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More data needed to better understand COVID-19 skin manifestations
Qing Zhao, MD, Xiaokai Fang, MD, and their colleagues at the Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, in Jinan, China, reported the results of a literature review of 44 articles published through May 2020 that included 507 patients with cutaneous manifestations of COVID-19. The review was published in the Journal of The European Academy of Dermatology and Venereology.
Nearly all of the patients (96%) were from Europe, and more than half were women (60%), with an average age of 49 years. Most patients had multiple skin symptoms, with the most common being erythema (44%), chilblain-like lesions (20%), urticaria-like lesions (16%), vesicular manifestations (13%), livedo/necrosis (6%), and petechiae (almost 2%). The authors described erythema as being present in specific sites, such as the trunk, extremities, flexural regions, face, and mucous membranes. Slightly less than half of all patients had significant pruritus.
Data on systemic COVID-19 symptoms were available for 431 patients and included fever in about two-thirds of patients and cough in almost 70%, with dyspnea in almost half of patients. Almost 60% had fatigue, and almost 60% had asthenia. Information about the onset of skin symptoms was available in 88 patients; of these patients, lesions were seen an average of almost 10 days after systemic symptoms appeared and, in almost 15%, were the first symptoms noted.
Histopathologic exams were done for only 23 patients and, in all cases, showed “inflammatory features without specific pathological changes, such as lymphocyte infiltration.” In one study, reverse transcription polymerase chain reaction testing of skin biopsy specimens tested negative for SARS-CoV-2.
Expression of ACE2, the receptor of SARS-CoV-2, in the skin was evaluated in six of the studies. “Higher ACE2 expression was identified in keratinocytes, mainly in differentiating keratinocytes and basal cells compared to the other cells of skin tissues,” the authors wrote. These results were confirmed with immunohistochemistry, which, they said, found “ACE2-positive keratinocytes in the stratum basal, the stratum spinosum, and the stratum granulosum of epiderma.” They added that this provides evidence “for percutaneous infection or the entry of virus into patients through skin tissues,” but cautioned that more research is needed.
The authors acknowledged that there are still many unanswered questions about COVID-19, and that more clinical data and research are needed, to improve the understanding of the cutaneous manifestations associated with COVID-19.
In an interview, Alisa N. Femia, MD, director of inpatient dermatology in the department of dermatology at New York University, said that the cutaneous signs described in the review align well with what she has seen in patients with COVID-19.
At this point, it is unclear whether cutaneous manifestations of COVID-19 are a result of SARS-CoV-2 invading the skin or an immune response related to SARS-CoV-2, noted Dr. Femia, who was not involved in the research. One method of entry could be through transmitting virus present on the skin to another part of the body where infection is more likely.
While it is possible COVID-19 could be contracted through the skin, she noted, it is much more likely an individual would be infected by SARS-CoV-2 through more traditionally understood means of transmission, such as through respiratory droplets in person-to-person contact. “I think we are far away from drawing that conclusion, that one could touch a surface or a person who has COVID and contract it through their skin,” Dr. Femia said. “The skin has a lot of other ways to protect against that from occurring,” she added.
“SAR-CoV-2 obviously enters through the ACE2 receptor, which is fairly ubiquitous, and it has been seen in keratinocytes,” she said. “But the skin is one of our biggest barriers ... and further, studies to date have shown that that receptor is expressed in relatively low levels of the keratinocytes.”
Pathogenesis of different cutaneous manifestations may be different, Dr. Femia said. For example, urticaria and morbilliform eruption were described by the authors of the review as more benign eruptions, but pathogenesis may differ from that of so-called COVID toes and from the pathogenesis of purpura and ulcerations seen in patients with more severe disease, she noted. It is plausible, she added, that purpura and ulcerations may be a “direct invasion of SARS-CoV-2 into endothelial cells,” which creates secondary processes “that ultimately destroy the skin.”
Urticaria and morbilliform eruptions, on the other hand, “are more simply that the immune system is recognizing COVID, and in doing so, is also recognizing some antigens in the skin and creating a hypersensitive response to the skin” and has “nothing to do with the SARS-CoV-2 virus actually being in that location,” she said.
It is important to differentiate between patients who have skin manifestations attributed to COVID-19 and those with manifestations independent of COVID-19, which is difficult, Dr. Femia noted. A patient with COVID-19 and a cutaneous manifestation may be having a reaction to a medication. “It’s important to have a critical eye and to remember that, when we see these manifestations, we should always be investigating whether there was an alternative cause so that we can better learn what exactly we should be attributing to this infection,” she said
Adam Friedman, MD, professor and interim chair of dermatology at George Washington University, Washington, said the authors of the review had presented interesting work, but made some “assumptions that need to be proven.” Dr. Friedman also was not involved in the research, but agreed in an interview with the assessment that it is unlikely SARS-CoV-2 would penetrate the skin. While some viruses – such as the poxvirus that causes molluscum contagiosum and the herpes simplex virus – invade keratinocytes specifically, there is a particular clinical phenotype that results that is associated with changes in the epidermis. However, “the skin manifestations of COVID-19 do not fit with direct skin invasion, [but] rather the immune response to systemic disease,” he said.
“[I]n terms of systemic invasion through the skin, it is possible, but this study certainly doesn’t show that. The presence/expression of ACE2 in the epidermis doesn’t translate to route of infection,” Dr. Friedman said..
The study received financial support from Shandong First Medical University, the Innovation Project of Shandong Academy of Medical Sciences and the Shandong Province Taishan Scholar Project. The authors report no relevant financial disclosures. Dr. Femia and Dr. Friedman had no relevant financial disclosures.
SOURCE: Zhao Q et al. J Eur Acad Dermatol Venereol. 2020 Jun 28. doi: 10.1111/jdv.16778.
Qing Zhao, MD, Xiaokai Fang, MD, and their colleagues at the Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, in Jinan, China, reported the results of a literature review of 44 articles published through May 2020 that included 507 patients with cutaneous manifestations of COVID-19. The review was published in the Journal of The European Academy of Dermatology and Venereology.
Nearly all of the patients (96%) were from Europe, and more than half were women (60%), with an average age of 49 years. Most patients had multiple skin symptoms, with the most common being erythema (44%), chilblain-like lesions (20%), urticaria-like lesions (16%), vesicular manifestations (13%), livedo/necrosis (6%), and petechiae (almost 2%). The authors described erythema as being present in specific sites, such as the trunk, extremities, flexural regions, face, and mucous membranes. Slightly less than half of all patients had significant pruritus.
Data on systemic COVID-19 symptoms were available for 431 patients and included fever in about two-thirds of patients and cough in almost 70%, with dyspnea in almost half of patients. Almost 60% had fatigue, and almost 60% had asthenia. Information about the onset of skin symptoms was available in 88 patients; of these patients, lesions were seen an average of almost 10 days after systemic symptoms appeared and, in almost 15%, were the first symptoms noted.
Histopathologic exams were done for only 23 patients and, in all cases, showed “inflammatory features without specific pathological changes, such as lymphocyte infiltration.” In one study, reverse transcription polymerase chain reaction testing of skin biopsy specimens tested negative for SARS-CoV-2.
Expression of ACE2, the receptor of SARS-CoV-2, in the skin was evaluated in six of the studies. “Higher ACE2 expression was identified in keratinocytes, mainly in differentiating keratinocytes and basal cells compared to the other cells of skin tissues,” the authors wrote. These results were confirmed with immunohistochemistry, which, they said, found “ACE2-positive keratinocytes in the stratum basal, the stratum spinosum, and the stratum granulosum of epiderma.” They added that this provides evidence “for percutaneous infection or the entry of virus into patients through skin tissues,” but cautioned that more research is needed.
The authors acknowledged that there are still many unanswered questions about COVID-19, and that more clinical data and research are needed, to improve the understanding of the cutaneous manifestations associated with COVID-19.
In an interview, Alisa N. Femia, MD, director of inpatient dermatology in the department of dermatology at New York University, said that the cutaneous signs described in the review align well with what she has seen in patients with COVID-19.
At this point, it is unclear whether cutaneous manifestations of COVID-19 are a result of SARS-CoV-2 invading the skin or an immune response related to SARS-CoV-2, noted Dr. Femia, who was not involved in the research. One method of entry could be through transmitting virus present on the skin to another part of the body where infection is more likely.
While it is possible COVID-19 could be contracted through the skin, she noted, it is much more likely an individual would be infected by SARS-CoV-2 through more traditionally understood means of transmission, such as through respiratory droplets in person-to-person contact. “I think we are far away from drawing that conclusion, that one could touch a surface or a person who has COVID and contract it through their skin,” Dr. Femia said. “The skin has a lot of other ways to protect against that from occurring,” she added.
“SAR-CoV-2 obviously enters through the ACE2 receptor, which is fairly ubiquitous, and it has been seen in keratinocytes,” she said. “But the skin is one of our biggest barriers ... and further, studies to date have shown that that receptor is expressed in relatively low levels of the keratinocytes.”
Pathogenesis of different cutaneous manifestations may be different, Dr. Femia said. For example, urticaria and morbilliform eruption were described by the authors of the review as more benign eruptions, but pathogenesis may differ from that of so-called COVID toes and from the pathogenesis of purpura and ulcerations seen in patients with more severe disease, she noted. It is plausible, she added, that purpura and ulcerations may be a “direct invasion of SARS-CoV-2 into endothelial cells,” which creates secondary processes “that ultimately destroy the skin.”
Urticaria and morbilliform eruptions, on the other hand, “are more simply that the immune system is recognizing COVID, and in doing so, is also recognizing some antigens in the skin and creating a hypersensitive response to the skin” and has “nothing to do with the SARS-CoV-2 virus actually being in that location,” she said.
It is important to differentiate between patients who have skin manifestations attributed to COVID-19 and those with manifestations independent of COVID-19, which is difficult, Dr. Femia noted. A patient with COVID-19 and a cutaneous manifestation may be having a reaction to a medication. “It’s important to have a critical eye and to remember that, when we see these manifestations, we should always be investigating whether there was an alternative cause so that we can better learn what exactly we should be attributing to this infection,” she said
Adam Friedman, MD, professor and interim chair of dermatology at George Washington University, Washington, said the authors of the review had presented interesting work, but made some “assumptions that need to be proven.” Dr. Friedman also was not involved in the research, but agreed in an interview with the assessment that it is unlikely SARS-CoV-2 would penetrate the skin. While some viruses – such as the poxvirus that causes molluscum contagiosum and the herpes simplex virus – invade keratinocytes specifically, there is a particular clinical phenotype that results that is associated with changes in the epidermis. However, “the skin manifestations of COVID-19 do not fit with direct skin invasion, [but] rather the immune response to systemic disease,” he said.
“[I]n terms of systemic invasion through the skin, it is possible, but this study certainly doesn’t show that. The presence/expression of ACE2 in the epidermis doesn’t translate to route of infection,” Dr. Friedman said..
The study received financial support from Shandong First Medical University, the Innovation Project of Shandong Academy of Medical Sciences and the Shandong Province Taishan Scholar Project. The authors report no relevant financial disclosures. Dr. Femia and Dr. Friedman had no relevant financial disclosures.
SOURCE: Zhao Q et al. J Eur Acad Dermatol Venereol. 2020 Jun 28. doi: 10.1111/jdv.16778.
Qing Zhao, MD, Xiaokai Fang, MD, and their colleagues at the Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, in Jinan, China, reported the results of a literature review of 44 articles published through May 2020 that included 507 patients with cutaneous manifestations of COVID-19. The review was published in the Journal of The European Academy of Dermatology and Venereology.
Nearly all of the patients (96%) were from Europe, and more than half were women (60%), with an average age of 49 years. Most patients had multiple skin symptoms, with the most common being erythema (44%), chilblain-like lesions (20%), urticaria-like lesions (16%), vesicular manifestations (13%), livedo/necrosis (6%), and petechiae (almost 2%). The authors described erythema as being present in specific sites, such as the trunk, extremities, flexural regions, face, and mucous membranes. Slightly less than half of all patients had significant pruritus.
Data on systemic COVID-19 symptoms were available for 431 patients and included fever in about two-thirds of patients and cough in almost 70%, with dyspnea in almost half of patients. Almost 60% had fatigue, and almost 60% had asthenia. Information about the onset of skin symptoms was available in 88 patients; of these patients, lesions were seen an average of almost 10 days after systemic symptoms appeared and, in almost 15%, were the first symptoms noted.
Histopathologic exams were done for only 23 patients and, in all cases, showed “inflammatory features without specific pathological changes, such as lymphocyte infiltration.” In one study, reverse transcription polymerase chain reaction testing of skin biopsy specimens tested negative for SARS-CoV-2.
Expression of ACE2, the receptor of SARS-CoV-2, in the skin was evaluated in six of the studies. “Higher ACE2 expression was identified in keratinocytes, mainly in differentiating keratinocytes and basal cells compared to the other cells of skin tissues,” the authors wrote. These results were confirmed with immunohistochemistry, which, they said, found “ACE2-positive keratinocytes in the stratum basal, the stratum spinosum, and the stratum granulosum of epiderma.” They added that this provides evidence “for percutaneous infection or the entry of virus into patients through skin tissues,” but cautioned that more research is needed.
The authors acknowledged that there are still many unanswered questions about COVID-19, and that more clinical data and research are needed, to improve the understanding of the cutaneous manifestations associated with COVID-19.
In an interview, Alisa N. Femia, MD, director of inpatient dermatology in the department of dermatology at New York University, said that the cutaneous signs described in the review align well with what she has seen in patients with COVID-19.
At this point, it is unclear whether cutaneous manifestations of COVID-19 are a result of SARS-CoV-2 invading the skin or an immune response related to SARS-CoV-2, noted Dr. Femia, who was not involved in the research. One method of entry could be through transmitting virus present on the skin to another part of the body where infection is more likely.
While it is possible COVID-19 could be contracted through the skin, she noted, it is much more likely an individual would be infected by SARS-CoV-2 through more traditionally understood means of transmission, such as through respiratory droplets in person-to-person contact. “I think we are far away from drawing that conclusion, that one could touch a surface or a person who has COVID and contract it through their skin,” Dr. Femia said. “The skin has a lot of other ways to protect against that from occurring,” she added.
“SAR-CoV-2 obviously enters through the ACE2 receptor, which is fairly ubiquitous, and it has been seen in keratinocytes,” she said. “But the skin is one of our biggest barriers ... and further, studies to date have shown that that receptor is expressed in relatively low levels of the keratinocytes.”
Pathogenesis of different cutaneous manifestations may be different, Dr. Femia said. For example, urticaria and morbilliform eruption were described by the authors of the review as more benign eruptions, but pathogenesis may differ from that of so-called COVID toes and from the pathogenesis of purpura and ulcerations seen in patients with more severe disease, she noted. It is plausible, she added, that purpura and ulcerations may be a “direct invasion of SARS-CoV-2 into endothelial cells,” which creates secondary processes “that ultimately destroy the skin.”
Urticaria and morbilliform eruptions, on the other hand, “are more simply that the immune system is recognizing COVID, and in doing so, is also recognizing some antigens in the skin and creating a hypersensitive response to the skin” and has “nothing to do with the SARS-CoV-2 virus actually being in that location,” she said.
It is important to differentiate between patients who have skin manifestations attributed to COVID-19 and those with manifestations independent of COVID-19, which is difficult, Dr. Femia noted. A patient with COVID-19 and a cutaneous manifestation may be having a reaction to a medication. “It’s important to have a critical eye and to remember that, when we see these manifestations, we should always be investigating whether there was an alternative cause so that we can better learn what exactly we should be attributing to this infection,” she said
Adam Friedman, MD, professor and interim chair of dermatology at George Washington University, Washington, said the authors of the review had presented interesting work, but made some “assumptions that need to be proven.” Dr. Friedman also was not involved in the research, but agreed in an interview with the assessment that it is unlikely SARS-CoV-2 would penetrate the skin. While some viruses – such as the poxvirus that causes molluscum contagiosum and the herpes simplex virus – invade keratinocytes specifically, there is a particular clinical phenotype that results that is associated with changes in the epidermis. However, “the skin manifestations of COVID-19 do not fit with direct skin invasion, [but] rather the immune response to systemic disease,” he said.
“[I]n terms of systemic invasion through the skin, it is possible, but this study certainly doesn’t show that. The presence/expression of ACE2 in the epidermis doesn’t translate to route of infection,” Dr. Friedman said..
The study received financial support from Shandong First Medical University, the Innovation Project of Shandong Academy of Medical Sciences and the Shandong Province Taishan Scholar Project. The authors report no relevant financial disclosures. Dr. Femia and Dr. Friedman had no relevant financial disclosures.
