

Hyperglycemia at hospital admission – regardless of diabetes status – is a key predictor of COVID-19-related death and severity among noncritical patients, new research from Spain finds.

The observational study, the largest to date to investigate this association, was published online Nov. 23 in Annals of Medicine by Francisco Javier Carrasco-Sánchez, MD, PhD, and colleagues.

Among more than 11,000 patients with confirmed COVID-19 from March to May 2020 in a nationwide Spanish registry involving 109 hospitals, admission hyperglycemia independently predicted progression from noncritical to critical condition and death, regardless of prior diabetes history. 

Those with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% vs 15.7%). They also had an increased need for a ventilator and intensive care unit (ICU) admission.

“These results provided a simple and practical way to stratify risk of death in hospitalized patients with COVID-19. Hence, admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes,” Dr. Carrasco-Sánchez and colleagues wrote.

The findings confirm those of previous retrospective observational studies, but the current study “has, by far, the biggest number of patients involved in this kind of study [to date]. All conclusions are consistent to other studies,” Dr. Carrasco-Sánchez, of University Hospital Juan Ramón Jiménez, Huelva, Spain, said in an interview.

However, a surprising finding, he said, “was how hyperglycemia works in the nondiabetic population and [that] glucose levels over 140 [mg/dL] ... increase the risk of death.”
 

Pay attention to even mild hyperglycemia from admission

The study also differs from some of the prior observational ones in that it examines outcome by admission glycemia rather than during the hospital stay, therefore eliminating the effect of any inpatient treatment, such as dexamethasone, he noted.

Although blood glucose measurement at admission is routine for all patients in Spain, as it is in the United States and elsewhere, a mildly elevated level in a person without a diagnosis of diabetes may not be recognized as important.

“In patients with diabetes we start the protocol to control and treat hyperglycemia during hospitalization. However, in nondiabetic patients blood glucose levels under 180 [mg/dL], and even greater, are usually overlooked. This means there is not a correct follow-up of the patients during hospitalization.

“After this study we learned that we need to pay attention to this population ... who develop hyperglycemia from the beginning,” he said.  

The study was limited in that patients who had previously undiagnosed diabetes couldn’t always be distinguished from those with acute “stress hyperglycemia.”

However, both need to be managed during hospitalization, he said. “Unfortunately, there is high variability in inpatient glucose management. The working group of diabetes of the Spanish Society of Internal Medicine is working on specific protocols,” said Dr. Carrasco-Sánchez.
 

All-cause death, progress to critical care higher with hyperglycemia

The retrospective, multicenter study was based on data from 11,312 adult patients with confirmed COVID-19 in 109 hospitals participating in Spain’s SEMI-COVID-19 registry as of May 29, 2020. They had a mean age of 67 years, 57% were male, and 19% had a diagnosis of diabetes. A total of 20% (n = 2,289) died during hospitalization.

Overall all-cause mortality was 41.1% among those with admission blood glucose levels above 180 mg/dL, 33.0% for those with glucose levels 140-180 mg/dL, and 15.7% for levels below 140 mg/dL. All differences were significant (P < .0001), but there were no differences in mortality rates within each blood glucose category between patients with or without a previous diagnosis of diabetes.

After adjustment for confounding factors, elevated admission blood glucose level remained a significant predictor of death. Compared to < 140 mg/dL, the hazard ratios for 140-180 mg/dL and > 180 mg/dL were 1.48 and 1.50, respectively (both P < .001). (Adjustments included age, gender, hypertension, diabetes, chronic obstructive pulmonary disease, lymphopenia, anemia (hemoglobin < 10 g/dL), serum creatinine, C-reactive protein > 60 mg/L, lactate dehydrogenase > 400 U/L and D-dimer >1000 ng/mL.)

Length of stay was 12, 11.5, and 11.1 days for those with admission blood glucose levels > 180, 140-180, and < 140 mg/dL, respectively (P = .011).

Use of mechanical ventilation and admission to intensive care also rose with higher admission blood glucose levels. For the composite of death, mechanical ventilation, and/or ICU admission, odds ratios for 140-180 mg/dL and > 180 mg/dL compared with < 140 mg/dL were 1.70 and 2.02, respectively (both P < .001). 

The study was supported by the Spanish Federation of Internal Medicine. The authors have reported no relevant financial relationships.

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

Hyperglycemia at hospital admission – regardless of diabetes status – is a key predictor of COVID-19-related death and severity among noncritical patients, new research from Spain finds.

The observational study, the largest to date to investigate this association, was published online Nov. 23 in Annals of Medicine by Francisco Javier Carrasco-Sánchez, MD, PhD, and colleagues.

Among more than 11,000 patients with confirmed COVID-19 from March to May 2020 in a nationwide Spanish registry involving 109 hospitals, admission hyperglycemia independently predicted progression from noncritical to critical condition and death, regardless of prior diabetes history. 

Those with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% vs 15.7%). They also had an increased need for a ventilator and intensive care unit (ICU) admission.

“These results provided a simple and practical way to stratify risk of death in hospitalized patients with COVID-19. Hence, admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes,” Dr. Carrasco-Sánchez and colleagues wrote.

The findings confirm those of previous retrospective observational studies, but the current study “has, by far, the biggest number of patients involved in this kind of study [to date]. All conclusions are consistent to other studies,” Dr. Carrasco-Sánchez, of University Hospital Juan Ramón Jiménez, Huelva, Spain, said in an interview.

However, a surprising finding, he said, “was how hyperglycemia works in the nondiabetic population and [that] glucose levels over 140 [mg/dL] ... increase the risk of death.”
 

Pay attention to even mild hyperglycemia from admission

The study also differs from some of the prior observational ones in that it examines outcome by admission glycemia rather than during the hospital stay, therefore eliminating the effect of any inpatient treatment, such as dexamethasone, he noted.

Although blood glucose measurement at admission is routine for all patients in Spain, as it is in the United States and elsewhere, a mildly elevated level in a person without a diagnosis of diabetes may not be recognized as important.

“In patients with diabetes we start the protocol to control and treat hyperglycemia during hospitalization. However, in nondiabetic patients blood glucose levels under 180 [mg/dL], and even greater, are usually overlooked. This means there is not a correct follow-up of the patients during hospitalization.

“After this study we learned that we need to pay attention to this population ... who develop hyperglycemia from the beginning,” he said.  

The study was limited in that patients who had previously undiagnosed diabetes couldn’t always be distinguished from those with acute “stress hyperglycemia.”

However, both need to be managed during hospitalization, he said. “Unfortunately, there is high variability in inpatient glucose management. The working group of diabetes of the Spanish Society of Internal Medicine is working on specific protocols,” said Dr. Carrasco-Sánchez.
 

All-cause death, progress to critical care higher with hyperglycemia

The retrospective, multicenter study was based on data from 11,312 adult patients with confirmed COVID-19 in 109 hospitals participating in Spain’s SEMI-COVID-19 registry as of May 29, 2020. They had a mean age of 67 years, 57% were male, and 19% had a diagnosis of diabetes. A total of 20% (n = 2,289) died during hospitalization.

Overall all-cause mortality was 41.1% among those with admission blood glucose levels above 180 mg/dL, 33.0% for those with glucose levels 140-180 mg/dL, and 15.7% for levels below 140 mg/dL. All differences were significant (P < .0001), but there were no differences in mortality rates within each blood glucose category between patients with or without a previous diagnosis of diabetes.

After adjustment for confounding factors, elevated admission blood glucose level remained a significant predictor of death. Compared to < 140 mg/dL, the hazard ratios for 140-180 mg/dL and > 180 mg/dL were 1.48 and 1.50, respectively (both P < .001). (Adjustments included age, gender, hypertension, diabetes, chronic obstructive pulmonary disease, lymphopenia, anemia (hemoglobin < 10 g/dL), serum creatinine, C-reactive protein > 60 mg/L, lactate dehydrogenase > 400 U/L and D-dimer >1000 ng/mL.)

Length of stay was 12, 11.5, and 11.1 days for those with admission blood glucose levels > 180, 140-180, and < 140 mg/dL, respectively (P = .011).

Use of mechanical ventilation and admission to intensive care also rose with higher admission blood glucose levels. For the composite of death, mechanical ventilation, and/or ICU admission, odds ratios for 140-180 mg/dL and > 180 mg/dL compared with < 140 mg/dL were 1.70 and 2.02, respectively (both P < .001). 

