Mothers who use cannabis during pregnancy risk disrupting immune gene networks in the placenta and potentially increasing the risk of anxiety and hyperactivity in their children.

These findings emerged from a study led by Yasmin Hurd, PhD, a professor of psychiatry and director of the Addiction Institute at the Icahn School of Medicine at Mount Sinai, New York, and Yoko Nomura, PhD, a professor of behavioral neuroscience at Queen’s College, City University of New York, that was published online in Proceedings of the National Academy of Sciences.

The analysis assessed the effects of gestational maternal cannabis use on psychosocial and physiological measures in young children as well as its potentially immunomodulatory effect on the in utero environment as reflected in the placental transcriptome.

Participants were drawn from a larger cohort in a study launched in 2012; the investigators evaluated offspring aged 3-6 years for hair hormone levels, neurobehavioral traits on the Behavioral Assessment System for Children survey, and heart rate variability (HRV) at rest and during auditory startle.

The cohort consisted of 322 mother-child dyads and children with prenatal exposure to cannabis were compared with those having no exposure. The cohort consisted of 251 non–cannabis-using mothers and 71 cannabis-using mothers, with mean maternal ages in the two groups of 28.46 years and 25.91 years, respectively, The mothers gave birth at Mount Sinai and they and their children were assessed annually at affiliated medical centers in Mount Sinai’s catchment area.

For a subset of children with behavioral assessments, placental specimens collected at birth were processed for RNA sequencing.

Among the findings:

• Maternal cannabis use was associated with reduced maternal and paternal age, more single-mother pregnancies, state anxiety, trait anxiety, depression, cigarette smoking, and African American race.
• Hair hormone analysis revealed increased cortisol levels in the children of cannabis-using mothers, and was associated with greater anxiety, aggression, and hyperactivity.
• Affected children showed a reduction in the high-frequency component of HRV at baseline, reflecting reduced vagal tone.
• In the placenta, there was reduced expression of many genes involved in immune system function. These included genes for type I interferon, neutrophil, and cytokine-signaling pathways.

Several of these genes organized into coexpression networks that correlated with child anxiety and hyperactivity.

The principal active component of cannabis, tetrahydrocannabinol (THC), targets the endocannabinoid system in placental tissue and the developing brain, the authors noted. Exposure during pregnancy is associated with a range of adverse outcomes from fetal growth restriction to low birth weight and preterm birth.

“There are cannabinoid receptors on immune cells, and it is known that cannabinoids can alter immune function, which is important for maintaining maternal tolerance and protecting the fetus,” Dr. Hurd said. “It’s not surprising that something that affects the immune cells can have an impact on the developing fetus.”

“Overall, our findings reveal a relationship between [maternal cannabis use] and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood,” Dr. Hurd and colleagues wrote, adding that the results have significant implications for defining mental health issues in the children gestated by cannabis-smoking mothers.

Their results align with previous research indicating a greater risk for psychiatric illness in children with prenatal cannabis exposure from maternal use.

“While data are pretty limited in this realm, there are other studies that demonstrate a relationship between early child developmental and behavioral measures and cannabis use during pregnancy,” Camille Hoffman, MD, MSc, a high-risk obstetrics specialist and an associate professor at the University of Colorado at Denver, Aurora, said in an interview. “Our research group found children exposed to cannabis in utero at 10 weeks’ gestation and beyond were less interactive and more withdrawn than children who were not exposed.”

And THC remains in maternal breast milk even 6 weeks after usage stops.

The long-term effects of prenatal cannabis exposure remain to be determined and it is unknown whether the effects of gestational THC might attenuate as a child grows older. “We use early childhood measures in research as a proxy for the later development of diagnosed mental health conditions or behavioral problems,” Dr. Hoffman explained. “We know when we do this that not every child with an abnormal score early will go on to develop an actual condition. Fortunately, or unfortunately, other factors and exposures during childhood can change the trajectory for the better or worse.”

According to Dr. Hurd, child development is a dynamic process and epigenetic events in utero need not be deterministic. “The important thing is to identify children at risk early and to be able to go in and try to improve the environment they’re being raised in – not in terms of impoverishment but in terms of positive nurturing and giving the mother and family support.”

At the prenatal level, what’s the best advice for cannabis-using mothers-to-be? “If a woman doesn’t know she’s pregnant and has been using cannabis, taking extra choline for the remainder of the pregnancy can help buffer the potential negative impact of the cannabis exposure,” Dr. Hoffman said. The Food and Drug Administration and the American Medical Association recommend a dose of 550 mg daily. “The same is true for alcohol, which we know is also very bad for fetal brain development. This is not to say go ahead and use these substances and just take choline. The choline is more to try and salvage damage to the fetal brain that may have already occurred.”

This study was supported by the National Institute of Mental Health and the National Institute on Drug Abuse. The authors declared no competing interests. Dr. Hoffman disclosed no conflicts of interest with respect to her comments.

Mothers who use cannabis during pregnancy risk disrupting immune gene networks in the placenta and potentially increasing the risk of anxiety and hyperactivity in their children.

These findings emerged from a study led by Yasmin Hurd, PhD, a professor of psychiatry and director of the Addiction Institute at the Icahn School of Medicine at Mount Sinai, New York, and Yoko Nomura, PhD, a professor of behavioral neuroscience at Queen’s College, City University of New York, that was published online in Proceedings of the National Academy of Sciences.

The analysis assessed the effects of gestational maternal cannabis use on psychosocial and physiological measures in young children as well as its potentially immunomodulatory effect on the in utero environment as reflected in the placental transcriptome.

Participants were drawn from a larger cohort in a study launched in 2012; the investigators evaluated offspring aged 3-6 years for hair hormone levels, neurobehavioral traits on the Behavioral Assessment System for Children survey, and heart rate variability (HRV) at rest and during auditory startle.

The cohort consisted of 322 mother-child dyads and children with prenatal exposure to cannabis were compared with those having no exposure. The cohort consisted of 251 non–cannabis-using mothers and 71 cannabis-using mothers, with mean maternal ages in the two groups of 28.46 years and 25.91 years, respectively, The mothers gave birth at Mount Sinai and they and their children were assessed annually at affiliated medical centers in Mount Sinai’s catchment area.

For a subset of children with behavioral assessments, placental specimens collected at birth were processed for RNA sequencing.

Among the findings:

• Maternal cannabis use was associated with reduced maternal and paternal age, more single-mother pregnancies, state anxiety, trait anxiety, depression, cigarette smoking, and African American race.
• Hair hormone analysis revealed increased cortisol levels in the children of cannabis-using mothers, and was associated with greater anxiety, aggression, and hyperactivity.
• Affected children showed a reduction in the high-frequency component of HRV at baseline, reflecting reduced vagal tone.
• In the placenta, there was reduced expression of many genes involved in immune system function. These included genes for type I interferon, neutrophil, and cytokine-signaling pathways.

Several of these genes organized into coexpression networks that correlated with child anxiety and hyperactivity.

The principal active component of cannabis, tetrahydrocannabinol (THC), targets the endocannabinoid system in placental tissue and the developing brain, the authors noted. Exposure during pregnancy is associated with a range of adverse outcomes from fetal growth restriction to low birth weight and preterm birth.

“There are cannabinoid receptors on immune cells, and it is known that cannabinoids can alter immune function, which is important for maintaining maternal tolerance and protecting the fetus,” Dr. Hurd said. “It’s not surprising that something that affects the immune cells can have an impact on the developing fetus.”

“Overall, our findings reveal a relationship between [maternal cannabis use] and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood,” Dr. Hurd and colleagues wrote, adding that the results have significant implications for defining mental health issues in the children gestated by cannabis-smoking mothers.

Their results align with previous research indicating a greater risk for psychiatric illness in children with prenatal cannabis exposure from maternal use.

“While data are pretty limited in this realm, there are other studies that demonstrate a relationship between early child developmental and behavioral measures and cannabis use during pregnancy,” Camille Hoffman, MD, MSc, a high-risk obstetrics specialist and an associate professor at the University of Colorado at Denver, Aurora, said in an interview. “Our research group found children exposed to cannabis in utero at 10 weeks’ gestation and beyond were less interactive and more withdrawn than children who were not exposed.”

And THC remains in maternal breast milk even 6 weeks after usage stops.

The long-term effects of prenatal cannabis exposure remain to be determined and it is unknown whether the effects of gestational THC might attenuate as a child grows older. “We use early childhood measures in research as a proxy for the later development of diagnosed mental health conditions or behavioral problems,” Dr. Hoffman explained. “We know when we do this that not every child with an abnormal score early will go on to develop an actual condition. Fortunately, or unfortunately, other factors and exposures during childhood can change the trajectory for the better or worse.”

According to Dr. Hurd, child development is a dynamic process and epigenetic events in utero need not be deterministic. “The important thing is to identify children at risk early and to be able to go in and try to improve the environment they’re being raised in – not in terms of impoverishment but in terms of positive nurturing and giving the mother and family support.”

At the prenatal level, what’s the best advice for cannabis-using mothers-to-be? “If a woman doesn’t know she’s pregnant and has been using cannabis, taking extra choline for the remainder of the pregnancy can help buffer the potential negative impact of the cannabis exposure,” Dr. Hoffman said. The Food and Drug Administration and the American Medical Association recommend a dose of 550 mg daily. “The same is true for alcohol, which we know is also very bad for fetal brain development. This is not to say go ahead and use these substances and just take choline. The choline is more to try and salvage damage to the fetal brain that may have already occurred.”

This study was supported by the National Institute of Mental Health and the National Institute on Drug Abuse. The authors declared no competing interests. Dr. Hoffman disclosed no conflicts of interest with respect to her comments.

Mothers who use cannabis during pregnancy risk disrupting immune gene networks in the placenta and potentially increasing the risk of anxiety and hyperactivity in their children.

These findings emerged from a study led by Yasmin Hurd, PhD, a professor of psychiatry and director of the Addiction Institute at the Icahn School of Medicine at Mount Sinai, New York, and Yoko Nomura, PhD, a professor of behavioral neuroscience at Queen’s College, City University of New York, that was published online in Proceedings of the National Academy of Sciences.

The analysis assessed the effects of gestational maternal cannabis use on psychosocial and physiological measures in young children as well as its potentially immunomodulatory effect on the in utero environment as reflected in the placental transcriptome.

Participants were drawn from a larger cohort in a study launched in 2012; the investigators evaluated offspring aged 3-6 years for hair hormone levels, neurobehavioral traits on the Behavioral Assessment System for Children survey, and heart rate variability (HRV) at rest and during auditory startle.

The cohort consisted of 322 mother-child dyads and children with prenatal exposure to cannabis were compared with those having no exposure. The cohort consisted of 251 non–cannabis-using mothers and 71 cannabis-using mothers, with mean maternal ages in the two groups of 28.46 years and 25.91 years, respectively, The mothers gave birth at Mount Sinai and they and their children were assessed annually at affiliated medical centers in Mount Sinai’s catchment area.

For a subset of children with behavioral assessments, placental specimens collected at birth were processed for RNA sequencing.

Among the findings:

• Maternal cannabis use was associated with reduced maternal and paternal age, more single-mother pregnancies, state anxiety, trait anxiety, depression, cigarette smoking, and African American race.
• Hair hormone analysis revealed increased cortisol levels in the children of cannabis-using mothers, and was associated with greater anxiety, aggression, and hyperactivity.
• Affected children showed a reduction in the high-frequency component of HRV at baseline, reflecting reduced vagal tone.
• In the placenta, there was reduced expression of many genes involved in immune system function. These included genes for type I interferon, neutrophil, and cytokine-signaling pathways.

Several of these genes organized into coexpression networks that correlated with child anxiety and hyperactivity.

The principal active component of cannabis, tetrahydrocannabinol (THC), targets the endocannabinoid system in placental tissue and the developing brain, the authors noted. Exposure during pregnancy is associated with a range of adverse outcomes from fetal growth restriction to low birth weight and preterm birth.

“There are cannabinoid receptors on immune cells, and it is known that cannabinoids can alter immune function, which is important for maintaining maternal tolerance and protecting the fetus,” Dr. Hurd said. “It’s not surprising that something that affects the immune cells can have an impact on the developing fetus.”

“Overall, our findings reveal a relationship between [maternal cannabis use] and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood,” Dr. Hurd and colleagues wrote, adding that the results have significant implications for defining mental health issues in the children gestated by cannabis-smoking mothers.

Their results align with previous research indicating a greater risk for psychiatric illness in children with prenatal cannabis exposure from maternal use.

“While data are pretty limited in this realm, there are other studies that demonstrate a relationship between early child developmental and behavioral measures and cannabis use during pregnancy,” Camille Hoffman, MD, MSc, a high-risk obstetrics specialist and an associate professor at the University of Colorado at Denver, Aurora, said in an interview. “Our research group found children exposed to cannabis in utero at 10 weeks’ gestation and beyond were less interactive and more withdrawn than children who were not exposed.”

And THC remains in maternal breast milk even 6 weeks after usage stops.

The long-term effects of prenatal cannabis exposure remain to be determined and it is unknown whether the effects of gestational THC might attenuate as a child grows older. “We use early childhood measures in research as a proxy for the later development of diagnosed mental health conditions or behavioral problems,” Dr. Hoffman explained. “We know when we do this that not every child with an abnormal score early will go on to develop an actual condition. Fortunately, or unfortunately, other factors and exposures during childhood can change the trajectory for the better or worse.”

According to Dr. Hurd, child development is a dynamic process and epigenetic events in utero need not be deterministic. “The important thing is to identify children at risk early and to be able to go in and try to improve the environment they’re being raised in – not in terms of impoverishment but in terms of positive nurturing and giving the mother and family support.”

At the prenatal level, what’s the best advice for cannabis-using mothers-to-be? “If a woman doesn’t know she’s pregnant and has been using cannabis, taking extra choline for the remainder of the pregnancy can help buffer the potential negative impact of the cannabis exposure,” Dr. Hoffman said. The Food and Drug Administration and the American Medical Association recommend a dose of 550 mg daily. “The same is true for alcohol, which we know is also very bad for fetal brain development. This is not to say go ahead and use these substances and just take choline. The choline is more to try and salvage damage to the fetal brain that may have already occurred.”

