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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
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
More U.S. cardiologists opting for larger practices
U.S. cardiologists are increasingly opting out of solo or small practices, and joining larger practices, according to a new analysis of U.S. data from 2013 and 2017.
In 2013, 34.2% of U.S. cardiologists worked in practices of five or fewer cardiologists. That number dropped to 27% by 2017. On the flip side, the proportion working in practices with 25 cardiologists or more rose from 26% in 2013 to 35.8% in 2017.
“This is a trend we’re seeing across health care – hospitals are merging and they’re acquiring physician practices, primary care doctors are joining larger practices, too – so to some extent it seems that cardiologists are just responding to changes in the market structure where they practice,” said Jose F. Figueroa, MD, MPH, of Harvard T.H. Chan School of Public Health and Brigham & Women’s Hospital, Boston.
Dr. Figueroa and colleagues published their findings as a research brief for the Aug. 4 issue of the Journal of the American College of Cardiology.
The average number of cardiologists in practice together rose from 3.6 in 2013 to 4.3 in 2017. This trend was less obvious in rural areas (2.05 to 2.20) than in urban areas (3.67 to 4.38).
The smallest change was seen in the mid-size practice tier. In 2013, 22.9% of cardiologists worked in a practice that included 11 to 24 cardiologists, and in 2017, the proportion was 23.2%.
To determine practices sizes, Dr. Figueroa and colleagues used publicly available data from 2013 and 2017 from the Centers for Medicare & Medicaid Services’ Physician Compare, a website that helps patients find and compare clinicians and groups enrolled in Medicare.
Market level variables were obtained from the Dartmouth Atlas Project, which uses CMS data to provide information and analysis about national, regional, and local health care markets, as well as hospitals and their affiliated physicians.
Market forces drive practice patterns
The investigators had no direct data from which to ascertain the reasons why cardiologists have tended to move from smaller to larger practices, but they did conduct a multivariable linear regression analysis to better understand possible market-level factors that may be influencing these trends.
What they found was that as hospital market concentration increased, practice sizes also increased. They found no association between any community-level and physician-level factors and changes in practice size.
So, for example, greater growth in the number of cardiologists in practice together was not associated with age or sex.
“It seems that cardiologists are responding to changes in the market structure where they practice, and in particular, to hospital market concentration. This is all in an effort basically to have more market power, which in part means better bargaining power when they’re negotiating with payers,” said Dr. Figueroa.
He also suggested that joining a large practice is almost a necessity these days given the administrative burdens imposed by value-based care initiatives and their attendant quality measure reporting.
“There are stringent requirements for electronic health records and a huge administrative burden related to requirements to ensure compliance and report on quality measures,” said Dr. Figueroa.
“And then there are also all of these new ‘alternative payment’ models to figure out, like accountable care organizations and bundled payments, so you can imagine that if you’re a solo practitioner, it would be really hard to manage all of these details yourself and still ensure you’re taking care of your patient.
“As a cardiologist you need to invest in a bunch of resources, including a workforce to help you manage all the quality measures and keeping track of patients, ensuring they all get their blood pressures checked on time, etc.,” he said.
Anecdotally, Dr. Figueroa suggests it’s also a quality-of-life decision for many cardiologists. “In terms of physician burnout, when you’re a solo practitioner or in a small practice, it’s really hard to go on vacation and find coverage.”
Larry Sobal, MBA, MHA, the CEO of the Heart and Vascular Institute of Wisconsin, agrees that this consolidation is in large part a reflection of the trend toward consolidation seen across the healthcare system.
“This is because hospitals that purchase cardiology practices often pursue a tactic of consolidating previously separate independent groups into one practice – either legally or virtually – for purposes of controlling cardiology market share,” he said in an interview.
But it also suits the younger cardiology workforce. “My experience has been that cardiologists graduating from fellowships increasingly want to subspecialize and are less likely to join smaller practices where they cannot focus on the area of their training. Positions that allow this type of subspecialization can most easily be found in larger practices.” said Mr. Sobal, cochair of the American College of Cardiology Management Publications Committee.
And if professional incentives aren’t enough, there is always money. While the study did not look at physician compensation by practice size, Mr. Sobal suspects physicians in larger practices have higher incomes.