SOURCE: Zhao Q et al. J Eur Acad Dermatol Venereol. 2020 Jun 28. doi: 10.1111/jdv.16778.
FROM THE JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
Are you SARS-CoV-2 vaccine hesitant?
When the pandemic was just emerging from its infancy and we were just beginning to think about social distancing, I was sitting around enjoying an adult beverage and some gluten free (not my choice) snacks with some friends. A retired nurse who had just celebrated her 80th birthday said, “I can’t wait until they’ve developed a vaccine.” A former electrical engineer sitting just short of 2 meters to her left responded, “Don’t save me a place near the front of the line for something that is being developed in a program called Warp Speed.”
How do you feel about the potential SARS-CoV-2 vaccine? Are you going to roll up your sleeve as soon as the vaccine becomes available in your community? What are you going to suggest to your patients, your children? I suspect many of you will answer, “It depends.”
Will it make any difference to you which biochemical-immune-bending strategy is being used to make the vaccine? All of them will probably be the result of a clever sounding but novel technique, all of them with a track record that is measured in months and not years. Will you be swayed by how large the trials were? Or how long the follow-up lasted? How effective must the vaccine be to convince you that it is worth receiving or recommending? Do you have the tools and experience to make a decision like that? I know I don’t. And should you and I even be put in a position to make that decision?
In the past, you and I may have relied on the Centers for Disease Control and Prevention for advice. But given the somewhat murky and stormy relationship between the CDC and the president, the vaccine recommendation may be issued by the White House and not the CDC.
For those of us who were practicing medicine during the Swine Flu fiasco of 1976, the pace and the politics surrounding the development of a SARS-CoV-2 vaccine has a discomforting déjà vu quality about it. The fact that like this year 1976 was an election year that infused the development process with a sense of urgency above and beyond any of the concerns about the pandemic that never happened. Although causality was never proven, there was a surge in Guillain-Barré syndrome cases that had been linked temporally to the vaccine.
Of course, our pandemic is real, and it would be imprudent to wait a year or more to watch for long-term vaccine sequelae. However, I am more than a little concerned that fast tracking the development process may result in unfortunate consequences in the short term that could have been avoided with a more measured approach to trialing the vaccines.
The sad reality is that as a nation we tend to be impatient. We are drawn to quick fixes that come in a vial or a capsule. We are learning that simple measures like mask wearing and social distancing can make a difference in slowing the spread of the virus. It would be tragic to rush a vaccine into production that at best turns out to simply be an expensive alternative to the measures that we know work or at worst injures more of us than it saves.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
When the pandemic was just emerging from its infancy and we were just beginning to think about social distancing, I was sitting around enjoying an adult beverage and some gluten free (not my choice) snacks with some friends. A retired nurse who had just celebrated her 80th birthday said, “I can’t wait until they’ve developed a vaccine.” A former electrical engineer sitting just short of 2 meters to her left responded, “Don’t save me a place near the front of the line for something that is being developed in a program called Warp Speed.”
How do you feel about the potential SARS-CoV-2 vaccine? Are you going to roll up your sleeve as soon as the vaccine becomes available in your community? What are you going to suggest to your patients, your children? I suspect many of you will answer, “It depends.”
Will it make any difference to you which biochemical-immune-bending strategy is being used to make the vaccine? All of them will probably be the result of a clever sounding but novel technique, all of them with a track record that is measured in months and not years. Will you be swayed by how large the trials were? Or how long the follow-up lasted? How effective must the vaccine be to convince you that it is worth receiving or recommending? Do you have the tools and experience to make a decision like that? I know I don’t. And should you and I even be put in a position to make that decision?
In the past, you and I may have relied on the Centers for Disease Control and Prevention for advice. But given the somewhat murky and stormy relationship between the CDC and the president, the vaccine recommendation may be issued by the White House and not the CDC.
For those of us who were practicing medicine during the Swine Flu fiasco of 1976, the pace and the politics surrounding the development of a SARS-CoV-2 vaccine has a discomforting déjà vu quality about it. The fact that like this year 1976 was an election year that infused the development process with a sense of urgency above and beyond any of the concerns about the pandemic that never happened. Although causality was never proven, there was a surge in Guillain-Barré syndrome cases that had been linked temporally to the vaccine.
Of course, our pandemic is real, and it would be imprudent to wait a year or more to watch for long-term vaccine sequelae. However, I am more than a little concerned that fast tracking the development process may result in unfortunate consequences in the short term that could have been avoided with a more measured approach to trialing the vaccines.
The sad reality is that as a nation we tend to be impatient. We are drawn to quick fixes that come in a vial or a capsule. We are learning that simple measures like mask wearing and social distancing can make a difference in slowing the spread of the virus. It would be tragic to rush a vaccine into production that at best turns out to simply be an expensive alternative to the measures that we know work or at worst injures more of us than it saves.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
When the pandemic was just emerging from its infancy and we were just beginning to think about social distancing, I was sitting around enjoying an adult beverage and some gluten free (not my choice) snacks with some friends. A retired nurse who had just celebrated her 80th birthday said, “I can’t wait until they’ve developed a vaccine.” A former electrical engineer sitting just short of 2 meters to her left responded, “Don’t save me a place near the front of the line for something that is being developed in a program called Warp Speed.”
How do you feel about the potential SARS-CoV-2 vaccine? Are you going to roll up your sleeve as soon as the vaccine becomes available in your community? What are you going to suggest to your patients, your children? I suspect many of you will answer, “It depends.”
Will it make any difference to you which biochemical-immune-bending strategy is being used to make the vaccine? All of them will probably be the result of a clever sounding but novel technique, all of them with a track record that is measured in months and not years. Will you be swayed by how large the trials were? Or how long the follow-up lasted? How effective must the vaccine be to convince you that it is worth receiving or recommending? Do you have the tools and experience to make a decision like that? I know I don’t. And should you and I even be put in a position to make that decision?
In the past, you and I may have relied on the Centers for Disease Control and Prevention for advice. But given the somewhat murky and stormy relationship between the CDC and the president, the vaccine recommendation may be issued by the White House and not the CDC.
For those of us who were practicing medicine during the Swine Flu fiasco of 1976, the pace and the politics surrounding the development of a SARS-CoV-2 vaccine has a discomforting déjà vu quality about it. The fact that like this year 1976 was an election year that infused the development process with a sense of urgency above and beyond any of the concerns about the pandemic that never happened. Although causality was never proven, there was a surge in Guillain-Barré syndrome cases that had been linked temporally to the vaccine.
Of course, our pandemic is real, and it would be imprudent to wait a year or more to watch for long-term vaccine sequelae. However, I am more than a little concerned that fast tracking the development process may result in unfortunate consequences in the short term that could have been avoided with a more measured approach to trialing the vaccines.
The sad reality is that as a nation we tend to be impatient. We are drawn to quick fixes that come in a vial or a capsule. We are learning that simple measures like mask wearing and social distancing can make a difference in slowing the spread of the virus. It would be tragic to rush a vaccine into production that at best turns out to simply be an expensive alternative to the measures that we know work or at worst injures more of us than it saves.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
COVID-19 bits and pieces
It turns out that a pandemic, at least this COVID-19 version, can be a challenge for folks like me who are seldom at a loss for words. The pandemic has so overwhelmed every corner of our lives that it is hard to think of another topic on which to pontificate and still not tromp on someone’s political toes. One can always write about the pandemic itself, and I’ve tried that, but as the curtain is gradually being pulled back on this crafty little germ one runs the risk of making an observation today that will be disproved in a week or 2. However, I can’t suppress my urge to write, and so I have decided to share a few brief random observations. Of course they are related to the pandemic. And of course I realize that there is a better than fifty percent chance that they will be proved wrong by the time you read my next Letters from Maine.
Under the radar
Two of the many mysteries about SARS-CoV-2 involve young children who as a group appear to be less easily infected than adults and even when infected seem to be less likely to spread the disease to other people, particularly adults. One explanation posited by some researchers in France is that young children are less likely to have symptoms such as cough and are less powerful speakers and so might be less likely to spew out a significant number of infected aerosolized droplets (“How to Reopen Schools: What Science and Other Countries Teach Us.” By Pam Belluck, Apoorva Mandavill, and Benedict Carey. New York Times, July 11, 2020). While there are probably several factors to explain this observation, one may be that young children are short, seldom taller than an adult waistline. I suspect the majority of aerosols they emit fall and inactivate harmlessly to the floor several feet below an adult’s nose and mouth. Regardless of the explanation, it appears to be good news for the opening of schools, at least for the early grades.
Forget the deep cleaning
There has been a glut of news stories about reopening schools, and many of these stories are accompanied by images of school custodians with buckets, mops, spray bottles, and sponges scouring desks and walls. The most recent image in our local newspaper was of someone scrubbing the underside of a desk. I know it’s taking the World Health Organization an unconscionable period of time to acknowledge that SARS-CoV-2 is airborne, but the rest of us should have gotten the message long ago and been directing our attention to air handling and ventilation. The urge to scrub and deep clean is a hard habit to break, but this nasty bug is not like influenza or a flesh eating bacteria in which deep cleaning might help. A better image to attach to a story on school reopening would be one of a custodian with a screwdriver struggling to pry open a classroom window that had been painted shut a decade ago.
Managing the inevitable
Middlebury College in Vermont and Bowdoin College here in Brunswick, Maine, are similar in many respects because they are small and situated in relatively isolated small New England towns with good track records for pandemic management. Middlebury has elected to invite all its 2,750 students back to campus, whereas Bowdoin has decided to allow only incoming first years and transfer students (for a total of about 600) to return. Both schools will institute similar testing and social distancing protocols and restrict students from access to their respective towns (“A Tale of 2 Colleges.” By Bill Burger. Inside Higher Ed, June 29,2020). It will be an interesting experiment. I’m voting for Middlebury and not because my son and daughter-in-law are alums, but because I think Middlebury seems to have acknowledged that no matter how diligent one is in creating a SARS-CoV-2–free environment at the outset, these are college kids and there will be some cases on both campuses. It is on how those inevitable realities are managed and contained that an institution should be judged.
Patience
Unfortunately, We always have been a restless and impatient population eager to get moving and it has driven us to greatness. Hopefully, patience will be a lesson that we will learn, along with many others.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
It turns out that a pandemic, at least this COVID-19 version, can be a challenge for folks like me who are seldom at a loss for words. The pandemic has so overwhelmed every corner of our lives that it is hard to think of another topic on which to pontificate and still not tromp on someone’s political toes. One can always write about the pandemic itself, and I’ve tried that, but as the curtain is gradually being pulled back on this crafty little germ one runs the risk of making an observation today that will be disproved in a week or 2. However, I can’t suppress my urge to write, and so I have decided to share a few brief random observations. Of course they are related to the pandemic. And of course I realize that there is a better than fifty percent chance that they will be proved wrong by the time you read my next Letters from Maine.
Under the radar
Two of the many mysteries about SARS-CoV-2 involve young children who as a group appear to be less easily infected than adults and even when infected seem to be less likely to spread the disease to other people, particularly adults. One explanation posited by some researchers in France is that young children are less likely to have symptoms such as cough and are less powerful speakers and so might be less likely to spew out a significant number of infected aerosolized droplets (“How to Reopen Schools: What Science and Other Countries Teach Us.” By Pam Belluck, Apoorva Mandavill, and Benedict Carey. New York Times, July 11, 2020). While there are probably several factors to explain this observation, one may be that young children are short, seldom taller than an adult waistline. I suspect the majority of aerosols they emit fall and inactivate harmlessly to the floor several feet below an adult’s nose and mouth. Regardless of the explanation, it appears to be good news for the opening of schools, at least for the early grades.
Forget the deep cleaning
There has been a glut of news stories about reopening schools, and many of these stories are accompanied by images of school custodians with buckets, mops, spray bottles, and sponges scouring desks and walls. The most recent image in our local newspaper was of someone scrubbing the underside of a desk. I know it’s taking the World Health Organization an unconscionable period of time to acknowledge that SARS-CoV-2 is airborne, but the rest of us should have gotten the message long ago and been directing our attention to air handling and ventilation. The urge to scrub and deep clean is a hard habit to break, but this nasty bug is not like influenza or a flesh eating bacteria in which deep cleaning might help. A better image to attach to a story on school reopening would be one of a custodian with a screwdriver struggling to pry open a classroom window that had been painted shut a decade ago.
Managing the inevitable
Middlebury College in Vermont and Bowdoin College here in Brunswick, Maine, are similar in many respects because they are small and situated in relatively isolated small New England towns with good track records for pandemic management. Middlebury has elected to invite all its 2,750 students back to campus, whereas Bowdoin has decided to allow only incoming first years and transfer students (for a total of about 600) to return. Both schools will institute similar testing and social distancing protocols and restrict students from access to their respective towns (“A Tale of 2 Colleges.” By Bill Burger. Inside Higher Ed, June 29,2020). It will be an interesting experiment. I’m voting for Middlebury and not because my son and daughter-in-law are alums, but because I think Middlebury seems to have acknowledged that no matter how diligent one is in creating a SARS-CoV-2–free environment at the outset, these are college kids and there will be some cases on both campuses. It is on how those inevitable realities are managed and contained that an institution should be judged.
Patience
Unfortunately, We always have been a restless and impatient population eager to get moving and it has driven us to greatness. Hopefully, patience will be a lesson that we will learn, along with many others.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
It turns out that a pandemic, at least this COVID-19 version, can be a challenge for folks like me who are seldom at a loss for words. The pandemic has so overwhelmed every corner of our lives that it is hard to think of another topic on which to pontificate and still not tromp on someone’s political toes. One can always write about the pandemic itself, and I’ve tried that, but as the curtain is gradually being pulled back on this crafty little germ one runs the risk of making an observation today that will be disproved in a week or 2. However, I can’t suppress my urge to write, and so I have decided to share a few brief random observations. Of course they are related to the pandemic. And of course I realize that there is a better than fifty percent chance that they will be proved wrong by the time you read my next Letters from Maine.
Under the radar
Two of the many mysteries about SARS-CoV-2 involve young children who as a group appear to be less easily infected than adults and even when infected seem to be less likely to spread the disease to other people, particularly adults. One explanation posited by some researchers in France is that young children are less likely to have symptoms such as cough and are less powerful speakers and so might be less likely to spew out a significant number of infected aerosolized droplets (“How to Reopen Schools: What Science and Other Countries Teach Us.” By Pam Belluck, Apoorva Mandavill, and Benedict Carey. New York Times, July 11, 2020). While there are probably several factors to explain this observation, one may be that young children are short, seldom taller than an adult waistline. I suspect the majority of aerosols they emit fall and inactivate harmlessly to the floor several feet below an adult’s nose and mouth. Regardless of the explanation, it appears to be good news for the opening of schools, at least for the early grades.
Forget the deep cleaning
There has been a glut of news stories about reopening schools, and many of these stories are accompanied by images of school custodians with buckets, mops, spray bottles, and sponges scouring desks and walls. The most recent image in our local newspaper was of someone scrubbing the underside of a desk. I know it’s taking the World Health Organization an unconscionable period of time to acknowledge that SARS-CoV-2 is airborne, but the rest of us should have gotten the message long ago and been directing our attention to air handling and ventilation. The urge to scrub and deep clean is a hard habit to break, but this nasty bug is not like influenza or a flesh eating bacteria in which deep cleaning might help. A better image to attach to a story on school reopening would be one of a custodian with a screwdriver struggling to pry open a classroom window that had been painted shut a decade ago.
Managing the inevitable
Middlebury College in Vermont and Bowdoin College here in Brunswick, Maine, are similar in many respects because they are small and situated in relatively isolated small New England towns with good track records for pandemic management. Middlebury has elected to invite all its 2,750 students back to campus, whereas Bowdoin has decided to allow only incoming first years and transfer students (for a total of about 600) to return. Both schools will institute similar testing and social distancing protocols and restrict students from access to their respective towns (“A Tale of 2 Colleges.” By Bill Burger. Inside Higher Ed, June 29,2020). It will be an interesting experiment. I’m voting for Middlebury and not because my son and daughter-in-law are alums, but because I think Middlebury seems to have acknowledged that no matter how diligent one is in creating a SARS-CoV-2–free environment at the outset, these are college kids and there will be some cases on both campuses. It is on how those inevitable realities are managed and contained that an institution should be judged.
Patience
Unfortunately, We always have been a restless and impatient population eager to get moving and it has driven us to greatness. Hopefully, patience will be a lesson that we will learn, along with many others.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
Higher death rate seen in cancer patients with nosocomial COVID-19
, according to researchers.
In an observational study of patients with COVID-19 and cancer, 19% of patients had COVID-19 acquired during a non-COVID-related hospital stay, and 81% had community-acquired COVID-19.