This study was supported by the National Institute of Mental Health and the National Institute on Drug Abuse. The authors declared no competing interests. Dr. Hoffman disclosed no conflicts of interest with respect to her comments.

Erenumab, a calcitonin-gene related peptide receptor (CGRP) inhibitor, is more tolerable and effective than topiramate for treating patients with migraine, according to data from almost 800 patients in the first head-to-head trial of its kind.

The findings suggest that erenumab may help overcome longstanding issues with migraine medication adherence, and additional supportive data may alter treatment sequencing, reported lead author Uwe Reuter, MD, professor at Charité Universitätsmedizin Berlin, and colleagues.

“So far, no study has been done in order to compare the efficacy of a monoclonal antibody targeting the CGRP pathway to that of a standard of care oral preventive drug,” the investigators wrote in Cephalalgia.

The phase 4 HER-MES trial aimed to address this knowledge gap by enrolling 777 adult patients with a history of migraine. All patients reported migraine with or without aura for at least 1 year prior to screening. At baseline, most patients (65%) reported 8-14 migraine days per months, followed by 4-7 days (24.0%), and at least 15 days (11.0%). No patients had previously received topiramate or a CGRP-targeting agent.

“HER-MES includes a broad migraine population with two-thirds of the patients in the high-frequency migraine spectrum,” the investigators noted. “Despite a mean disease duration of about 20 years, almost 60% of the patients had not received previous prophylactic treatment, which underlines the long-standing problem of undertreatment in migraine.”

The trial had a double-dummy design; patients were randomized in a 1:1 ratio to receive either subcutaneous erenumab (70 or 140 mg/month) plus oral placebo, or oral topiramate (50-100 mg/day) plus subcutaneous placebo. The topiramate dose was uptitrated over the first 6 weeks. Treatments were given for a total of 24 weeks or until discontinuation due to adverse events, which was the primary endpoint. The secondary endpoint was efficacy over months 4-6, defined as at least 50% reduction in monthly migraine days, compared with baseline. Other patient-reported outcomes were also evaluated.

After 24 weeks, 95.1% of patients were still enrolled in the trial. Discontinuations due to adverse events were almost four times as common in the topiramate group than the erenumab group (38.9% vs. 10.6%; odds ratio [OR], 0.19; confidence interval, 0.13-0.27; P less than .001). Efficacy findings followed suit, with 55.4% of patients in the erenumab group reporting at least 50% reduction in monthly migraine days, compared with 31.2% of patients in the topiramate group (OR, 2.76; 95% CI, 2.06-3.71; P less than.001).

Erenumab significantly improved monthly migraine days, headache impact test (HIT-6) scores, and short form health survey version (SF-35v2) scores, including physical and mental components (P less than .001 for all).

Safety profiles aligned with previous findings.

“Compared to topiramate, treatment with erenumab has a superior tolerability profile and a significantly higher efficacy,” the investigators concluded. “HER-MES supports the potential of erenumab in overcoming issues of low adherence in clinical practice observed with topiramate, lessening migraine burden, and improving quality of life in a broad migraine population.”
 

Superior tolerability

Commenting on the study, Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews, said this is “a very important, very well conducted trial that documents what many of us already suspected; erenumab clearly has better tolerability than topiramate as well as better efficacy.”

Dr. Rapoport, a past president of the International Headache Society, said the study highlights an area of unmet need in neurology practice.

“Despite most patients in the trial having chronic headaches for 20 years, 60% of them had never received preventive treatment,” he said, noting that this reflects current practice in the United States.

Dr. Rapoport said primary care providers in the United States prescribe preventive migraine medications to 10%-15% of eligible patients. Prescribing rates for general neurologists are slightly higher, he said, ranging from 35% to 40%, while headache specialists prescribe 70%-90% of the time.

“How can we improve this situation?” Dr. Rapoport asked. “For years we have tried to improve it with education, but we need to do a better job. We need to educate our primary care physicians in more practical ways. We have to teach them how to make a diagnosis of high frequency migraine and chronic migraine and strongly suggest that those patients be put on appropriate preventive medications.”

Barriers to care may be systemic, according to Dr. Rapoport.

“One issue in the U.S. is that patients with commercial insurance are almost always required to fail two or three categories of older oral preventive migraine medications before they can get a monoclonal antibody or gepants for prevention,” he said. “It would be good if we could change that system so that patients that absolutely need the better tolerated, more effective preventive medications could get them sooner rather than later. This will help them feel and function better, with less pain, and eventually bring down the cost of migraine therapy.”

While Dr. Reuter and colleagues concluded that revised treatment sequencing may be warranted after more trials show similar results, Dr. Rapoport suggested that “this was such a large, well-performed, 6-month study with few dropouts, that further trials to confirm these findings are unnecessary, in my opinion.”

The HER-MES trial was funded by Novartis. Dr. Reuter and colleagues disclosed additional relationships with Eli Lilly, Teva Pharmaceutical, Allergan, and others. Dr. Rapoport was involved in early topiramate trials for prevention and migraine, and is a speaker for Amgen.

Erenumab, a calcitonin-gene related peptide receptor (CGRP) inhibitor, is more tolerable and effective than topiramate for treating patients with migraine, according to data from almost 800 patients in the first head-to-head trial of its kind.

The findings suggest that erenumab may help overcome longstanding issues with migraine medication adherence, and additional supportive data may alter treatment sequencing, reported lead author Uwe Reuter, MD, professor at Charité Universitätsmedizin Berlin, and colleagues.

“So far, no study has been done in order to compare the efficacy of a monoclonal antibody targeting the CGRP pathway to that of a standard of care oral preventive drug,” the investigators wrote in Cephalalgia.

The phase 4 HER-MES trial aimed to address this knowledge gap by enrolling 777 adult patients with a history of migraine. All patients reported migraine with or without aura for at least 1 year prior to screening. At baseline, most patients (65%) reported 8-14 migraine days per months, followed by 4-7 days (24.0%), and at least 15 days (11.0%). No patients had previously received topiramate or a CGRP-targeting agent.

“HER-MES includes a broad migraine population with two-thirds of the patients in the high-frequency migraine spectrum,” the investigators noted. “Despite a mean disease duration of about 20 years, almost 60% of the patients had not received previous prophylactic treatment, which underlines the long-standing problem of undertreatment in migraine.”

The trial had a double-dummy design; patients were randomized in a 1:1 ratio to receive either subcutaneous erenumab (70 or 140 mg/month) plus oral placebo, or oral topiramate (50-100 mg/day) plus subcutaneous placebo. The topiramate dose was uptitrated over the first 6 weeks. Treatments were given for a total of 24 weeks or until discontinuation due to adverse events, which was the primary endpoint. The secondary endpoint was efficacy over months 4-6, defined as at least 50% reduction in monthly migraine days, compared with baseline. Other patient-reported outcomes were also evaluated.

After 24 weeks, 95.1% of patients were still enrolled in the trial. Discontinuations due to adverse events were almost four times as common in the topiramate group than the erenumab group (38.9% vs. 10.6%; odds ratio [OR], 0.19; confidence interval, 0.13-0.27; P less than .001). Efficacy findings followed suit, with 55.4% of patients in the erenumab group reporting at least 50% reduction in monthly migraine days, compared with 31.2% of patients in the topiramate group (OR, 2.76; 95% CI, 2.06-3.71; P less than.001).

Erenumab significantly improved monthly migraine days, headache impact test (HIT-6) scores, and short form health survey version (SF-35v2) scores, including physical and mental components (P less than .001 for all).

Safety profiles aligned with previous findings.

“Compared to topiramate, treatment with erenumab has a superior tolerability profile and a significantly higher efficacy,” the investigators concluded. “HER-MES supports the potential of erenumab in overcoming issues of low adherence in clinical practice observed with topiramate, lessening migraine burden, and improving quality of life in a broad migraine population.”
 

Superior tolerability

Commenting on the study, Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews, said this is “a very important, very well conducted trial that documents what many of us already suspected; erenumab clearly has better tolerability than topiramate as well as better efficacy.”

Dr. Rapoport, a past president of the International Headache Society, said the study highlights an area of unmet need in neurology practice.

“Despite most patients in the trial having chronic headaches for 20 years, 60% of them had never received preventive treatment,” he said, noting that this reflects current practice in the United States.

Dr. Rapoport said primary care providers in the United States prescribe preventive migraine medications to 10%-15% of eligible patients. Prescribing rates for general neurologists are slightly higher, he said, ranging from 35% to 40%, while headache specialists prescribe 70%-90% of the time.

“How can we improve this situation?” Dr. Rapoport asked. “For years we have tried to improve it with education, but we need to do a better job. We need to educate our primary care physicians in more practical ways. We have to teach them how to make a diagnosis of high frequency migraine and chronic migraine and strongly suggest that those patients be put on appropriate preventive medications.”

Barriers to care may be systemic, according to Dr. Rapoport.

“One issue in the U.S. is that patients with commercial insurance are almost always required to fail two or three categories of older oral preventive migraine medications before they can get a monoclonal antibody or gepants for prevention,” he said. “It would be good if we could change that system so that patients that absolutely need the better tolerated, more effective preventive medications could get them sooner rather than later. This will help them feel and function better, with less pain, and eventually bring down the cost of migraine therapy.”

While Dr. Reuter and colleagues concluded that revised treatment sequencing may be warranted after more trials show similar results, Dr. Rapoport suggested that “this was such a large, well-performed, 6-month study with few dropouts, that further trials to confirm these findings are unnecessary, in my opinion.”

The HER-MES trial was funded by Novartis. Dr. Reuter and colleagues disclosed additional relationships with Eli Lilly, Teva Pharmaceutical, Allergan, and others. Dr. Rapoport was involved in early topiramate trials for prevention and migraine, and is a speaker for Amgen.

Erenumab, a calcitonin-gene related peptide receptor (CGRP) inhibitor, is more tolerable and effective than topiramate for treating patients with migraine, according to data from almost 800 patients in the first head-to-head trial of its kind.

The findings suggest that erenumab may help overcome longstanding issues with migraine medication adherence, and additional supportive data may alter treatment sequencing, reported lead author Uwe Reuter, MD, professor at Charité Universitätsmedizin Berlin, and colleagues.

“So far, no study has been done in order to compare the efficacy of a monoclonal antibody targeting the CGRP pathway to that of a standard of care oral preventive drug,” the investigators wrote in Cephalalgia.

The phase 4 HER-MES trial aimed to address this knowledge gap by enrolling 777 adult patients with a history of migraine. All patients reported migraine with or without aura for at least 1 year prior to screening. At baseline, most patients (65%) reported 8-14 migraine days per months, followed by 4-7 days (24.0%), and at least 15 days (11.0%). No patients had previously received topiramate or a CGRP-targeting agent.

“HER-MES includes a broad migraine population with two-thirds of the patients in the high-frequency migraine spectrum,” the investigators noted. “Despite a mean disease duration of about 20 years, almost 60% of the patients had not received previous prophylactic treatment, which underlines the long-standing problem of undertreatment in migraine.”

The trial had a double-dummy design; patients were randomized in a 1:1 ratio to receive either subcutaneous erenumab (70 or 140 mg/month) plus oral placebo, or oral topiramate (50-100 mg/day) plus subcutaneous placebo. The topiramate dose was uptitrated over the first 6 weeks. Treatments were given for a total of 24 weeks or until discontinuation due to adverse events, which was the primary endpoint. The secondary endpoint was efficacy over months 4-6, defined as at least 50% reduction in monthly migraine days, compared with baseline. Other patient-reported outcomes were also evaluated.

After 24 weeks, 95.1% of patients were still enrolled in the trial. Discontinuations due to adverse events were almost four times as common in the topiramate group than the erenumab group (38.9% vs. 10.6%; odds ratio [OR], 0.19; confidence interval, 0.13-0.27; P less than .001). Efficacy findings followed suit, with 55.4% of patients in the erenumab group reporting at least 50% reduction in monthly migraine days, compared with 31.2% of patients in the topiramate group (OR, 2.76; 95% CI, 2.06-3.71; P less than.001).

Erenumab significantly improved monthly migraine days, headache impact test (HIT-6) scores, and short form health survey version (SF-35v2) scores, including physical and mental components (P less than .001 for all).

Safety profiles aligned with previous findings.

“Compared to topiramate, treatment with erenumab has a superior tolerability profile and a significantly higher efficacy,” the investigators concluded. “HER-MES supports the potential of erenumab in overcoming issues of low adherence in clinical practice observed with topiramate, lessening migraine burden, and improving quality of life in a broad migraine population.”
 

Superior tolerability

Commenting on the study, Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews, said this is “a very important, very well conducted trial that documents what many of us already suspected; erenumab clearly has better tolerability than topiramate as well as better efficacy.”

Dr. Rapoport, a past president of the International Headache Society, said the study highlights an area of unmet need in neurology practice.

“Despite most patients in the trial having chronic headaches for 20 years, 60% of them had never received preventive treatment,” he said, noting that this reflects current practice in the United States.

Dr. Rapoport said primary care providers in the United States prescribe preventive migraine medications to 10%-15% of eligible patients. Prescribing rates for general neurologists are slightly higher, he said, ranging from 35% to 40%, while headache specialists prescribe 70%-90% of the time.

“How can we improve this situation?” Dr. Rapoport asked. “For years we have tried to improve it with education, but we need to do a better job. We need to educate our primary care physicians in more practical ways. We have to teach them how to make a diagnosis of high frequency migraine and chronic migraine and strongly suggest that those patients be put on appropriate preventive medications.”

Barriers to care may be systemic, according to Dr. Rapoport.

“One issue in the U.S. is that patients with commercial insurance are almost always required to fail two or three categories of older oral preventive migraine medications before they can get a monoclonal antibody or gepants for prevention,” he said. “It would be good if we could change that system so that patients that absolutely need the better tolerated, more effective preventive medications could get them sooner rather than later. This will help them feel and function better, with less pain, and eventually bring down the cost of migraine therapy.”

While Dr. Reuter and colleagues concluded that revised treatment sequencing may be warranted after more trials show similar results, Dr. Rapoport suggested that “this was such a large, well-performed, 6-month study with few dropouts, that further trials to confirm these findings are unnecessary, in my opinion.”