Dr. Figueroa has disclosed no relevant financial relationships. Mr. Sobal is the CEO of a midsized cardiology practice (13 cardiologists).
A version of this article originally appeared on Medscape.com.
U.S. cardiologists are increasingly opting out of solo or small practices, and joining larger practices, according to a new analysis of U.S. data from 2013 and 2017.
In 2013, 34.2% of U.S. cardiologists worked in practices of five or fewer cardiologists. That number dropped to 27% by 2017. On the flip side, the proportion working in practices with 25 cardiologists or more rose from 26% in 2013 to 35.8% in 2017.
“This is a trend we’re seeing across health care – hospitals are merging and they’re acquiring physician practices, primary care doctors are joining larger practices, too – so to some extent it seems that cardiologists are just responding to changes in the market structure where they practice,” said Jose F. Figueroa, MD, MPH, of Harvard T.H. Chan School of Public Health and Brigham & Women’s Hospital, Boston.
Dr. Figueroa and colleagues published their findings as a research brief for the Aug. 4 issue of the Journal of the American College of Cardiology.
The average number of cardiologists in practice together rose from 3.6 in 2013 to 4.3 in 2017. This trend was less obvious in rural areas (2.05 to 2.20) than in urban areas (3.67 to 4.38).
The smallest change was seen in the mid-size practice tier. In 2013, 22.9% of cardiologists worked in a practice that included 11 to 24 cardiologists, and in 2017, the proportion was 23.2%.
To determine practices sizes, Dr. Figueroa and colleagues used publicly available data from 2013 and 2017 from the Centers for Medicare & Medicaid Services’ Physician Compare, a website that helps patients find and compare clinicians and groups enrolled in Medicare.
Market level variables were obtained from the Dartmouth Atlas Project, which uses CMS data to provide information and analysis about national, regional, and local health care markets, as well as hospitals and their affiliated physicians.
Market forces drive practice patterns
The investigators had no direct data from which to ascertain the reasons why cardiologists have tended to move from smaller to larger practices, but they did conduct a multivariable linear regression analysis to better understand possible market-level factors that may be influencing these trends.
What they found was that as hospital market concentration increased, practice sizes also increased. They found no association between any community-level and physician-level factors and changes in practice size.
So, for example, greater growth in the number of cardiologists in practice together was not associated with age or sex.
“It seems that cardiologists are responding to changes in the market structure where they practice, and in particular, to hospital market concentration. This is all in an effort basically to have more market power, which in part means better bargaining power when they’re negotiating with payers,” said Dr. Figueroa.
He also suggested that joining a large practice is almost a necessity these days given the administrative burdens imposed by value-based care initiatives and their attendant quality measure reporting.
“There are stringent requirements for electronic health records and a huge administrative burden related to requirements to ensure compliance and report on quality measures,” said Dr. Figueroa.
“And then there are also all of these new ‘alternative payment’ models to figure out, like accountable care organizations and bundled payments, so you can imagine that if you’re a solo practitioner, it would be really hard to manage all of these details yourself and still ensure you’re taking care of your patient.
“As a cardiologist you need to invest in a bunch of resources, including a workforce to help you manage all the quality measures and keeping track of patients, ensuring they all get their blood pressures checked on time, etc.,” he said.
Anecdotally, Dr. Figueroa suggests it’s also a quality-of-life decision for many cardiologists. “In terms of physician burnout, when you’re a solo practitioner or in a small practice, it’s really hard to go on vacation and find coverage.”
Larry Sobal, MBA, MHA, the CEO of the Heart and Vascular Institute of Wisconsin, agrees that this consolidation is in large part a reflection of the trend toward consolidation seen across the healthcare system.
“This is because hospitals that purchase cardiology practices often pursue a tactic of consolidating previously separate independent groups into one practice – either legally or virtually – for purposes of controlling cardiology market share,” he said in an interview.
But it also suits the younger cardiology workforce. “My experience has been that cardiologists graduating from fellowships increasingly want to subspecialize and are less likely to join smaller practices where they cannot focus on the area of their training. Positions that allow this type of subspecialization can most easily be found in larger practices.” said Mr. Sobal, cochair of the American College of Cardiology Management Publications Committee.