At a median follow-up of 23 days, the overall mortality rate was 28%. However, the all-cause mortality rate in patients with nosocomial COVID-19 was more than double that of patients with community-acquired COVID-19, at 47% and 23%, respectively.
Arielle Elkrief, MD, of the University of Montreal, reported these results during the AACR virtual meeting: COVID-19 and Cancer.
“This is the first report that describes a high rate of hospital-acquired COVID-19 in patients with cancer, at a rate of 19%,” Dr. Elkrief said. “This was associated with high mortality in both univariate and multivariate analyses.”
The study included 250 adults and 3 children with COVID-19 and cancer who were identified between March 3 and May 23, 2020. They ranged in age from 4 to 95 years, but the median age was 73 years.
All patients had either laboratory-confirmed (95%) or presumed COVID-19 (5%) and invasive cancer. The most common cancer types were similar to those seen in the general population. Lung and breast cancer were the most common, followed by lymphoma, prostate cancer, and colorectal cancer. Most patients were on active anticancer therapy, most often chemotherapy.
Most patients (n = 236) were residents of Quebec, but 17 patients were residents of British Columbia.
“It is important to note that Quebec was one of the most heavily affected areas in North America at the time of the study,” Dr. Elkrief said.
Outcomes by group
There were 206 patients (81%) who had community-acquired COVID-19 and 47 (19%) who had nosocomial COVID-19. The two groups were similar with respect to sex, performance status, and cancer stage. A small trend toward more patients on active therapy was seen in the nosocomial group, but the difference did not reach statistical significance.
The median overall survival was 27 days in the nosocomial group and 71 days in the community-acquired group (hazard ratio, 2.2; P = .002).
A multivariate analysis showed that nosocomial infection was “strongly and independently associated with death,” Dr. Elkrief said. “Other risk factors for poor prognosis included age, poor [performance] status, and advanced stage of cancer.”
There were no significant differences between the hospital-acquired and community-acquired groups for other outcomes, including oxygen requirements (43% and 47%, respectively), ICU admission (13% and 11%), need for mechanical ventilation (6% and 5%), or length of stay (median, 9.5 days and 8.5 days).
The low rate of ICU admission, considering the mortality rate of 28%, “could reflect that patients with cancer are less likely to be admitted to the ICU,” Dr. Elkrief noted.
Applying the findings to practice
The findings reinforce the importance of adherence to stringent infection control guidelines to protect vulnerable patients, such as those with cancer, Dr. Elkrief said.
In ambulatory settings, this means decreasing in-person visits through increased use of teleconsultations, and for those who need to be seen in person, screening for symptoms or use of polymerase chain reaction testing should be used when resources are available, she said.
“Similar principles apply to chemotherapy treatment units,” Dr. Elkrief said. She added that staff must avoid cross-contamination between COVID and COVID-free zones, and that “dedicated personnel and equipment should be maintained and separate between these two zones.
“Adequate protective personal equipment and strict hand hygiene protocols are also of utmost importance,” Dr. Elkrief said. “The threat of COVID-19 is not behind us, and so we continue to enforce these strategies to protect our patients.”
Session moderator Gypsyamber D’Souza, PhD, an infectious disease epidemiologist at Johns Hopkins University in Baltimore, raised the question of whether the high nosocomial infection and death rate in this study was related to patients having more severe disease because of underlying comorbidities.
Dr. Elkrief explained that the overall mortality rate was indeed higher than the 13% reported in other studies, and it may reflect an overrepresentation of hospitalized or more severely ill patients in the cohort.
However, the investigators made every effort to include all patients with both cancer and COVID-19 by using systematic screening of inpatient and outpatients lists and registries.
Further, the multivariate analysis included both inpatients and outpatients and adjusted for known negative prognostic factors for COVID-19 outcomes. These included increasing age, poor performance status, and different comorbidities.
The finding that nosocomial infection was an independent predictor of death “pushed us to look at nosocomial infection as a new independent risk factor,” Dr. Elkrief said.
Dr. Elkrief reported grant support from AstraZeneca. Dr. D’Souza did not report any disclosures.
SOURCE: Elkrief A et al. AACR: COVID and Cancer, Abstract S12-01.
, according to researchers.
In an observational study of patients with COVID-19 and cancer, 19% of patients had COVID-19 acquired during a non-COVID-related hospital stay, and 81% had community-acquired COVID-19.
At a median follow-up of 23 days, the overall mortality rate was 28%. However, the all-cause mortality rate in patients with nosocomial COVID-19 was more than double that of patients with community-acquired COVID-19, at 47% and 23%, respectively.
Arielle Elkrief, MD, of the University of Montreal, reported these results during the AACR virtual meeting: COVID-19 and Cancer.
“This is the first report that describes a high rate of hospital-acquired COVID-19 in patients with cancer, at a rate of 19%,” Dr. Elkrief said. “This was associated with high mortality in both univariate and multivariate analyses.”
The study included 250 adults and 3 children with COVID-19 and cancer who were identified between March 3 and May 23, 2020. They ranged in age from 4 to 95 years, but the median age was 73 years.
All patients had either laboratory-confirmed (95%) or presumed COVID-19 (5%) and invasive cancer. The most common cancer types were similar to those seen in the general population. Lung and breast cancer were the most common, followed by lymphoma, prostate cancer, and colorectal cancer. Most patients were on active anticancer therapy, most often chemotherapy.
Most patients (n = 236) were residents of Quebec, but 17 patients were residents of British Columbia.
“It is important to note that Quebec was one of the most heavily affected areas in North America at the time of the study,” Dr. Elkrief said.
Outcomes by group
There were 206 patients (81%) who had community-acquired COVID-19 and 47 (19%) who had nosocomial COVID-19. The two groups were similar with respect to sex, performance status, and cancer stage. A small trend toward more patients on active therapy was seen in the nosocomial group, but the difference did not reach statistical significance.
The median overall survival was 27 days in the nosocomial group and 71 days in the community-acquired group (hazard ratio, 2.2; P = .002).
A multivariate analysis showed that nosocomial infection was “strongly and independently associated with death,” Dr. Elkrief said. “Other risk factors for poor prognosis included age, poor [performance] status, and advanced stage of cancer.”
There were no significant differences between the hospital-acquired and community-acquired groups for other outcomes, including oxygen requirements (43% and 47%, respectively), ICU admission (13% and 11%), need for mechanical ventilation (6% and 5%), or length of stay (median, 9.5 days and 8.5 days).
The low rate of ICU admission, considering the mortality rate of 28%, “could reflect that patients with cancer are less likely to be admitted to the ICU,” Dr. Elkrief noted.
Applying the findings to practice
The findings reinforce the importance of adherence to stringent infection control guidelines to protect vulnerable patients, such as those with cancer, Dr. Elkrief said.
In ambulatory settings, this means decreasing in-person visits through increased use of teleconsultations, and for those who need to be seen in person, screening for symptoms or use of polymerase chain reaction testing should be used when resources are available, she said.
“Similar principles apply to chemotherapy treatment units,” Dr. Elkrief said. She added that staff must avoid cross-contamination between COVID and COVID-free zones, and that “dedicated personnel and equipment should be maintained and separate between these two zones.
“Adequate protective personal equipment and strict hand hygiene protocols are also of utmost importance,” Dr. Elkrief said. “The threat of COVID-19 is not behind us, and so we continue to enforce these strategies to protect our patients.”
Session moderator Gypsyamber D’Souza, PhD, an infectious disease epidemiologist at Johns Hopkins University in Baltimore, raised the question of whether the high nosocomial infection and death rate in this study was related to patients having more severe disease because of underlying comorbidities.
Dr. Elkrief explained that the overall mortality rate was indeed higher than the 13% reported in other studies, and it may reflect an overrepresentation of hospitalized or more severely ill patients in the cohort.
However, the investigators made every effort to include all patients with both cancer and COVID-19 by using systematic screening of inpatient and outpatients lists and registries.
Further, the multivariate analysis included both inpatients and outpatients and adjusted for known negative prognostic factors for COVID-19 outcomes. These included increasing age, poor performance status, and different comorbidities.
The finding that nosocomial infection was an independent predictor of death “pushed us to look at nosocomial infection as a new independent risk factor,” Dr. Elkrief said.
Dr. Elkrief reported grant support from AstraZeneca. Dr. D’Souza did not report any disclosures.
SOURCE: Elkrief A et al. AACR: COVID and Cancer, Abstract S12-01.
, according to researchers.
In an observational study of patients with COVID-19 and cancer, 19% of patients had COVID-19 acquired during a non-COVID-related hospital stay, and 81% had community-acquired COVID-19.
At a median follow-up of 23 days, the overall mortality rate was 28%. However, the all-cause mortality rate in patients with nosocomial COVID-19 was more than double that of patients with community-acquired COVID-19, at 47% and 23%, respectively.
Arielle Elkrief, MD, of the University of Montreal, reported these results during the AACR virtual meeting: COVID-19 and Cancer.
“This is the first report that describes a high rate of hospital-acquired COVID-19 in patients with cancer, at a rate of 19%,” Dr. Elkrief said. “This was associated with high mortality in both univariate and multivariate analyses.”
The study included 250 adults and 3 children with COVID-19 and cancer who were identified between March 3 and May 23, 2020. They ranged in age from 4 to 95 years, but the median age was 73 years.
All patients had either laboratory-confirmed (95%) or presumed COVID-19 (5%) and invasive cancer. The most common cancer types were similar to those seen in the general population. Lung and breast cancer were the most common, followed by lymphoma, prostate cancer, and colorectal cancer. Most patients were on active anticancer therapy, most often chemotherapy.
Most patients (n = 236) were residents of Quebec, but 17 patients were residents of British Columbia.
“It is important to note that Quebec was one of the most heavily affected areas in North America at the time of the study,” Dr. Elkrief said.
Outcomes by group
There were 206 patients (81%) who had community-acquired COVID-19 and 47 (19%) who had nosocomial COVID-19. The two groups were similar with respect to sex, performance status, and cancer stage. A small trend toward more patients on active therapy was seen in the nosocomial group, but the difference did not reach statistical significance.
The median overall survival was 27 days in the nosocomial group and 71 days in the community-acquired group (hazard ratio, 2.2; P = .002).
A multivariate analysis showed that nosocomial infection was “strongly and independently associated with death,” Dr. Elkrief said. “Other risk factors for poor prognosis included age, poor [performance] status, and advanced stage of cancer.”
There were no significant differences between the hospital-acquired and community-acquired groups for other outcomes, including oxygen requirements (43% and 47%, respectively), ICU admission (13% and 11%), need for mechanical ventilation (6% and 5%), or length of stay (median, 9.5 days and 8.5 days).
The low rate of ICU admission, considering the mortality rate of 28%, “could reflect that patients with cancer are less likely to be admitted to the ICU,” Dr. Elkrief noted.
Applying the findings to practice
The findings reinforce the importance of adherence to stringent infection control guidelines to protect vulnerable patients, such as those with cancer, Dr. Elkrief said.
In ambulatory settings, this means decreasing in-person visits through increased use of teleconsultations, and for those who need to be seen in person, screening for symptoms or use of polymerase chain reaction testing should be used when resources are available, she said.
“Similar principles apply to chemotherapy treatment units,” Dr. Elkrief said. She added that staff must avoid cross-contamination between COVID and COVID-free zones, and that “dedicated personnel and equipment should be maintained and separate between these two zones.
“Adequate protective personal equipment and strict hand hygiene protocols are also of utmost importance,” Dr. Elkrief said. “The threat of COVID-19 is not behind us, and so we continue to enforce these strategies to protect our patients.”
Session moderator Gypsyamber D’Souza, PhD, an infectious disease epidemiologist at Johns Hopkins University in Baltimore, raised the question of whether the high nosocomial infection and death rate in this study was related to patients having more severe disease because of underlying comorbidities.
Dr. Elkrief explained that the overall mortality rate was indeed higher than the 13% reported in other studies, and it may reflect an overrepresentation of hospitalized or more severely ill patients in the cohort.
However, the investigators made every effort to include all patients with both cancer and COVID-19 by using systematic screening of inpatient and outpatients lists and registries.
Further, the multivariate analysis included both inpatients and outpatients and adjusted for known negative prognostic factors for COVID-19 outcomes. These included increasing age, poor performance status, and different comorbidities.
The finding that nosocomial infection was an independent predictor of death “pushed us to look at nosocomial infection as a new independent risk factor,” Dr. Elkrief said.
Dr. Elkrief reported grant support from AstraZeneca. Dr. D’Souza did not report any disclosures.
SOURCE: Elkrief A et al. AACR: COVID and Cancer, Abstract S12-01.
FROM AACR: COVID-19 AND CANCER
Low vitamin D linked to increased COVID-19 risk
Low plasma vitamin D levels emerged as an independent risk factor for COVID-19 infection and hospitalization in a large, population-based study.
Participants positive for COVID-19 were 50% more likely to have low vs normal 25(OH)D levels in a multivariate analysis that controlled for other confounders, for example.
The take home message for physicians is to “test patients’ vitamin D levels and keep them optimal for the overall health – as well as for a better immunoresponse to COVID-19,” senior author Milana Frenkel-Morgenstern, PhD, head of the Cancer Genomics and BioComputing of Complex Diseases Lab at Bar-Ilan University in Ramat Gan, Israel, said in an interview.
The study was published online July 23 in The FEBS Journal.
Previous and ongoing studies are evaluating a potential role for vitamin D to prevent or minimize the severity of SARS-CoV-2 infection, building on years of research addressing vitamin D for other viral respiratory infections. The evidence to date regarding COVID-19, primarily observational studies, has yielded mixed results.
Multiple experts weighed in on the controversy in a previous report. Many point out the limitations of observational data, particularly when it comes to ruling out other factors that could affect the severity of COVID-19 infection. In addition, in a video report, JoAnn E. Manson, MD, DrPH, of Harvard Medical School in Boston, cited an observational study from three South Asian hospitals that found more severe COVID-19 patients had lower vitamin D levels, as well as other “compelling evidence” suggesting an association.
Dr. Frenkel-Morgenstern and colleagues studied data for 7,807 people, of whom 10.1% were COVID-19 positive. They assessed electronic health records for demographics, potential confounders, and outcomes between February 1 and April 30.
Participants positive for COVID-19 tended to be younger and were more likely to be men and live in a lower socioeconomic area, compared with the participants who were negative for COVID-19, in a univariate analysis.
Key findings
A higher proportion of COVID-19–positive patients had low plasma 25(OH)D concentrations, about 90% versus 85% of participants who were negative for COVID-19. The difference was statistically significant (P < .001). Furthermore, the increased likelihood for low vitamin D levels among those positive for COVID-19 held in a multivariate analysis that controlled for demographics and psychiatric and somatic disorders (adjusted odds ratio, 1.50). The difference remained statistically significant (P < .001).
The study also was noteworthy for what it did not find among participants with COVID-19. For example, the prevalence of dementia, cardiovascular disease, chronic lung disorders, and hypertension were significantly higher among the COVID-19 negative participants.
“Severe social contacts restrictions that were imposed on all the population and were even more emphasized in this highly vulnerable population” could explain these findings, the researchers noted.
“We assume that following the Israeli Ministry of Health instructions, patients with chronic medical conditions significantly reduced their social contacts” and thereby reduced their infection risk.
In contrast to previous reports, obesity was not a significant factor associated with increased likelihood for COVID-19 infection or hospitalization in the current study.
The researchers also linked low plasma 25(OH)D level to an increased likelihood of hospitalization for COVID-19 infection (crude OR, 2.09; P < .05).
After controlling for demographics and chronic disorders, the aOR decreased to 1.95 (P = .061) in a multivariate analysis. The only factor that remained statistically significant for hospitalization was age over 50 years (aOR, 2.71; P < .001).
Implications and future plans
The large number of participants and the “real world,” population-based design are strengths of the study. Considering potential confounders is another strength, the researchers noted. The retrospective database design was a limitation.
Going forward, Dr. Frenkel-Morgenstern and colleagues will “try to decipher the potential role of vitamin D in prevention and/or treatment of COVID-19” through three additional studies, she said. Also, they would like to conduct a meta-analysis to combine data from different countries to further explore the potential role of vitamin D in COVID-19.
“A compelling case”
“This is a strong study – large, adjusted for confounders, consistent with the biology and other clinical studies of vitamin D, infections, and COVID-19,” Wayne Jonas, MD, a practicing family physician and executive director of Samueli Integrative Health Programs, said in an interview.
Because the research was retrospective and observational, a causative link between vitamin D levels and COVID-19 risk cannot be interpreted from the findings. “That would need a prospective, randomized study,” said Dr. Jonas, who was not involved with the current study.