The study was supported by the Spanish Federation of Internal Medicine. The authors have reported no relevant financial relationships.

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

Hyperglycemia at hospital admission – regardless of diabetes status – is a key predictor of COVID-19-related death and severity among noncritical patients, new research from Spain finds.

The observational study, the largest to date to investigate this association, was published online Nov. 23 in Annals of Medicine by Francisco Javier Carrasco-Sánchez, MD, PhD, and colleagues.

Among more than 11,000 patients with confirmed COVID-19 from March to May 2020 in a nationwide Spanish registry involving 109 hospitals, admission hyperglycemia independently predicted progression from noncritical to critical condition and death, regardless of prior diabetes history. 

Those with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% vs 15.7%). They also had an increased need for a ventilator and intensive care unit (ICU) admission.

“These results provided a simple and practical way to stratify risk of death in hospitalized patients with COVID-19. Hence, admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes,” Dr. Carrasco-Sánchez and colleagues wrote.

The findings confirm those of previous retrospective observational studies, but the current study “has, by far, the biggest number of patients involved in this kind of study [to date]. All conclusions are consistent to other studies,” Dr. Carrasco-Sánchez, of University Hospital Juan Ramón Jiménez, Huelva, Spain, said in an interview.

However, a surprising finding, he said, “was how hyperglycemia works in the nondiabetic population and [that] glucose levels over 140 [mg/dL] ... increase the risk of death.”
 

Pay attention to even mild hyperglycemia from admission

The study also differs from some of the prior observational ones in that it examines outcome by admission glycemia rather than during the hospital stay, therefore eliminating the effect of any inpatient treatment, such as dexamethasone, he noted.

Although blood glucose measurement at admission is routine for all patients in Spain, as it is in the United States and elsewhere, a mildly elevated level in a person without a diagnosis of diabetes may not be recognized as important.

“In patients with diabetes we start the protocol to control and treat hyperglycemia during hospitalization. However, in nondiabetic patients blood glucose levels under 180 [mg/dL], and even greater, are usually overlooked. This means there is not a correct follow-up of the patients during hospitalization.

“After this study we learned that we need to pay attention to this population ... who develop hyperglycemia from the beginning,” he said.  

The study was limited in that patients who had previously undiagnosed diabetes couldn’t always be distinguished from those with acute “stress hyperglycemia.”

However, both need to be managed during hospitalization, he said. “Unfortunately, there is high variability in inpatient glucose management. The working group of diabetes of the Spanish Society of Internal Medicine is working on specific protocols,” said Dr. Carrasco-Sánchez.
 

All-cause death, progress to critical care higher with hyperglycemia

The retrospective, multicenter study was based on data from 11,312 adult patients with confirmed COVID-19 in 109 hospitals participating in Spain’s SEMI-COVID-19 registry as of May 29, 2020. They had a mean age of 67 years, 57% were male, and 19% had a diagnosis of diabetes. A total of 20% (n = 2,289) died during hospitalization.

Overall all-cause mortality was 41.1% among those with admission blood glucose levels above 180 mg/dL, 33.0% for those with glucose levels 140-180 mg/dL, and 15.7% for levels below 140 mg/dL. All differences were significant (P < .0001), but there were no differences in mortality rates within each blood glucose category between patients with or without a previous diagnosis of diabetes.

After adjustment for confounding factors, elevated admission blood glucose level remained a significant predictor of death. Compared to < 140 mg/dL, the hazard ratios for 140-180 mg/dL and > 180 mg/dL were 1.48 and 1.50, respectively (both P < .001). (Adjustments included age, gender, hypertension, diabetes, chronic obstructive pulmonary disease, lymphopenia, anemia (hemoglobin < 10 g/dL), serum creatinine, C-reactive protein > 60 mg/L, lactate dehydrogenase > 400 U/L and D-dimer >1000 ng/mL.)

Length of stay was 12, 11.5, and 11.1 days for those with admission blood glucose levels > 180, 140-180, and < 140 mg/dL, respectively (P = .011).

Use of mechanical ventilation and admission to intensive care also rose with higher admission blood glucose levels. For the composite of death, mechanical ventilation, and/or ICU admission, odds ratios for 140-180 mg/dL and > 180 mg/dL compared with < 140 mg/dL were 1.70 and 2.02, respectively (both P < .001). 

The study was supported by the Spanish Federation of Internal Medicine. The authors have reported no relevant financial relationships.

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

The known reduction in the risk of type 2 diabetes associated with adoption of the Mediterranean diet appears specifically attributed to its beneficial effects on some key factors, a new study published online in JAMA Network Open reveals.

While a reduction in body mass index may be somewhat obvious, other mechanisms include beneficial effects on insulin resistance, lipoprotein metabolism, and inflammation.

However, the diet’s antidiabetes effect does not appear to extend to people whose weight is considered healthy (BMI under 25 kg/m²), according to the findings.

“It is striking to see in these U.S. women how strong the long-term antidiabetic properties of a Mediterranean-type dietary pattern are,” senior author Samia Mora, MD, of the Center for Lipid Metabolomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, said in an interview.

“While it was known that the Mediterranean diet has many health benefits in particular on metabolism and inflammation, it was not previously known which of these biological pathways may be contributing to the lower risk of diabetes and to what magnitude.

“Our findings support the idea that by improving their diet, people can improve their future risk of type 2 diabetes, particularly if they are overweight or have obesity,” she added.

“And it’s important to note that many of these changes don’t happen right away. While metabolism can change over a short period of time, our study indicates that there are longer term changes happening that may provide protection over decades.”
 

Mediterranean diet reduced diabetes risk in those with BMI ≥ 25 kg/m²

The Mediterranean diet, with an emphasis on healthy olive oil as the predominant source of oil, favors fruits, vegetables, legumes, nuts, seeds, fish, and dairy products, while limiting intake of red and processed meats as well as sweets.

The diet has been linked to as much as a 25%-30% reduction in the risk of diabetes in previous observational studies.

To investigate the precise mechanisms that underlie the prevention of diabetes, lead author Shafqat Ahmad, PhD, also of Harvard, and colleagues examined data from 25,317 healthy women participating in the Women’s Health Study who had baseline assessments between September 1992 and May 1995. They were a mean age of 52.9 years at baseline.

Over the course of the study, 2,307 participants developed type 2 diabetes.

With a mean follow-up of 19.8 years, those who had the highest self-reported adherence to the Mediterranean diet (a score ≥ 6 on a scale of 0-6) at baseline, had as much as a 30% lower risk of developing type 2 diabetes after multivariate adjustments, compared to those with a lower Mediterranean diet score (a score ≤ 3; hazard ratio, 0.70).

The diabetes-related biomarkers that contributed the most to the reduced risk were insulin resistance, accounting for 65% of the reduction, followed by BMI (55.5%), high-density lipoprotein measures (53%), and inflammation (52.5%).

Other factors, though to a lesser degree, included branched-chain amino acids (34.5%), very low-density lipoprotein measures (32.0%), low-density lipoprotein measures (31.0%), blood pressure (29.0%), and apolipoproteins (23.5%).

Differences in hemoglobin A1c levels had a limited effect on the risk (2%).

Notably, a subgroup analysis looking at effects of the diet according to baseline BMI showed the reductions in type 2 diabetes associated with higher intake of the Mediterranean diet extended only to those with an above normal weight (BMI ≥ 25 kg/m²).

Dr. Mora noted that, as this was not a prespecified analysis, these findings should be viewed as hypothesis-generating, but are consistent with the well-known increase in diabetes risk seen with a higher BMI.

“[The finding] fits with the biology and pathogenesis of type 2 diabetes that is driven in large part by excess weight, in particular for visceral adiposity and its resulting metabolic dysregulation and inflammation,” she said.

“We know from other studies, such as the Nurses’ Health Study, that the risk for type 2 diabetes in women increases even at BMI levels below 25 kg/m², but the risk goes up exponentially at around a BMI of 25 and higher.”

Strong role of insulin resistance a surprise

The strong role of insulin resistance was a surprise, Dr. Mora added.

“We were surprised that insulin resistance, measured by a simple blood biomarker, would have the strongest mediating effect – even stronger than BMI – for the Mediterranean diet on risk of diabetes,” she noted.