The HER-MES trial was funded by Novartis. Dr. Reuter and colleagues disclosed additional relationships with Eli Lilly, Teva Pharmaceutical, Allergan, and others. Dr. Rapoport was involved in early topiramate trials for prevention and migraine, and is a speaker for Amgen.

At the height of the COVID-19 pandemic’s terrifying first wave in the spring of 2020, dozens of hospitals in high-incidence areas either planned or opened temporary, emergency field hospitals to cover anticipated demand for beds beyond the capacity of local permanent hospitals.

Chastened by images of overwhelmed health care systems in Northern Italy and other hard-hit areas,¹ the planners used available modeling tools and estimates for projecting maximum potential need in worst-case scenarios. Some of these temporary hospitals never opened. Others opened in convention centers, parking garages, or parking lot tents, and ended up being used to a lesser degree than the worst-case scenarios.

But those who participated in the planning – including, in many cases, hospitalists – believe they created alternate care site manuals that could be quickly revived in the event of future COVID surges or other, similar crises. Better to plan for too much, they say, than not plan for enough.

Field hospitals or alternate care sites are defined in a recent journal article in Prehospital Disaster Medicine as “locations that can be converted to provide either inpatient and/or outpatient health services when existing facilities are compromised by a hazard impact or the volume of patients exceeds available capacity and/or capabilities.”²

University of Michigan Institute for Healthcare Policy and Innovation

The lead author of that report, Sue Anne Bell, PhD, FNP-BC, a disaster expert and assistant professor of nursing at the University of Michigan (UM), was one of five members of the leadership team for planning UM’s field hospital. They used an organizational unit structure based on the U.S. military’s staffing structure, with their work organized around six units of planning: personnel and labor, security, clinical operations, logistics and supply, planning and training, and communications. This team planned a 519-bed step-down care facility, the Michigan Medicine Field Hospital, for a 73,000-foot indoor track and performance facility at the university, three miles from UM’s main hospital. The aim was to provide safe care in a resource-limited environment.

“We were prepared, but the need never materialized as the peak of COVID cases started to subside,” Dr. Bell said. The team was ready to open within days using a “T-Minus” framework of days remaining on an official countdown clock. But when the need and deadlines kept getting pushed back, that gave them more time to develop clearer procedures.

Two Michigan Medicine hospitalists, Christopher Smith, MD, and David Paje, MD, MPH, both professors at UM’s medical school, were intimately involved in the process. “I was the medical director for the respiratory care unit that was opened for COVID patients, so I was pulled in to assist in the field hospital planning,” said Dr. Smith.

Baltimore builds a convention center hospital

A COVID-19 field hospital was planned and executed at an exhibit hall in the Baltimore Convention Center, starting in March 2020 under the leadership of Johns Hopkins Bayview hospitalist Eric Howell, MD, MHM, who eventually handed over responsibilities as chief medical officer when he assumed the position of CEO for the Society of Hospital Medicine in July of that year.

Courtesy Dr. Eric Howell

Hopkins collaborated with the University of Maryland health system and state leaders, including the Secretary of Health, to open a 252-bed temporary facility, which at its peak carried a census of 48 patients, with no on-site mortality or cardiac arrests, before it was closed in June 2021 – ready to reopen if necessary. It also served as Baltimore’s major site for polymerase chain reaction COVID-19 testing, vaccinations, and monoclonal antibody infusions, along with medical research.

“My belief at the time we started was that my entire 20-year career as a hospitalist had prepared me for the challenge of opening a COVID field hospital,” Dr. Howell said. “I had learned how to build clinical programs. The difference was that instead of months and years to build a program, we only had a few weeks.”

His first request was to bring on an associate medical director for the field hospital, Melinda E. Kantsiper, MD, a hospitalist and director of clinical operations in the Division of Hospital Medicine at Johns Hopkins Bayview. She became the field hospital’s CMO when Dr. Howell moved to SHM. “As hospitalists, we are trained to care for the patient in front of us while at the same time creating systems that can adjust to rapidly changing circumstances,” Dr. Kantsiper said. “We did what was asked and set up a field hospital that cared for a total of 1,500 COVID patients.”

Courtesy Johns Hopkins Medicine

“They gave us a lot of autonomy and helped us break down barriers. They gave us the political capital to say proper PPE was absolutely essential. As hard and devastating as the pandemic has been, one take-away is that we showed that we can be more flexible and elastic in response to actual needs than we used to think.”

Range of challenges

Among the questions that need to be answered by a field hospital’s planners, the first is ‘where to put it?’ The answer is, hopefully, someplace not too far away, large enough, with ready access to supplies and intake. The next question is ‘who is the patient?’ Clinicians must determine who goes to the field hospital versus who stays at the standing hospital. How sick should these patients be? And when do they need to go back to the permanent hospital? Can staff be trained to recognize when patients in the field hospital are starting to decompensate? The EPIC Deterioration Index³ is a proprietary prediction model that was used by more than a hundred hospitals during the pandemic.

The hospitalist team may develop specific inclusion and exclusion criteria – for example, don’t admit patients who are receiving oxygen therapy above a certain threshold or who are hemodynamically unstable. These criteria should reflect the capacity of the field hospital and the needs of the permanent hospital. At Michigan, as at other field hospital sites, the goal was to offer a step-down or postacute setting for patients with COVID-19 who were too sick to return home but didn’t need acute or ICU-level care, thereby freeing up beds at the permanent hospital for patients who were sicker.

Other questions: What is the process for admissions and discharges? How will patients be transported? What kind of staffing is needed, and what levels of care will be provided? What about rehabilitation services, or palliative care? What about patients with substance abuse or psychiatric comorbidities?

“Are we going to do paper charting? How will that work out for long-term documentation and billing?” Dr. Bell said. A clear reporting structure and communication pathways are essential. Among the other operational processes to address, outlined in Dr. Bell’s article, are orientation and training, PPE donning and doffing procedures, the code or rapid response team, patient and staff food and nutrition, infection control protocols, pharmacy services, access to radiology, rounding procedures, staff support, and the morgue.

One other issue that shouldn’t be overlooked is health equity in the field hospital. “Providing safe and equitable care should be the focus. Thinking who goes to the field hospital should be done within a health equity framework,” Dr. Bell said.⁴ She also wonders if field hospital planners are sharing their experience with colleagues across the country and developing more collaborative relationships with other hospitals in their communities.

“Field hospitals can be different things,” Dr. Bell said. “The important take-home is it doesn’t have to be in a tent or a parking garage, which can be suboptimal.” In many cases, it may be better to focus on finding unused space within the hospital – whether a lobby, staff lounge, or unoccupied unit – closer to personnel, supplies, pharmacy, and the like. “I think the pandemic showed us how unprepared we were as a health care system, and how much more we need to do in preparation for future crises.”

Limits to the temporary hospital

In New York City, which had the country’s worst COVID-19 outbreak during the first surge in the spring of 2020, a 1,000-bed field hospital was opened at the Jacob Javits Center in March 2020 and closed that June. “I was in the field hospital early, in March and April, when our hospitals were temporarily overrun,” said hospitalist Mona Krouss, MD, FACP, CPPS, NYC Health + Hospitals’ director of patient safety. “My role was to figure out how to get patients on our medical floors into these field hospitals, with responsibility for helping to revise admission criteria,” she said.

“No one knew how horrible it would become. This was so unanticipated, so difficult to operationalize. What they were able to create was amazing, but there were just too many barriers to have it work smoothly,” Dr. Krouss said.

Courtesy of Renown Regional Medical Center

Replicating hospital work flows

“We ensured that everybody who needed to be within the walls of the permanent hospitals was able to stay there,” said Dr. Lee’s colleague, hospitalist Adnan (Eddy) Akbar, MD. “The postacute system we ordinarily rely on was no longer accepting patients. Other hospitals in the area were able to manage within their capacity because Renown’s field hospital could admit excess patients. We tried to replicate in the field hospital, as much as possible, the work flows and systems of our main hospital.”

When the field hospital finally opened, Dr. Akbar said, “we had a good feeling. We were ready. If something more catastrophic had come down, we were ready to care for more patients. In the field hospital you have to keep monitoring your work flow – almost on a daily basis. But we felt privileged to be working for a system where you knew you can go and care for everyone who needed care.”

One upside of the field hospital experience for participating clinicians, Dr. Lee added, is the opportunity to practice creatively. “The downside is it’s extremely expensive, and has consequences for the mental health of staff. Like so many of these things, it wore on people over time – such as all the time spent donning and doffing protective equipment. And recently the patients have become a lot less gracious.”

Amy Baughman, MD, a hospitalist at Massachusetts General Hospital in Boston, was co-medical director of the postacute care section of a 1,000-bed field hospital, Boston Hope Medical Center, opened in April 2020 at the Boston Convention and Exhibition Center. The other half of the facility was dedicated to undomiciled COVID-19 patients who had no place else to go. Peak census was around 100 patients, housed on four units, each with a clinical team led by a physician.

Partners HealthCare

References

1. Horowitz J. Italy’s health care system groans under coronavirus – a warning to the world. New York Times. 2020 Mar 12.

2. Bell SA et al. T-Minus 10 days: The role of an academic medical institution in field hospital planning. Prehosp Disaster Med. 2021 Feb 18:1-6. doi: 10.1017/S1049023X21000224.

3. Singh K et al. Evaluating a widely implemented proprietary deterioration index model among hospitalized patients with COVID-19. Ann Am Thorac Soc. 2021 Jul;18(7):1129-37. doi: 10.1513/AnnalsATS.202006-698OC.

4. Bell SA et al. Alternate care sites during COVID-19 pandemic: Policy implications for pandemic surge planning. Disaster Med Public Health Prep. 2021 Jul 23;1-3. doi: 10.1017/dmp.2021.241.

At the height of the COVID-19 pandemic’s terrifying first wave in the spring of 2020, dozens of hospitals in high-incidence areas either planned or opened temporary, emergency field hospitals to cover anticipated demand for beds beyond the capacity of local permanent hospitals.

Chastened by images of overwhelmed health care systems in Northern Italy and other hard-hit areas,¹ the planners used available modeling tools and estimates for projecting maximum potential need in worst-case scenarios. Some of these temporary hospitals never opened. Others opened in convention centers, parking garages, or parking lot tents, and ended up being used to a lesser degree than the worst-case scenarios.

But those who participated in the planning – including, in many cases, hospitalists – believe they created alternate care site manuals that could be quickly revived in the event of future COVID surges or other, similar crises. Better to plan for too much, they say, than not plan for enough.

Field hospitals or alternate care sites are defined in a recent journal article in Prehospital Disaster Medicine as “locations that can be converted to provide either inpatient and/or outpatient health services when existing facilities are compromised by a hazard impact or the volume of patients exceeds available capacity and/or capabilities.”²

University of Michigan Institute for Healthcare Policy and Innovation

The lead author of that report, Sue Anne Bell, PhD, FNP-BC, a disaster expert and assistant professor of nursing at the University of Michigan (UM), was one of five members of the leadership team for planning UM’s field hospital. They used an organizational unit structure based on the U.S. military’s staffing structure, with their work organized around six units of planning: personnel and labor, security, clinical operations, logistics and supply, planning and training, and communications. This team planned a 519-bed step-down care facility, the Michigan Medicine Field Hospital, for a 73,000-foot indoor track and performance facility at the university, three miles from UM’s main hospital. The aim was to provide safe care in a resource-limited environment.

“We were prepared, but the need never materialized as the peak of COVID cases started to subside,” Dr. Bell said. The team was ready to open within days using a “T-Minus” framework of days remaining on an official countdown clock. But when the need and deadlines kept getting pushed back, that gave them more time to develop clearer procedures.

Two Michigan Medicine hospitalists, Christopher Smith, MD, and David Paje, MD, MPH, both professors at UM’s medical school, were intimately involved in the process. “I was the medical director for the respiratory care unit that was opened for COVID patients, so I was pulled in to assist in the field hospital planning,” said Dr. Smith.

Baltimore builds a convention center hospital

A COVID-19 field hospital was planned and executed at an exhibit hall in the Baltimore Convention Center, starting in March 2020 under the leadership of Johns Hopkins Bayview hospitalist Eric Howell, MD, MHM, who eventually handed over responsibilities as chief medical officer when he assumed the position of CEO for the Society of Hospital Medicine in July of that year.

Courtesy Dr. Eric Howell

Hopkins collaborated with the University of Maryland health system and state leaders, including the Secretary of Health, to open a 252-bed temporary facility, which at its peak carried a census of 48 patients, with no on-site mortality or cardiac arrests, before it was closed in June 2021 – ready to reopen if necessary. It also served as Baltimore’s major site for polymerase chain reaction COVID-19 testing, vaccinations, and monoclonal antibody infusions, along with medical research.

“My belief at the time we started was that my entire 20-year career as a hospitalist had prepared me for the challenge of opening a COVID field hospital,” Dr. Howell said. “I had learned how to build clinical programs. The difference was that instead of months and years to build a program, we only had a few weeks.”

His first request was to bring on an associate medical director for the field hospital, Melinda E. Kantsiper, MD, a hospitalist and director of clinical operations in the Division of Hospital Medicine at Johns Hopkins Bayview. She became the field hospital’s CMO when Dr. Howell moved to SHM. “As hospitalists, we are trained to care for the patient in front of us while at the same time creating systems that can adjust to rapidly changing circumstances,” Dr. Kantsiper said. “We did what was asked and set up a field hospital that cared for a total of 1,500 COVID patients.”

Courtesy Johns Hopkins Medicine

“They gave us a lot of autonomy and helped us break down barriers. They gave us the political capital to say proper PPE was absolutely essential. As hard and devastating as the pandemic has been, one take-away is that we showed that we can be more flexible and elastic in response to actual needs than we used to think.”

Range of challenges

Among the questions that need to be answered by a field hospital’s planners, the first is ‘where to put it?’ The answer is, hopefully, someplace not too far away, large enough, with ready access to supplies and intake. The next question is ‘who is the patient?’ Clinicians must determine who goes to the field hospital versus who stays at the standing hospital. How sick should these patients be? And when do they need to go back to the permanent hospital? Can staff be trained to recognize when patients in the field hospital are starting to decompensate? The EPIC Deterioration Index³ is a proprietary prediction model that was used by more than a hundred hospitals during the pandemic.