However, “the study makes a compelling case for possibly screening vitamin D levels for judging risk of COVID infection and hospitalization,” Dr. Jonas said, “and the compelling need for a large, randomized vitamin D supplement study to see if it can help prevent infection.”
“Given that vitamin D is largely safe, such a study could be done quickly and on healthy people with minimal risk for harm,” he added.
More confounders likely?
“I think the study is of interest,” Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow, who also was not affiliated with the research, said in an interview.
“Whilst the authors adjusted for some confounders, there is a strong potential for residual confounding,” said Dr. Sattar, a coauthor of a UK Biobank study that did not find an association between vitamin D stages and COVID-19 infection in multivariate models.
For example, Dr. Sattar said, “Robust adjustment for social class is important since both Vitamin D levels and COVID-19 severity are both strongly associated with social class.” Further, it remains unknown when and what time of year the vitamin D concentrations were measured in the current study.
“In the end, only a robust randomized trial can tell us whether vitamin D supplementation helps lessen COVID-19 severity,” Dr. Sattar added. “I am not hopeful we will find this is the case – but I am glad some such trials are [ongoing].”
Dr. Frenkel-Morgenstern received a COVID-19 Data Sciences Institute grant to support this work. Dr. Frenkel-Morgenstern, Dr. Jonas, and Dr. Sattar have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Low plasma vitamin D levels emerged as an independent risk factor for COVID-19 infection and hospitalization in a large, population-based study.
Participants positive for COVID-19 were 50% more likely to have low vs normal 25(OH)D levels in a multivariate analysis that controlled for other confounders, for example.
The take home message for physicians is to “test patients’ vitamin D levels and keep them optimal for the overall health – as well as for a better immunoresponse to COVID-19,” senior author Milana Frenkel-Morgenstern, PhD, head of the Cancer Genomics and BioComputing of Complex Diseases Lab at Bar-Ilan University in Ramat Gan, Israel, said in an interview.
The study was published online July 23 in The FEBS Journal.
Previous and ongoing studies are evaluating a potential role for vitamin D to prevent or minimize the severity of SARS-CoV-2 infection, building on years of research addressing vitamin D for other viral respiratory infections. The evidence to date regarding COVID-19, primarily observational studies, has yielded mixed results.
Multiple experts weighed in on the controversy in a previous report. Many point out the limitations of observational data, particularly when it comes to ruling out other factors that could affect the severity of COVID-19 infection. In addition, in a video report, JoAnn E. Manson, MD, DrPH, of Harvard Medical School in Boston, cited an observational study from three South Asian hospitals that found more severe COVID-19 patients had lower vitamin D levels, as well as other “compelling evidence” suggesting an association.
Dr. Frenkel-Morgenstern and colleagues studied data for 7,807 people, of whom 10.1% were COVID-19 positive. They assessed electronic health records for demographics, potential confounders, and outcomes between February 1 and April 30.
Participants positive for COVID-19 tended to be younger and were more likely to be men and live in a lower socioeconomic area, compared with the participants who were negative for COVID-19, in a univariate analysis.
Key findings
A higher proportion of COVID-19–positive patients had low plasma 25(OH)D concentrations, about 90% versus 85% of participants who were negative for COVID-19. The difference was statistically significant (P < .001). Furthermore, the increased likelihood for low vitamin D levels among those positive for COVID-19 held in a multivariate analysis that controlled for demographics and psychiatric and somatic disorders (adjusted odds ratio, 1.50). The difference remained statistically significant (P < .001).
The study also was noteworthy for what it did not find among participants with COVID-19. For example, the prevalence of dementia, cardiovascular disease, chronic lung disorders, and hypertension were significantly higher among the COVID-19 negative participants.
“Severe social contacts restrictions that were imposed on all the population and were even more emphasized in this highly vulnerable population” could explain these findings, the researchers noted.
“We assume that following the Israeli Ministry of Health instructions, patients with chronic medical conditions significantly reduced their social contacts” and thereby reduced their infection risk.
In contrast to previous reports, obesity was not a significant factor associated with increased likelihood for COVID-19 infection or hospitalization in the current study.
The researchers also linked low plasma 25(OH)D level to an increased likelihood of hospitalization for COVID-19 infection (crude OR, 2.09; P < .05).
After controlling for demographics and chronic disorders, the aOR decreased to 1.95 (P = .061) in a multivariate analysis. The only factor that remained statistically significant for hospitalization was age over 50 years (aOR, 2.71; P < .001).
Implications and future plans
The large number of participants and the “real world,” population-based design are strengths of the study. Considering potential confounders is another strength, the researchers noted. The retrospective database design was a limitation.
Going forward, Dr. Frenkel-Morgenstern and colleagues will “try to decipher the potential role of vitamin D in prevention and/or treatment of COVID-19” through three additional studies, she said. Also, they would like to conduct a meta-analysis to combine data from different countries to further explore the potential role of vitamin D in COVID-19.
“A compelling case”
“This is a strong study – large, adjusted for confounders, consistent with the biology and other clinical studies of vitamin D, infections, and COVID-19,” Wayne Jonas, MD, a practicing family physician and executive director of Samueli Integrative Health Programs, said in an interview.
Because the research was retrospective and observational, a causative link between vitamin D levels and COVID-19 risk cannot be interpreted from the findings. “That would need a prospective, randomized study,” said Dr. Jonas, who was not involved with the current study.
However, “the study makes a compelling case for possibly screening vitamin D levels for judging risk of COVID infection and hospitalization,” Dr. Jonas said, “and the compelling need for a large, randomized vitamin D supplement study to see if it can help prevent infection.”
“Given that vitamin D is largely safe, such a study could be done quickly and on healthy people with minimal risk for harm,” he added.
More confounders likely?
“I think the study is of interest,” Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow, who also was not affiliated with the research, said in an interview.
“Whilst the authors adjusted for some confounders, there is a strong potential for residual confounding,” said Dr. Sattar, a coauthor of a UK Biobank study that did not find an association between vitamin D stages and COVID-19 infection in multivariate models.
For example, Dr. Sattar said, “Robust adjustment for social class is important since both Vitamin D levels and COVID-19 severity are both strongly associated with social class.” Further, it remains unknown when and what time of year the vitamin D concentrations were measured in the current study.
“In the end, only a robust randomized trial can tell us whether vitamin D supplementation helps lessen COVID-19 severity,” Dr. Sattar added. “I am not hopeful we will find this is the case – but I am glad some such trials are [ongoing].”
Dr. Frenkel-Morgenstern received a COVID-19 Data Sciences Institute grant to support this work. Dr. Frenkel-Morgenstern, Dr. Jonas, and Dr. Sattar have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Low plasma vitamin D levels emerged as an independent risk factor for COVID-19 infection and hospitalization in a large, population-based study.
Participants positive for COVID-19 were 50% more likely to have low vs normal 25(OH)D levels in a multivariate analysis that controlled for other confounders, for example.
The take home message for physicians is to “test patients’ vitamin D levels and keep them optimal for the overall health – as well as for a better immunoresponse to COVID-19,” senior author Milana Frenkel-Morgenstern, PhD, head of the Cancer Genomics and BioComputing of Complex Diseases Lab at Bar-Ilan University in Ramat Gan, Israel, said in an interview.
The study was published online July 23 in The FEBS Journal.
Previous and ongoing studies are evaluating a potential role for vitamin D to prevent or minimize the severity of SARS-CoV-2 infection, building on years of research addressing vitamin D for other viral respiratory infections. The evidence to date regarding COVID-19, primarily observational studies, has yielded mixed results.
Multiple experts weighed in on the controversy in a previous report. Many point out the limitations of observational data, particularly when it comes to ruling out other factors that could affect the severity of COVID-19 infection. In addition, in a video report, JoAnn E. Manson, MD, DrPH, of Harvard Medical School in Boston, cited an observational study from three South Asian hospitals that found more severe COVID-19 patients had lower vitamin D levels, as well as other “compelling evidence” suggesting an association.
Dr. Frenkel-Morgenstern and colleagues studied data for 7,807 people, of whom 10.1% were COVID-19 positive. They assessed electronic health records for demographics, potential confounders, and outcomes between February 1 and April 30.
Participants positive for COVID-19 tended to be younger and were more likely to be men and live in a lower socioeconomic area, compared with the participants who were negative for COVID-19, in a univariate analysis.
Key findings
A higher proportion of COVID-19–positive patients had low plasma 25(OH)D concentrations, about 90% versus 85% of participants who were negative for COVID-19. The difference was statistically significant (P < .001). Furthermore, the increased likelihood for low vitamin D levels among those positive for COVID-19 held in a multivariate analysis that controlled for demographics and psychiatric and somatic disorders (adjusted odds ratio, 1.50). The difference remained statistically significant (P < .001).
The study also was noteworthy for what it did not find among participants with COVID-19. For example, the prevalence of dementia, cardiovascular disease, chronic lung disorders, and hypertension were significantly higher among the COVID-19 negative participants.
“Severe social contacts restrictions that were imposed on all the population and were even more emphasized in this highly vulnerable population” could explain these findings, the researchers noted.
“We assume that following the Israeli Ministry of Health instructions, patients with chronic medical conditions significantly reduced their social contacts” and thereby reduced their infection risk.
In contrast to previous reports, obesity was not a significant factor associated with increased likelihood for COVID-19 infection or hospitalization in the current study.
The researchers also linked low plasma 25(OH)D level to an increased likelihood of hospitalization for COVID-19 infection (crude OR, 2.09; P < .05).
After controlling for demographics and chronic disorders, the aOR decreased to 1.95 (P = .061) in a multivariate analysis. The only factor that remained statistically significant for hospitalization was age over 50 years (aOR, 2.71; P < .001).
Implications and future plans
The large number of participants and the “real world,” population-based design are strengths of the study. Considering potential confounders is another strength, the researchers noted. The retrospective database design was a limitation.
Going forward, Dr. Frenkel-Morgenstern and colleagues will “try to decipher the potential role of vitamin D in prevention and/or treatment of COVID-19” through three additional studies, she said. Also, they would like to conduct a meta-analysis to combine data from different countries to further explore the potential role of vitamin D in COVID-19.
“A compelling case”
“This is a strong study – large, adjusted for confounders, consistent with the biology and other clinical studies of vitamin D, infections, and COVID-19,” Wayne Jonas, MD, a practicing family physician and executive director of Samueli Integrative Health Programs, said in an interview.
Because the research was retrospective and observational, a causative link between vitamin D levels and COVID-19 risk cannot be interpreted from the findings. “That would need a prospective, randomized study,” said Dr. Jonas, who was not involved with the current study.
However, “the study makes a compelling case for possibly screening vitamin D levels for judging risk of COVID infection and hospitalization,” Dr. Jonas said, “and the compelling need for a large, randomized vitamin D supplement study to see if it can help prevent infection.”
“Given that vitamin D is largely safe, such a study could be done quickly and on healthy people with minimal risk for harm,” he added.
More confounders likely?
“I think the study is of interest,” Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow, who also was not affiliated with the research, said in an interview.
“Whilst the authors adjusted for some confounders, there is a strong potential for residual confounding,” said Dr. Sattar, a coauthor of a UK Biobank study that did not find an association between vitamin D stages and COVID-19 infection in multivariate models.
For example, Dr. Sattar said, “Robust adjustment for social class is important since both Vitamin D levels and COVID-19 severity are both strongly associated with social class.” Further, it remains unknown when and what time of year the vitamin D concentrations were measured in the current study.
“In the end, only a robust randomized trial can tell us whether vitamin D supplementation helps lessen COVID-19 severity,” Dr. Sattar added. “I am not hopeful we will find this is the case – but I am glad some such trials are [ongoing].”
Dr. Frenkel-Morgenstern received a COVID-19 Data Sciences Institute grant to support this work. Dr. Frenkel-Morgenstern, Dr. Jonas, and Dr. Sattar have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Sleepless in the pandemic
Sleep difficulties during the COVID-19 crisis may be exacerbated by media overexposure and other factors causing fear and stress, according to findings from a large survey of French individuals.
“Physicians usually recommend coping with sleep disorders by exercising, going outside, avoiding screen time, and having a regular schedule – all recommendations difficult to apply during lockdown. Being forced to stay home and the ensuing boredom and loneliness may have led to increased [media exposure], especially among disadvantaged people and overexposure to media COVID-19 content may have contributed to fright and emotional distress,” Damien Leger of the Centre du Sommeil et de la Vigilance, Hôtel Dieu APHP, Université de Paris, and his colleagues wrote in the journal Sleep.
The investigators analyzed data from survey respondents about their sleep problems since the COVID-19 lockdown and other topics such as employment, daily activities, and sleep medications. The survey was part of a large research project, COCONEL, that has been developed to study the French population on a variety of behaviors and comprises 750,000 permanent panelists who respond to surveys. The survey was sent to random sample of panelists with no topic label to avoid selection bias. Of the 25,800 surveys sent, 1,005 responses were recorded.
Respondents were classified as having severe sleep problems if they reported that their daytime activities were affected or if their sleeping medications had increased since the lockdown. While 73% of respondents reported poor sleep in the 8 previous days, 25% reported severe sleep problems, and 54% reported that their sleep problems had worsened during the COVID-19 lockdown.
A media exposure score was created with a Likert scale (strongly agree, agree, disagree, strongly disagree) about media exposures of different types. The investigators also queried respondents about the degree to which they found media coverage of the pandemic provoked a fear response. Overall, 68% of respondents agreed that media images and stories about COVD-19 were frightening.
The researchers found a strong association between severe sleeping problems and a high media exposure score (risk ratio, 1.49; 95% confidence interval, 1.10-2.01; P < .05).
In addition, trepidation and fear from media exposure to COVID-19 news were also associated with severe sleep problems (RR, 1.27; 95% CI, 0.92-1.75; P < .05). “Suffering from sleep problems may have increased media use at night, and thus increased stress and/or psychological distress and reinforced sleeping problems,” the investigators wrote.
Not surprisingly, respondents with financial difficulties due to the pandemic also reported severe sleeping difficulties (RR, 1.99; 95% CI, 1.49-2.65; P < .05).
For individuals who have been treated for sleep problems, the COVID-19 pandemic may ratchet up their sleep challenges. The strongest association with severe sleep problems was found in those respondents who were already taking sleeping medications before the pandemic (RR, 2.72; 95% CI, 2.04-3.61; P < .05).
The COCONEL survey has been funded by the French and National Agency for Research, the Fondation de France, and the National Research Institute for Sustainable Development.
SOURCE: Leger D et al. Sleep. 2020, Jul 25. doi: 10.1093/sleep/zsaa125.
Sleep difficulties during the COVID-19 crisis may be exacerbated by media overexposure and other factors causing fear and stress, according to findings from a large survey of French individuals.
“Physicians usually recommend coping with sleep disorders by exercising, going outside, avoiding screen time, and having a regular schedule – all recommendations difficult to apply during lockdown. Being forced to stay home and the ensuing boredom and loneliness may have led to increased [media exposure], especially among disadvantaged people and overexposure to media COVID-19 content may have contributed to fright and emotional distress,” Damien Leger of the Centre du Sommeil et de la Vigilance, Hôtel Dieu APHP, Université de Paris, and his colleagues wrote in the journal Sleep.
The investigators analyzed data from survey respondents about their sleep problems since the COVID-19 lockdown and other topics such as employment, daily activities, and sleep medications. The survey was part of a large research project, COCONEL, that has been developed to study the French population on a variety of behaviors and comprises 750,000 permanent panelists who respond to surveys. The survey was sent to random sample of panelists with no topic label to avoid selection bias. Of the 25,800 surveys sent, 1,005 responses were recorded.
Respondents were classified as having severe sleep problems if they reported that their daytime activities were affected or if their sleeping medications had increased since the lockdown. While 73% of respondents reported poor sleep in the 8 previous days, 25% reported severe sleep problems, and 54% reported that their sleep problems had worsened during the COVID-19 lockdown.
A media exposure score was created with a Likert scale (strongly agree, agree, disagree, strongly disagree) about media exposures of different types. The investigators also queried respondents about the degree to which they found media coverage of the pandemic provoked a fear response. Overall, 68% of respondents agreed that media images and stories about COVD-19 were frightening.
The researchers found a strong association between severe sleeping problems and a high media exposure score (risk ratio, 1.49; 95% confidence interval, 1.10-2.01; P < .05).
In addition, trepidation and fear from media exposure to COVID-19 news were also associated with severe sleep problems (RR, 1.27; 95% CI, 0.92-1.75; P < .05). “Suffering from sleep problems may have increased media use at night, and thus increased stress and/or psychological distress and reinforced sleeping problems,” the investigators wrote.