“This could represent an opportunity to intervene earlier and more intensively on improving insulin resistance through dietary approaches such as the Mediterranean diet, especially [because] insulin resistance can precede by years and decades the overt hyperglycemia and clinical diagnosis of diabetes.”

Yet another surprise was that A1c had no substantial mediating effect on the reduction of diabetes risk with the Mediterranean diet.

“This could suggest that the cat is out of the bag by the time the A1c rises,” Dr. Mora observed.

A study limitation is that the Women’s Health Study consisted of well-educated U.S. women who were health professionals and predominantly White, so the results may not be generalizable to men or individuals of other races or ethnicities.

In addition, BMI was self-reported and participants were not uniformly screened for diabetes, therefore surveillance bias could be possible.

However, the findings suggest that “even a small increase in adherence to the Mediterranean diet has substantial benefits over many years in preventing diabetes, among many other health benefits such as lowering insulin resistance and inflammation, improving lipid metabolism, and lowering blood pressure,” Mora said.

“And of course, the more the adherence, the more the benefit.” 

The study received support through grants from the National Institutes of Health, the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association, and the Molino Family Trust. A coauthor is listed as a coinventor on patents held by Brigham and Women’s Hospital related to the use of inflammatory biomarkers in cardiovascular disease (licensed to AstraZeneca and Siemens).

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

The known reduction in the risk of type 2 diabetes associated with adoption of the Mediterranean diet appears specifically attributed to its beneficial effects on some key factors, a new study published online in JAMA Network Open reveals.

While a reduction in body mass index may be somewhat obvious, other mechanisms include beneficial effects on insulin resistance, lipoprotein metabolism, and inflammation.

However, the diet’s antidiabetes effect does not appear to extend to people whose weight is considered healthy (BMI under 25 kg/m²), according to the findings.

“It is striking to see in these U.S. women how strong the long-term antidiabetic properties of a Mediterranean-type dietary pattern are,” senior author Samia Mora, MD, of the Center for Lipid Metabolomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, said in an interview.

“While it was known that the Mediterranean diet has many health benefits in particular on metabolism and inflammation, it was not previously known which of these biological pathways may be contributing to the lower risk of diabetes and to what magnitude.

“Our findings support the idea that by improving their diet, people can improve their future risk of type 2 diabetes, particularly if they are overweight or have obesity,” she added.

“And it’s important to note that many of these changes don’t happen right away. While metabolism can change over a short period of time, our study indicates that there are longer term changes happening that may provide protection over decades.”
 

Mediterranean diet reduced diabetes risk in those with BMI ≥ 25 kg/m²

The Mediterranean diet, with an emphasis on healthy olive oil as the predominant source of oil, favors fruits, vegetables, legumes, nuts, seeds, fish, and dairy products, while limiting intake of red and processed meats as well as sweets.

The diet has been linked to as much as a 25%-30% reduction in the risk of diabetes in previous observational studies.

To investigate the precise mechanisms that underlie the prevention of diabetes, lead author Shafqat Ahmad, PhD, also of Harvard, and colleagues examined data from 25,317 healthy women participating in the Women’s Health Study who had baseline assessments between September 1992 and May 1995. They were a mean age of 52.9 years at baseline.

Over the course of the study, 2,307 participants developed type 2 diabetes.

With a mean follow-up of 19.8 years, those who had the highest self-reported adherence to the Mediterranean diet (a score ≥ 6 on a scale of 0-6) at baseline, had as much as a 30% lower risk of developing type 2 diabetes after multivariate adjustments, compared to those with a lower Mediterranean diet score (a score ≤ 3; hazard ratio, 0.70).

The diabetes-related biomarkers that contributed the most to the reduced risk were insulin resistance, accounting for 65% of the reduction, followed by BMI (55.5%), high-density lipoprotein measures (53%), and inflammation (52.5%).

Other factors, though to a lesser degree, included branched-chain amino acids (34.5%), very low-density lipoprotein measures (32.0%), low-density lipoprotein measures (31.0%), blood pressure (29.0%), and apolipoproteins (23.5%).

Differences in hemoglobin A1c levels had a limited effect on the risk (2%).

Notably, a subgroup analysis looking at effects of the diet according to baseline BMI showed the reductions in type 2 diabetes associated with higher intake of the Mediterranean diet extended only to those with an above normal weight (BMI ≥ 25 kg/m²).

Dr. Mora noted that, as this was not a prespecified analysis, these findings should be viewed as hypothesis-generating, but are consistent with the well-known increase in diabetes risk seen with a higher BMI.

“[The finding] fits with the biology and pathogenesis of type 2 diabetes that is driven in large part by excess weight, in particular for visceral adiposity and its resulting metabolic dysregulation and inflammation,” she said.

“We know from other studies, such as the Nurses’ Health Study, that the risk for type 2 diabetes in women increases even at BMI levels below 25 kg/m², but the risk goes up exponentially at around a BMI of 25 and higher.”

Strong role of insulin resistance a surprise

The strong role of insulin resistance was a surprise, Dr. Mora added.

“We were surprised that insulin resistance, measured by a simple blood biomarker, would have the strongest mediating effect – even stronger than BMI – for the Mediterranean diet on risk of diabetes,” she noted.

“This could represent an opportunity to intervene earlier and more intensively on improving insulin resistance through dietary approaches such as the Mediterranean diet, especially [because] insulin resistance can precede by years and decades the overt hyperglycemia and clinical diagnosis of diabetes.”

Yet another surprise was that A1c had no substantial mediating effect on the reduction of diabetes risk with the Mediterranean diet.

“This could suggest that the cat is out of the bag by the time the A1c rises,” Dr. Mora observed.

A study limitation is that the Women’s Health Study consisted of well-educated U.S. women who were health professionals and predominantly White, so the results may not be generalizable to men or individuals of other races or ethnicities.

In addition, BMI was self-reported and participants were not uniformly screened for diabetes, therefore surveillance bias could be possible.

However, the findings suggest that “even a small increase in adherence to the Mediterranean diet has substantial benefits over many years in preventing diabetes, among many other health benefits such as lowering insulin resistance and inflammation, improving lipid metabolism, and lowering blood pressure,” Mora said.

“And of course, the more the adherence, the more the benefit.” 

The study received support through grants from the National Institutes of Health, the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association, and the Molino Family Trust. A coauthor is listed as a coinventor on patents held by Brigham and Women’s Hospital related to the use of inflammatory biomarkers in cardiovascular disease (licensed to AstraZeneca and Siemens).

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

The known reduction in the risk of type 2 diabetes associated with adoption of the Mediterranean diet appears specifically attributed to its beneficial effects on some key factors, a new study published online in JAMA Network Open reveals.

While a reduction in body mass index may be somewhat obvious, other mechanisms include beneficial effects on insulin resistance, lipoprotein metabolism, and inflammation.

However, the diet’s antidiabetes effect does not appear to extend to people whose weight is considered healthy (BMI under 25 kg/m²), according to the findings.

“It is striking to see in these U.S. women how strong the long-term antidiabetic properties of a Mediterranean-type dietary pattern are,” senior author Samia Mora, MD, of the Center for Lipid Metabolomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, said in an interview.

“While it was known that the Mediterranean diet has many health benefits in particular on metabolism and inflammation, it was not previously known which of these biological pathways may be contributing to the lower risk of diabetes and to what magnitude.

“Our findings support the idea that by improving their diet, people can improve their future risk of type 2 diabetes, particularly if they are overweight or have obesity,” she added.

“And it’s important to note that many of these changes don’t happen right away. While metabolism can change over a short period of time, our study indicates that there are longer term changes happening that may provide protection over decades.”
 

Mediterranean diet reduced diabetes risk in those with BMI ≥ 25 kg/m²

The Mediterranean diet, with an emphasis on healthy olive oil as the predominant source of oil, favors fruits, vegetables, legumes, nuts, seeds, fish, and dairy products, while limiting intake of red and processed meats as well as sweets.

The diet has been linked to as much as a 25%-30% reduction in the risk of diabetes in previous observational studies.

To investigate the precise mechanisms that underlie the prevention of diabetes, lead author Shafqat Ahmad, PhD, also of Harvard, and colleagues examined data from 25,317 healthy women participating in the Women’s Health Study who had baseline assessments between September 1992 and May 1995. They were a mean age of 52.9 years at baseline.

Over the course of the study, 2,307 participants developed type 2 diabetes.