The hospitalist team may develop specific inclusion and exclusion criteria – for example, don’t admit patients who are receiving oxygen therapy above a certain threshold or who are hemodynamically unstable. These criteria should reflect the capacity of the field hospital and the needs of the permanent hospital. At Michigan, as at other field hospital sites, the goal was to offer a step-down or postacute setting for patients with COVID-19 who were too sick to return home but didn’t need acute or ICU-level care, thereby freeing up beds at the permanent hospital for patients who were sicker.

Other questions: What is the process for admissions and discharges? How will patients be transported? What kind of staffing is needed, and what levels of care will be provided? What about rehabilitation services, or palliative care? What about patients with substance abuse or psychiatric comorbidities?

“Are we going to do paper charting? How will that work out for long-term documentation and billing?” Dr. Bell said. A clear reporting structure and communication pathways are essential. Among the other operational processes to address, outlined in Dr. Bell’s article, are orientation and training, PPE donning and doffing procedures, the code or rapid response team, patient and staff food and nutrition, infection control protocols, pharmacy services, access to radiology, rounding procedures, staff support, and the morgue.

One other issue that shouldn’t be overlooked is health equity in the field hospital. “Providing safe and equitable care should be the focus. Thinking who goes to the field hospital should be done within a health equity framework,” Dr. Bell said.⁴ She also wonders if field hospital planners are sharing their experience with colleagues across the country and developing more collaborative relationships with other hospitals in their communities.

“Field hospitals can be different things,” Dr. Bell said. “The important take-home is it doesn’t have to be in a tent or a parking garage, which can be suboptimal.” In many cases, it may be better to focus on finding unused space within the hospital – whether a lobby, staff lounge, or unoccupied unit – closer to personnel, supplies, pharmacy, and the like. “I think the pandemic showed us how unprepared we were as a health care system, and how much more we need to do in preparation for future crises.”

Limits to the temporary hospital

In New York City, which had the country’s worst COVID-19 outbreak during the first surge in the spring of 2020, a 1,000-bed field hospital was opened at the Jacob Javits Center in March 2020 and closed that June. “I was in the field hospital early, in March and April, when our hospitals were temporarily overrun,” said hospitalist Mona Krouss, MD, FACP, CPPS, NYC Health + Hospitals’ director of patient safety. “My role was to figure out how to get patients on our medical floors into these field hospitals, with responsibility for helping to revise admission criteria,” she said.

“No one knew how horrible it would become. This was so unanticipated, so difficult to operationalize. What they were able to create was amazing, but there were just too many barriers to have it work smoothly,” Dr. Krouss said.

Courtesy of Renown Regional Medical Center

Replicating hospital work flows

“We ensured that everybody who needed to be within the walls of the permanent hospitals was able to stay there,” said Dr. Lee’s colleague, hospitalist Adnan (Eddy) Akbar, MD. “The postacute system we ordinarily rely on was no longer accepting patients. Other hospitals in the area were able to manage within their capacity because Renown’s field hospital could admit excess patients. We tried to replicate in the field hospital, as much as possible, the work flows and systems of our main hospital.”

When the field hospital finally opened, Dr. Akbar said, “we had a good feeling. We were ready. If something more catastrophic had come down, we were ready to care for more patients. In the field hospital you have to keep monitoring your work flow – almost on a daily basis. But we felt privileged to be working for a system where you knew you can go and care for everyone who needed care.”

One upside of the field hospital experience for participating clinicians, Dr. Lee added, is the opportunity to practice creatively. “The downside is it’s extremely expensive, and has consequences for the mental health of staff. Like so many of these things, it wore on people over time – such as all the time spent donning and doffing protective equipment. And recently the patients have become a lot less gracious.”

Amy Baughman, MD, a hospitalist at Massachusetts General Hospital in Boston, was co-medical director of the postacute care section of a 1,000-bed field hospital, Boston Hope Medical Center, opened in April 2020 at the Boston Convention and Exhibition Center. The other half of the facility was dedicated to undomiciled COVID-19 patients who had no place else to go. Peak census was around 100 patients, housed on four units, each with a clinical team led by a physician.

Partners HealthCare

References

1. Horowitz J. Italy’s health care system groans under coronavirus – a warning to the world. New York Times. 2020 Mar 12.

2. Bell SA et al. T-Minus 10 days: The role of an academic medical institution in field hospital planning. Prehosp Disaster Med. 2021 Feb 18:1-6. doi: 10.1017/S1049023X21000224.

3. Singh K et al. Evaluating a widely implemented proprietary deterioration index model among hospitalized patients with COVID-19. Ann Am Thorac Soc. 2021 Jul;18(7):1129-37. doi: 10.1513/AnnalsATS.202006-698OC.

4. Bell SA et al. Alternate care sites during COVID-19 pandemic: Policy implications for pandemic surge planning. Disaster Med Public Health Prep. 2021 Jul 23;1-3. doi: 10.1017/dmp.2021.241.

At the height of the COVID-19 pandemic’s terrifying first wave in the spring of 2020, dozens of hospitals in high-incidence areas either planned or opened temporary, emergency field hospitals to cover anticipated demand for beds beyond the capacity of local permanent hospitals.

Chastened by images of overwhelmed health care systems in Northern Italy and other hard-hit areas,¹ the planners used available modeling tools and estimates for projecting maximum potential need in worst-case scenarios. Some of these temporary hospitals never opened. Others opened in convention centers, parking garages, or parking lot tents, and ended up being used to a lesser degree than the worst-case scenarios.

But those who participated in the planning – including, in many cases, hospitalists – believe they created alternate care site manuals that could be quickly revived in the event of future COVID surges or other, similar crises. Better to plan for too much, they say, than not plan for enough.

Field hospitals or alternate care sites are defined in a recent journal article in Prehospital Disaster Medicine as “locations that can be converted to provide either inpatient and/or outpatient health services when existing facilities are compromised by a hazard impact or the volume of patients exceeds available capacity and/or capabilities.”²

University of Michigan Institute for Healthcare Policy and Innovation

The lead author of that report, Sue Anne Bell, PhD, FNP-BC, a disaster expert and assistant professor of nursing at the University of Michigan (UM), was one of five members of the leadership team for planning UM’s field hospital. They used an organizational unit structure based on the U.S. military’s staffing structure, with their work organized around six units of planning: personnel and labor, security, clinical operations, logistics and supply, planning and training, and communications. This team planned a 519-bed step-down care facility, the Michigan Medicine Field Hospital, for a 73,000-foot indoor track and performance facility at the university, three miles from UM’s main hospital. The aim was to provide safe care in a resource-limited environment.

“We were prepared, but the need never materialized as the peak of COVID cases started to subside,” Dr. Bell said. The team was ready to open within days using a “T-Minus” framework of days remaining on an official countdown clock. But when the need and deadlines kept getting pushed back, that gave them more time to develop clearer procedures.

Two Michigan Medicine hospitalists, Christopher Smith, MD, and David Paje, MD, MPH, both professors at UM’s medical school, were intimately involved in the process. “I was the medical director for the respiratory care unit that was opened for COVID patients, so I was pulled in to assist in the field hospital planning,” said Dr. Smith.

Baltimore builds a convention center hospital

A COVID-19 field hospital was planned and executed at an exhibit hall in the Baltimore Convention Center, starting in March 2020 under the leadership of Johns Hopkins Bayview hospitalist Eric Howell, MD, MHM, who eventually handed over responsibilities as chief medical officer when he assumed the position of CEO for the Society of Hospital Medicine in July of that year.

Courtesy Dr. Eric Howell

Hopkins collaborated with the University of Maryland health system and state leaders, including the Secretary of Health, to open a 252-bed temporary facility, which at its peak carried a census of 48 patients, with no on-site mortality or cardiac arrests, before it was closed in June 2021 – ready to reopen if necessary. It also served as Baltimore’s major site for polymerase chain reaction COVID-19 testing, vaccinations, and monoclonal antibody infusions, along with medical research.

“My belief at the time we started was that my entire 20-year career as a hospitalist had prepared me for the challenge of opening a COVID field hospital,” Dr. Howell said. “I had learned how to build clinical programs. The difference was that instead of months and years to build a program, we only had a few weeks.”

His first request was to bring on an associate medical director for the field hospital, Melinda E. Kantsiper, MD, a hospitalist and director of clinical operations in the Division of Hospital Medicine at Johns Hopkins Bayview. She became the field hospital’s CMO when Dr. Howell moved to SHM. “As hospitalists, we are trained to care for the patient in front of us while at the same time creating systems that can adjust to rapidly changing circumstances,” Dr. Kantsiper said. “We did what was asked and set up a field hospital that cared for a total of 1,500 COVID patients.”

Courtesy Johns Hopkins Medicine

“They gave us a lot of autonomy and helped us break down barriers. They gave us the political capital to say proper PPE was absolutely essential. As hard and devastating as the pandemic has been, one take-away is that we showed that we can be more flexible and elastic in response to actual needs than we used to think.”

Range of challenges

Among the questions that need to be answered by a field hospital’s planners, the first is ‘where to put it?’ The answer is, hopefully, someplace not too far away, large enough, with ready access to supplies and intake. The next question is ‘who is the patient?’ Clinicians must determine who goes to the field hospital versus who stays at the standing hospital. How sick should these patients be? And when do they need to go back to the permanent hospital? Can staff be trained to recognize when patients in the field hospital are starting to decompensate? The EPIC Deterioration Index³ is a proprietary prediction model that was used by more than a hundred hospitals during the pandemic.

The hospitalist team may develop specific inclusion and exclusion criteria – for example, don’t admit patients who are receiving oxygen therapy above a certain threshold or who are hemodynamically unstable. These criteria should reflect the capacity of the field hospital and the needs of the permanent hospital. At Michigan, as at other field hospital sites, the goal was to offer a step-down or postacute setting for patients with COVID-19 who were too sick to return home but didn’t need acute or ICU-level care, thereby freeing up beds at the permanent hospital for patients who were sicker.

Other questions: What is the process for admissions and discharges? How will patients be transported? What kind of staffing is needed, and what levels of care will be provided? What about rehabilitation services, or palliative care? What about patients with substance abuse or psychiatric comorbidities?

“Are we going to do paper charting? How will that work out for long-term documentation and billing?” Dr. Bell said. A clear reporting structure and communication pathways are essential. Among the other operational processes to address, outlined in Dr. Bell’s article, are orientation and training, PPE donning and doffing procedures, the code or rapid response team, patient and staff food and nutrition, infection control protocols, pharmacy services, access to radiology, rounding procedures, staff support, and the morgue.

One other issue that shouldn’t be overlooked is health equity in the field hospital. “Providing safe and equitable care should be the focus. Thinking who goes to the field hospital should be done within a health equity framework,” Dr. Bell said.⁴ She also wonders if field hospital planners are sharing their experience with colleagues across the country and developing more collaborative relationships with other hospitals in their communities.

“Field hospitals can be different things,” Dr. Bell said. “The important take-home is it doesn’t have to be in a tent or a parking garage, which can be suboptimal.” In many cases, it may be better to focus on finding unused space within the hospital – whether a lobby, staff lounge, or unoccupied unit – closer to personnel, supplies, pharmacy, and the like. “I think the pandemic showed us how unprepared we were as a health care system, and how much more we need to do in preparation for future crises.”

Limits to the temporary hospital

In New York City, which had the country’s worst COVID-19 outbreak during the first surge in the spring of 2020, a 1,000-bed field hospital was opened at the Jacob Javits Center in March 2020 and closed that June. “I was in the field hospital early, in March and April, when our hospitals were temporarily overrun,” said hospitalist Mona Krouss, MD, FACP, CPPS, NYC Health + Hospitals’ director of patient safety. “My role was to figure out how to get patients on our medical floors into these field hospitals, with responsibility for helping to revise admission criteria,” she said.

“No one knew how horrible it would become. This was so unanticipated, so difficult to operationalize. What they were able to create was amazing, but there were just too many barriers to have it work smoothly,” Dr. Krouss said.

Courtesy of Renown Regional Medical Center

Replicating hospital work flows

“We ensured that everybody who needed to be within the walls of the permanent hospitals was able to stay there,” said Dr. Lee’s colleague, hospitalist Adnan (Eddy) Akbar, MD. “The postacute system we ordinarily rely on was no longer accepting patients. Other hospitals in the area were able to manage within their capacity because Renown’s field hospital could admit excess patients. We tried to replicate in the field hospital, as much as possible, the work flows and systems of our main hospital.”

When the field hospital finally opened, Dr. Akbar said, “we had a good feeling. We were ready. If something more catastrophic had come down, we were ready to care for more patients. In the field hospital you have to keep monitoring your work flow – almost on a daily basis. But we felt privileged to be working for a system where you knew you can go and care for everyone who needed care.”

One upside of the field hospital experience for participating clinicians, Dr. Lee added, is the opportunity to practice creatively. “The downside is it’s extremely expensive, and has consequences for the mental health of staff. Like so many of these things, it wore on people over time – such as all the time spent donning and doffing protective equipment. And recently the patients have become a lot less gracious.”

Amy Baughman, MD, a hospitalist at Massachusetts General Hospital in Boston, was co-medical director of the postacute care section of a 1,000-bed field hospital, Boston Hope Medical Center, opened in April 2020 at the Boston Convention and Exhibition Center. The other half of the facility was dedicated to undomiciled COVID-19 patients who had no place else to go. Peak census was around 100 patients, housed on four units, each with a clinical team led by a physician.

Partners HealthCare

References

1. Horowitz J. Italy’s health care system groans under coronavirus – a warning to the world. New York Times. 2020 Mar 12.

2. Bell SA et al. T-Minus 10 days: The role of an academic medical institution in field hospital planning. Prehosp Disaster Med. 2021 Feb 18:1-6. doi: 10.1017/S1049023X21000224.

3. Singh K et al. Evaluating a widely implemented proprietary deterioration index model among hospitalized patients with COVID-19. Ann Am Thorac Soc. 2021 Jul;18(7):1129-37. doi: 10.1513/AnnalsATS.202006-698OC.

4. Bell SA et al. Alternate care sites during COVID-19 pandemic: Policy implications for pandemic surge planning. Disaster Med Public Health Prep. 2021 Jul 23;1-3. doi: 10.1017/dmp.2021.241.