And if professional incentives aren’t enough, there is always money. While the study did not look at physician compensation by practice size, Mr. Sobal suspects physicians in larger practices have higher incomes.
Dr. Figueroa has disclosed no relevant financial relationships. Mr. Sobal is the CEO of a midsized cardiology practice (13 cardiologists).
A version of this article originally appeared on Medscape.com.
U.S. cardiologists are increasingly opting out of solo or small practices, and joining larger practices, according to a new analysis of U.S. data from 2013 and 2017.
In 2013, 34.2% of U.S. cardiologists worked in practices of five or fewer cardiologists. That number dropped to 27% by 2017. On the flip side, the proportion working in practices with 25 cardiologists or more rose from 26% in 2013 to 35.8% in 2017.
“This is a trend we’re seeing across health care – hospitals are merging and they’re acquiring physician practices, primary care doctors are joining larger practices, too – so to some extent it seems that cardiologists are just responding to changes in the market structure where they practice,” said Jose F. Figueroa, MD, MPH, of Harvard T.H. Chan School of Public Health and Brigham & Women’s Hospital, Boston.
Dr. Figueroa and colleagues published their findings as a research brief for the Aug. 4 issue of the Journal of the American College of Cardiology.
The average number of cardiologists in practice together rose from 3.6 in 2013 to 4.3 in 2017. This trend was less obvious in rural areas (2.05 to 2.20) than in urban areas (3.67 to 4.38).
The smallest change was seen in the mid-size practice tier. In 2013, 22.9% of cardiologists worked in a practice that included 11 to 24 cardiologists, and in 2017, the proportion was 23.2%.
To determine practices sizes, Dr. Figueroa and colleagues used publicly available data from 2013 and 2017 from the Centers for Medicare & Medicaid Services’ Physician Compare, a website that helps patients find and compare clinicians and groups enrolled in Medicare.
Market level variables were obtained from the Dartmouth Atlas Project, which uses CMS data to provide information and analysis about national, regional, and local health care markets, as well as hospitals and their affiliated physicians.
Market forces drive practice patterns
The investigators had no direct data from which to ascertain the reasons why cardiologists have tended to move from smaller to larger practices, but they did conduct a multivariable linear regression analysis to better understand possible market-level factors that may be influencing these trends.
What they found was that as hospital market concentration increased, practice sizes also increased. They found no association between any community-level and physician-level factors and changes in practice size.
So, for example, greater growth in the number of cardiologists in practice together was not associated with age or sex.
“It seems that cardiologists are responding to changes in the market structure where they practice, and in particular, to hospital market concentration. This is all in an effort basically to have more market power, which in part means better bargaining power when they’re negotiating with payers,” said Dr. Figueroa.
He also suggested that joining a large practice is almost a necessity these days given the administrative burdens imposed by value-based care initiatives and their attendant quality measure reporting.
“There are stringent requirements for electronic health records and a huge administrative burden related to requirements to ensure compliance and report on quality measures,” said Dr. Figueroa.
“And then there are also all of these new ‘alternative payment’ models to figure out, like accountable care organizations and bundled payments, so you can imagine that if you’re a solo practitioner, it would be really hard to manage all of these details yourself and still ensure you’re taking care of your patient.
“As a cardiologist you need to invest in a bunch of resources, including a workforce to help you manage all the quality measures and keeping track of patients, ensuring they all get their blood pressures checked on time, etc.,” he said.
Anecdotally, Dr. Figueroa suggests it’s also a quality-of-life decision for many cardiologists. “In terms of physician burnout, when you’re a solo practitioner or in a small practice, it’s really hard to go on vacation and find coverage.”
Larry Sobal, MBA, MHA, the CEO of the Heart and Vascular Institute of Wisconsin, agrees that this consolidation is in large part a reflection of the trend toward consolidation seen across the healthcare system.
“This is because hospitals that purchase cardiology practices often pursue a tactic of consolidating previously separate independent groups into one practice – either legally or virtually – for purposes of controlling cardiology market share,” he said in an interview.