With a mean follow-up of 19.8 years, those who had the highest self-reported adherence to the Mediterranean diet (a score ≥ 6 on a scale of 0-6) at baseline, had as much as a 30% lower risk of developing type 2 diabetes after multivariate adjustments, compared to those with a lower Mediterranean diet score (a score ≤ 3; hazard ratio, 0.70).

The diabetes-related biomarkers that contributed the most to the reduced risk were insulin resistance, accounting for 65% of the reduction, followed by BMI (55.5%), high-density lipoprotein measures (53%), and inflammation (52.5%).

Other factors, though to a lesser degree, included branched-chain amino acids (34.5%), very low-density lipoprotein measures (32.0%), low-density lipoprotein measures (31.0%), blood pressure (29.0%), and apolipoproteins (23.5%).

Differences in hemoglobin A1c levels had a limited effect on the risk (2%).

Notably, a subgroup analysis looking at effects of the diet according to baseline BMI showed the reductions in type 2 diabetes associated with higher intake of the Mediterranean diet extended only to those with an above normal weight (BMI ≥ 25 kg/m²).

Dr. Mora noted that, as this was not a prespecified analysis, these findings should be viewed as hypothesis-generating, but are consistent with the well-known increase in diabetes risk seen with a higher BMI.

“[The finding] fits with the biology and pathogenesis of type 2 diabetes that is driven in large part by excess weight, in particular for visceral adiposity and its resulting metabolic dysregulation and inflammation,” she said.

“We know from other studies, such as the Nurses’ Health Study, that the risk for type 2 diabetes in women increases even at BMI levels below 25 kg/m², but the risk goes up exponentially at around a BMI of 25 and higher.”

Strong role of insulin resistance a surprise

The strong role of insulin resistance was a surprise, Dr. Mora added.

“We were surprised that insulin resistance, measured by a simple blood biomarker, would have the strongest mediating effect – even stronger than BMI – for the Mediterranean diet on risk of diabetes,” she noted.

“This could represent an opportunity to intervene earlier and more intensively on improving insulin resistance through dietary approaches such as the Mediterranean diet, especially [because] insulin resistance can precede by years and decades the overt hyperglycemia and clinical diagnosis of diabetes.”

Yet another surprise was that A1c had no substantial mediating effect on the reduction of diabetes risk with the Mediterranean diet.

“This could suggest that the cat is out of the bag by the time the A1c rises,” Dr. Mora observed.

A study limitation is that the Women’s Health Study consisted of well-educated U.S. women who were health professionals and predominantly White, so the results may not be generalizable to men or individuals of other races or ethnicities.

In addition, BMI was self-reported and participants were not uniformly screened for diabetes, therefore surveillance bias could be possible.

However, the findings suggest that “even a small increase in adherence to the Mediterranean diet has substantial benefits over many years in preventing diabetes, among many other health benefits such as lowering insulin resistance and inflammation, improving lipid metabolism, and lowering blood pressure,” Mora said.

“And of course, the more the adherence, the more the benefit.” 

The study received support through grants from the National Institutes of Health, the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association, and the Molino Family Trust. A coauthor is listed as a coinventor on patents held by Brigham and Women’s Hospital related to the use of inflammatory biomarkers in cardiovascular disease (licensed to AstraZeneca and Siemens).

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

While stressing the urgent need to vaccinate the whole U.S. population, infectious disease experts and medical ethicists are raising questions about the clinical trials needed to answer important questions about the new COVID-19 vaccines.

In a statement released on Nov. 20, Barbara Alexander, MD, president of the Infectious Diseases Society of America (IDSA) and a professor at Duke University, Durham, N.C., commented on Pfizer and BioNTech’s application to the Food and Drug Administration for an emergency use authorization (EUA) for its COVID-19 vaccine. Besides emphasizing the need for a transparent review of the companies’ trial data prior to the FDA’s granting an EUA, she said, “If emergency use authorization is granted, clinical trials and data collection must continue.”

In an interview, Dr. Alexander said she is convinced that both Pfizer and Moderna, which is also expected to seek an EUA soon, will continue their clinical trials to monitor the long-term safety and efficacy of their vaccines.

“The EUA guidance for COVID vaccine authorization is very clear that clinical trials will move forward,” she said. “Any EUA request would have to include a strategy to ensure that the long-term safety and efficacy of a vaccine could be monitored. I see no evidence that either Pfizer or Moderna is not prepared to follow those regulations.”

Eventually, she added, the drug makers will have to seek full FDA approval to replace an EUA, which as its name signifies, is designed for public health emergencies. “The EUA is a tool to help us get the vaccine into circulation and have it start working as quickly as possible in the current health crisis,” she said. “But once the crisis is over, if the sponsors want to continue to market their vaccines, they have to go forward and get full approval.”

Medical ethicists, however, point out there may be ethical and practical dilemmas involved in continuing or initiating clinical trials once a vaccine has been approved for use even on an emergency basis.

In a commentary in Annals of Internal Medicine, Rafael Dal-Re, MD, PhD, Arthur L. Caplan, PhD, and two other ethicists stipulated that the pandemic requires early licensing and deployment of COVID-19 vaccines. Nevertheless, they noted, additional months of data are required to establish the long-term efficacy and safety of the vaccines. “Moreover, early deployment could interfere with the acquisition of long-term data,” both on these vaccines and on others coming through the pipeline, they wrote.

In countries where an approved vaccine is deployed, the ethicists noted, investigators must inform participants in an ongoing trial about the approved vaccine’s status and ask if they want to continue in the study. If enough participants decline, the trial might have to be terminated early. At that point, researchers may not have sufficient long-term data to identify late-term safety issues, determine how long efficacy lasts, determine whether waning immunity is associated with reduced levels of antibodies, or identify the level of neutralizing antibodies that correlates with immunity.

Moreover, they observed, long-term trials are especially important for vaccines that use mRNA technology, because less is known about them than about traditional kinds of vaccines.

The authors also pointed out that early licensing of any vaccine might make it harder to evaluate vaccines that haven’t yet been approved. “Once a vaccine is licensed, new placebo-controlled RCTs [randomized controlled trials] of other vaccines will not be acceptable ethically, and noninferiority RCTs will be the most likely alternative.

“The goal of noninferiority trials will be to demonstrate that the immune response (that is, neutralizing antibody titers or levels) of the candidate vaccine is not inferior to that of the approved vaccine within a prespecified margin, which the FDA has established as less than 10% for COVID-19 vaccines,” the authors noted. 
 

More data with more study designs

Dial Hewlett Jr., MD, medical director for disease control services, Westchester County Department of Health, White Plains, N.Y., said in an interview that the ethicists raise important issues that have been discussed in other forums, including a recent webinar of the National Academy of Medicine.

“As the authors point out, once you have a vaccine that has been shown to be effective and safe, it’s no longer ethical to enroll people in placebo trials,” he said.

Therefore, he said, Pfizer and Moderna will undoubtedly offer their vaccines to the people in their studies’ placebo groups after the vaccines receive an EUA. Then they will follow everyone who has been vaccinated for 2 years to determine long-term safety. Efficacy will also continue to be measured as an adjunct of safety, he said.

With regard to the difficulty of reconsenting individuals to enter a new clinical trial after a vaccine has been approved, he said, “I’d agree that trying to get all the same participants to come into another study would be a challenge. You can, however, design studies that will allow you to obtain the same information. You will have a large number of people out there who haven’t been vaccinated, and you can do single-arm longitudinal studies and measure a number of things in the individuals who are enrolled in those studies,” he said.

“You can look at the immunologic markers, both antibody and T-cell. You can follow these individuals longitudinally to see if they do develop disease over a period of time. If they do, you can determine what their levels of response were,” he added. “So there are opportunities to design studies that would give you some of the same information, although it would not be in the same population that was in the randomized trials.”

For newer vaccines that have yet to be tested, he said, developers can compare “historical controls” from the trials of approved vaccines, i.e., data from the unvaccinated participants in those studies, with the data from inoculating people with the novel agents. The historical data can be sex- and age-matched, among other things, to individuals in the new trials. Moreover, because the study protocols have been harmonized for all trials under Operation Warp Speed, it doesn’t matter what kind of vaccine they’re testing, he said.

It may be necessary to do additional studies to find out how long immunity lasts after people have been vaccinated, Dr. Hewlett pointed out.