I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m²) seen in the pediatric emergency department with tachycardia, O₂ saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.¹

She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.

Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”

The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.²

Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?

Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.

Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.³

Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.

Implementation challenges

The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.

Summary

Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.⁴ Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].

References

1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.

2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.

3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.

4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.

I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m²) seen in the pediatric emergency department with tachycardia, O₂ saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.¹

She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.

Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”

The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.²

Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?

Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.

Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.³

Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.

Implementation challenges

The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.

Summary

Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.⁴ Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].

References

1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.

2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.

3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.

4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.

I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m²) seen in the pediatric emergency department with tachycardia, O₂ saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.¹

She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.

Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”

The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.²

Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?

Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.

Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.³

Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.

Implementation challenges

The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.

Summary

Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.⁴ Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].

References

1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.

2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.

3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.

4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.

With deer hunting season underway or starting in states across the United States, people should wear a mask and gloves when handling deer to prevent coronavirus transmission, experts say.

A recent study by researchers at Penn State University found that more than 80% of the deer sampled during last year’s hunting season in counties across Iowa tested positive for COVID-19. Overall, a third of the deer sampled between September 2020 and January 2021 tested positive.

“The findings suggest that white-tailed deer may be a reservoir for the virus to continually circulate and raise concerns about the emergence of new strains that may prove a threat to wildlife and, possibly, to humans,” the researchers said in a statement.

The deer were likely infected due to “multiple human-to-deer spillover events and deer-to-deer transmission,” they noted.

Studies haven’t shown whether deer have infected humans, but public health experts are recommending that hunters and deer handlers consider possible transmission avenues, The Plain Dealer, a Cleveland newspaper, reported.

To limit deer-to-deer transmission, homeowners and hunters should avoid concentrating deer at backyard feeders or in hunting situations, according to the Ohio Department of Natural Resources Division of Wildlife. The department also urged people to not allow contact between wildlife and domestic animals, including pets and hunting dogs.

Eating venison shouldn’t be a concern if people cook the meat thoroughly, the newspaper reported. Until more is known, people should wear a mask and gloves when handling deer.

In the study, Penn State researchers examined 283 deer between December 2020 and January 2021. They took samples from lymph nodes in the head and neck as part of Iowa’s chronic wasting disease surveillance program.

“This is the first direct evidence of SARS-CoV-2 virus in any free-living species, and our findings have important implications for the ecology and long-term persistence of the virus,” Suresh Kuchipudi, PhD, associate director of the Animal Diagnostics Laboratory at Penn State, said in the statement.

“These include spillover to other free-living or captive animals and potential spillback to human hosts,” he said. “Of course, this highlights that many urgent steps are needed to monitor the spread of the virus in deer and prevent spillback to humans.”

The research team sequenced genomes from all the positive samples and identified 12 coronavirus lineages. The prominent ones corresponded to the same lineages found in humans at the time.

The U.S. Department of Agriculture has also inspected 480 samples this year from white-tailed deer in Illinois, Michigan, New York, and Pennsylvania. Researchers detected virus antibodies in 33% of samples, according to a statement from the department. The department has confirmed the virus in deer in Ohio as well.

Health officials have recommended that hunters also take precautions while around other people by getting vaccinated and wearing a mask, according to WMTV in Wisconsin.

“If someone comes to deer camp and they have COVID and other folks aren’t vaccinated, in that enclosed space with the laughing and good times that are had, the likelihood that those other hunters would be infected is pretty high,” Jeff Pothof, MD, an emergency medicine doctor at UW Health, told the news outlet.

“I think the biggest risk to deer hunters is going to be other hunters, not so much the deer,” he said.

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

With deer hunting season underway or starting in states across the United States, people should wear a mask and gloves when handling deer to prevent coronavirus transmission, experts say.

A recent study by researchers at Penn State University found that more than 80% of the deer sampled during last year’s hunting season in counties across Iowa tested positive for COVID-19. Overall, a third of the deer sampled between September 2020 and January 2021 tested positive.

“The findings suggest that white-tailed deer may be a reservoir for the virus to continually circulate and raise concerns about the emergence of new strains that may prove a threat to wildlife and, possibly, to humans,” the researchers said in a statement.

The deer were likely infected due to “multiple human-to-deer spillover events and deer-to-deer transmission,” they noted.

Studies haven’t shown whether deer have infected humans, but public health experts are recommending that hunters and deer handlers consider possible transmission avenues, The Plain Dealer, a Cleveland newspaper, reported.

To limit deer-to-deer transmission, homeowners and hunters should avoid concentrating deer at backyard feeders or in hunting situations, according to the Ohio Department of Natural Resources Division of Wildlife. The department also urged people to not allow contact between wildlife and domestic animals, including pets and hunting dogs.

Eating venison shouldn’t be a concern if people cook the meat thoroughly, the newspaper reported. Until more is known, people should wear a mask and gloves when handling deer.

In the study, Penn State researchers examined 283 deer between December 2020 and January 2021. They took samples from lymph nodes in the head and neck as part of Iowa’s chronic wasting disease surveillance program.

“This is the first direct evidence of SARS-CoV-2 virus in any free-living species, and our findings have important implications for the ecology and long-term persistence of the virus,” Suresh Kuchipudi, PhD, associate director of the Animal Diagnostics Laboratory at Penn State, said in the statement.

“These include spillover to other free-living or captive animals and potential spillback to human hosts,” he said. “Of course, this highlights that many urgent steps are needed to monitor the spread of the virus in deer and prevent spillback to humans.”

The research team sequenced genomes from all the positive samples and identified 12 coronavirus lineages. The prominent ones corresponded to the same lineages found in humans at the time.

The U.S. Department of Agriculture has also inspected 480 samples this year from white-tailed deer in Illinois, Michigan, New York, and Pennsylvania. Researchers detected virus antibodies in 33% of samples, according to a statement from the department. The department has confirmed the virus in deer in Ohio as well.

Health officials have recommended that hunters also take precautions while around other people by getting vaccinated and wearing a mask, according to WMTV in Wisconsin.

“If someone comes to deer camp and they have COVID and other folks aren’t vaccinated, in that enclosed space with the laughing and good times that are had, the likelihood that those other hunters would be infected is pretty high,” Jeff Pothof, MD, an emergency medicine doctor at UW Health, told the news outlet.

“I think the biggest risk to deer hunters is going to be other hunters, not so much the deer,” he said.

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

With deer hunting season underway or starting in states across the United States, people should wear a mask and gloves when handling deer to prevent coronavirus transmission, experts say.

A recent study by researchers at Penn State University found that more than 80% of the deer sampled during last year’s hunting season in counties across Iowa tested positive for COVID-19. Overall, a third of the deer sampled between September 2020 and January 2021 tested positive.

“The findings suggest that white-tailed deer may be a reservoir for the virus to continually circulate and raise concerns about the emergence of new strains that may prove a threat to wildlife and, possibly, to humans,” the researchers said in a statement.

The deer were likely infected due to “multiple human-to-deer spillover events and deer-to-deer transmission,” they noted.

Studies haven’t shown whether deer have infected humans, but public health experts are recommending that hunters and deer handlers consider possible transmission avenues, The Plain Dealer, a Cleveland newspaper, reported.

To limit deer-to-deer transmission, homeowners and hunters should avoid concentrating deer at backyard feeders or in hunting situations, according to the Ohio Department of Natural Resources Division of Wildlife. The department also urged people to not allow contact between wildlife and domestic animals, including pets and hunting dogs.

Eating venison shouldn’t be a concern if people cook the meat thoroughly, the newspaper reported. Until more is known, people should wear a mask and gloves when handling deer.

In the study, Penn State researchers examined 283 deer between December 2020 and January 2021. They took samples from lymph nodes in the head and neck as part of Iowa’s chronic wasting disease surveillance program.

“This is the first direct evidence of SARS-CoV-2 virus in any free-living species, and our findings have important implications for the ecology and long-term persistence of the virus,” Suresh Kuchipudi, PhD, associate director of the Animal Diagnostics Laboratory at Penn State, said in the statement.

“These include spillover to other free-living or captive animals and potential spillback to human hosts,” he said. “Of course, this highlights that many urgent steps are needed to monitor the spread of the virus in deer and prevent spillback to humans.”

The research team sequenced genomes from all the positive samples and identified 12 coronavirus lineages. The prominent ones corresponded to the same lineages found in humans at the time.

The U.S. Department of Agriculture has also inspected 480 samples this year from white-tailed deer in Illinois, Michigan, New York, and Pennsylvania. Researchers detected virus antibodies in 33% of samples, according to a statement from the department. The department has confirmed the virus in deer in Ohio as well.

Health officials have recommended that hunters also take precautions while around other people by getting vaccinated and wearing a mask, according to WMTV in Wisconsin.

“If someone comes to deer camp and they have COVID and other folks aren’t vaccinated, in that enclosed space with the laughing and good times that are had, the likelihood that those other hunters would be infected is pretty high,” Jeff Pothof, MD, an emergency medicine doctor at UW Health, told the news outlet.

“I think the biggest risk to deer hunters is going to be other hunters, not so much the deer,” he said.

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

A systematic review of studies of infections found no evidence of airborne transmission of respiratory or enteric pathogens in public washrooms, but some experts disagree with the study’s conclusions. The study was published in Science of the Total Environment.

Sotiris Vardoulakis, PhD, of the Australian National University, Canberra, and colleagues reviewed studies of infections associated with public washrooms.

The researchers used keywords to identify potential articles. After screening study abstracts to ensure that only publicly available washrooms with toilets, sinks, and hand dryers were included, 65 studies remained. The investigators excluded washrooms on public transportation (ships, planes, trains, and buses).

“What most of the studies concluded was that what’s really important is to have good hand hygiene and proper maintenance and ventilation of washrooms,” Dr. Vardoulakis said in an interview. “So if the hand washing and drying is effective in the first place, it’s unlikely that the bathroom air or surfaces will pose an infectious disease transmission risk.”

There has been ongoing debate on whether electric hand dryers or paper towels are better. Some studies focused on hygiene. Others focused on the environmental cost of paper towels. One concern is that air dryers might spread germs further.

One study focused on the idea that the air recirculation from electric dryers may spread infective aerosols. Another study determined that the Airblade filters in some electric dryers clean more than 99% of the bacteria. The first study, published in Mayo Clinic Proceedings by Cunrui Huang, MMed, MSPH, and colleagues, concluded that “drying hands thoroughly with single-use, disposable paper towels is the preferred method of hand drying in terms of hand hygiene.” Many people prefer to use paper towels because they can be used as a barrier when opening the washroom door.

Dr. Vardoulakis dismissed the air-versus-paper debate, saying, “If the hand washing and drying is effective in the first place, it’s unlikely that the bathroom air or surfaces will pose an infectious disease transmission risk.”

Although Dr. Vardoulakis’ review did not find that public washrooms pose a risk for infection, other researchers have shown that some settings do pose problems. For example, toilet plumes are thought to have contributed to the 2003 outbreak of severe acute respiratory syndrome at the Amoy Gardens housing complex in Hong Kong and nearby buildings by aerosolization of fecal waste. Also, norovirus has long been shown to be transmitted by aerosolized particles in vomitus or stool.

Rodney E. Rohde, PhD, professor and chair, clinical lab science program, Texas State University, San Marcos, expressed concern about this systematic review in an interview with this news organization. “I believe one of the major limitations is that studies which involved restrooms on planes, hotels, camping (those camp kids are nasty), and other similar public-access restrooms MUST be included in this type of review. I also believe they excluded restrooms from low-income/rural areas. WHAT? Their ultimate conclusions seem to be in line with the most current understanding about hand hygiene (including drying without devices that create strong air currents, which may create widespread emission of microbes).”

In an interview, Emanuel Goldman, PhD, professor of microbiology, biochemistry, and molecular genetics, New Jersey Medical School, Newark, focused on the COVID-specific aspects of the review. “The chances are less than 1 in 10,000 of getting COVID from a fomite, and that’s very conservative,” he said. “I think it’s a lot lower than that. The virus is fragile. It dies very quickly outside of a human host.” He emphasized, “virtually no infectious virus has been found on fomites over the last 2 years. ... A big mistake in a lot of papers is they confuse viral RNA with the virus. It’s not the same. Viral RNA is the genetic material of the virus, but it also is the ghost of the virus after the virus is dead, and that’s what people are finding. They’re finding the ghost of the virus.”

Because “studies show that the transfer from a surface to fingers is in the neighborhood of 10% efficiency” and one’s fingers also kill the virus, “transmission through your fingers is not easy,” Dr. Goldman said. “You’ve got to really work at it to deliberately infect yourself” with COVID from a fomite.

Dr. Rohde’s conclusion about Dr. Vardoulakis’s review? “So, the question may be, have there been enough studies, in general, of these other areas to include in a review? Otherwise, can we really generalize from this study? I don’t think so.”

Dr. Goldman is not worried about COVID transmission in public bathrooms. His summation: “I think indoor dining is more risky than anything else right now.”

The study was funded by Dyson Technology. Dr. Vardoulakis is a member of the Dyson scientific advisory board.

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

A systematic review of studies of infections found no evidence of airborne transmission of respiratory or enteric pathogens in public washrooms, but some experts disagree with the study’s conclusions. The study was published in Science of the Total Environment.

Sotiris Vardoulakis, PhD, of the Australian National University, Canberra, and colleagues reviewed studies of infections associated with public washrooms.

The researchers used keywords to identify potential articles. After screening study abstracts to ensure that only publicly available washrooms with toilets, sinks, and hand dryers were included, 65 studies remained. The investigators excluded washrooms on public transportation (ships, planes, trains, and buses).

“What most of the studies concluded was that what’s really important is to have good hand hygiene and proper maintenance and ventilation of washrooms,” Dr. Vardoulakis said in an interview. “So if the hand washing and drying is effective in the first place, it’s unlikely that the bathroom air or surfaces will pose an infectious disease transmission risk.”

There has been ongoing debate on whether electric hand dryers or paper towels are better. Some studies focused on hygiene. Others focused on the environmental cost of paper towels. One concern is that air dryers might spread germs further.

One study focused on the idea that the air recirculation from electric dryers may spread infective aerosols. Another study determined that the Airblade filters in some electric dryers clean more than 99% of the bacteria. The first study, published in Mayo Clinic Proceedings by Cunrui Huang, MMed, MSPH, and colleagues, concluded that “drying hands thoroughly with single-use, disposable paper towels is the preferred method of hand drying in terms of hand hygiene.” Many people prefer to use paper towels because they can be used as a barrier when opening the washroom door.