Not surprisingly, respondents with financial difficulties due to the pandemic also reported severe sleeping difficulties (RR, 1.99; 95% CI, 1.49-2.65; P < .05).
For individuals who have been treated for sleep problems, the COVID-19 pandemic may ratchet up their sleep challenges. The strongest association with severe sleep problems was found in those respondents who were already taking sleeping medications before the pandemic (RR, 2.72; 95% CI, 2.04-3.61; P < .05).
The COCONEL survey has been funded by the French and National Agency for Research, the Fondation de France, and the National Research Institute for Sustainable Development.
SOURCE: Leger D et al. Sleep. 2020, Jul 25. doi: 10.1093/sleep/zsaa125.
Sleep difficulties during the COVID-19 crisis may be exacerbated by media overexposure and other factors causing fear and stress, according to findings from a large survey of French individuals.
“Physicians usually recommend coping with sleep disorders by exercising, going outside, avoiding screen time, and having a regular schedule – all recommendations difficult to apply during lockdown. Being forced to stay home and the ensuing boredom and loneliness may have led to increased [media exposure], especially among disadvantaged people and overexposure to media COVID-19 content may have contributed to fright and emotional distress,” Damien Leger of the Centre du Sommeil et de la Vigilance, Hôtel Dieu APHP, Université de Paris, and his colleagues wrote in the journal Sleep.
The investigators analyzed data from survey respondents about their sleep problems since the COVID-19 lockdown and other topics such as employment, daily activities, and sleep medications. The survey was part of a large research project, COCONEL, that has been developed to study the French population on a variety of behaviors and comprises 750,000 permanent panelists who respond to surveys. The survey was sent to random sample of panelists with no topic label to avoid selection bias. Of the 25,800 surveys sent, 1,005 responses were recorded.
Respondents were classified as having severe sleep problems if they reported that their daytime activities were affected or if their sleeping medications had increased since the lockdown. While 73% of respondents reported poor sleep in the 8 previous days, 25% reported severe sleep problems, and 54% reported that their sleep problems had worsened during the COVID-19 lockdown.
A media exposure score was created with a Likert scale (strongly agree, agree, disagree, strongly disagree) about media exposures of different types. The investigators also queried respondents about the degree to which they found media coverage of the pandemic provoked a fear response. Overall, 68% of respondents agreed that media images and stories about COVD-19 were frightening.
The researchers found a strong association between severe sleeping problems and a high media exposure score (risk ratio, 1.49; 95% confidence interval, 1.10-2.01; P < .05).
In addition, trepidation and fear from media exposure to COVID-19 news were also associated with severe sleep problems (RR, 1.27; 95% CI, 0.92-1.75; P < .05). “Suffering from sleep problems may have increased media use at night, and thus increased stress and/or psychological distress and reinforced sleeping problems,” the investigators wrote.
Not surprisingly, respondents with financial difficulties due to the pandemic also reported severe sleeping difficulties (RR, 1.99; 95% CI, 1.49-2.65; P < .05).
For individuals who have been treated for sleep problems, the COVID-19 pandemic may ratchet up their sleep challenges. The strongest association with severe sleep problems was found in those respondents who were already taking sleeping medications before the pandemic (RR, 2.72; 95% CI, 2.04-3.61; P < .05).
The COCONEL survey has been funded by the French and National Agency for Research, the Fondation de France, and the National Research Institute for Sustainable Development.
SOURCE: Leger D et al. Sleep. 2020, Jul 25. doi: 10.1093/sleep/zsaa125.
FROM SLEEP
Experimental blood test detects cancer years before symptoms
A blood test that may be able to detect cancer years before any symptoms appear is under development. The PanSeer assay, which detects methylation markers in blood, was used in healthy individuals and successfully detected five cancer types in 91% of samples from individuals who were diagnosed with cancer 1 to 4 years later.
“We can’t say for sure that the patients didn’t have any symptoms, but we detected the cancer years before they ever walked into the hospital,” said study author Kun Zhang, PhD, a professor of bioengineering at the University of California, San Diego. “We were also able to follow up with patients, so we actually knew that they had cancer.”
Zhang noted that they also followed the individuals whose tests indicated they were cancer free. “They were healthy at the time the samples were obtained, and they remained healthy,” he said. “Follow-up was key to validating these data.”
The PanSeer test is being developed by Singlera Genomics. Zhang is a cofounder and a paid consultant of the company.
The study was published online July 21 in Nature Communications.
Unique among tests
Several blood tests for the detection of cancer have been reported in recent years. A test developed by Grail was able to detect more than 50 types of cancer and also identified the tissues where the cancer originated. The CancerSEEK test identified eight common cancers by measuring circulating tumor DNA from 16 genes, as well as eight protein biomarkers.
Findings regarding the CellMax Life FirstSight blood test were released last month. The test detected all 11 cases of colorectal cancer in a cohort of 354 patients and detected 40 of 53 advanced adenomas.
The latest study with the PanSeer assay is unique, say the investigators, because they had access to blood samples from patients who may have been completely asymptomatic and had not yet been diagnosed with cancer. Other blood tests have typically involved the use of specimens from people with a known diagnosis.
The specimens were collected as part of a 10-year longitudinal study that began in 2007 in China. Zhang and his team were able to test blood samples before individuals had experienced any signs or symptoms of cancer, and they were able to conduct long-term follow-up of the cohort.
Study details
The PanSeer assay uses DNA methylation analysis and screens for a DNA signature called CpG methylation. The results of an early-stage proof-of-concept study were published 3 years ago (Nat Genet. 2017;49:635–642).
For the current study, data were drawn from the Taizhou Longitudinal Study, which included 123,115 individuals aged 25 to 90 years who provided blood samples for long-term storage from 2007 to 2014. Participants were monitored indefinitely for cancer occurrence using local cancer registries and health insurance databases.
The team identified 575 individuals who were initially asymptomatic and healthy but were subsequently diagnosed with one of five common cancer types (stomach, esophagus, colorectum, lung, or liver cancer) within 4 years of their initial blood sampling. The authors selected these five cancer types to study because the incidence rates of these cancers in this population are high and, taken together, account for the highest mortality.
The study design allowed the authors to evaluate specimens both from patients with cancer and from those who were healthy within the same cohort. Using 191 prediagnosis samples, 223 postdiagnosis samples, and 414 healthy samples, they created a training set and validation model.
A machine learning method was created to classify samples as being either from healthy individuals or from those with cancer, using blood samples from the training set. The final classifier achieved 88% sensitivity for postdiagnosis samples and 91% sensitivity for prediagnosis samples at a specificity of 95%.
Zhang feels that initially it would be more appropriate to use the test for high-risk patients and to then evaluate the clinical benefit. “For any test, it is always more prudent to begin with a high-risk population,” he said. “You want to see some benefit with the high-risk population first, and then it can slowly be extended to others at lower risk.”
He emphasized that more rigorous testing is needing before the PanSeer assay is ready for clinical use. The logistics of designing and conducting a clinical trial that would include more than one cancer type would be very complicated. “The option was to break it down to five different studies,” he said. “We decided to begin with colon cancer, and we are currently in the process of talking with the FDA and designing the study.”
High bar to reach
Approached for comment, Benjamin Weinberg, MD, assistant professor of medicine, Division of Hematology and Oncology, the Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, noted that there is “quite a ways to go before this can be clinically actionable.
“A lot of us are looking at combining methylation with circulating tumor DNA and throw the kitchen sink at it, but as the paper nicely describes, there are pros and cons to all of these,” he said.
Many tests of this type are in development. Weinberg explained that a circulating tumor DNA test for colon cancer may hit the market soon, pending FDA approval, although that test will be used in a different setting. “This is something that’s used to assess for minimal residual disease in patients who have undergone surgery and appear to be ‘cured’ of the disease,” he said. “The test is looking to see if there is any circulating tumor DNA being shed from whatever tumor is left behind.”
The type of test that has piqued the most interest is one that is “tumor informed,” meaning that the company receives tumor tissue and develops a personalized test of that tumor on the basis of tumor genetics. “That is a very targeted way of surveillance,” said Weinberg, “But it would be very difficult to use a tumor-informed test on the population described in this study because you don’t know if there is going to be a tumor or not.”
The PanSeer test may also prove difficult to use in the clinic because it detects multiple cancers, Weinberg said. “If there is a positive finding, then which cancer do you look for?” he commented. “It has an issue in that regard, and that’s the problem with this type of test, as it is easier if there is one site of origin.”
Overall, the test was fairly sensitive and specific, with a very low false negative rate. Going forward, he noted, there is a very high bar for tests used as screening tools, although the authors do say that their focus is for use in a high-risk population.
“There would have to be a randomized trial, and the test will have to show a survival benefit,” Weinberg said. He noted that it can sometimes be challenging to do so.
“Colonoscopy has been shown to be beneficial, but early mammography has become controversial, and prostate cancer is a whole different animal,” he added. “And these are established tests, and they show how difficult this can be.”
The Taizhou Longitudinal Study study was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Key Basic Research grants from the Science and Technology Commission of Shanghai Municipality, the International S&T Cooperation Program of China, the Municipal Science and Technology Major Project program, the International Science and Technology Cooperation Program of China, and the 111 Project (B13016). Funding for the DNA methylation assays was provided by Singlera Genomics. Zhang is a cofounder, equity holder, and paid consultant of Singlera Genomics, a company that is developing early cancer detection tests, including the PanSeer test. Weinberg is a speaker or a member of a speakers bureau for Taiho Pharmaceutical Co Ltd, Bayer HealthCare Pharmaceuticals, and Eli Lilly and Company; has received research grant from Novartis Pharmaceuticals Corporation; and has received travel reimbursement from Caris Life Sciences.
This article first appeared on Medscape.com.
A blood test that may be able to detect cancer years before any symptoms appear is under development. The PanSeer assay, which detects methylation markers in blood, was used in healthy individuals and successfully detected five cancer types in 91% of samples from individuals who were diagnosed with cancer 1 to 4 years later.
“We can’t say for sure that the patients didn’t have any symptoms, but we detected the cancer years before they ever walked into the hospital,” said study author Kun Zhang, PhD, a professor of bioengineering at the University of California, San Diego. “We were also able to follow up with patients, so we actually knew that they had cancer.”
Zhang noted that they also followed the individuals whose tests indicated they were cancer free. “They were healthy at the time the samples were obtained, and they remained healthy,” he said. “Follow-up was key to validating these data.”
The PanSeer test is being developed by Singlera Genomics. Zhang is a cofounder and a paid consultant of the company.
The study was published online July 21 in Nature Communications.
Unique among tests
Several blood tests for the detection of cancer have been reported in recent years. A test developed by Grail was able to detect more than 50 types of cancer and also identified the tissues where the cancer originated. The CancerSEEK test identified eight common cancers by measuring circulating tumor DNA from 16 genes, as well as eight protein biomarkers.
Findings regarding the CellMax Life FirstSight blood test were released last month. The test detected all 11 cases of colorectal cancer in a cohort of 354 patients and detected 40 of 53 advanced adenomas.
The latest study with the PanSeer assay is unique, say the investigators, because they had access to blood samples from patients who may have been completely asymptomatic and had not yet been diagnosed with cancer. Other blood tests have typically involved the use of specimens from people with a known diagnosis.
The specimens were collected as part of a 10-year longitudinal study that began in 2007 in China. Zhang and his team were able to test blood samples before individuals had experienced any signs or symptoms of cancer, and they were able to conduct long-term follow-up of the cohort.
Study details
The PanSeer assay uses DNA methylation analysis and screens for a DNA signature called CpG methylation. The results of an early-stage proof-of-concept study were published 3 years ago (Nat Genet. 2017;49:635–642).
For the current study, data were drawn from the Taizhou Longitudinal Study, which included 123,115 individuals aged 25 to 90 years who provided blood samples for long-term storage from 2007 to 2014. Participants were monitored indefinitely for cancer occurrence using local cancer registries and health insurance databases.
The team identified 575 individuals who were initially asymptomatic and healthy but were subsequently diagnosed with one of five common cancer types (stomach, esophagus, colorectum, lung, or liver cancer) within 4 years of their initial blood sampling. The authors selected these five cancer types to study because the incidence rates of these cancers in this population are high and, taken together, account for the highest mortality.
The study design allowed the authors to evaluate specimens both from patients with cancer and from those who were healthy within the same cohort. Using 191 prediagnosis samples, 223 postdiagnosis samples, and 414 healthy samples, they created a training set and validation model.
A machine learning method was created to classify samples as being either from healthy individuals or from those with cancer, using blood samples from the training set. The final classifier achieved 88% sensitivity for postdiagnosis samples and 91% sensitivity for prediagnosis samples at a specificity of 95%.
Zhang feels that initially it would be more appropriate to use the test for high-risk patients and to then evaluate the clinical benefit. “For any test, it is always more prudent to begin with a high-risk population,” he said. “You want to see some benefit with the high-risk population first, and then it can slowly be extended to others at lower risk.”
He emphasized that more rigorous testing is needing before the PanSeer assay is ready for clinical use. The logistics of designing and conducting a clinical trial that would include more than one cancer type would be very complicated. “The option was to break it down to five different studies,” he said. “We decided to begin with colon cancer, and we are currently in the process of talking with the FDA and designing the study.”
High bar to reach
Approached for comment, Benjamin Weinberg, MD, assistant professor of medicine, Division of Hematology and Oncology, the Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, noted that there is “quite a ways to go before this can be clinically actionable.
“A lot of us are looking at combining methylation with circulating tumor DNA and throw the kitchen sink at it, but as the paper nicely describes, there are pros and cons to all of these,” he said.
Many tests of this type are in development. Weinberg explained that a circulating tumor DNA test for colon cancer may hit the market soon, pending FDA approval, although that test will be used in a different setting. “This is something that’s used to assess for minimal residual disease in patients who have undergone surgery and appear to be ‘cured’ of the disease,” he said. “The test is looking to see if there is any circulating tumor DNA being shed from whatever tumor is left behind.”
The type of test that has piqued the most interest is one that is “tumor informed,” meaning that the company receives tumor tissue and develops a personalized test of that tumor on the basis of tumor genetics. “That is a very targeted way of surveillance,” said Weinberg, “But it would be very difficult to use a tumor-informed test on the population described in this study because you don’t know if there is going to be a tumor or not.”
The PanSeer test may also prove difficult to use in the clinic because it detects multiple cancers, Weinberg said. “If there is a positive finding, then which cancer do you look for?” he commented. “It has an issue in that regard, and that’s the problem with this type of test, as it is easier if there is one site of origin.”
Overall, the test was fairly sensitive and specific, with a very low false negative rate. Going forward, he noted, there is a very high bar for tests used as screening tools, although the authors do say that their focus is for use in a high-risk population.
“There would have to be a randomized trial, and the test will have to show a survival benefit,” Weinberg said. He noted that it can sometimes be challenging to do so.
“Colonoscopy has been shown to be beneficial, but early mammography has become controversial, and prostate cancer is a whole different animal,” he added. “And these are established tests, and they show how difficult this can be.”
The Taizhou Longitudinal Study study was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Key Basic Research grants from the Science and Technology Commission of Shanghai Municipality, the International S&T Cooperation Program of China, the Municipal Science and Technology Major Project program, the International Science and Technology Cooperation Program of China, and the 111 Project (B13016). Funding for the DNA methylation assays was provided by Singlera Genomics. Zhang is a cofounder, equity holder, and paid consultant of Singlera Genomics, a company that is developing early cancer detection tests, including the PanSeer test. Weinberg is a speaker or a member of a speakers bureau for Taiho Pharmaceutical Co Ltd, Bayer HealthCare Pharmaceuticals, and Eli Lilly and Company; has received research grant from Novartis Pharmaceuticals Corporation; and has received travel reimbursement from Caris Life Sciences.
This article first appeared on Medscape.com.
A blood test that may be able to detect cancer years before any symptoms appear is under development. The PanSeer assay, which detects methylation markers in blood, was used in healthy individuals and successfully detected five cancer types in 91% of samples from individuals who were diagnosed with cancer 1 to 4 years later.
“We can’t say for sure that the patients didn’t have any symptoms, but we detected the cancer years before they ever walked into the hospital,” said study author Kun Zhang, PhD, a professor of bioengineering at the University of California, San Diego. “We were also able to follow up with patients, so we actually knew that they had cancer.”
Zhang noted that they also followed the individuals whose tests indicated they were cancer free. “They were healthy at the time the samples were obtained, and they remained healthy,” he said. “Follow-up was key to validating these data.”
The PanSeer test is being developed by Singlera Genomics. Zhang is a cofounder and a paid consultant of the company.
The study was published online July 21 in Nature Communications.