“You may have a different trial design. You don’t need a control arm to determine how long immunity lasts. You’re just comparing the patients who were vaccinated to nothing,” he said. “So you could have a single-arm trial on a group of people who consent to be immunized and followed. You can see what their antibody levels are and other surrogate markers, and you can see when they might develop disease, if they do. You’d need a large sample, but you can do that.”

Dr. Hewlett noted that additional studies will be required to determine whether the new vaccines stop transmission of the coronavirus or just prevent symptoms of COVID-19. Until it’s established that a vaccine halts transmission or the country achieves herd immunity, he said, “we’ll still have to wear masks and take other precautions, because a significant portion of people will still be at risk.”
 

‘A lot of redundancy’

Dr. Alexander emphasized that any safety or efficacy issues with the first COVID-19 vaccines must be identified before the vaccine is offered to a large portion of the U.S. population.

“While the data from the Pfizer and Moderna trials are said to be favorable, we at IDSA want to make sure that whatever vaccine comes to market is safe,” she said. “Having an unsafe vaccine on the market would be worse than no vaccine, because you’re compromising the public confidence. We have to make sure the public trusts the process and that sufficient data have been evaluated to ensure the vaccine is safe and efficacious.

“I believe the FDA is being very careful and thoughtful in [its] response,” Dr. Alexander said. “They realize how important it is to get a vaccine and save lives. While they’re doing things differently and moving much faster than before, they’re still trying to be thoughtful and reasonable. They don’t seem to be putting people at risk or circumventing the regulatory standards.”

Moreover, she pointed out, the FDA’s Vaccines and Related Biological Products Advisory Committee, which is expected to meet on Dec. 10, will review the trial data before the agency grants an EUA to Pfizer or Moderna. Then the FDA will post the data publicly.

The next step is for the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention to look at the data and decide who in the United States should receive the vaccine first, she pointed out. And both Pfizer and Moderna have shown their data to advisory panels of outside experts.

“There’s a lot of redundancy, and a lot of people are looking at the data,” Dr. Alexander said. “So I don’t think we’re cutting corners to get it out there more quickly.”

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

While stressing the urgent need to vaccinate the whole U.S. population, infectious disease experts and medical ethicists are raising questions about the clinical trials needed to answer important questions about the new COVID-19 vaccines.

In a statement released on Nov. 20, Barbara Alexander, MD, president of the Infectious Diseases Society of America (IDSA) and a professor at Duke University, Durham, N.C., commented on Pfizer and BioNTech’s application to the Food and Drug Administration for an emergency use authorization (EUA) for its COVID-19 vaccine. Besides emphasizing the need for a transparent review of the companies’ trial data prior to the FDA’s granting an EUA, she said, “If emergency use authorization is granted, clinical trials and data collection must continue.”

In an interview, Dr. Alexander said she is convinced that both Pfizer and Moderna, which is also expected to seek an EUA soon, will continue their clinical trials to monitor the long-term safety and efficacy of their vaccines.

“The EUA guidance for COVID vaccine authorization is very clear that clinical trials will move forward,” she said. “Any EUA request would have to include a strategy to ensure that the long-term safety and efficacy of a vaccine could be monitored. I see no evidence that either Pfizer or Moderna is not prepared to follow those regulations.”

Eventually, she added, the drug makers will have to seek full FDA approval to replace an EUA, which as its name signifies, is designed for public health emergencies. “The EUA is a tool to help us get the vaccine into circulation and have it start working as quickly as possible in the current health crisis,” she said. “But once the crisis is over, if the sponsors want to continue to market their vaccines, they have to go forward and get full approval.”

Medical ethicists, however, point out there may be ethical and practical dilemmas involved in continuing or initiating clinical trials once a vaccine has been approved for use even on an emergency basis.

In a commentary in Annals of Internal Medicine, Rafael Dal-Re, MD, PhD, Arthur L. Caplan, PhD, and two other ethicists stipulated that the pandemic requires early licensing and deployment of COVID-19 vaccines. Nevertheless, they noted, additional months of data are required to establish the long-term efficacy and safety of the vaccines. “Moreover, early deployment could interfere with the acquisition of long-term data,” both on these vaccines and on others coming through the pipeline, they wrote.

In countries where an approved vaccine is deployed, the ethicists noted, investigators must inform participants in an ongoing trial about the approved vaccine’s status and ask if they want to continue in the study. If enough participants decline, the trial might have to be terminated early. At that point, researchers may not have sufficient long-term data to identify late-term safety issues, determine how long efficacy lasts, determine whether waning immunity is associated with reduced levels of antibodies, or identify the level of neutralizing antibodies that correlates with immunity.

Moreover, they observed, long-term trials are especially important for vaccines that use mRNA technology, because less is known about them than about traditional kinds of vaccines.

The authors also pointed out that early licensing of any vaccine might make it harder to evaluate vaccines that haven’t yet been approved. “Once a vaccine is licensed, new placebo-controlled RCTs [randomized controlled trials] of other vaccines will not be acceptable ethically, and noninferiority RCTs will be the most likely alternative.

“The goal of noninferiority trials will be to demonstrate that the immune response (that is, neutralizing antibody titers or levels) of the candidate vaccine is not inferior to that of the approved vaccine within a prespecified margin, which the FDA has established as less than 10% for COVID-19 vaccines,” the authors noted. 
 

More data with more study designs

Dial Hewlett Jr., MD, medical director for disease control services, Westchester County Department of Health, White Plains, N.Y., said in an interview that the ethicists raise important issues that have been discussed in other forums, including a recent webinar of the National Academy of Medicine.

“As the authors point out, once you have a vaccine that has been shown to be effective and safe, it’s no longer ethical to enroll people in placebo trials,” he said.

Therefore, he said, Pfizer and Moderna will undoubtedly offer their vaccines to the people in their studies’ placebo groups after the vaccines receive an EUA. Then they will follow everyone who has been vaccinated for 2 years to determine long-term safety. Efficacy will also continue to be measured as an adjunct of safety, he said.

With regard to the difficulty of reconsenting individuals to enter a new clinical trial after a vaccine has been approved, he said, “I’d agree that trying to get all the same participants to come into another study would be a challenge. You can, however, design studies that will allow you to obtain the same information. You will have a large number of people out there who haven’t been vaccinated, and you can do single-arm longitudinal studies and measure a number of things in the individuals who are enrolled in those studies,” he said.

“You can look at the immunologic markers, both antibody and T-cell. You can follow these individuals longitudinally to see if they do develop disease over a period of time. If they do, you can determine what their levels of response were,” he added. “So there are opportunities to design studies that would give you some of the same information, although it would not be in the same population that was in the randomized trials.”

For newer vaccines that have yet to be tested, he said, developers can compare “historical controls” from the trials of approved vaccines, i.e., data from the unvaccinated participants in those studies, with the data from inoculating people with the novel agents. The historical data can be sex- and age-matched, among other things, to individuals in the new trials. Moreover, because the study protocols have been harmonized for all trials under Operation Warp Speed, it doesn’t matter what kind of vaccine they’re testing, he said.

It may be necessary to do additional studies to find out how long immunity lasts after people have been vaccinated, Dr. Hewlett pointed out.

“You may have a different trial design. You don’t need a control arm to determine how long immunity lasts. You’re just comparing the patients who were vaccinated to nothing,” he said. “So you could have a single-arm trial on a group of people who consent to be immunized and followed. You can see what their antibody levels are and other surrogate markers, and you can see when they might develop disease, if they do. You’d need a large sample, but you can do that.”

Dr. Hewlett noted that additional studies will be required to determine whether the new vaccines stop transmission of the coronavirus or just prevent symptoms of COVID-19. Until it’s established that a vaccine halts transmission or the country achieves herd immunity, he said, “we’ll still have to wear masks and take other precautions, because a significant portion of people will still be at risk.”
 

‘A lot of redundancy’

Dr. Alexander emphasized that any safety or efficacy issues with the first COVID-19 vaccines must be identified before the vaccine is offered to a large portion of the U.S. population.

“While the data from the Pfizer and Moderna trials are said to be favorable, we at IDSA want to make sure that whatever vaccine comes to market is safe,” she said. “Having an unsafe vaccine on the market would be worse than no vaccine, because you’re compromising the public confidence. We have to make sure the public trusts the process and that sufficient data have been evaluated to ensure the vaccine is safe and efficacious.