But it also suits the younger cardiology workforce. “My experience has been that cardiologists graduating from fellowships increasingly want to subspecialize and are less likely to join smaller practices where they cannot focus on the area of their training. Positions that allow this type of subspecialization can most easily be found in larger practices.” said Mr. Sobal, cochair of the American College of Cardiology Management Publications Committee.
And if professional incentives aren’t enough, there is always money. While the study did not look at physician compensation by practice size, Mr. Sobal suspects physicians in larger practices have higher incomes.
Dr. Figueroa has disclosed no relevant financial relationships. Mr. Sobal is the CEO of a midsized cardiology practice (13 cardiologists).
A version of this article originally 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.
Tendyne transcatheter mitral valve shows sustained benefits at 2 years
Two-year outcomes following transcatheter mitral valve replacement with the Tendyne prosthesis showed durable control of mitral regurgitation, sustained improvement in quality of life and functional capacity, and a marked drop-off in the rate of hospitalization for heart failure, David W.M. Muller, MBBS, MD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
“The outcomes can be considered very acceptable considering the advanced age and underlying comorbidities. The data show that, at 2 years, we still have excellent control of the MR [mitral regurgitation], with more than 93% of patients having no MR at all, and there were no patients with 1+ or greater MR,” said Dr. Muller, director of cardiac catheterization laboratories at St. Vincent’s Hospital in Sydney.
He presented for the first time the 2-year results for the first 100 patients enrolled in the long-term Tendyne Expanded Clinical Study. The 1-year outcomes were reported previously (J Am Coll Cardiol. 2019 Mar 26;73[11]:1250-60).
The transcatheter Tendyne mitral valve system received European marketing approval in early 2020 for commercial use in patients with severe symptomatic MR who aren’t candidates for open surgery or transcatheter mitral repair using the MitraClip device. The Tendyne remains investigational in the United States, where a large phase 3 randomized head-to-head trial of the Tendyne device and the FDA-approved MitraClip is ongoing.
At enrollment, the first 100 patients in the long-term prospective Tendyne study averaged 75 years of age, 66% were New York Heart Association functional class III or IV, 89% had secondary or mixed etiology MR, and 39% had been hospitalized for heart failure during the preceding 6 months. Ninety-two percent of participants had 4+ MR before implantation. The group’s average Society of Thoracic Surgeons Predicted Risk of Mortality score was 7.8%.
The all-cause mortality rate was 27% at 1 year and 39% at 2 years, with 87% of deaths being attributable to cardiovascular causes. At 2 years, 82% of survivors were NYHA class I or II. Their Kansas City Cardiomyopathy Questionnaire score improved by 19.1 points from an average of 49 at baseline. There was no evidence of structural valve dysfunction. Their heart failure hospitalization rate improved from 1.3 events per patient per year to 0.6 per patient-year at 1 year and 0.51 at 2 years.
Discussant Francesco Maisano, MD, was favorably impressed by the acute outcomes of transcatheter mitral valve replacement with the Tendyne device.
“There were very few procedural or in-hospital complications. Success was obtained in almost every patient. There was no procedural mortality. The 30-day mortality of 6.0% was reasonable in patients with a baseline STS score of 7.8%; that’s pretty good, I would say,” observed Dr. Maisano, professor of cardiac surgery at the University of Zürich and a pioneer of catheter-based mitral and tricuspid interventions.
However, he voiced concerns about the 35% incidence of major bleeding and 5% rate of disabling stroke at 2 years, which he deemed “pretty high.”
“This underlies the open issue of anticoagulation following these kinds of procedures. This obviously requires further work in the next years,” he said.
Dr. Muller reported receiving research grants from and serving as a consultant to Abbott, which markets the MitraClip and is developing the Tendyne system. He also serves as a consultant to Edwards Lifesciences and Medtronic. Dr. Maisano also reported serving as a consultant to several medical device companies.
Two-year outcomes following transcatheter mitral valve replacement with the Tendyne prosthesis showed durable control of mitral regurgitation, sustained improvement in quality of life and functional capacity, and a marked drop-off in the rate of hospitalization for heart failure, David W.M. Muller, MBBS, MD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
“The outcomes can be considered very acceptable considering the advanced age and underlying comorbidities. The data show that, at 2 years, we still have excellent control of the MR [mitral regurgitation], with more than 93% of patients having no MR at all, and there were no patients with 1+ or greater MR,” said Dr. Muller, director of cardiac catheterization laboratories at St. Vincent’s Hospital in Sydney.