Dr. Vardoulakis dismissed the air-versus-paper debate, saying, “If the hand washing and drying is effective in the first place, it’s unlikely that the bathroom air or surfaces will pose an infectious disease transmission risk.”

Although Dr. Vardoulakis’ review did not find that public washrooms pose a risk for infection, other researchers have shown that some settings do pose problems. For example, toilet plumes are thought to have contributed to the 2003 outbreak of severe acute respiratory syndrome at the Amoy Gardens housing complex in Hong Kong and nearby buildings by aerosolization of fecal waste. Also, norovirus has long been shown to be transmitted by aerosolized particles in vomitus or stool.

Rodney E. Rohde, PhD, professor and chair, clinical lab science program, Texas State University, San Marcos, expressed concern about this systematic review in an interview with this news organization. “I believe one of the major limitations is that studies which involved restrooms on planes, hotels, camping (those camp kids are nasty), and other similar public-access restrooms MUST be included in this type of review. I also believe they excluded restrooms from low-income/rural areas. WHAT? Their ultimate conclusions seem to be in line with the most current understanding about hand hygiene (including drying without devices that create strong air currents, which may create widespread emission of microbes).”

In an interview, Emanuel Goldman, PhD, professor of microbiology, biochemistry, and molecular genetics, New Jersey Medical School, Newark, focused on the COVID-specific aspects of the review. “The chances are less than 1 in 10,000 of getting COVID from a fomite, and that’s very conservative,” he said. “I think it’s a lot lower than that. The virus is fragile. It dies very quickly outside of a human host.” He emphasized, “virtually no infectious virus has been found on fomites over the last 2 years. ... A big mistake in a lot of papers is they confuse viral RNA with the virus. It’s not the same. Viral RNA is the genetic material of the virus, but it also is the ghost of the virus after the virus is dead, and that’s what people are finding. They’re finding the ghost of the virus.”

Because “studies show that the transfer from a surface to fingers is in the neighborhood of 10% efficiency” and one’s fingers also kill the virus, “transmission through your fingers is not easy,” Dr. Goldman said. “You’ve got to really work at it to deliberately infect yourself” with COVID from a fomite.

Dr. Rohde’s conclusion about Dr. Vardoulakis’s review? “So, the question may be, have there been enough studies, in general, of these other areas to include in a review? Otherwise, can we really generalize from this study? I don’t think so.”

Dr. Goldman is not worried about COVID transmission in public bathrooms. His summation: “I think indoor dining is more risky than anything else right now.”

The study was funded by Dyson Technology. Dr. Vardoulakis is a member of the Dyson scientific advisory board.

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

A systematic review of studies of infections found no evidence of airborne transmission of respiratory or enteric pathogens in public washrooms, but some experts disagree with the study’s conclusions. The study was published in Science of the Total Environment.

Sotiris Vardoulakis, PhD, of the Australian National University, Canberra, and colleagues reviewed studies of infections associated with public washrooms.

The researchers used keywords to identify potential articles. After screening study abstracts to ensure that only publicly available washrooms with toilets, sinks, and hand dryers were included, 65 studies remained. The investigators excluded washrooms on public transportation (ships, planes, trains, and buses).

“What most of the studies concluded was that what’s really important is to have good hand hygiene and proper maintenance and ventilation of washrooms,” Dr. Vardoulakis said in an interview. “So if the hand washing and drying is effective in the first place, it’s unlikely that the bathroom air or surfaces will pose an infectious disease transmission risk.”

There has been ongoing debate on whether electric hand dryers or paper towels are better. Some studies focused on hygiene. Others focused on the environmental cost of paper towels. One concern is that air dryers might spread germs further.

One study focused on the idea that the air recirculation from electric dryers may spread infective aerosols. Another study determined that the Airblade filters in some electric dryers clean more than 99% of the bacteria. The first study, published in Mayo Clinic Proceedings by Cunrui Huang, MMed, MSPH, and colleagues, concluded that “drying hands thoroughly with single-use, disposable paper towels is the preferred method of hand drying in terms of hand hygiene.” Many people prefer to use paper towels because they can be used as a barrier when opening the washroom door.

Dr. Vardoulakis dismissed the air-versus-paper debate, saying, “If the hand washing and drying is effective in the first place, it’s unlikely that the bathroom air or surfaces will pose an infectious disease transmission risk.”

Although Dr. Vardoulakis’ review did not find that public washrooms pose a risk for infection, other researchers have shown that some settings do pose problems. For example, toilet plumes are thought to have contributed to the 2003 outbreak of severe acute respiratory syndrome at the Amoy Gardens housing complex in Hong Kong and nearby buildings by aerosolization of fecal waste. Also, norovirus has long been shown to be transmitted by aerosolized particles in vomitus or stool.

Rodney E. Rohde, PhD, professor and chair, clinical lab science program, Texas State University, San Marcos, expressed concern about this systematic review in an interview with this news organization. “I believe one of the major limitations is that studies which involved restrooms on planes, hotels, camping (those camp kids are nasty), and other similar public-access restrooms MUST be included in this type of review. I also believe they excluded restrooms from low-income/rural areas. WHAT? Their ultimate conclusions seem to be in line with the most current understanding about hand hygiene (including drying without devices that create strong air currents, which may create widespread emission of microbes).”

In an interview, Emanuel Goldman, PhD, professor of microbiology, biochemistry, and molecular genetics, New Jersey Medical School, Newark, focused on the COVID-specific aspects of the review. “The chances are less than 1 in 10,000 of getting COVID from a fomite, and that’s very conservative,” he said. “I think it’s a lot lower than that. The virus is fragile. It dies very quickly outside of a human host.” He emphasized, “virtually no infectious virus has been found on fomites over the last 2 years. ... A big mistake in a lot of papers is they confuse viral RNA with the virus. It’s not the same. Viral RNA is the genetic material of the virus, but it also is the ghost of the virus after the virus is dead, and that’s what people are finding. They’re finding the ghost of the virus.”

Because “studies show that the transfer from a surface to fingers is in the neighborhood of 10% efficiency” and one’s fingers also kill the virus, “transmission through your fingers is not easy,” Dr. Goldman said. “You’ve got to really work at it to deliberately infect yourself” with COVID from a fomite.

Dr. Rohde’s conclusion about Dr. Vardoulakis’s review? “So, the question may be, have there been enough studies, in general, of these other areas to include in a review? Otherwise, can we really generalize from this study? I don’t think so.”

Dr. Goldman is not worried about COVID transmission in public bathrooms. His summation: “I think indoor dining is more risky than anything else right now.”

The study was funded by Dyson Technology. Dr. Vardoulakis is a member of the Dyson scientific advisory board.

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

At its November meeting, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) voted against Biogen’s controversial Alzheimer’s drug aducanumab (Aduhelm), making it highly unlikely the drug will be recommended for approval at its December meeting.

In a news release issued Nov. 17, Biogen said the company received a “negative trend vote” on the aducanumab marketing authorization application in Europe.

“While we are disappointed with the trend vote, we strongly believe in the strength of our data and that aducanumab has the potential to make a positive and meaningful difference for people and families affected by Alzheimer’s disease [AD],” Priya Singhal, MD, MPH, head of global safety and regulatory sciences and interim head of research and development at Biogen, said in the release.

The EMA committee is expected to adopt a formal opinion on the marketing application at its December meeting (Dec. 13-16, 2021).

“Biogen will continue to engage with the EMA and CHMP as it considers next steps towards the goal of providing access to aducanumab to patients in Europe,” the company said.

At the recent Clinical Trials on Alzheimer’s Disease conference, Biogen announced new phase 3 findings that “provide further evidence of aducanumab’s effect on lowering amyloid beta plaque and downstream tau pathology, the two defining pathologies of Alzheimer’s disease,” the company said.
 

No clinically meaningful effect

In a statement from the nonprofit U.K. Science Media Centre, Prof. Robert Howard, from University College London, said the result of the CHMP vote “is absolutely the decision that we should have expected from the EMA’s expert advisory panel and is consistent with the FDA’s [U.S. Food and Drug Administration’s] Advisory Committee who voted unanimously 12 months ago against approval of aducanumab because of a lack of demonstrable efficacy in the pivotal phase 3 trials ENGAGE and EMERGE.”

“The FDA’s accelerated approval of aducanumab, solely on the grounds that it was reasonable to expect that reduction in amyloid would lead to improvement in the course of Alzheimer’s disease, despite all the evidence indicating no meaningful correlation between amyloid reduction and symptom improvement, has been highly controversial and has called into question the impartiality of the FDA and its staff,” Prof. Howard noted.

He anticipates that when the EMA panel meets in December they will not grant a license to aducanumab.

“Aducanumab is a treatment without convincing efficacy, with serious associated adverse effects and a high financial cost. On the basis of the available evidence and in the best interests of people with Alzheimer’s disease, their families and those who care for them, EMA and MHRA [Medicines and Healthcare products Regulatory Agency] should not approve a license for aducanumab,” Prof. Howard said.

Also weighing in, David Thomas, head of policy at Alzheimer’s Research UK, said the need for new AD treatments is “urgent,” but added that “it’s vital that regulators judge that any new treatment is safe and effective.”

“Results of aducanumab’s phase 3 trials, EMERGE and ENGAGE, have sparked much debate among the research community about how to judge the effectiveness of any new Alzheimer’s treatment,” Mr. Thomas noted.

“The FDA’s approval of aducanumab in the U.S. was based on the drug’s ability to clear the hallmark Alzheimer’s protein amyloid from the brain. As part of this approval the regulator now requires further trials to be carried out to ensure that aducanumab brings long-term improvement to people’s memory, thinking and day-to-day lives,” Mr. Thomas said.

EMA is now undertaking its own review of the data and “it’s important that we wait for the committee’s official recommendation, which is expected next month. In the meantime, we must continue to work at pace to ensure researchers are developing a broad pipeline of potential new treatments for diseases like Alzheimer’s, and that health systems like the NHS [National Health Service] will be ready to deliver them in the years ahead,” he added.
 

‘Reckless’ FDA decision

In related news, the Centers for Medicare and Medicaid Services (CMS) has announced that the Medicare Part B standard premium would rise to $170 per month for all enrollees, a 15% spike over the 2021 premium level.

“All Part B Medicare beneficiaries soon will be forced to bear significant financial burden as a direct result of the FDA’s reckless decision to approve aducanumab, a drug that has not been proven to provide any clinically meaningful benefit to Alzheimer’s patients but nevertheless carries an indefensible annual price tag set by Biogen at $56,000 per year for just the drug alone,” Michael Carome, MD, director of Public Citizen’s Health Research Group, said in a statement.

“To protect the many Medicare beneficiaries who cannot afford the unacceptable 15% jump in Part B premiums, CMS must promptly announce that it will exclude aducanumab from coverage under the Medicare program until there is definitive evidence that the drug provides substantial evidence of cognitive benefit to Alzheimer’s disease patients,” Dr. Carome said.

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

At its November meeting, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) voted against Biogen’s controversial Alzheimer’s drug aducanumab (Aduhelm), making it highly unlikely the drug will be recommended for approval at its December meeting.

In a news release issued Nov. 17, Biogen said the company received a “negative trend vote” on the aducanumab marketing authorization application in Europe.

“While we are disappointed with the trend vote, we strongly believe in the strength of our data and that aducanumab has the potential to make a positive and meaningful difference for people and families affected by Alzheimer’s disease [AD],” Priya Singhal, MD, MPH, head of global safety and regulatory sciences and interim head of research and development at Biogen, said in the release.

The EMA committee is expected to adopt a formal opinion on the marketing application at its December meeting (Dec. 13-16, 2021).

“Biogen will continue to engage with the EMA and CHMP as it considers next steps towards the goal of providing access to aducanumab to patients in Europe,” the company said.

At the recent Clinical Trials on Alzheimer’s Disease conference, Biogen announced new phase 3 findings that “provide further evidence of aducanumab’s effect on lowering amyloid beta plaque and downstream tau pathology, the two defining pathologies of Alzheimer’s disease,” the company said.
 

No clinically meaningful effect

In a statement from the nonprofit U.K. Science Media Centre, Prof. Robert Howard, from University College London, said the result of the CHMP vote “is absolutely the decision that we should have expected from the EMA’s expert advisory panel and is consistent with the FDA’s [U.S. Food and Drug Administration’s] Advisory Committee who voted unanimously 12 months ago against approval of aducanumab because of a lack of demonstrable efficacy in the pivotal phase 3 trials ENGAGE and EMERGE.”

“The FDA’s accelerated approval of aducanumab, solely on the grounds that it was reasonable to expect that reduction in amyloid would lead to improvement in the course of Alzheimer’s disease, despite all the evidence indicating no meaningful correlation between amyloid reduction and symptom improvement, has been highly controversial and has called into question the impartiality of the FDA and its staff,” Prof. Howard noted.

He anticipates that when the EMA panel meets in December they will not grant a license to aducanumab.

“Aducanumab is a treatment without convincing efficacy, with serious associated adverse effects and a high financial cost. On the basis of the available evidence and in the best interests of people with Alzheimer’s disease, their families and those who care for them, EMA and MHRA [Medicines and Healthcare products Regulatory Agency] should not approve a license for aducanumab,” Prof. Howard said.

Also weighing in, David Thomas, head of policy at Alzheimer’s Research UK, said the need for new AD treatments is “urgent,” but added that “it’s vital that regulators judge that any new treatment is safe and effective.”

“Results of aducanumab’s phase 3 trials, EMERGE and ENGAGE, have sparked much debate among the research community about how to judge the effectiveness of any new Alzheimer’s treatment,” Mr. Thomas noted.

“The FDA’s approval of aducanumab in the U.S. was based on the drug’s ability to clear the hallmark Alzheimer’s protein amyloid from the brain. As part of this approval the regulator now requires further trials to be carried out to ensure that aducanumab brings long-term improvement to people’s memory, thinking and day-to-day lives,” Mr. Thomas said.