“I believe the FDA is being very careful and thoughtful in [its] response,” Dr. Alexander said. “They realize how important it is to get a vaccine and save lives. While they’re doing things differently and moving much faster than before, they’re still trying to be thoughtful and reasonable. They don’t seem to be putting people at risk or circumventing the regulatory standards.”

Moreover, she pointed out, the FDA’s Vaccines and Related Biological Products Advisory Committee, which is expected to meet on Dec. 10, will review the trial data before the agency grants an EUA to Pfizer or Moderna. Then the FDA will post the data publicly.

The next step is for the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention to look at the data and decide who in the United States should receive the vaccine first, she pointed out. And both Pfizer and Moderna have shown their data to advisory panels of outside experts.

“There’s a lot of redundancy, and a lot of people are looking at the data,” Dr. Alexander said. “So I don’t think we’re cutting corners to get it out there more quickly.”

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

While stressing the urgent need to vaccinate the whole U.S. population, infectious disease experts and medical ethicists are raising questions about the clinical trials needed to answer important questions about the new COVID-19 vaccines.

In a statement released on Nov. 20, Barbara Alexander, MD, president of the Infectious Diseases Society of America (IDSA) and a professor at Duke University, Durham, N.C., commented on Pfizer and BioNTech’s application to the Food and Drug Administration for an emergency use authorization (EUA) for its COVID-19 vaccine. Besides emphasizing the need for a transparent review of the companies’ trial data prior to the FDA’s granting an EUA, she said, “If emergency use authorization is granted, clinical trials and data collection must continue.”

In an interview, Dr. Alexander said she is convinced that both Pfizer and Moderna, which is also expected to seek an EUA soon, will continue their clinical trials to monitor the long-term safety and efficacy of their vaccines.

“The EUA guidance for COVID vaccine authorization is very clear that clinical trials will move forward,” she said. “Any EUA request would have to include a strategy to ensure that the long-term safety and efficacy of a vaccine could be monitored. I see no evidence that either Pfizer or Moderna is not prepared to follow those regulations.”

Eventually, she added, the drug makers will have to seek full FDA approval to replace an EUA, which as its name signifies, is designed for public health emergencies. “The EUA is a tool to help us get the vaccine into circulation and have it start working as quickly as possible in the current health crisis,” she said. “But once the crisis is over, if the sponsors want to continue to market their vaccines, they have to go forward and get full approval.”

Medical ethicists, however, point out there may be ethical and practical dilemmas involved in continuing or initiating clinical trials once a vaccine has been approved for use even on an emergency basis.

In a commentary in Annals of Internal Medicine, Rafael Dal-Re, MD, PhD, Arthur L. Caplan, PhD, and two other ethicists stipulated that the pandemic requires early licensing and deployment of COVID-19 vaccines. Nevertheless, they noted, additional months of data are required to establish the long-term efficacy and safety of the vaccines. “Moreover, early deployment could interfere with the acquisition of long-term data,” both on these vaccines and on others coming through the pipeline, they wrote.

In countries where an approved vaccine is deployed, the ethicists noted, investigators must inform participants in an ongoing trial about the approved vaccine’s status and ask if they want to continue in the study. If enough participants decline, the trial might have to be terminated early. At that point, researchers may not have sufficient long-term data to identify late-term safety issues, determine how long efficacy lasts, determine whether waning immunity is associated with reduced levels of antibodies, or identify the level of neutralizing antibodies that correlates with immunity.

Moreover, they observed, long-term trials are especially important for vaccines that use mRNA technology, because less is known about them than about traditional kinds of vaccines.

The authors also pointed out that early licensing of any vaccine might make it harder to evaluate vaccines that haven’t yet been approved. “Once a vaccine is licensed, new placebo-controlled RCTs [randomized controlled trials] of other vaccines will not be acceptable ethically, and noninferiority RCTs will be the most likely alternative.

“The goal of noninferiority trials will be to demonstrate that the immune response (that is, neutralizing antibody titers or levels) of the candidate vaccine is not inferior to that of the approved vaccine within a prespecified margin, which the FDA has established as less than 10% for COVID-19 vaccines,” the authors noted. 
 

More data with more study designs

Dial Hewlett Jr., MD, medical director for disease control services, Westchester County Department of Health, White Plains, N.Y., said in an interview that the ethicists raise important issues that have been discussed in other forums, including a recent webinar of the National Academy of Medicine.

“As the authors point out, once you have a vaccine that has been shown to be effective and safe, it’s no longer ethical to enroll people in placebo trials,” he said.

Therefore, he said, Pfizer and Moderna will undoubtedly offer their vaccines to the people in their studies’ placebo groups after the vaccines receive an EUA. Then they will follow everyone who has been vaccinated for 2 years to determine long-term safety. Efficacy will also continue to be measured as an adjunct of safety, he said.

With regard to the difficulty of reconsenting individuals to enter a new clinical trial after a vaccine has been approved, he said, “I’d agree that trying to get all the same participants to come into another study would be a challenge. You can, however, design studies that will allow you to obtain the same information. You will have a large number of people out there who haven’t been vaccinated, and you can do single-arm longitudinal studies and measure a number of things in the individuals who are enrolled in those studies,” he said.

“You can look at the immunologic markers, both antibody and T-cell. You can follow these individuals longitudinally to see if they do develop disease over a period of time. If they do, you can determine what their levels of response were,” he added. “So there are opportunities to design studies that would give you some of the same information, although it would not be in the same population that was in the randomized trials.”

For newer vaccines that have yet to be tested, he said, developers can compare “historical controls” from the trials of approved vaccines, i.e., data from the unvaccinated participants in those studies, with the data from inoculating people with the novel agents. The historical data can be sex- and age-matched, among other things, to individuals in the new trials. Moreover, because the study protocols have been harmonized for all trials under Operation Warp Speed, it doesn’t matter what kind of vaccine they’re testing, he said.

It may be necessary to do additional studies to find out how long immunity lasts after people have been vaccinated, Dr. Hewlett pointed out.

“You may have a different trial design. You don’t need a control arm to determine how long immunity lasts. You’re just comparing the patients who were vaccinated to nothing,” he said. “So you could have a single-arm trial on a group of people who consent to be immunized and followed. You can see what their antibody levels are and other surrogate markers, and you can see when they might develop disease, if they do. You’d need a large sample, but you can do that.”

Dr. Hewlett noted that additional studies will be required to determine whether the new vaccines stop transmission of the coronavirus or just prevent symptoms of COVID-19. Until it’s established that a vaccine halts transmission or the country achieves herd immunity, he said, “we’ll still have to wear masks and take other precautions, because a significant portion of people will still be at risk.”
 

‘A lot of redundancy’

Dr. Alexander emphasized that any safety or efficacy issues with the first COVID-19 vaccines must be identified before the vaccine is offered to a large portion of the U.S. population.

“While the data from the Pfizer and Moderna trials are said to be favorable, we at IDSA want to make sure that whatever vaccine comes to market is safe,” she said. “Having an unsafe vaccine on the market would be worse than no vaccine, because you’re compromising the public confidence. We have to make sure the public trusts the process and that sufficient data have been evaluated to ensure the vaccine is safe and efficacious.

“I believe the FDA is being very careful and thoughtful in [its] response,” Dr. Alexander said. “They realize how important it is to get a vaccine and save lives. While they’re doing things differently and moving much faster than before, they’re still trying to be thoughtful and reasonable. They don’t seem to be putting people at risk or circumventing the regulatory standards.”

Moreover, she pointed out, the FDA’s Vaccines and Related Biological Products Advisory Committee, which is expected to meet on Dec. 10, will review the trial data before the agency grants an EUA to Pfizer or Moderna. Then the FDA will post the data publicly.

The next step is for the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention to look at the data and decide who in the United States should receive the vaccine first, she pointed out. And both Pfizer and Moderna have shown their data to advisory panels of outside experts.

“There’s a lot of redundancy, and a lot of people are looking at the data,” Dr. Alexander said. “So I don’t think we’re cutting corners to get it out there more quickly.”

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

On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.

An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.

ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.

“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”

There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.

But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.

ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.

In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.

ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.

“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.

ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.

“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.

Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.

“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
 

Broader access

Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.

The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.

Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.

Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.

In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”

In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.

“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.

Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.

“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.

Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.

There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.

Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.

The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.

“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.

Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.

“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.

ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.

“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.

This article first appeared on Medscape.com.