He presented for the first time the 2-year results for the first 100 patients enrolled in the long-term Tendyne Expanded Clinical Study. The 1-year outcomes were reported previously (J Am Coll Cardiol. 2019 Mar 26;73[11]:1250-60).
The transcatheter Tendyne mitral valve system received European marketing approval in early 2020 for commercial use in patients with severe symptomatic MR who aren’t candidates for open surgery or transcatheter mitral repair using the MitraClip device. The Tendyne remains investigational in the United States, where a large phase 3 randomized head-to-head trial of the Tendyne device and the FDA-approved MitraClip is ongoing.
At enrollment, the first 100 patients in the long-term prospective Tendyne study averaged 75 years of age, 66% were New York Heart Association functional class III or IV, 89% had secondary or mixed etiology MR, and 39% had been hospitalized for heart failure during the preceding 6 months. Ninety-two percent of participants had 4+ MR before implantation. The group’s average Society of Thoracic Surgeons Predicted Risk of Mortality score was 7.8%.
The all-cause mortality rate was 27% at 1 year and 39% at 2 years, with 87% of deaths being attributable to cardiovascular causes. At 2 years, 82% of survivors were NYHA class I or II. Their Kansas City Cardiomyopathy Questionnaire score improved by 19.1 points from an average of 49 at baseline. There was no evidence of structural valve dysfunction. Their heart failure hospitalization rate improved from 1.3 events per patient per year to 0.6 per patient-year at 1 year and 0.51 at 2 years.
Discussant Francesco Maisano, MD, was favorably impressed by the acute outcomes of transcatheter mitral valve replacement with the Tendyne device.
“There were very few procedural or in-hospital complications. Success was obtained in almost every patient. There was no procedural mortality. The 30-day mortality of 6.0% was reasonable in patients with a baseline STS score of 7.8%; that’s pretty good, I would say,” observed Dr. Maisano, professor of cardiac surgery at the University of Zürich and a pioneer of catheter-based mitral and tricuspid interventions.
However, he voiced concerns about the 35% incidence of major bleeding and 5% rate of disabling stroke at 2 years, which he deemed “pretty high.”
“This underlies the open issue of anticoagulation following these kinds of procedures. This obviously requires further work in the next years,” he said.
Dr. Muller reported receiving research grants from and serving as a consultant to Abbott, which markets the MitraClip and is developing the Tendyne system. He also serves as a consultant to Edwards Lifesciences and Medtronic. Dr. Maisano also reported serving as a consultant to several medical device companies.
Two-year outcomes following transcatheter mitral valve replacement with the Tendyne prosthesis showed durable control of mitral regurgitation, sustained improvement in quality of life and functional capacity, and a marked drop-off in the rate of hospitalization for heart failure, David W.M. Muller, MBBS, MD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
“The outcomes can be considered very acceptable considering the advanced age and underlying comorbidities. The data show that, at 2 years, we still have excellent control of the MR [mitral regurgitation], with more than 93% of patients having no MR at all, and there were no patients with 1+ or greater MR,” said Dr. Muller, director of cardiac catheterization laboratories at St. Vincent’s Hospital in Sydney.
He presented for the first time the 2-year results for the first 100 patients enrolled in the long-term Tendyne Expanded Clinical Study. The 1-year outcomes were reported previously (J Am Coll Cardiol. 2019 Mar 26;73[11]:1250-60).
The transcatheter Tendyne mitral valve system received European marketing approval in early 2020 for commercial use in patients with severe symptomatic MR who aren’t candidates for open surgery or transcatheter mitral repair using the MitraClip device. The Tendyne remains investigational in the United States, where a large phase 3 randomized head-to-head trial of the Tendyne device and the FDA-approved MitraClip is ongoing.