Unique among tests
Several blood tests for the detection of cancer have been reported in recent years. A test developed by Grail was able to detect more than 50 types of cancer and also identified the tissues where the cancer originated. The CancerSEEK test identified eight common cancers by measuring circulating tumor DNA from 16 genes, as well as eight protein biomarkers.
Findings regarding the CellMax Life FirstSight blood test were released last month. The test detected all 11 cases of colorectal cancer in a cohort of 354 patients and detected 40 of 53 advanced adenomas.
The latest study with the PanSeer assay is unique, say the investigators, because they had access to blood samples from patients who may have been completely asymptomatic and had not yet been diagnosed with cancer. Other blood tests have typically involved the use of specimens from people with a known diagnosis.
The specimens were collected as part of a 10-year longitudinal study that began in 2007 in China. Zhang and his team were able to test blood samples before individuals had experienced any signs or symptoms of cancer, and they were able to conduct long-term follow-up of the cohort.
Study details
The PanSeer assay uses DNA methylation analysis and screens for a DNA signature called CpG methylation. The results of an early-stage proof-of-concept study were published 3 years ago (Nat Genet. 2017;49:635–642).
For the current study, data were drawn from the Taizhou Longitudinal Study, which included 123,115 individuals aged 25 to 90 years who provided blood samples for long-term storage from 2007 to 2014. Participants were monitored indefinitely for cancer occurrence using local cancer registries and health insurance databases.
The team identified 575 individuals who were initially asymptomatic and healthy but were subsequently diagnosed with one of five common cancer types (stomach, esophagus, colorectum, lung, or liver cancer) within 4 years of their initial blood sampling. The authors selected these five cancer types to study because the incidence rates of these cancers in this population are high and, taken together, account for the highest mortality.
The study design allowed the authors to evaluate specimens both from patients with cancer and from those who were healthy within the same cohort. Using 191 prediagnosis samples, 223 postdiagnosis samples, and 414 healthy samples, they created a training set and validation model.
A machine learning method was created to classify samples as being either from healthy individuals or from those with cancer, using blood samples from the training set. The final classifier achieved 88% sensitivity for postdiagnosis samples and 91% sensitivity for prediagnosis samples at a specificity of 95%.
Zhang feels that initially it would be more appropriate to use the test for high-risk patients and to then evaluate the clinical benefit. “For any test, it is always more prudent to begin with a high-risk population,” he said. “You want to see some benefit with the high-risk population first, and then it can slowly be extended to others at lower risk.”
He emphasized that more rigorous testing is needing before the PanSeer assay is ready for clinical use. The logistics of designing and conducting a clinical trial that would include more than one cancer type would be very complicated. “The option was to break it down to five different studies,” he said. “We decided to begin with colon cancer, and we are currently in the process of talking with the FDA and designing the study.”
High bar to reach
Approached for comment, Benjamin Weinberg, MD, assistant professor of medicine, Division of Hematology and Oncology, the Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, noted that there is “quite a ways to go before this can be clinically actionable.
“A lot of us are looking at combining methylation with circulating tumor DNA and throw the kitchen sink at it, but as the paper nicely describes, there are pros and cons to all of these,” he said.
Many tests of this type are in development. Weinberg explained that a circulating tumor DNA test for colon cancer may hit the market soon, pending FDA approval, although that test will be used in a different setting. “This is something that’s used to assess for minimal residual disease in patients who have undergone surgery and appear to be ‘cured’ of the disease,” he said. “The test is looking to see if there is any circulating tumor DNA being shed from whatever tumor is left behind.”
The type of test that has piqued the most interest is one that is “tumor informed,” meaning that the company receives tumor tissue and develops a personalized test of that tumor on the basis of tumor genetics. “That is a very targeted way of surveillance,” said Weinberg, “But it would be very difficult to use a tumor-informed test on the population described in this study because you don’t know if there is going to be a tumor or not.”
The PanSeer test may also prove difficult to use in the clinic because it detects multiple cancers, Weinberg said. “If there is a positive finding, then which cancer do you look for?” he commented. “It has an issue in that regard, and that’s the problem with this type of test, as it is easier if there is one site of origin.”
Overall, the test was fairly sensitive and specific, with a very low false negative rate. Going forward, he noted, there is a very high bar for tests used as screening tools, although the authors do say that their focus is for use in a high-risk population.
“There would have to be a randomized trial, and the test will have to show a survival benefit,” Weinberg said. He noted that it can sometimes be challenging to do so.
“Colonoscopy has been shown to be beneficial, but early mammography has become controversial, and prostate cancer is a whole different animal,” he added. “And these are established tests, and they show how difficult this can be.”
The Taizhou Longitudinal Study study was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Key Basic Research grants from the Science and Technology Commission of Shanghai Municipality, the International S&T Cooperation Program of China, the Municipal Science and Technology Major Project program, the International Science and Technology Cooperation Program of China, and the 111 Project (B13016). Funding for the DNA methylation assays was provided by Singlera Genomics. Zhang is a cofounder, equity holder, and paid consultant of Singlera Genomics, a company that is developing early cancer detection tests, including the PanSeer test. Weinberg is a speaker or a member of a speakers bureau for Taiho Pharmaceutical Co Ltd, Bayer HealthCare Pharmaceuticals, and Eli Lilly and Company; has received research grant from Novartis Pharmaceuticals Corporation; and has received travel reimbursement from Caris Life Sciences.
This article first appeared on Medscape.com.
Real-world data show SGLT2 inhibitors for diabetes triple DKA risk
according to a new large database analysis.
The findings, which include data on the use of three different SGLT2 inhibitors in Canada and the United Kingdom and suggest a class effect, were published online July 27 in Annals of Internal Medicine by Antonios Douros, MD, PhD, of McGill University and the Centre for Clinical Epidemiology, Lady Davis Institute, Montreal, and colleagues.
“Our results provide robust evidence that SGLT2 inhibitors are associated with an increased risk for DKA. Of note, increased risks were observed in all molecule-specific analyses, with canagliflozin [Invokana, Janssen] showing the highest effect estimate,” they noted.
And because the beneficial effects of SGLT2 inhibitors in the prevention of cardiovascular and renal disease will probably increase their uptake in the coming years, “Physicians should be aware of DKA as a potential adverse effect,” Dr. Douros and colleagues wrote.
Analysis “generally confirms what has already been published”
Asked for comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, said that the study “generally confirms what has already been published” on the topic. He noted that overall “the risk of SGLT2 inhibitor–induced ketoacidosis is quite low in type 2 diabetes, perhaps on the order of 1 episode per 1000 patient-years.”
However, Dr. Taylor cautioned: “Published evidence suggests that the risk of DKA is increased if patients are unable to eat,” such as when hospitalized patients are not permitted to eat.
“In that setting, it is probably prudent to discontinue an SGLT2 inhibitor. Also, it may be prudent not to prescribe SGLT2 inhibitors to patients with a history of DKA,” he added.
Dr. Taylor also advised: “Although not necessarily supported by this publication, I think that caution should be exercised in prescribing SGLT2 inhibitors to insulin-dependent type 2 diabetes patients. ... Some late-stage type 2 diabetes patients may have severe insulin deficiency, and their physiology may resemble that of a type 1 diabetes patient.”
Dr. Taylor has previously advised against using SGLT2 inhibitors altogether in patients with type 1 diabetes.
Increased DKA risk seen across all SGLT2 inhibitors
The study involved electronic health care databases from seven Canadian provinces and the United Kingdom, from which 208,757 new users of SGLT2 inhibitors were propensity-matched 1:1 to new dipeptidyl peptidase-4 (DPP-4) inhibitor users.
Of those taking an SGLT2 inhibitor, 42.3% took canagliflozin, 30.7% dapagliflozin (Farxiga/Forxiga, AstraZeneca), and 27.0% empagliflozin (Jardiance, Boehringer Ingelheim).
Over a mean 0.9-year follow-up, 521 patients were hospitalized with DKA, for an overall incidence rate of 1.41 per 1,000 person-years.
The rate with SGLT2 inhibitors, 2.03 per 1,000 person-years, was nearly three times that seen with DPP-4 inhibitors, at 0.75 per 1,000 person-years, a significant difference (hazard ratio, 2.85).
By individual SGLT2 inhibitor, the hazard ratios compared with DPP-4 inhibitors were 1.86 for dapagliflozin, 2.52 for empagliflozin, and 3.58 for canagliflozin, all statistically significant. Stratification by age, sex, and incident versus prevalent user did not change the association between SGLT2 inhibitors and DKA.
Asked about the higher rate for canagliflozin, Dr. Taylor commented: “It is hard to know whether there are real and reproducible differences in the risks of DKA among the various SGLT2 inhibitors. The differences are not huge and the populations are not well matched.”
But, he noted, “If canagliflozin triggers more glucosuria, it is not surprising that it would also induce more ketosis and possibly ketoacidosis.”
He also noted that the threefold relative increase in DKA with canagliflozin versus comparators is consistent with Janssen’s data, published in 2015.
“It is, of course, reassuring that both [randomized clinical trials] and epidemiology produce similar estimates of the risk of drug-induced adverse events. Interestingly, the incidence of DKA is approximately threefold higher in the Canadian [data] as compared to Janssen’s clinical trials.”
Dr. Taylor also pointed out that, in the Janssen studies, the risk of canagliflozin-induced DKA appeared to be higher among patients with anti-islet antibodies, which suggests that some may have actually had autoimmune (type 1) diabetes. “So the overall risk of SGLT2 inhibitor-induced DKA may depend at least in part on the mix of patients.”
In the current study, individuals who never used insulin had a greater relative increase in risk of DKA with SGLT2 inhibitors, compared with DPP-4 inhibitors, than did those who did use insulin (hazard ratios, 3.96 vs. 2.24, both compared with DPP-4 inhibitors). However, just among those taking SGLT2 inhibitors, the absolute risk for DKA was higher for those with prior insulin use (3.52 vs. 1.43 per 1,000 person-years).
The results of sensitivity analyses were consistent with those of the primary analysis.
The study was funded by the Canadian Institutes of Health Research and supported by ICES. Dr. Douros has reported receiving a salary support award from Fonds de recherche du Quebec – sante. Dr. Taylor was previously employed at Bristol-Myers Squibb. He is currently a consultant for Ionis Pharmaceuticals and has reported receiving research support provided to the University of Maryland School of Medicine by Regeneron.
A version of this article originally appeared on Medscape.com.
according to a new large database analysis.
The findings, which include data on the use of three different SGLT2 inhibitors in Canada and the United Kingdom and suggest a class effect, were published online July 27 in Annals of Internal Medicine by Antonios Douros, MD, PhD, of McGill University and the Centre for Clinical Epidemiology, Lady Davis Institute, Montreal, and colleagues.
“Our results provide robust evidence that SGLT2 inhibitors are associated with an increased risk for DKA. Of note, increased risks were observed in all molecule-specific analyses, with canagliflozin [Invokana, Janssen] showing the highest effect estimate,” they noted.
And because the beneficial effects of SGLT2 inhibitors in the prevention of cardiovascular and renal disease will probably increase their uptake in the coming years, “Physicians should be aware of DKA as a potential adverse effect,” Dr. Douros and colleagues wrote.
Analysis “generally confirms what has already been published”
Asked for comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, said that the study “generally confirms what has already been published” on the topic. He noted that overall “the risk of SGLT2 inhibitor–induced ketoacidosis is quite low in type 2 diabetes, perhaps on the order of 1 episode per 1000 patient-years.”
However, Dr. Taylor cautioned: “Published evidence suggests that the risk of DKA is increased if patients are unable to eat,” such as when hospitalized patients are not permitted to eat.
“In that setting, it is probably prudent to discontinue an SGLT2 inhibitor. Also, it may be prudent not to prescribe SGLT2 inhibitors to patients with a history of DKA,” he added.
Dr. Taylor also advised: “Although not necessarily supported by this publication, I think that caution should be exercised in prescribing SGLT2 inhibitors to insulin-dependent type 2 diabetes patients. ... Some late-stage type 2 diabetes patients may have severe insulin deficiency, and their physiology may resemble that of a type 1 diabetes patient.”
Dr. Taylor has previously advised against using SGLT2 inhibitors altogether in patients with type 1 diabetes.
Increased DKA risk seen across all SGLT2 inhibitors
The study involved electronic health care databases from seven Canadian provinces and the United Kingdom, from which 208,757 new users of SGLT2 inhibitors were propensity-matched 1:1 to new dipeptidyl peptidase-4 (DPP-4) inhibitor users.
Of those taking an SGLT2 inhibitor, 42.3% took canagliflozin, 30.7% dapagliflozin (Farxiga/Forxiga, AstraZeneca), and 27.0% empagliflozin (Jardiance, Boehringer Ingelheim).
Over a mean 0.9-year follow-up, 521 patients were hospitalized with DKA, for an overall incidence rate of 1.41 per 1,000 person-years.
The rate with SGLT2 inhibitors, 2.03 per 1,000 person-years, was nearly three times that seen with DPP-4 inhibitors, at 0.75 per 1,000 person-years, a significant difference (hazard ratio, 2.85).
By individual SGLT2 inhibitor, the hazard ratios compared with DPP-4 inhibitors were 1.86 for dapagliflozin, 2.52 for empagliflozin, and 3.58 for canagliflozin, all statistically significant. Stratification by age, sex, and incident versus prevalent user did not change the association between SGLT2 inhibitors and DKA.
Asked about the higher rate for canagliflozin, Dr. Taylor commented: “It is hard to know whether there are real and reproducible differences in the risks of DKA among the various SGLT2 inhibitors. The differences are not huge and the populations are not well matched.”
But, he noted, “If canagliflozin triggers more glucosuria, it is not surprising that it would also induce more ketosis and possibly ketoacidosis.”
He also noted that the threefold relative increase in DKA with canagliflozin versus comparators is consistent with Janssen’s data, published in 2015.
“It is, of course, reassuring that both [randomized clinical trials] and epidemiology produce similar estimates of the risk of drug-induced adverse events. Interestingly, the incidence of DKA is approximately threefold higher in the Canadian [data] as compared to Janssen’s clinical trials.”
Dr. Taylor also pointed out that, in the Janssen studies, the risk of canagliflozin-induced DKA appeared to be higher among patients with anti-islet antibodies, which suggests that some may have actually had autoimmune (type 1) diabetes. “So the overall risk of SGLT2 inhibitor-induced DKA may depend at least in part on the mix of patients.”
In the current study, individuals who never used insulin had a greater relative increase in risk of DKA with SGLT2 inhibitors, compared with DPP-4 inhibitors, than did those who did use insulin (hazard ratios, 3.96 vs. 2.24, both compared with DPP-4 inhibitors). However, just among those taking SGLT2 inhibitors, the absolute risk for DKA was higher for those with prior insulin use (3.52 vs. 1.43 per 1,000 person-years).
The results of sensitivity analyses were consistent with those of the primary analysis.
The study was funded by the Canadian Institutes of Health Research and supported by ICES. Dr. Douros has reported receiving a salary support award from Fonds de recherche du Quebec – sante. Dr. Taylor was previously employed at Bristol-Myers Squibb. He is currently a consultant for Ionis Pharmaceuticals and has reported receiving research support provided to the University of Maryland School of Medicine by Regeneron.
A version of this article originally appeared on Medscape.com.
according to a new large database analysis.
The findings, which include data on the use of three different SGLT2 inhibitors in Canada and the United Kingdom and suggest a class effect, were published online July 27 in Annals of Internal Medicine by Antonios Douros, MD, PhD, of McGill University and the Centre for Clinical Epidemiology, Lady Davis Institute, Montreal, and colleagues.
“Our results provide robust evidence that SGLT2 inhibitors are associated with an increased risk for DKA. Of note, increased risks were observed in all molecule-specific analyses, with canagliflozin [Invokana, Janssen] showing the highest effect estimate,” they noted.
And because the beneficial effects of SGLT2 inhibitors in the prevention of cardiovascular and renal disease will probably increase their uptake in the coming years, “Physicians should be aware of DKA as a potential adverse effect,” Dr. Douros and colleagues wrote.
Analysis “generally confirms what has already been published”
Asked for comment, Simeon I. Taylor, MD, PhD, professor of medicine at the University of Maryland, Baltimore, said that the study “generally confirms what has already been published” on the topic. He noted that overall “the risk of SGLT2 inhibitor–induced ketoacidosis is quite low in type 2 diabetes, perhaps on the order of 1 episode per 1000 patient-years.”
However, Dr. Taylor cautioned: “Published evidence suggests that the risk of DKA is increased if patients are unable to eat,” such as when hospitalized patients are not permitted to eat.
“In that setting, it is probably prudent to discontinue an SGLT2 inhibitor. Also, it may be prudent not to prescribe SGLT2 inhibitors to patients with a history of DKA,” he added.