On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.

An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.

ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.

“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”

There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.

But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.

ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.

In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.

ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.

“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.

ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.

“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.

Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.

“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
 

Broader access

Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.

The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.

Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.

Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.

In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”

In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.

“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.

Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.

“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.

Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.

There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.

Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.

The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.

“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.

Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.

“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.

ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.

“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.

This article first appeared on Medscape.com.

On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.

An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.

ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.

“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”

There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.

But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.

ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.

In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.

ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.

“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.

ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.

“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.

Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.

“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
 

Broader access

Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.

The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.

Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.

Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.

In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”

In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.

“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.

Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.

“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.

Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.

There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.

Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.

The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.

“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.

Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.

“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.

ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.

“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.

This article first appeared on Medscape.com.

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

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

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

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

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

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

The human monoclonal antibody golimumab (Simponi) preserved endogenous insulin secretion in patients with new-onset type 1 diabetes and reduced their exogenous insulin requirements at 1 year, newly published phase 2 data indicate.

Results from the multicenter, double-blind, placebo-controlled trial were first reported as a poster at the virtual American Diabetes Association 80th Scientific Sessions in June. They were published online Nov. 18 in the New England Journal of Medicine.

In the 52-week study of 84 children and adults with new-onset type 1 diabetes, those given golimumab injections every 2 weeks had significantly higher levels of C-peptide, a marker of insulin secretion, and required less injected or infused insulin than did those who received placebo injections. There were no treatment-associated serious adverse events.

Golimumab is a human monoclonal antibody specific for tumor necrosis factor–alpha. It is approved for the treatment of several autoimmune diseases, including rheumatoid arthritis and ulcerative colitis, in the United States, Europe, and elsewhere.
 

An intermediate step toward a cure

Although none of the patients were able to stop taking insulin entirely, the results have important clinical implications, lead author Teresa Quattrin, MD, said in an interview.

“People want a cure, but the fact is, a cure is not available yet. So, this is an intermediate step towards a cure.... There are advantages to being on a small insulin dose,” including lower rates of hypoglycemia and maintenance of intraportal insulin, said Dr. Quattrin, of the State University of New York at Buffalo.

But in an accompanying editorial, Domenico Accili, MD, points to potential risks from immunotherapy and from attempting additional interventions at an “emotionally fraught” time when patients and families are coping with the new diabetes diagnosis.

He said of golimumab, “the effect is actually very small. ... There’s nothing wrong in and of itself with improving those outcomes. I just wouldn’t assign them as game changers.”

If this or a similar immunotherapeutic intervention were approved for this indication, “I would tell patients it exists and let them make the decision whether they want to try it. I wouldn’t say you must try it,” said Dr. Accili, of the Columbia University Diabetes and Endocrinology Research Center, New York.
 

With golimumab, higher C-peptide, lower insulin requirement

Of the 84 patients, who ranged in age from 6 to 21 years, 56 were randomly assigned within 100 days of being diagnosed with type 1 diabetes to receive golimumab, and 28 were assigned to receive placebo injections, given every 2 weeks.

The drug resulted in lower insulin use (0.51U/Kg per day vs. 0.69 U/kg per day), and the increase in insulin use over 52 weeks was less with golimumab than with placebo (0.07 vs. 0.24 U/kg per day; P = .001).

The mean percent decrease of C-peptide production from baseline was 12% with golimumab versus 56% with placebo.

Although the mean number of overall hypoglycemic events was similar, the mean number of level 2 hypoglycemic events (<54 mg/dL) was 36% lower with golimumab (11.5 vs. 17.6). There were no severe cases of hypoglycemia in either group.

No severe or serious infections occurred in either group, although mild to moderate infections were reported in 71% with golimumab versus 61% with placebo. More patients in the golimumab group experienced a decrease in neutrophils (29% vs. 19%).
 

Immunotherapy: Which one, and when should it start?

These findings come on the heels of the 2019 landmark results with another monoclonal antibody, the investigational anti-CD3 teplizumab (PRV-031). Among patients at risk, a diagnosis of type 1 diabetes was delayed by 2 years, and continued benefit was seen at 3 years.

However, Dr. Quattrin said teplizumab is limited by the fact that it must be administered via a 14-day infusion, whereas golimumab can be injected by patients themselves at home.

Moreover, the phase 2 teplizumab study was conducted in people who had antibodies that placed them at high risk for type 1 diabetes, but those patients did not yet have the condition. They were identified because they had close relatives with type 1 diabetes and were enrolled in the federally funded TrialNet screening program.

Dr. Quattrin is now participating in an ongoing phase 3 study of teplizumab that involves patients newly diagnosed with type 1 diabetes.

A Janssen spokesperson said in an interview that the company isn’t planning to further develop golimumab for use in type 1 diabetes.

“Our focus is to apply insights from the phase 2 ... proof-of-concept study to progress what we believe are novel, immunologically targeted pipeline candidates in stage 2 disease or presymptomatic stages of type 1 diabetes, which is consistent with our mission to intercept and prevent type 1 diabetes,” the spokesperson said.

To identify more individuals at risk for type 1 diabetes beyond the close relatives of those who already have it, so as to be able to intervene at a presymptomatic stage, Janssen is organizing a public-private effort to advocate for routine population screening for type 1 diabetes–related autoantibodies.

Dr. Quattrin said: “Preserving some insulin is key. Having somebody with beta cell functioning still is an intermediate step to a cure and will make their life easier, and that’s what people should care about.”

Dr. Accili, who cofounded and leads a company working on a novel approach to type 1 diabetes treatment, writes in his editorial: “We should also be mindful that this treatment debate is first world–centric.

“Current treatments for type 1 diabetes require resources not readily available in most parts of the world, where something as simple as refrigeration of insulin can become a logistic nightmare. While combinations of [approaches] tailored to individual risk and potential benefits are likely to make inroads in clinical practice, the need for a simpler, safer, and equally effective alternative to insulin remains,” he wrote.

Dr. Quattrin is a researcher and consultant for Janssen and conducts clinical trials for Provention Bio, Opko, and Ascendis. Dr. Accili is founder and director of Forkhead Therapeutics.

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

The human monoclonal antibody golimumab (Simponi) preserved endogenous insulin secretion in patients with new-onset type 1 diabetes and reduced their exogenous insulin requirements at 1 year, newly published phase 2 data indicate.

Results from the multicenter, double-blind, placebo-controlled trial were first reported as a poster at the virtual American Diabetes Association 80th Scientific Sessions in June. They were published online Nov. 18 in the New England Journal of Medicine.

In the 52-week study of 84 children and adults with new-onset type 1 diabetes, those given golimumab injections every 2 weeks had significantly higher levels of C-peptide, a marker of insulin secretion, and required less injected or infused insulin than did those who received placebo injections. There were no treatment-associated serious adverse events.

Golimumab is a human monoclonal antibody specific for tumor necrosis factor–alpha. It is approved for the treatment of several autoimmune diseases, including rheumatoid arthritis and ulcerative colitis, in the United States, Europe, and elsewhere.
 

An intermediate step toward a cure

Although none of the patients were able to stop taking insulin entirely, the results have important clinical implications, lead author Teresa Quattrin, MD, said in an interview.

“People want a cure, but the fact is, a cure is not available yet. So, this is an intermediate step towards a cure.... There are advantages to being on a small insulin dose,” including lower rates of hypoglycemia and maintenance of intraportal insulin, said Dr. Quattrin, of the State University of New York at Buffalo.

But in an accompanying editorial, Domenico Accili, MD, points to potential risks from immunotherapy and from attempting additional interventions at an “emotionally fraught” time when patients and families are coping with the new diabetes diagnosis.

He said of golimumab, “the effect is actually very small. ... There’s nothing wrong in and of itself with improving those outcomes. I just wouldn’t assign them as game changers.”

If this or a similar immunotherapeutic intervention were approved for this indication, “I would tell patients it exists and let them make the decision whether they want to try it. I wouldn’t say you must try it,” said Dr. Accili, of the Columbia University Diabetes and Endocrinology Research Center, New York.
 

With golimumab, higher C-peptide, lower insulin requirement

Of the 84 patients, who ranged in age from 6 to 21 years, 56 were randomly assigned within 100 days of being diagnosed with type 1 diabetes to receive golimumab, and 28 were assigned to receive placebo injections, given every 2 weeks.