At enrollment, the first 100 patients in the long-term prospective Tendyne study averaged 75 years of age, 66% were New York Heart Association functional class III or IV, 89% had secondary or mixed etiology MR, and 39% had been hospitalized for heart failure during the preceding 6 months. Ninety-two percent of participants had 4+ MR before implantation. The group’s average Society of Thoracic Surgeons Predicted Risk of Mortality score was 7.8%.
The all-cause mortality rate was 27% at 1 year and 39% at 2 years, with 87% of deaths being attributable to cardiovascular causes. At 2 years, 82% of survivors were NYHA class I or II. Their Kansas City Cardiomyopathy Questionnaire score improved by 19.1 points from an average of 49 at baseline. There was no evidence of structural valve dysfunction. Their heart failure hospitalization rate improved from 1.3 events per patient per year to 0.6 per patient-year at 1 year and 0.51 at 2 years.
Discussant Francesco Maisano, MD, was favorably impressed by the acute outcomes of transcatheter mitral valve replacement with the Tendyne device.
“There were very few procedural or in-hospital complications. Success was obtained in almost every patient. There was no procedural mortality. The 30-day mortality of 6.0% was reasonable in patients with a baseline STS score of 7.8%; that’s pretty good, I would say,” observed Dr. Maisano, professor of cardiac surgery at the University of Zürich and a pioneer of catheter-based mitral and tricuspid interventions.
However, he voiced concerns about the 35% incidence of major bleeding and 5% rate of disabling stroke at 2 years, which he deemed “pretty high.”
“This underlies the open issue of anticoagulation following these kinds of procedures. This obviously requires further work in the next years,” he said.
Dr. Muller reported receiving research grants from and serving as a consultant to Abbott, which markets the MitraClip and is developing the Tendyne system. He also serves as a consultant to Edwards Lifesciences and Medtronic. Dr. Maisano also reported serving as a consultant to several medical device companies.
FROM EUROPCR 2020
AHA statement addresses genetic testing for CVD
A new scientific statement from the American Heart Association recommends that genetic testing for inherited cardiovascular disease should be reserved for four specific types of heart diseases – cardiomyopathies, thoracic aortic aneurysms and dissections, arrhythmias, and familial hypercholesterolemia – and should enlist skilled geneticists and genetic counselors in the care team.
The guidance comes in a scientific statement published online in the journal Circulation: Genomic and Precision Medicine.
Kiran Musunuru, MD, PhD, MPH, ML, chair of the writing group for the scientific statement, described in an interview the rationale for publishing the statement at this time. “There was no prior single statement that summarized best practices for the whole gamut of inherited cardiovascular diseases in adults, only statements for individual diseases,” he said in an interview. “With genetic testing seeing explosive growth in the past few years, both in the clinical setting and with direct-to-consumer testing, we felt that cardiovascular practitioners would benefit from having a single document to serve as a general resource on genetic testing.”
The statement describes two types of patients who would be suitable for genetic testing for cardiovascular disease (CVD), Dr. Musunuru noted: “Patients who have been diagnosed with or are strongly suspected to have a cardiovascular disease that is often inherited and family members of patients who have been diagnosed with an inherited cardiovascular disease and found by genetic testing to have a mutation that is felt to be the cause of the disease.”
The statement also spells out two crucial elements for genetic testing: thorough disease-specific phenotyping – that is, using genetic information to identify the individual’s disease characteristics and a comprehensive family history that spans at least three generations. Testing should only proceed after patients has had genetic counseling and made a shared decision with their doctors.
“Genetic counseling is absolutely essential both before genetic testing to educate patients on what genetic testing entails and what potential results to expect, as well as the risks of testing; and after genetic testing, to review the results of the genetic testing and explain the potential consequences for the patient’s health and the health of family members, including children,” Dr. Musunuru said.
The process should involve board-certified geneticists or at least cardiovascular specialists well-versed in genetics and genetic counselors, the statement noted. The latter are “critical” in the care team, Dr. Musunuru said.
After the decision is made to do genetic testing, the next step is to decide the scope of the testing. That can range from targeted sequencing of a single gene or a few genes linked to the disease to large gene panels; the latter “may not increase the likelihood of clinically actionable results in adult patients,” Dr. Musunuru and colleagues wrote.