EMA is now undertaking its own review of the data and “it’s important that we wait for the committee’s official recommendation, which is expected next month. In the meantime, we must continue to work at pace to ensure researchers are developing a broad pipeline of potential new treatments for diseases like Alzheimer’s, and that health systems like the NHS [National Health Service] will be ready to deliver them in the years ahead,” he added.
 

‘Reckless’ FDA decision

In related news, the Centers for Medicare and Medicaid Services (CMS) has announced that the Medicare Part B standard premium would rise to $170 per month for all enrollees, a 15% spike over the 2021 premium level.

“All Part B Medicare beneficiaries soon will be forced to bear significant financial burden as a direct result of the FDA’s reckless decision to approve aducanumab, a drug that has not been proven to provide any clinically meaningful benefit to Alzheimer’s patients but nevertheless carries an indefensible annual price tag set by Biogen at $56,000 per year for just the drug alone,” Michael Carome, MD, director of Public Citizen’s Health Research Group, said in a statement.

“To protect the many Medicare beneficiaries who cannot afford the unacceptable 15% jump in Part B premiums, CMS must promptly announce that it will exclude aducanumab from coverage under the Medicare program until there is definitive evidence that the drug provides substantial evidence of cognitive benefit to Alzheimer’s disease patients,” Dr. Carome said.

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

At its November meeting, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) voted against Biogen’s controversial Alzheimer’s drug aducanumab (Aduhelm), making it highly unlikely the drug will be recommended for approval at its December meeting.

In a news release issued Nov. 17, Biogen said the company received a “negative trend vote” on the aducanumab marketing authorization application in Europe.

“While we are disappointed with the trend vote, we strongly believe in the strength of our data and that aducanumab has the potential to make a positive and meaningful difference for people and families affected by Alzheimer’s disease [AD],” Priya Singhal, MD, MPH, head of global safety and regulatory sciences and interim head of research and development at Biogen, said in the release.

The EMA committee is expected to adopt a formal opinion on the marketing application at its December meeting (Dec. 13-16, 2021).

“Biogen will continue to engage with the EMA and CHMP as it considers next steps towards the goal of providing access to aducanumab to patients in Europe,” the company said.

At the recent Clinical Trials on Alzheimer’s Disease conference, Biogen announced new phase 3 findings that “provide further evidence of aducanumab’s effect on lowering amyloid beta plaque and downstream tau pathology, the two defining pathologies of Alzheimer’s disease,” the company said.
 

No clinically meaningful effect

In a statement from the nonprofit U.K. Science Media Centre, Prof. Robert Howard, from University College London, said the result of the CHMP vote “is absolutely the decision that we should have expected from the EMA’s expert advisory panel and is consistent with the FDA’s [U.S. Food and Drug Administration’s] Advisory Committee who voted unanimously 12 months ago against approval of aducanumab because of a lack of demonstrable efficacy in the pivotal phase 3 trials ENGAGE and EMERGE.”

“The FDA’s accelerated approval of aducanumab, solely on the grounds that it was reasonable to expect that reduction in amyloid would lead to improvement in the course of Alzheimer’s disease, despite all the evidence indicating no meaningful correlation between amyloid reduction and symptom improvement, has been highly controversial and has called into question the impartiality of the FDA and its staff,” Prof. Howard noted.

He anticipates that when the EMA panel meets in December they will not grant a license to aducanumab.

“Aducanumab is a treatment without convincing efficacy, with serious associated adverse effects and a high financial cost. On the basis of the available evidence and in the best interests of people with Alzheimer’s disease, their families and those who care for them, EMA and MHRA [Medicines and Healthcare products Regulatory Agency] should not approve a license for aducanumab,” Prof. Howard said.

Also weighing in, David Thomas, head of policy at Alzheimer’s Research UK, said the need for new AD treatments is “urgent,” but added that “it’s vital that regulators judge that any new treatment is safe and effective.”

“Results of aducanumab’s phase 3 trials, EMERGE and ENGAGE, have sparked much debate among the research community about how to judge the effectiveness of any new Alzheimer’s treatment,” Mr. Thomas noted.

“The FDA’s approval of aducanumab in the U.S. was based on the drug’s ability to clear the hallmark Alzheimer’s protein amyloid from the brain. As part of this approval the regulator now requires further trials to be carried out to ensure that aducanumab brings long-term improvement to people’s memory, thinking and day-to-day lives,” Mr. Thomas said.

EMA is now undertaking its own review of the data and “it’s important that we wait for the committee’s official recommendation, which is expected next month. In the meantime, we must continue to work at pace to ensure researchers are developing a broad pipeline of potential new treatments for diseases like Alzheimer’s, and that health systems like the NHS [National Health Service] will be ready to deliver them in the years ahead,” he added.
 

‘Reckless’ FDA decision

In related news, the Centers for Medicare and Medicaid Services (CMS) has announced that the Medicare Part B standard premium would rise to $170 per month for all enrollees, a 15% spike over the 2021 premium level.

“All Part B Medicare beneficiaries soon will be forced to bear significant financial burden as a direct result of the FDA’s reckless decision to approve aducanumab, a drug that has not been proven to provide any clinically meaningful benefit to Alzheimer’s patients but nevertheless carries an indefensible annual price tag set by Biogen at $56,000 per year for just the drug alone,” Michael Carome, MD, director of Public Citizen’s Health Research Group, said in a statement.

“To protect the many Medicare beneficiaries who cannot afford the unacceptable 15% jump in Part B premiums, CMS must promptly announce that it will exclude aducanumab from coverage under the Medicare program until there is definitive evidence that the drug provides substantial evidence of cognitive benefit to Alzheimer’s disease patients,” Dr. Carome said.

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

The Centers for Disease Control and Prevention reported that an estimated 100,306 Americans died from drug overdoses during the period from April 2020 to April 2021, a 28.5% increase from the previous year.

Deaths in some states rose even more precipitously. Vermont saw an almost 70% increase, and drug overdose deaths in West Virginia increased by 62%. Many states, including Alabama, California, Kansas, Kentucky, Louisiana, Tennessee, and Washington, had a 45%-50% rise in overdose deaths.

The data released by the CDC was provisional, as there is generally a lag between a reported overdose and confirmation of the death to the National Vital Statistics System. The agency uses statistical models that render the counts almost 100% accurate, the CDC says.

The vast majority (73,757) of overdose deaths involved opioids – with most of those (62,338) involving synthetic opioids such as fentanyl. Federal officials said that one American died every 5 minutes from an overdose, or 265 a day.

“We have to acknowledge what this is – it is a crisis,” Department of Health & Human Services Secretary Xavier Becerra told reporters on a call.

“As much as the numbers speak so vividly, they don’t tell the whole story. We see it in the faces of grieving families and all those overworked caregivers. You hear it every time you get that panicked 911 phone call, you read it in obituaries of sons and daughters who left us way too soon,” Mr. Becerra said.

Rahul Gupta, MD, director of the White House Office of National Drug Control Policy, said that “this is unacceptable, and it requires an unprecedented response.”

Dr. Gupta, who noted that he has a waiver to treat substance use disorder patients with buprenorphine, said he’s seen “first-hand the heartbreak of the overdose epidemic,” adding that, with 23 years in practice, “I’ve learned that an overdose is a cry for help and for far too many people that cry goes unanswered.”

Both Mr. Becerra and Dr. Gupta called on Congress to pass President Joe Biden’s fiscal 2022 budget request, noting that it calls for $41 billion – a $669 million increase from fiscal year 2021 – to go to agencies working on drug interdiction and substance use prevention, treatment, and recovery support. 

Dr. Gupta also announced that the administration was releasing a model law that could be used by state legislatures to help standardize policies on making the overdose antidote naloxone more accessible. Currently, such policies are a patchwork across the nation.

In addition, the federal government is newly supporting harm reduction, Mr. Becerra said. This means federal money can be used by clinics and outreach programs to buy fentanyl test strips, which they can then distribute to drug users.

“It’s important for Americans to have the ability to make sure that they can test for fentanyl in the substance,” Dr. Gupta said.
 

Fake pills, fentanyl a huge issue

Federal officials said that both fentanyl and methamphetamine are contributing to rising numbers of fatalities.

“Drug cartels in Mexico are mass-producing fentanyl and methamphetamine largely sourced from chemicals in China and they are distributing these substances throughout the United States,” Anne Milgram, administrator of the Drug Enforcement Administration, said on the call.

Ms. Milgram said the agency had seized 12,000 pounds of fentanyl in 2021, enough to provide every American with a lethal dose. Fentanyl is also mixed in with cocaine, heroin, methamphetamine, and marijuana – often in counterfeit pills, Ms. Milgram said.

The DEA and other law enforcement agencies have seized more than 14 million such pills in 2021. “These types of pills are easily accessible today on social media and e-commerce platforms, Ms. Milgram said.

“Drug dealers are now in our homes,” she said. “Wherever there is a smart phone or a computer, a dealer is one click away,” Ms. Milgram said.

National Institute on Drug Abuse Director Nora D. Volkow, MD, said that dealers will continue to push both fentanyl and methamphetamine because they are among the most addictive substances. They also are more profitable because they don’t require cultivation and harvesting, she said on the call.

Dr. Volkow also noted that naloxone is not as effective in reversing fentanyl overdoses because fentanyl is more potent than heroin and other opioids, and “it gets into the brain extremely rapidly.”

Ongoing research is aimed at developing a faster delivery mechanism and a longer-lasting formulation to counter overdoses, Dr. Volkow said.

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

The Centers for Disease Control and Prevention reported that an estimated 100,306 Americans died from drug overdoses during the period from April 2020 to April 2021, a 28.5% increase from the previous year.

Deaths in some states rose even more precipitously. Vermont saw an almost 70% increase, and drug overdose deaths in West Virginia increased by 62%. Many states, including Alabama, California, Kansas, Kentucky, Louisiana, Tennessee, and Washington, had a 45%-50% rise in overdose deaths.

The data released by the CDC was provisional, as there is generally a lag between a reported overdose and confirmation of the death to the National Vital Statistics System. The agency uses statistical models that render the counts almost 100% accurate, the CDC says.

The vast majority (73,757) of overdose deaths involved opioids – with most of those (62,338) involving synthetic opioids such as fentanyl. Federal officials said that one American died every 5 minutes from an overdose, or 265 a day.

“We have to acknowledge what this is – it is a crisis,” Department of Health & Human Services Secretary Xavier Becerra told reporters on a call.

“As much as the numbers speak so vividly, they don’t tell the whole story. We see it in the faces of grieving families and all those overworked caregivers. You hear it every time you get that panicked 911 phone call, you read it in obituaries of sons and daughters who left us way too soon,” Mr. Becerra said.

Rahul Gupta, MD, director of the White House Office of National Drug Control Policy, said that “this is unacceptable, and it requires an unprecedented response.”

Dr. Gupta, who noted that he has a waiver to treat substance use disorder patients with buprenorphine, said he’s seen “first-hand the heartbreak of the overdose epidemic,” adding that, with 23 years in practice, “I’ve learned that an overdose is a cry for help and for far too many people that cry goes unanswered.”

Both Mr. Becerra and Dr. Gupta called on Congress to pass President Joe Biden’s fiscal 2022 budget request, noting that it calls for $41 billion – a $669 million increase from fiscal year 2021 – to go to agencies working on drug interdiction and substance use prevention, treatment, and recovery support. 

Dr. Gupta also announced that the administration was releasing a model law that could be used by state legislatures to help standardize policies on making the overdose antidote naloxone more accessible. Currently, such policies are a patchwork across the nation.

In addition, the federal government is newly supporting harm reduction, Mr. Becerra said. This means federal money can be used by clinics and outreach programs to buy fentanyl test strips, which they can then distribute to drug users.

“It’s important for Americans to have the ability to make sure that they can test for fentanyl in the substance,” Dr. Gupta said.
 

Fake pills, fentanyl a huge issue

Federal officials said that both fentanyl and methamphetamine are contributing to rising numbers of fatalities.

“Drug cartels in Mexico are mass-producing fentanyl and methamphetamine largely sourced from chemicals in China and they are distributing these substances throughout the United States,” Anne Milgram, administrator of the Drug Enforcement Administration, said on the call.

Ms. Milgram said the agency had seized 12,000 pounds of fentanyl in 2021, enough to provide every American with a lethal dose. Fentanyl is also mixed in with cocaine, heroin, methamphetamine, and marijuana – often in counterfeit pills, Ms. Milgram said.

The DEA and other law enforcement agencies have seized more than 14 million such pills in 2021. “These types of pills are easily accessible today on social media and e-commerce platforms, Ms. Milgram said.

“Drug dealers are now in our homes,” she said. “Wherever there is a smart phone or a computer, a dealer is one click away,” Ms. Milgram said.

National Institute on Drug Abuse Director Nora D. Volkow, MD, said that dealers will continue to push both fentanyl and methamphetamine because they are among the most addictive substances. They also are more profitable because they don’t require cultivation and harvesting, she said on the call.

Dr. Volkow also noted that naloxone is not as effective in reversing fentanyl overdoses because fentanyl is more potent than heroin and other opioids, and “it gets into the brain extremely rapidly.”

Ongoing research is aimed at developing a faster delivery mechanism and a longer-lasting formulation to counter overdoses, Dr. Volkow said.

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

The Centers for Disease Control and Prevention reported that an estimated 100,306 Americans died from drug overdoses during the period from April 2020 to April 2021, a 28.5% increase from the previous year.

Deaths in some states rose even more precipitously. Vermont saw an almost 70% increase, and drug overdose deaths in West Virginia increased by 62%. Many states, including Alabama, California, Kansas, Kentucky, Louisiana, Tennessee, and Washington, had a 45%-50% rise in overdose deaths.

The data released by the CDC was provisional, as there is generally a lag between a reported overdose and confirmation of the death to the National Vital Statistics System. The agency uses statistical models that render the counts almost 100% accurate, the CDC says.

The vast majority (73,757) of overdose deaths involved opioids – with most of those (62,338) involving synthetic opioids such as fentanyl. Federal officials said that one American died every 5 minutes from an overdose, or 265 a day.

“We have to acknowledge what this is – it is a crisis,” Department of Health & Human Services Secretary Xavier Becerra told reporters on a call.

“As much as the numbers speak so vividly, they don’t tell the whole story. We see it in the faces of grieving families and all those overworked caregivers. You hear it every time you get that panicked 911 phone call, you read it in obituaries of sons and daughters who left us way too soon,” Mr. Becerra said.