The drug resulted in lower insulin use (0.51U/Kg per day vs. 0.69 U/kg per day), and the increase in insulin use over 52 weeks was less with golimumab than with placebo (0.07 vs. 0.24 U/kg per day; P = .001).

The mean percent decrease of C-peptide production from baseline was 12% with golimumab versus 56% with placebo.

Although the mean number of overall hypoglycemic events was similar, the mean number of level 2 hypoglycemic events (<54 mg/dL) was 36% lower with golimumab (11.5 vs. 17.6). There were no severe cases of hypoglycemia in either group.

No severe or serious infections occurred in either group, although mild to moderate infections were reported in 71% with golimumab versus 61% with placebo. More patients in the golimumab group experienced a decrease in neutrophils (29% vs. 19%).
 

Immunotherapy: Which one, and when should it start?

These findings come on the heels of the 2019 landmark results with another monoclonal antibody, the investigational anti-CD3 teplizumab (PRV-031). Among patients at risk, a diagnosis of type 1 diabetes was delayed by 2 years, and continued benefit was seen at 3 years.

However, Dr. Quattrin said teplizumab is limited by the fact that it must be administered via a 14-day infusion, whereas golimumab can be injected by patients themselves at home.

Moreover, the phase 2 teplizumab study was conducted in people who had antibodies that placed them at high risk for type 1 diabetes, but those patients did not yet have the condition. They were identified because they had close relatives with type 1 diabetes and were enrolled in the federally funded TrialNet screening program.

Dr. Quattrin is now participating in an ongoing phase 3 study of teplizumab that involves patients newly diagnosed with type 1 diabetes.

A Janssen spokesperson said in an interview that the company isn’t planning to further develop golimumab for use in type 1 diabetes.

“Our focus is to apply insights from the phase 2 ... proof-of-concept study to progress what we believe are novel, immunologically targeted pipeline candidates in stage 2 disease or presymptomatic stages of type 1 diabetes, which is consistent with our mission to intercept and prevent type 1 diabetes,” the spokesperson said.

To identify more individuals at risk for type 1 diabetes beyond the close relatives of those who already have it, so as to be able to intervene at a presymptomatic stage, Janssen is organizing a public-private effort to advocate for routine population screening for type 1 diabetes–related autoantibodies.

Dr. Quattrin said: “Preserving some insulin is key. Having somebody with beta cell functioning still is an intermediate step to a cure and will make their life easier, and that’s what people should care about.”

Dr. Accili, who cofounded and leads a company working on a novel approach to type 1 diabetes treatment, writes in his editorial: “We should also be mindful that this treatment debate is first world–centric.

“Current treatments for type 1 diabetes require resources not readily available in most parts of the world, where something as simple as refrigeration of insulin can become a logistic nightmare. While combinations of [approaches] tailored to individual risk and potential benefits are likely to make inroads in clinical practice, the need for a simpler, safer, and equally effective alternative to insulin remains,” he wrote.

Dr. Quattrin is a researcher and consultant for Janssen and conducts clinical trials for Provention Bio, Opko, and Ascendis. Dr. Accili is founder and director of Forkhead Therapeutics.

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

The human monoclonal antibody golimumab (Simponi) preserved endogenous insulin secretion in patients with new-onset type 1 diabetes and reduced their exogenous insulin requirements at 1 year, newly published phase 2 data indicate.

Results from the multicenter, double-blind, placebo-controlled trial were first reported as a poster at the virtual American Diabetes Association 80th Scientific Sessions in June. They were published online Nov. 18 in the New England Journal of Medicine.

In the 52-week study of 84 children and adults with new-onset type 1 diabetes, those given golimumab injections every 2 weeks had significantly higher levels of C-peptide, a marker of insulin secretion, and required less injected or infused insulin than did those who received placebo injections. There were no treatment-associated serious adverse events.

Golimumab is a human monoclonal antibody specific for tumor necrosis factor–alpha. It is approved for the treatment of several autoimmune diseases, including rheumatoid arthritis and ulcerative colitis, in the United States, Europe, and elsewhere.
 

An intermediate step toward a cure

Although none of the patients were able to stop taking insulin entirely, the results have important clinical implications, lead author Teresa Quattrin, MD, said in an interview.

“People want a cure, but the fact is, a cure is not available yet. So, this is an intermediate step towards a cure.... There are advantages to being on a small insulin dose,” including lower rates of hypoglycemia and maintenance of intraportal insulin, said Dr. Quattrin, of the State University of New York at Buffalo.

But in an accompanying editorial, Domenico Accili, MD, points to potential risks from immunotherapy and from attempting additional interventions at an “emotionally fraught” time when patients and families are coping with the new diabetes diagnosis.

He said of golimumab, “the effect is actually very small. ... There’s nothing wrong in and of itself with improving those outcomes. I just wouldn’t assign them as game changers.”

If this or a similar immunotherapeutic intervention were approved for this indication, “I would tell patients it exists and let them make the decision whether they want to try it. I wouldn’t say you must try it,” said Dr. Accili, of the Columbia University Diabetes and Endocrinology Research Center, New York.
 

With golimumab, higher C-peptide, lower insulin requirement

Of the 84 patients, who ranged in age from 6 to 21 years, 56 were randomly assigned within 100 days of being diagnosed with type 1 diabetes to receive golimumab, and 28 were assigned to receive placebo injections, given every 2 weeks.

The drug resulted in lower insulin use (0.51U/Kg per day vs. 0.69 U/kg per day), and the increase in insulin use over 52 weeks was less with golimumab than with placebo (0.07 vs. 0.24 U/kg per day; P = .001).

The mean percent decrease of C-peptide production from baseline was 12% with golimumab versus 56% with placebo.

Although the mean number of overall hypoglycemic events was similar, the mean number of level 2 hypoglycemic events (<54 mg/dL) was 36% lower with golimumab (11.5 vs. 17.6). There were no severe cases of hypoglycemia in either group.

No severe or serious infections occurred in either group, although mild to moderate infections were reported in 71% with golimumab versus 61% with placebo. More patients in the golimumab group experienced a decrease in neutrophils (29% vs. 19%).
 

Immunotherapy: Which one, and when should it start?

These findings come on the heels of the 2019 landmark results with another monoclonal antibody, the investigational anti-CD3 teplizumab (PRV-031). Among patients at risk, a diagnosis of type 1 diabetes was delayed by 2 years, and continued benefit was seen at 3 years.

However, Dr. Quattrin said teplizumab is limited by the fact that it must be administered via a 14-day infusion, whereas golimumab can be injected by patients themselves at home.

Moreover, the phase 2 teplizumab study was conducted in people who had antibodies that placed them at high risk for type 1 diabetes, but those patients did not yet have the condition. They were identified because they had close relatives with type 1 diabetes and were enrolled in the federally funded TrialNet screening program.

Dr. Quattrin is now participating in an ongoing phase 3 study of teplizumab that involves patients newly diagnosed with type 1 diabetes.

A Janssen spokesperson said in an interview that the company isn’t planning to further develop golimumab for use in type 1 diabetes.

“Our focus is to apply insights from the phase 2 ... proof-of-concept study to progress what we believe are novel, immunologically targeted pipeline candidates in stage 2 disease or presymptomatic stages of type 1 diabetes, which is consistent with our mission to intercept and prevent type 1 diabetes,” the spokesperson said.

To identify more individuals at risk for type 1 diabetes beyond the close relatives of those who already have it, so as to be able to intervene at a presymptomatic stage, Janssen is organizing a public-private effort to advocate for routine population screening for type 1 diabetes–related autoantibodies.

Dr. Quattrin said: “Preserving some insulin is key. Having somebody with beta cell functioning still is an intermediate step to a cure and will make their life easier, and that’s what people should care about.”

Dr. Accili, who cofounded and leads a company working on a novel approach to type 1 diabetes treatment, writes in his editorial: “We should also be mindful that this treatment debate is first world–centric.

“Current treatments for type 1 diabetes require resources not readily available in most parts of the world, where something as simple as refrigeration of insulin can become a logistic nightmare. While combinations of [approaches] tailored to individual risk and potential benefits are likely to make inroads in clinical practice, the need for a simpler, safer, and equally effective alternative to insulin remains,” he wrote.

Dr. Quattrin is a researcher and consultant for Janssen and conducts clinical trials for Provention Bio, Opko, and Ascendis. Dr. Accili is founder and director of Forkhead Therapeutics.

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