But genetic testing is no guarantee to identify a cause or confirm a diagnosis of CVD, the statement noted. “The yield for any genetic testing for any inherited cardiovascular disease remains <100%, usually much less than 100%,” the writing committee stated.
Dr. Musunuru explained that the results can sometimes be inconclusive. “In many cases, genetic testing reveals a mutation that is uninterpretable, what we call a variant of uncertain significance,” he said. “It is not clear whether the mutation increases the risk of disease or is entirely benign, which makes it very challenging to counsel patients as to whether anything should be done about the mutation.”
Even in a diagnosed patient the test results can be uncertain. “This makes it challenging to explain why the patient has the disease and whether any of the family members are at risk,” Dr. Musunuru said.
According to the statement, providers should encourage patients with a confirmed or likely pathogenic variant for CVD to share that information with “all of their at-risk relative,” the statement noted, suggesting “family letters” given to patients are a way to navigate HIPAA’s privacy limits.
The statement was written on behalf of the American Heart Association’s Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology.
Dr. Musunuru and writing group members have no relevant financial relationships to disclose.
SOURCE: Musunuru K et al. Circ Genom Precis Med. 2020 Jul 23. doi: 10.1161/HCG.0000000000000067.
A new scientific statement from the American Heart Association recommends that genetic testing for inherited cardiovascular disease should be reserved for four specific types of heart diseases – cardiomyopathies, thoracic aortic aneurysms and dissections, arrhythmias, and familial hypercholesterolemia – and should enlist skilled geneticists and genetic counselors in the care team.
The guidance comes in a scientific statement published online in the journal Circulation: Genomic and Precision Medicine.
Kiran Musunuru, MD, PhD, MPH, ML, chair of the writing group for the scientific statement, described in an interview the rationale for publishing the statement at this time. “There was no prior single statement that summarized best practices for the whole gamut of inherited cardiovascular diseases in adults, only statements for individual diseases,” he said in an interview. “With genetic testing seeing explosive growth in the past few years, both in the clinical setting and with direct-to-consumer testing, we felt that cardiovascular practitioners would benefit from having a single document to serve as a general resource on genetic testing.”
The statement describes two types of patients who would be suitable for genetic testing for cardiovascular disease (CVD), Dr. Musunuru noted: “Patients who have been diagnosed with or are strongly suspected to have a cardiovascular disease that is often inherited and family members of patients who have been diagnosed with an inherited cardiovascular disease and found by genetic testing to have a mutation that is felt to be the cause of the disease.”
The statement also spells out two crucial elements for genetic testing: thorough disease-specific phenotyping – that is, using genetic information to identify the individual’s disease characteristics and a comprehensive family history that spans at least three generations. Testing should only proceed after patients has had genetic counseling and made a shared decision with their doctors.
“Genetic counseling is absolutely essential both before genetic testing to educate patients on what genetic testing entails and what potential results to expect, as well as the risks of testing; and after genetic testing, to review the results of the genetic testing and explain the potential consequences for the patient’s health and the health of family members, including children,” Dr. Musunuru said.
The process should involve board-certified geneticists or at least cardiovascular specialists well-versed in genetics and genetic counselors, the statement noted. The latter are “critical” in the care team, Dr. Musunuru said.
After the decision is made to do genetic testing, the next step is to decide the scope of the testing. That can range from targeted sequencing of a single gene or a few genes linked to the disease to large gene panels; the latter “may not increase the likelihood of clinically actionable results in adult patients,” Dr. Musunuru and colleagues wrote.
But genetic testing is no guarantee to identify a cause or confirm a diagnosis of CVD, the statement noted. “The yield for any genetic testing for any inherited cardiovascular disease remains <100%, usually much less than 100%,” the writing committee stated.
Dr. Musunuru explained that the results can sometimes be inconclusive. “In many cases, genetic testing reveals a mutation that is uninterpretable, what we call a variant of uncertain significance,” he said. “It is not clear whether the mutation increases the risk of disease or is entirely benign, which makes it very challenging to counsel patients as to whether anything should be done about the mutation.”
Even in a diagnosed patient the test results can be uncertain. “This makes it challenging to explain why the patient has the disease and whether any of the family members are at risk,” Dr. Musunuru said.