Rahul Gupta, MD, director of the White House Office of National Drug Control Policy, said that “this is unacceptable, and it requires an unprecedented response.”

Dr. Gupta, who noted that he has a waiver to treat substance use disorder patients with buprenorphine, said he’s seen “first-hand the heartbreak of the overdose epidemic,” adding that, with 23 years in practice, “I’ve learned that an overdose is a cry for help and for far too many people that cry goes unanswered.”

Both Mr. Becerra and Dr. Gupta called on Congress to pass President Joe Biden’s fiscal 2022 budget request, noting that it calls for $41 billion – a $669 million increase from fiscal year 2021 – to go to agencies working on drug interdiction and substance use prevention, treatment, and recovery support. 

Dr. Gupta also announced that the administration was releasing a model law that could be used by state legislatures to help standardize policies on making the overdose antidote naloxone more accessible. Currently, such policies are a patchwork across the nation.

In addition, the federal government is newly supporting harm reduction, Mr. Becerra said. This means federal money can be used by clinics and outreach programs to buy fentanyl test strips, which they can then distribute to drug users.

“It’s important for Americans to have the ability to make sure that they can test for fentanyl in the substance,” Dr. Gupta said.
 

Fake pills, fentanyl a huge issue

Federal officials said that both fentanyl and methamphetamine are contributing to rising numbers of fatalities.

“Drug cartels in Mexico are mass-producing fentanyl and methamphetamine largely sourced from chemicals in China and they are distributing these substances throughout the United States,” Anne Milgram, administrator of the Drug Enforcement Administration, said on the call.

Ms. Milgram said the agency had seized 12,000 pounds of fentanyl in 2021, enough to provide every American with a lethal dose. Fentanyl is also mixed in with cocaine, heroin, methamphetamine, and marijuana – often in counterfeit pills, Ms. Milgram said.

The DEA and other law enforcement agencies have seized more than 14 million such pills in 2021. “These types of pills are easily accessible today on social media and e-commerce platforms, Ms. Milgram said.

“Drug dealers are now in our homes,” she said. “Wherever there is a smart phone or a computer, a dealer is one click away,” Ms. Milgram said.

National Institute on Drug Abuse Director Nora D. Volkow, MD, said that dealers will continue to push both fentanyl and methamphetamine because they are among the most addictive substances. They also are more profitable because they don’t require cultivation and harvesting, she said on the call.

Dr. Volkow also noted that naloxone is not as effective in reversing fentanyl overdoses because fentanyl is more potent than heroin and other opioids, and “it gets into the brain extremely rapidly.”

Ongoing research is aimed at developing a faster delivery mechanism and a longer-lasting formulation to counter overdoses, Dr. Volkow said.

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

Background: Prior studies have failed to show a benefit to earlier endoscopic intervention in acute GI bleeding. However, those studies were performed in all-comers without attention to the varying risk within the patient population.

Dr. Lee is a hospitalist at Northwestern Memorial Hospital and Lurie Children’s Hospital and assistant professor of medicine, Feinberg School of Medicine, all in Chicago.

Background: Prior studies have failed to show a benefit to earlier endoscopic intervention in acute GI bleeding. However, those studies were performed in all-comers without attention to the varying risk within the patient population.

Dr. Lee is a hospitalist at Northwestern Memorial Hospital and Lurie Children’s Hospital and assistant professor of medicine, Feinberg School of Medicine, all in Chicago.

Background: Prior studies have failed to show a benefit to earlier endoscopic intervention in acute GI bleeding. However, those studies were performed in all-comers without attention to the varying risk within the patient population.

Dr. Lee is a hospitalist at Northwestern Memorial Hospital and Lurie Children’s Hospital and assistant professor of medicine, Feinberg School of Medicine, all in Chicago.

To the Editor:

There is emerging evidence of skin findings in patients with COVID-19, including perniolike changes of the toes as well as urticarial and vesicular eruptions.¹ Magro et al² reported 3 cases of livedoid and purpuric skin eruptions in critically ill COVID-19 patients with evidence of thrombotic vasculopathy on skin biopsy, including a 32-year-old man with striking buttocks retiform purpura. Histopathologic analysis revealed thrombotic vasculopathy and pressure-induced ischemic necrosis. Since that patient was first evaluated (March 2020), we identified 6 more cases of critically ill COVID-19 patients from a single academic hospital in New York City with essentially identical clinical findings. Herein, we report those 6 cases of critically ill and intubated patients with COVID-19 who developed retiform purpura on the buttocks only, approximately 11 to 21 days after onset of COVID-19 symptoms.

We provided consultation for 5 men and 1 woman (age range, 42–78 years) who were critically ill with COVID-19 and developed retiform purpura on the buttocks (Figures 1 and 2). All had an elevated D-dimer concentration: 2 patients, >700 ng/mL; 2 patients, >2000 ng/mL; 2 patients, >6000 ng/mL (reference, 229 ng/mL). Three patients experienced a peak D-dimer concentration on the day retiform purpura was reported.

Further evidence of coagulopathy in these patients included 1 patient with a newly diagnosed left popliteal deep vein thrombosis and 1 patient with a known history of protein C deficiency and deep vein thromboses. Five patients were receiving anticoagulation on the day the skin changes were documented; anticoagulation was contraindicated in the sixth patient because of oropharyngeal bleeding. Anticoagulation was continued at the treatment dosage (enoxaparin 80 mg twice daily) in 3 patients, and in 2 patients receiving a prophylactic dose (enoxaparin 40 mg daily), anticoagulation was escalated to treatment dose due to rising D-dimer levels and newly diagnosed retiform purpura. Skin biopsy was deferred for all patients due to positional and ventilatory restrictions. At that point in their care, 3 patients remained admitted on medicine floors, 2 were in the intensive care unit, and 1 had died.

Although the differential diagnosis for retiform purpura is broad and should be fully considered in any patient with this finding, based on the elevated D-dimer concentration, critical illness secondary to COVID-19, and striking similarity to earlier reported case of buttocks retiform purpura with thrombotic vasculopathy and pressure injury noted histopathologically,² we suspect the buttocks retiform purpura in our 6 cases also represent a combination of cutaneous thrombosis and pressure injury. In addition to acral livedoid eruptions (also reported by Magro and colleagues²), we suspect that this cutaneous manifestation might be associated with a hypercoagulable state in some patients, especially in the setting of a rising D-dimer concentration. One study found that 31% of 184 patients with severe COVID-19 had thrombotic complications,³ a clinical picture that portends a poor prognosis.⁴

COVID-19 patients presenting with retiform purpura should be fully evaluated based on the broad differential for this morphology. We present 6 cases of buttocks retiform purpura in critically ill COVID-19 patients—all with strikingly similar morphologic findings, an elevated D-dimer concentration, and critical illness due to COVID-19—to alert clinicians to this constellation of findings and propose that this cutaneous manifestation could indicate an associated hypercoaguable state and should prompt a hematology consultation. Additionally, biopsy of this skin finding should be considered, especially if biopsy results might serve to guide management; however, obtaining a biopsy specimen can be technically difficult because of ventilatory requirements.

Given the magnitude of the COVID-19 pandemic and the propensity of these patients to experience thrombotic events, recognition of this skin finding in COVID-19 is important and might allow timely intervention.

To the Editor:

There is emerging evidence of skin findings in patients with COVID-19, including perniolike changes of the toes as well as urticarial and vesicular eruptions.¹ Magro et al² reported 3 cases of livedoid and purpuric skin eruptions in critically ill COVID-19 patients with evidence of thrombotic vasculopathy on skin biopsy, including a 32-year-old man with striking buttocks retiform purpura. Histopathologic analysis revealed thrombotic vasculopathy and pressure-induced ischemic necrosis. Since that patient was first evaluated (March 2020), we identified 6 more cases of critically ill COVID-19 patients from a single academic hospital in New York City with essentially identical clinical findings. Herein, we report those 6 cases of critically ill and intubated patients with COVID-19 who developed retiform purpura on the buttocks only, approximately 11 to 21 days after onset of COVID-19 symptoms.

We provided consultation for 5 men and 1 woman (age range, 42–78 years) who were critically ill with COVID-19 and developed retiform purpura on the buttocks (Figures 1 and 2). All had an elevated D-dimer concentration: 2 patients, >700 ng/mL; 2 patients, >2000 ng/mL; 2 patients, >6000 ng/mL (reference, 229 ng/mL). Three patients experienced a peak D-dimer concentration on the day retiform purpura was reported.

Further evidence of coagulopathy in these patients included 1 patient with a newly diagnosed left popliteal deep vein thrombosis and 1 patient with a known history of protein C deficiency and deep vein thromboses. Five patients were receiving anticoagulation on the day the skin changes were documented; anticoagulation was contraindicated in the sixth patient because of oropharyngeal bleeding. Anticoagulation was continued at the treatment dosage (enoxaparin 80 mg twice daily) in 3 patients, and in 2 patients receiving a prophylactic dose (enoxaparin 40 mg daily), anticoagulation was escalated to treatment dose due to rising D-dimer levels and newly diagnosed retiform purpura. Skin biopsy was deferred for all patients due to positional and ventilatory restrictions. At that point in their care, 3 patients remained admitted on medicine floors, 2 were in the intensive care unit, and 1 had died.

Although the differential diagnosis for retiform purpura is broad and should be fully considered in any patient with this finding, based on the elevated D-dimer concentration, critical illness secondary to COVID-19, and striking similarity to earlier reported case of buttocks retiform purpura with thrombotic vasculopathy and pressure injury noted histopathologically,² we suspect the buttocks retiform purpura in our 6 cases also represent a combination of cutaneous thrombosis and pressure injury. In addition to acral livedoid eruptions (also reported by Magro and colleagues²), we suspect that this cutaneous manifestation might be associated with a hypercoagulable state in some patients, especially in the setting of a rising D-dimer concentration. One study found that 31% of 184 patients with severe COVID-19 had thrombotic complications,³ a clinical picture that portends a poor prognosis.⁴

COVID-19 patients presenting with retiform purpura should be fully evaluated based on the broad differential for this morphology. We present 6 cases of buttocks retiform purpura in critically ill COVID-19 patients—all with strikingly similar morphologic findings, an elevated D-dimer concentration, and critical illness due to COVID-19—to alert clinicians to this constellation of findings and propose that this cutaneous manifestation could indicate an associated hypercoaguable state and should prompt a hematology consultation. Additionally, biopsy of this skin finding should be considered, especially if biopsy results might serve to guide management; however, obtaining a biopsy specimen can be technically difficult because of ventilatory requirements.

Given the magnitude of the COVID-19 pandemic and the propensity of these patients to experience thrombotic events, recognition of this skin finding in COVID-19 is important and might allow timely intervention.

To the Editor:

There is emerging evidence of skin findings in patients with COVID-19, including perniolike changes of the toes as well as urticarial and vesicular eruptions.¹ Magro et al² reported 3 cases of livedoid and purpuric skin eruptions in critically ill COVID-19 patients with evidence of thrombotic vasculopathy on skin biopsy, including a 32-year-old man with striking buttocks retiform purpura. Histopathologic analysis revealed thrombotic vasculopathy and pressure-induced ischemic necrosis. Since that patient was first evaluated (March 2020), we identified 6 more cases of critically ill COVID-19 patients from a single academic hospital in New York City with essentially identical clinical findings. Herein, we report those 6 cases of critically ill and intubated patients with COVID-19 who developed retiform purpura on the buttocks only, approximately 11 to 21 days after onset of COVID-19 symptoms.

We provided consultation for 5 men and 1 woman (age range, 42–78 years) who were critically ill with COVID-19 and developed retiform purpura on the buttocks (Figures 1 and 2). All had an elevated D-dimer concentration: 2 patients, >700 ng/mL; 2 patients, >2000 ng/mL; 2 patients, >6000 ng/mL (reference, 229 ng/mL). Three patients experienced a peak D-dimer concentration on the day retiform purpura was reported.

Further evidence of coagulopathy in these patients included 1 patient with a newly diagnosed left popliteal deep vein thrombosis and 1 patient with a known history of protein C deficiency and deep vein thromboses. Five patients were receiving anticoagulation on the day the skin changes were documented; anticoagulation was contraindicated in the sixth patient because of oropharyngeal bleeding. Anticoagulation was continued at the treatment dosage (enoxaparin 80 mg twice daily) in 3 patients, and in 2 patients receiving a prophylactic dose (enoxaparin 40 mg daily), anticoagulation was escalated to treatment dose due to rising D-dimer levels and newly diagnosed retiform purpura. Skin biopsy was deferred for all patients due to positional and ventilatory restrictions. At that point in their care, 3 patients remained admitted on medicine floors, 2 were in the intensive care unit, and 1 had died.

Although the differential diagnosis for retiform purpura is broad and should be fully considered in any patient with this finding, based on the elevated D-dimer concentration, critical illness secondary to COVID-19, and striking similarity to earlier reported case of buttocks retiform purpura with thrombotic vasculopathy and pressure injury noted histopathologically,² we suspect the buttocks retiform purpura in our 6 cases also represent a combination of cutaneous thrombosis and pressure injury. In addition to acral livedoid eruptions (also reported by Magro and colleagues²), we suspect that this cutaneous manifestation might be associated with a hypercoagulable state in some patients, especially in the setting of a rising D-dimer concentration. One study found that 31% of 184 patients with severe COVID-19 had thrombotic complications,³ a clinical picture that portends a poor prognosis.⁴

COVID-19 patients presenting with retiform purpura should be fully evaluated based on the broad differential for this morphology. We present 6 cases of buttocks retiform purpura in critically ill COVID-19 patients—all with strikingly similar morphologic findings, an elevated D-dimer concentration, and critical illness due to COVID-19—to alert clinicians to this constellation of findings and propose that this cutaneous manifestation could indicate an associated hypercoaguable state and should prompt a hematology consultation. Additionally, biopsy of this skin finding should be considered, especially if biopsy results might serve to guide management; however, obtaining a biopsy specimen can be technically difficult because of ventilatory requirements.

Given the magnitude of the COVID-19 pandemic and the propensity of these patients to experience thrombotic events, recognition of this skin finding in COVID-19 is important and might allow timely intervention.