Dr. Taylor also advised: “Although not necessarily supported by this publication, I think that caution should be exercised in prescribing SGLT2 inhibitors to insulin-dependent type 2 diabetes patients. ... Some late-stage type 2 diabetes patients may have severe insulin deficiency, and their physiology may resemble that of a type 1 diabetes patient.”
Dr. Taylor has previously advised against using SGLT2 inhibitors altogether in patients with type 1 diabetes.
Increased DKA risk seen across all SGLT2 inhibitors
The study involved electronic health care databases from seven Canadian provinces and the United Kingdom, from which 208,757 new users of SGLT2 inhibitors were propensity-matched 1:1 to new dipeptidyl peptidase-4 (DPP-4) inhibitor users.
Of those taking an SGLT2 inhibitor, 42.3% took canagliflozin, 30.7% dapagliflozin (Farxiga/Forxiga, AstraZeneca), and 27.0% empagliflozin (Jardiance, Boehringer Ingelheim).
Over a mean 0.9-year follow-up, 521 patients were hospitalized with DKA, for an overall incidence rate of 1.41 per 1,000 person-years.
The rate with SGLT2 inhibitors, 2.03 per 1,000 person-years, was nearly three times that seen with DPP-4 inhibitors, at 0.75 per 1,000 person-years, a significant difference (hazard ratio, 2.85).
By individual SGLT2 inhibitor, the hazard ratios compared with DPP-4 inhibitors were 1.86 for dapagliflozin, 2.52 for empagliflozin, and 3.58 for canagliflozin, all statistically significant. Stratification by age, sex, and incident versus prevalent user did not change the association between SGLT2 inhibitors and DKA.
Asked about the higher rate for canagliflozin, Dr. Taylor commented: “It is hard to know whether there are real and reproducible differences in the risks of DKA among the various SGLT2 inhibitors. The differences are not huge and the populations are not well matched.”
But, he noted, “If canagliflozin triggers more glucosuria, it is not surprising that it would also induce more ketosis and possibly ketoacidosis.”
He also noted that the threefold relative increase in DKA with canagliflozin versus comparators is consistent with Janssen’s data, published in 2015.
“It is, of course, reassuring that both [randomized clinical trials] and epidemiology produce similar estimates of the risk of drug-induced adverse events. Interestingly, the incidence of DKA is approximately threefold higher in the Canadian [data] as compared to Janssen’s clinical trials.”
Dr. Taylor also pointed out that, in the Janssen studies, the risk of canagliflozin-induced DKA appeared to be higher among patients with anti-islet antibodies, which suggests that some may have actually had autoimmune (type 1) diabetes. “So the overall risk of SGLT2 inhibitor-induced DKA may depend at least in part on the mix of patients.”
In the current study, individuals who never used insulin had a greater relative increase in risk of DKA with SGLT2 inhibitors, compared with DPP-4 inhibitors, than did those who did use insulin (hazard ratios, 3.96 vs. 2.24, both compared with DPP-4 inhibitors). However, just among those taking SGLT2 inhibitors, the absolute risk for DKA was higher for those with prior insulin use (3.52 vs. 1.43 per 1,000 person-years).
The results of sensitivity analyses were consistent with those of the primary analysis.
The study was funded by the Canadian Institutes of Health Research and supported by ICES. Dr. Douros has reported receiving a salary support award from Fonds de recherche du Quebec – sante. Dr. Taylor was previously employed at Bristol-Myers Squibb. He is currently a consultant for Ionis Pharmaceuticals and has reported receiving research support provided to the University of Maryland School of Medicine by Regeneron.
A version of this article originally appeared on Medscape.com.
MIS-C is a serious immune-mediated response to COVID-19 infection
One of the take-away messages from a review of multisystem inflammatory syndrome in children (MIS-C) is that clinicians treating this condition “need to be comfortable with uncertainty,” Melissa Hazen, MD, said at a synthesis of multiple published case series and personal experience summarized at the virtual Pediatric Hospital Medicine meeting.
She emphasized MIS-C patient care “requires flexibility,” and she advised clinicians managing these patients to open the lines of communication with the many specialists who often are required to deal with complications affecting an array of organ systems.
MIS-C might best be understood as the most serious manifestation of an immune-mediated response to COVID-19 infection that ranges from transient mild symptoms to the life-threatening multiple organ involvement that characterizes this newly recognized threat. Although “most children who encounter this pathogen only develop mild disease,” the spectrum of the disease can move in a subset of patients to a “Kawasaki-like illness” without hemodynamic instability and then to MIS-C “with highly elevated systemic inflammatory markers and multiple organ involvement,” explained Dr. Hazen, an attending physician in the rheumatology program at Boston Children’s Hospital.
most of which have only recently reached publication, according to Dr. Hazen. In general, the description of the most common symptoms and their course has been relatively consistent.
In 186 cases of MIS-C collected in a study funded by the Centers for Disease Control and Prevention, 148 (80%) were admitted to intensive care, 90 patients (48%) received vasoactive support, 37 (20%) received mechanical ventilation, and 4 (2%) died.1 The median age was 8 years (range, 3-13 years) in this study. The case definition was fever for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of COVID-19 infection. In this cohort of 186 children, 92% had gastrointestinal, 80% had cardiovascular, 76% had hematologic, and 70% had respiratory system involvement.
In a different series of 95 cases collected in New York State, 79 (80%) were admitted to intensive care, 61 (62%) received vasoactive support, 10 (10%) received mechanical ventilation, 4 (4%) received extracorporeal membrane oxygenation (ECMO), and 2 (2%) died. 2 Thirty-one percent patients were aged 0-5 years, 42% were 6-12 years, and 26% were 13-20 years of age. In that series, for which the case definition was elevation of two or more inflammatory markers, virologic evidence of COVID-19 infection, 80% had gastrointestinal system involvement, and 53% had evidence of myocarditis.
In both of these series, as well as others published and unpublished, the peak in MIS-C cases has occurred about 3 to 4 weeks after peak COVID-19 activity, according to Diana Lee, MD, a pediatrician at Icahn School of Medicine at Mount Sinai, New York. This pattern, reported by others, was observed in New York State, where 230 cases of MIS-C were collected from the beginning of May until the end of June, which reflected this 3- to 4-week delay in peak incidence.
“This does seem to be a rare syndrome since this [group of] 230 cases is amongst the entire population of children in New York State. So, yes, we should be keeping this in mind in our differential, but we should not forget all the other reasons that children can have a fever,” she said.
Both Dr. Hazen and Dr. Lee cautioned that MIS-C, despite a general consistency among published studies, remains a moving target in regard to how it is being characterized. In a 2-day period in May, the CDC, the World Health Organization, and New York State all issued descriptions of MIS-C, employing compatible but slightly different terminology and diagnostic criteria. Many questions regarding optimal methods of diagnosis, treatment, and follow-up remain unanswered.
Questions regarding the risk to the cardiovascular system, one of the organs most commonly affected in MIS-C, are among the most urgent. It is not now clear how best to monitor cardiovascular involvement, how to intervene, and how to follow patients in the postinfection period, according to Kevin G. Friedman, MD, a pediatrician at Harvard Medical School, Boston, and an attending physician in the department of cardiology at Boston Children’s Hospital.
“The most frequent complication we have seen is ventricular dysfunction, which occurs in about half of these patients,” he reported. “Usually it is in the mild to moderate range, but occasionally patients have an ejection fraction of less than 40%.”
Coronary abnormalities, typically in the form of dilations or small aneurysms, occur in 10%-20% of children with MIS-C, according to Dr. Friedman. Giant aneurysms have been reported.
“Some of these findings can progress including in both the acute phase and, particularly for the coronary aneurysms, in the subacute phase. We recommend echocardiograms and EKGs at diagnosis and at 1-2 weeks to recheck coronary size or sooner if there are clinical indications,” Dr. Friedman advised.
Protocols like these are constantly under review as more information becomes available. There are as yet no guidelines, and practice differs across institutions, according to the investigators summarizing this information.
None of the speakers had any relevant financial disclosures.
References
1. Feldstein LR et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383:334-46.
2. Dufort EM et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med 2020;383:347-58.
One of the take-away messages from a review of multisystem inflammatory syndrome in children (MIS-C) is that clinicians treating this condition “need to be comfortable with uncertainty,” Melissa Hazen, MD, said at a synthesis of multiple published case series and personal experience summarized at the virtual Pediatric Hospital Medicine meeting.
She emphasized MIS-C patient care “requires flexibility,” and she advised clinicians managing these patients to open the lines of communication with the many specialists who often are required to deal with complications affecting an array of organ systems.
MIS-C might best be understood as the most serious manifestation of an immune-mediated response to COVID-19 infection that ranges from transient mild symptoms to the life-threatening multiple organ involvement that characterizes this newly recognized threat. Although “most children who encounter this pathogen only develop mild disease,” the spectrum of the disease can move in a subset of patients to a “Kawasaki-like illness” without hemodynamic instability and then to MIS-C “with highly elevated systemic inflammatory markers and multiple organ involvement,” explained Dr. Hazen, an attending physician in the rheumatology program at Boston Children’s Hospital.
most of which have only recently reached publication, according to Dr. Hazen. In general, the description of the most common symptoms and their course has been relatively consistent.
In 186 cases of MIS-C collected in a study funded by the Centers for Disease Control and Prevention, 148 (80%) were admitted to intensive care, 90 patients (48%) received vasoactive support, 37 (20%) received mechanical ventilation, and 4 (2%) died.1 The median age was 8 years (range, 3-13 years) in this study. The case definition was fever for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of COVID-19 infection. In this cohort of 186 children, 92% had gastrointestinal, 80% had cardiovascular, 76% had hematologic, and 70% had respiratory system involvement.
In a different series of 95 cases collected in New York State, 79 (80%) were admitted to intensive care, 61 (62%) received vasoactive support, 10 (10%) received mechanical ventilation, 4 (4%) received extracorporeal membrane oxygenation (ECMO), and 2 (2%) died. 2 Thirty-one percent patients were aged 0-5 years, 42% were 6-12 years, and 26% were 13-20 years of age. In that series, for which the case definition was elevation of two or more inflammatory markers, virologic evidence of COVID-19 infection, 80% had gastrointestinal system involvement, and 53% had evidence of myocarditis.
In both of these series, as well as others published and unpublished, the peak in MIS-C cases has occurred about 3 to 4 weeks after peak COVID-19 activity, according to Diana Lee, MD, a pediatrician at Icahn School of Medicine at Mount Sinai, New York. This pattern, reported by others, was observed in New York State, where 230 cases of MIS-C were collected from the beginning of May until the end of June, which reflected this 3- to 4-week delay in peak incidence.
“This does seem to be a rare syndrome since this [group of] 230 cases is amongst the entire population of children in New York State. So, yes, we should be keeping this in mind in our differential, but we should not forget all the other reasons that children can have a fever,” she said.
Both Dr. Hazen and Dr. Lee cautioned that MIS-C, despite a general consistency among published studies, remains a moving target in regard to how it is being characterized. In a 2-day period in May, the CDC, the World Health Organization, and New York State all issued descriptions of MIS-C, employing compatible but slightly different terminology and diagnostic criteria. Many questions regarding optimal methods of diagnosis, treatment, and follow-up remain unanswered.
Questions regarding the risk to the cardiovascular system, one of the organs most commonly affected in MIS-C, are among the most urgent. It is not now clear how best to monitor cardiovascular involvement, how to intervene, and how to follow patients in the postinfection period, according to Kevin G. Friedman, MD, a pediatrician at Harvard Medical School, Boston, and an attending physician in the department of cardiology at Boston Children’s Hospital.
“The most frequent complication we have seen is ventricular dysfunction, which occurs in about half of these patients,” he reported. “Usually it is in the mild to moderate range, but occasionally patients have an ejection fraction of less than 40%.”
Coronary abnormalities, typically in the form of dilations or small aneurysms, occur in 10%-20% of children with MIS-C, according to Dr. Friedman. Giant aneurysms have been reported.
“Some of these findings can progress including in both the acute phase and, particularly for the coronary aneurysms, in the subacute phase. We recommend echocardiograms and EKGs at diagnosis and at 1-2 weeks to recheck coronary size or sooner if there are clinical indications,” Dr. Friedman advised.
Protocols like these are constantly under review as more information becomes available. There are as yet no guidelines, and practice differs across institutions, according to the investigators summarizing this information.
None of the speakers had any relevant financial disclosures.
References
1. Feldstein LR et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383:334-46.
2. Dufort EM et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med 2020;383:347-58.
One of the take-away messages from a review of multisystem inflammatory syndrome in children (MIS-C) is that clinicians treating this condition “need to be comfortable with uncertainty,” Melissa Hazen, MD, said at a synthesis of multiple published case series and personal experience summarized at the virtual Pediatric Hospital Medicine meeting.
She emphasized MIS-C patient care “requires flexibility,” and she advised clinicians managing these patients to open the lines of communication with the many specialists who often are required to deal with complications affecting an array of organ systems.
MIS-C might best be understood as the most serious manifestation of an immune-mediated response to COVID-19 infection that ranges from transient mild symptoms to the life-threatening multiple organ involvement that characterizes this newly recognized threat. Although “most children who encounter this pathogen only develop mild disease,” the spectrum of the disease can move in a subset of patients to a “Kawasaki-like illness” without hemodynamic instability and then to MIS-C “with highly elevated systemic inflammatory markers and multiple organ involvement,” explained Dr. Hazen, an attending physician in the rheumatology program at Boston Children’s Hospital.
most of which have only recently reached publication, according to Dr. Hazen. In general, the description of the most common symptoms and their course has been relatively consistent.
In 186 cases of MIS-C collected in a study funded by the Centers for Disease Control and Prevention, 148 (80%) were admitted to intensive care, 90 patients (48%) received vasoactive support, 37 (20%) received mechanical ventilation, and 4 (2%) died.1 The median age was 8 years (range, 3-13 years) in this study. The case definition was fever for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of COVID-19 infection. In this cohort of 186 children, 92% had gastrointestinal, 80% had cardiovascular, 76% had hematologic, and 70% had respiratory system involvement.
In a different series of 95 cases collected in New York State, 79 (80%) were admitted to intensive care, 61 (62%) received vasoactive support, 10 (10%) received mechanical ventilation, 4 (4%) received extracorporeal membrane oxygenation (ECMO), and 2 (2%) died. 2 Thirty-one percent patients were aged 0-5 years, 42% were 6-12 years, and 26% were 13-20 years of age. In that series, for which the case definition was elevation of two or more inflammatory markers, virologic evidence of COVID-19 infection, 80% had gastrointestinal system involvement, and 53% had evidence of myocarditis.
In both of these series, as well as others published and unpublished, the peak in MIS-C cases has occurred about 3 to 4 weeks after peak COVID-19 activity, according to Diana Lee, MD, a pediatrician at Icahn School of Medicine at Mount Sinai, New York. This pattern, reported by others, was observed in New York State, where 230 cases of MIS-C were collected from the beginning of May until the end of June, which reflected this 3- to 4-week delay in peak incidence.
“This does seem to be a rare syndrome since this [group of] 230 cases is amongst the entire population of children in New York State. So, yes, we should be keeping this in mind in our differential, but we should not forget all the other reasons that children can have a fever,” she said.
Both Dr. Hazen and Dr. Lee cautioned that MIS-C, despite a general consistency among published studies, remains a moving target in regard to how it is being characterized. In a 2-day period in May, the CDC, the World Health Organization, and New York State all issued descriptions of MIS-C, employing compatible but slightly different terminology and diagnostic criteria. Many questions regarding optimal methods of diagnosis, treatment, and follow-up remain unanswered.
Questions regarding the risk to the cardiovascular system, one of the organs most commonly affected in MIS-C, are among the most urgent. It is not now clear how best to monitor cardiovascular involvement, how to intervene, and how to follow patients in the postinfection period, according to Kevin G. Friedman, MD, a pediatrician at Harvard Medical School, Boston, and an attending physician in the department of cardiology at Boston Children’s Hospital.
“The most frequent complication we have seen is ventricular dysfunction, which occurs in about half of these patients,” he reported. “Usually it is in the mild to moderate range, but occasionally patients have an ejection fraction of less than 40%.”
Coronary abnormalities, typically in the form of dilations or small aneurysms, occur in 10%-20% of children with MIS-C, according to Dr. Friedman. Giant aneurysms have been reported.
“Some of these findings can progress including in both the acute phase and, particularly for the coronary aneurysms, in the subacute phase. We recommend echocardiograms and EKGs at diagnosis and at 1-2 weeks to recheck coronary size or sooner if there are clinical indications,” Dr. Friedman advised.