According to the statement, providers should encourage patients with a confirmed or likely pathogenic variant for CVD to share that information with “all of their at-risk relative,” the statement noted, suggesting “family letters” given to patients are a way to navigate HIPAA’s privacy limits.
The statement was written on behalf of the American Heart Association’s Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology.
Dr. Musunuru and writing group members have no relevant financial relationships to disclose.
SOURCE: Musunuru K et al. Circ Genom Precis Med. 2020 Jul 23. doi: 10.1161/HCG.0000000000000067.
A new scientific statement from the American Heart Association recommends that genetic testing for inherited cardiovascular disease should be reserved for four specific types of heart diseases – cardiomyopathies, thoracic aortic aneurysms and dissections, arrhythmias, and familial hypercholesterolemia – and should enlist skilled geneticists and genetic counselors in the care team.
The guidance comes in a scientific statement published online in the journal Circulation: Genomic and Precision Medicine.
Kiran Musunuru, MD, PhD, MPH, ML, chair of the writing group for the scientific statement, described in an interview the rationale for publishing the statement at this time. “There was no prior single statement that summarized best practices for the whole gamut of inherited cardiovascular diseases in adults, only statements for individual diseases,” he said in an interview. “With genetic testing seeing explosive growth in the past few years, both in the clinical setting and with direct-to-consumer testing, we felt that cardiovascular practitioners would benefit from having a single document to serve as a general resource on genetic testing.”
The statement describes two types of patients who would be suitable for genetic testing for cardiovascular disease (CVD), Dr. Musunuru noted: “Patients who have been diagnosed with or are strongly suspected to have a cardiovascular disease that is often inherited and family members of patients who have been diagnosed with an inherited cardiovascular disease and found by genetic testing to have a mutation that is felt to be the cause of the disease.”
The statement also spells out two crucial elements for genetic testing: thorough disease-specific phenotyping – that is, using genetic information to identify the individual’s disease characteristics and a comprehensive family history that spans at least three generations. Testing should only proceed after patients has had genetic counseling and made a shared decision with their doctors.
“Genetic counseling is absolutely essential both before genetic testing to educate patients on what genetic testing entails and what potential results to expect, as well as the risks of testing; and after genetic testing, to review the results of the genetic testing and explain the potential consequences for the patient’s health and the health of family members, including children,” Dr. Musunuru said.
The process should involve board-certified geneticists or at least cardiovascular specialists well-versed in genetics and genetic counselors, the statement noted. The latter are “critical” in the care team, Dr. Musunuru said.
After the decision is made to do genetic testing, the next step is to decide the scope of the testing. That can range from targeted sequencing of a single gene or a few genes linked to the disease to large gene panels; the latter “may not increase the likelihood of clinically actionable results in adult patients,” Dr. Musunuru and colleagues wrote.
But genetic testing is no guarantee to identify a cause or confirm a diagnosis of CVD, the statement noted. “The yield for any genetic testing for any inherited cardiovascular disease remains <100%, usually much less than 100%,” the writing committee stated.
Dr. Musunuru explained that the results can sometimes be inconclusive. “In many cases, genetic testing reveals a mutation that is uninterpretable, what we call a variant of uncertain significance,” he said. “It is not clear whether the mutation increases the risk of disease or is entirely benign, which makes it very challenging to counsel patients as to whether anything should be done about the mutation.”
Even in a diagnosed patient the test results can be uncertain. “This makes it challenging to explain why the patient has the disease and whether any of the family members are at risk,” Dr. Musunuru said.
According to the statement, providers should encourage patients with a confirmed or likely pathogenic variant for CVD to share that information with “all of their at-risk relative,” the statement noted, suggesting “family letters” given to patients are a way to navigate HIPAA’s privacy limits.
The statement was written on behalf of the American Heart Association’s Council on Genomic and Precision Medicine; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology.
Dr. Musunuru and writing group members have no relevant financial relationships to disclose.
SOURCE: Musunuru K et al. Circ Genom Precis Med. 2020 Jul 23. doi: 10.1161/HCG.0000000000000067.
FROM CIRCULATION: GENOMIC AND PRECISION MEDICINE
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.
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