Protocols like these are constantly under review as more information becomes available. There are as yet no guidelines, and practice differs across institutions, according to the investigators summarizing this information.
None of the speakers had any relevant financial disclosures.
References
1. Feldstein LR et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383:334-46.
2. Dufort EM et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med 2020;383:347-58.
FROM PHM20 VIRTUAL
Physician recruitment drops by 30% because of pandemic
the firm reported.
“Rather than having many practice opportunities to choose from, physicians now may have to compete to secure practice opportunities that meet their needs,” the authors wrote in Merritt Hawkins’ report on the impact of COVID-19.
Most of the report concerns physician recruitment from April 1, 2019, to March 31, 2020. The data were mostly derived from searches that Merritt Hawkins conducted before the effects of the pandemic was fully felt.
Family medicine was again the most sought-after specialty, as it has been for the past 14 years. But demand for primary care doctors – including family physicians, internists, and pediatricians – leveled off, and average starting salaries for primary care doctors dropped during 2019-2020. In contrast, the number of searches conducted for nurse practitioners (NPs) and physician assistants (PAs) increased by 54%, and their salaries increased slightly.
To explain the lackluster prospects for primary care before the pandemic, the authors cited research showing that patients were turning away from the traditional office visit model. At the same time, there was a rise in visits to NPs and PAs, including those in urgent care centers and retail clinics.
As a result of decreased demand for primary care physicians and the rising prevalence of telehealth, Merritt Hawkins expects primary care salaries to drop overall. With telehealth generating a larger portion of revenues, “it is uncertain whether primary care physicians will be able to sustain levels of reimbursement that were prevalent pre-COVID even at such time as the economy is improved and utilization increases,” the authors reported.
Demand for specialists was increasing prior to the COVID-19 crisis, partly as a result of the aging of the population. Seventy-eight percent of all searches were for medical specialists, compared with 67% 5 years ago. However, the pandemic has set back specialist searches. “Demand and compensation for specialists also will change as a result of COVID-19 in response to declines in the volume of medical procedures,” according to the authors.
In contrast, the recruitment of doctors who are on the front line of COVID-19 care is expected to increase. Among the fields anticipated to be in demand are emergency department specialists, infectious disease specialists, and pulmonology/critical care physicians. Travis Singleton, executive vice president of Merritt Hawkins, said in an interview that this trend is already happening and will accelerate as COVID-19 hot spots arise across the country.
Specialists in different fields received either higher or lower offers than during the previous year. Starting salaries for noninvasive cardiologists, for example, dropped 7.3%; gastroenterologists earned 7.7% less; and neurologists, 6.9% less. In contrast, orthopedic surgeons saw offers surge 16.7%; radiologists, 9.3%; and pulmonologists/critical care specialists, 7.7%.
Physicians were offered salaries plus bonuses in three-quarters of searches. Relative value unit–based production remained the most common basis for bonuses. Quality/value-based metrics were used in computing 64% of bonuses – up from 56% the previous year – but still determined only 11% of total physician compensation.
Pandemic outlook
Whereas health care helped drive the U.S. economy in 2018-2019, the pace of job growth in health care has decreased since March. As a result of the pandemic, health care spending in the United States declined by 18% in the first quarter of 2020. Physician practice revenue dropped by 55% during the first quarter, and many small and solo practices are still struggling.
In a 2018 Merritt Hawkins survey, 18% of physicians said they had used telehealth to treat patients. Because of the pandemic, that percentage jumped to 48% in April 2020. But telehealth hasn’t made up for the loss of patient revenue from in-office procedures, tests, and other services, and it still isn’t being reimbursed at the same level as in-office visits.
With practices under severe financial strain, the authors explained, “A majority of private practices have curtailed most physician recruiting activity since the virus emerged.”
In some states, many specialty practices have been adversely affected by the suspension of elective procedures, and specialty practices that rely on nonessential procedures are unlikely to recruit additional physicians.
One-third of practices could close
The survival of many private practices is now in question. “Based on the losses physician practices have sustained as a result of COVID-19, some markets could lose up to 35% or more of their most vulnerable group practices while a large percent of others will be acquired,” the authors wrote.
Hospitals and health systems will acquire the bulk of these practices, in many cases at fire-sale prices, Mr. Singleton predicted. This enormous shift from private practice to employment, he added, “will have as much to do with the [physician] income levels we’re going to see as the demand for the specialties themselves.”
Right now, he said, Merritt Hawkins is fielding a huge number of requests from doctors seeking employment, but there aren’t many jobs out there. “We haven’t seen an employer-friendly market like this since the 1970s,” he noted. “Before the pandemic, a physician might have had five to 10 jobs to choose from. Now it’s the opposite: We have one job, and 5 to 10 physicians are applying for it.”
Singleton believes the market will adjust by the second quarter of next year. Even if the pandemic worsens, he said, the system will have made the necessary corrections and adjustments “because we have to start seeing patients again, both in terms of demand and economics. So these doctors will be in demand again and will have work.”
Contingent employment
Although the COVID-related falloff in revenue has hit private practices the hardest, some employed physicians have also found themselves in a bind. According to a Merritt Hawkins/Physicians Foundation survey conducted in April, 21% of physicians said they had been furloughed or had taken a pay cut.
Mr. Singleton views this trend as part of hospitals’ reassessment of how they’re going to deal with labor going forward. To cope with utilization ebbs and flows in response to the virus, hospitals are now considering what the report calls a “contingent labor/flex staffing model.”
Under this type of arrangement, which some hospitals have already adopted, physicians may no longer work full time in a single setting, Mr. Singleton said. They may be asked to conduct telehealth visits on nights and weekends and work 20 hours a week in the clinic, or they may have shifts in multiple hospitals or clinics.
“You can make as much or more on a temporary basis as on a permanent basis,” he said. “But you have to be more flexible. You may have to travel or do a different scope of work, or work in different settings.”
A version of this article originally appeared on Medscape.com.
the firm reported.
“Rather than having many practice opportunities to choose from, physicians now may have to compete to secure practice opportunities that meet their needs,” the authors wrote in Merritt Hawkins’ report on the impact of COVID-19.
Most of the report concerns physician recruitment from April 1, 2019, to March 31, 2020. The data were mostly derived from searches that Merritt Hawkins conducted before the effects of the pandemic was fully felt.
Family medicine was again the most sought-after specialty, as it has been for the past 14 years. But demand for primary care doctors – including family physicians, internists, and pediatricians – leveled off, and average starting salaries for primary care doctors dropped during 2019-2020. In contrast, the number of searches conducted for nurse practitioners (NPs) and physician assistants (PAs) increased by 54%, and their salaries increased slightly.
To explain the lackluster prospects for primary care before the pandemic, the authors cited research showing that patients were turning away from the traditional office visit model. At the same time, there was a rise in visits to NPs and PAs, including those in urgent care centers and retail clinics.
As a result of decreased demand for primary care physicians and the rising prevalence of telehealth, Merritt Hawkins expects primary care salaries to drop overall. With telehealth generating a larger portion of revenues, “it is uncertain whether primary care physicians will be able to sustain levels of reimbursement that were prevalent pre-COVID even at such time as the economy is improved and utilization increases,” the authors reported.
Demand for specialists was increasing prior to the COVID-19 crisis, partly as a result of the aging of the population. Seventy-eight percent of all searches were for medical specialists, compared with 67% 5 years ago. However, the pandemic has set back specialist searches. “Demand and compensation for specialists also will change as a result of COVID-19 in response to declines in the volume of medical procedures,” according to the authors.
In contrast, the recruitment of doctors who are on the front line of COVID-19 care is expected to increase. Among the fields anticipated to be in demand are emergency department specialists, infectious disease specialists, and pulmonology/critical care physicians. Travis Singleton, executive vice president of Merritt Hawkins, said in an interview that this trend is already happening and will accelerate as COVID-19 hot spots arise across the country.
Specialists in different fields received either higher or lower offers than during the previous year. Starting salaries for noninvasive cardiologists, for example, dropped 7.3%; gastroenterologists earned 7.7% less; and neurologists, 6.9% less. In contrast, orthopedic surgeons saw offers surge 16.7%; radiologists, 9.3%; and pulmonologists/critical care specialists, 7.7%.
Physicians were offered salaries plus bonuses in three-quarters of searches. Relative value unit–based production remained the most common basis for bonuses. Quality/value-based metrics were used in computing 64% of bonuses – up from 56% the previous year – but still determined only 11% of total physician compensation.
Pandemic outlook
Whereas health care helped drive the U.S. economy in 2018-2019, the pace of job growth in health care has decreased since March. As a result of the pandemic, health care spending in the United States declined by 18% in the first quarter of 2020. Physician practice revenue dropped by 55% during the first quarter, and many small and solo practices are still struggling.
In a 2018 Merritt Hawkins survey, 18% of physicians said they had used telehealth to treat patients. Because of the pandemic, that percentage jumped to 48% in April 2020. But telehealth hasn’t made up for the loss of patient revenue from in-office procedures, tests, and other services, and it still isn’t being reimbursed at the same level as in-office visits.
With practices under severe financial strain, the authors explained, “A majority of private practices have curtailed most physician recruiting activity since the virus emerged.”
In some states, many specialty practices have been adversely affected by the suspension of elective procedures, and specialty practices that rely on nonessential procedures are unlikely to recruit additional physicians.
One-third of practices could close
The survival of many private practices is now in question. “Based on the losses physician practices have sustained as a result of COVID-19, some markets could lose up to 35% or more of their most vulnerable group practices while a large percent of others will be acquired,” the authors wrote.
Hospitals and health systems will acquire the bulk of these practices, in many cases at fire-sale prices, Mr. Singleton predicted. This enormous shift from private practice to employment, he added, “will have as much to do with the [physician] income levels we’re going to see as the demand for the specialties themselves.”
Right now, he said, Merritt Hawkins is fielding a huge number of requests from doctors seeking employment, but there aren’t many jobs out there. “We haven’t seen an employer-friendly market like this since the 1970s,” he noted. “Before the pandemic, a physician might have had five to 10 jobs to choose from. Now it’s the opposite: We have one job, and 5 to 10 physicians are applying for it.”
Singleton believes the market will adjust by the second quarter of next year. Even if the pandemic worsens, he said, the system will have made the necessary corrections and adjustments “because we have to start seeing patients again, both in terms of demand and economics. So these doctors will be in demand again and will have work.”
Contingent employment
Although the COVID-related falloff in revenue has hit private practices the hardest, some employed physicians have also found themselves in a bind. According to a Merritt Hawkins/Physicians Foundation survey conducted in April, 21% of physicians said they had been furloughed or had taken a pay cut.
Mr. Singleton views this trend as part of hospitals’ reassessment of how they’re going to deal with labor going forward. To cope with utilization ebbs and flows in response to the virus, hospitals are now considering what the report calls a “contingent labor/flex staffing model.”
Under this type of arrangement, which some hospitals have already adopted, physicians may no longer work full time in a single setting, Mr. Singleton said. They may be asked to conduct telehealth visits on nights and weekends and work 20 hours a week in the clinic, or they may have shifts in multiple hospitals or clinics.
“You can make as much or more on a temporary basis as on a permanent basis,” he said. “But you have to be more flexible. You may have to travel or do a different scope of work, or work in different settings.”
A version of this article originally appeared on Medscape.com.
the firm reported.
“Rather than having many practice opportunities to choose from, physicians now may have to compete to secure practice opportunities that meet their needs,” the authors wrote in Merritt Hawkins’ report on the impact of COVID-19.
Most of the report concerns physician recruitment from April 1, 2019, to March 31, 2020. The data were mostly derived from searches that Merritt Hawkins conducted before the effects of the pandemic was fully felt.
Family medicine was again the most sought-after specialty, as it has been for the past 14 years. But demand for primary care doctors – including family physicians, internists, and pediatricians – leveled off, and average starting salaries for primary care doctors dropped during 2019-2020. In contrast, the number of searches conducted for nurse practitioners (NPs) and physician assistants (PAs) increased by 54%, and their salaries increased slightly.
To explain the lackluster prospects for primary care before the pandemic, the authors cited research showing that patients were turning away from the traditional office visit model. At the same time, there was a rise in visits to NPs and PAs, including those in urgent care centers and retail clinics.
As a result of decreased demand for primary care physicians and the rising prevalence of telehealth, Merritt Hawkins expects primary care salaries to drop overall. With telehealth generating a larger portion of revenues, “it is uncertain whether primary care physicians will be able to sustain levels of reimbursement that were prevalent pre-COVID even at such time as the economy is improved and utilization increases,” the authors reported.
Demand for specialists was increasing prior to the COVID-19 crisis, partly as a result of the aging of the population. Seventy-eight percent of all searches were for medical specialists, compared with 67% 5 years ago. However, the pandemic has set back specialist searches. “Demand and compensation for specialists also will change as a result of COVID-19 in response to declines in the volume of medical procedures,” according to the authors.
In contrast, the recruitment of doctors who are on the front line of COVID-19 care is expected to increase. Among the fields anticipated to be in demand are emergency department specialists, infectious disease specialists, and pulmonology/critical care physicians. Travis Singleton, executive vice president of Merritt Hawkins, said in an interview that this trend is already happening and will accelerate as COVID-19 hot spots arise across the country.
Specialists in different fields received either higher or lower offers than during the previous year. Starting salaries for noninvasive cardiologists, for example, dropped 7.3%; gastroenterologists earned 7.7% less; and neurologists, 6.9% less. In contrast, orthopedic surgeons saw offers surge 16.7%; radiologists, 9.3%; and pulmonologists/critical care specialists, 7.7%.
Physicians were offered salaries plus bonuses in three-quarters of searches. Relative value unit–based production remained the most common basis for bonuses. Quality/value-based metrics were used in computing 64% of bonuses – up from 56% the previous year – but still determined only 11% of total physician compensation.
Pandemic outlook
Whereas health care helped drive the U.S. economy in 2018-2019, the pace of job growth in health care has decreased since March. As a result of the pandemic, health care spending in the United States declined by 18% in the first quarter of 2020. Physician practice revenue dropped by 55% during the first quarter, and many small and solo practices are still struggling.
In a 2018 Merritt Hawkins survey, 18% of physicians said they had used telehealth to treat patients. Because of the pandemic, that percentage jumped to 48% in April 2020. But telehealth hasn’t made up for the loss of patient revenue from in-office procedures, tests, and other services, and it still isn’t being reimbursed at the same level as in-office visits.
With practices under severe financial strain, the authors explained, “A majority of private practices have curtailed most physician recruiting activity since the virus emerged.”
In some states, many specialty practices have been adversely affected by the suspension of elective procedures, and specialty practices that rely on nonessential procedures are unlikely to recruit additional physicians.
One-third of practices could close
The survival of many private practices is now in question. “Based on the losses physician practices have sustained as a result of COVID-19, some markets could lose up to 35% or more of their most vulnerable group practices while a large percent of others will be acquired,” the authors wrote.
Hospitals and health systems will acquire the bulk of these practices, in many cases at fire-sale prices, Mr. Singleton predicted. This enormous shift from private practice to employment, he added, “will have as much to do with the [physician] income levels we’re going to see as the demand for the specialties themselves.”
Right now, he said, Merritt Hawkins is fielding a huge number of requests from doctors seeking employment, but there aren’t many jobs out there. “We haven’t seen an employer-friendly market like this since the 1970s,” he noted. “Before the pandemic, a physician might have had five to 10 jobs to choose from. Now it’s the opposite: We have one job, and 5 to 10 physicians are applying for it.”
Singleton believes the market will adjust by the second quarter of next year. Even if the pandemic worsens, he said, the system will have made the necessary corrections and adjustments “because we have to start seeing patients again, both in terms of demand and economics. So these doctors will be in demand again and will have work.”
Contingent employment
Although the COVID-related falloff in revenue has hit private practices the hardest, some employed physicians have also found themselves in a bind. According to a Merritt Hawkins/Physicians Foundation survey conducted in April, 21% of physicians said they had been furloughed or had taken a pay cut.
Mr. Singleton views this trend as part of hospitals’ reassessment of how they’re going to deal with labor going forward. To cope with utilization ebbs and flows in response to the virus, hospitals are now considering what the report calls a “contingent labor/flex staffing model.”
Under this type of arrangement, which some hospitals have already adopted, physicians may no longer work full time in a single setting, Mr. Singleton said. They may be asked to conduct telehealth visits on nights and weekends and work 20 hours a week in the clinic, or they may have shifts in multiple hospitals or clinics.
“You can make as much or more on a temporary basis as on a permanent basis,” he said. “But you have to be more flexible. You may have to travel or do a different scope of work, or work in different settings.”
A version of this article originally appeared on Medscape.com.