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FDA removes pregnancy category C warning from certain MS medications
The FDA based the decision on data from more than 1,000 real-world pregnancies, including pregnancies from a large epidemiologic study and published studies over several decades, which found no connection between use of interferon-beta products during early pregnancy and an increased risk of major birth defects, according to the FDA.
As a result, the labels for both medications will no longer have the pregnancy category C designation; however, patients should continue to notify their health care provider if they are pregnant or plan to become pregnant.
The FDA decision to remove the warning follows a similar decision by the European Medicines Agency last year.
“Many women with MS are diagnosed during their childbearing years. With this important update for Plegridy and Avonex, healthcare providers have more data to inform appropriate treatment paths for patients who may be pregnant or planning for pregnancy,” said Bernd Kieseier, MD, MHBA, executive director and head of global MS at Worldwide Medical, Biogen, in a press release.
The FDA based the decision on data from more than 1,000 real-world pregnancies, including pregnancies from a large epidemiologic study and published studies over several decades, which found no connection between use of interferon-beta products during early pregnancy and an increased risk of major birth defects, according to the FDA.
As a result, the labels for both medications will no longer have the pregnancy category C designation; however, patients should continue to notify their health care provider if they are pregnant or plan to become pregnant.
The FDA decision to remove the warning follows a similar decision by the European Medicines Agency last year.
“Many women with MS are diagnosed during their childbearing years. With this important update for Plegridy and Avonex, healthcare providers have more data to inform appropriate treatment paths for patients who may be pregnant or planning for pregnancy,” said Bernd Kieseier, MD, MHBA, executive director and head of global MS at Worldwide Medical, Biogen, in a press release.
The FDA based the decision on data from more than 1,000 real-world pregnancies, including pregnancies from a large epidemiologic study and published studies over several decades, which found no connection between use of interferon-beta products during early pregnancy and an increased risk of major birth defects, according to the FDA.
As a result, the labels for both medications will no longer have the pregnancy category C designation; however, patients should continue to notify their health care provider if they are pregnant or plan to become pregnant.
The FDA decision to remove the warning follows a similar decision by the European Medicines Agency last year.
“Many women with MS are diagnosed during their childbearing years. With this important update for Plegridy and Avonex, healthcare providers have more data to inform appropriate treatment paths for patients who may be pregnant or planning for pregnancy,” said Bernd Kieseier, MD, MHBA, executive director and head of global MS at Worldwide Medical, Biogen, in a press release.
20% with cancer on checkpoint inhibitors get thyroid dysfunction
new research suggests.
Immune checkpoint inhibitors have revolutionized the treatment of many different types of cancers, but can also trigger a variety of immune-related adverse effects. As these drugs become more widely used, rates of these events appear to be more common in the real-world compared with clinical trial settings.
In their new study, Zoe Quandt, MD, of the University of California, San Francisco (UCSF), and colleagues specifically looked at thyroid dysfunction in their own institution’s EHR data and found more than double the rate of hypothyroidism and more than triple the rate of hyperthyroidism, compared with rates in published trials.
Moreover, in contrast to previous studies that have found differences in thyroid dysfunction by checkpoint inhibitor type, Dr. Quandt and colleagues instead found significant differences by cancer type.
Dr. Quandt presented the findings during a virtual press briefing held March 31originally scheduled for ENDO 2020.
“Thyroid dysfunction following checkpoint inhibitor therapy appears to be much more common than was previously reported in clinical trials, and this is one of the first studies to show differences by cancer type rather than by checkpoint inhibitor type,” Dr. Quandt said during the presentation.
However, she also cautioned that there’s “a lot more research to be done to validate case definitions and validate these findings.”
Asked to comment, endocrinologist David C. Lieb, MD, associate professor of medicine at Eastern Virginia Medical School in Norfolk, said in an interview, “These drugs are becoming so much more commonly used, so it’s not surprising that we’re seeing more endocrine complications, especially thyroid disease.”
“Endocrinologists need to work closely with oncologists to make sure patients are being screened and followed appropriately.”
‘A much higher percentage than we were expecting’
Dr. Quandt’s study included 1,146 individuals treated with checkpoint inhibitors at UCSF during 2012-2018 who did not have thyroid cancer or preexisting thyroid dysfunction.
Pembrolizumab (Keytruda) was the most common treatment (45%), followed by nivolumab (Opdivo) (20%). Less than 10% of patients received atezolizumab (Tecentriq), durvalumab (Imfizi), ipilimumab (Yervoy) monotherapy, combined ipilimumab/nivolumab, or other combinations of checkpoint inhibitors.
A total of 19.1% developed thyroid disease, with 13.4% having hypothyroidism and 9.5% hyperthyroidism. These figures far exceed those found in a recent meta-analysis of 38 randomized clinical trials of checkpoint inhibitors that included 7551 patients.
“Using this approach, we found a much higher percentage of patients who developed thyroid dysfunction than we were expecting,” Dr. Quandt said.
In both cases, the two categories – hypothyroidism and hyperthyroidism – aren’t mutually exclusive as hypothyroidism can arise de novo or subsequent to hyperthyroidism.
Dr Lieb commented, “It would be interesting to see what the causes of hyperthyroidism are – thyroiditis or Graves disease.”
Dr. Quandt mentioned a possible reason for the large difference between clinical trial and real-world data.
“Once we’re actually using these drugs outside of clinical trials, some of the restrictions about using them in people with other autoimmune diseases have been lifted, so my guess is that as we give them to a broader population we’re seeing more of these [adverse effects],” she suggested.
Also, “In the initial trials, people weren’t quite as aware of the possibilities of these side effects, so now we’re doing many more labs. Patients get thyroid function tests with every infusion, so I think we’re probably catching more patients who develop disease.”
Differences by cancer type, not checkpoint inhibitor type
And in a new twist, Dr. Quandt found that, in contrast to the differences seen by checkpoint inhibitor type in randomized trials, “surprisingly, we found that this difference did not reach statistical significance.”
“Instead, we saw that cancer type was associated with development of thyroid dysfunction, even after taking checkpoint inhibitor type into account.”
The percentages of patients who developed thyroid dysfunction ranged from 9.7% of those with glioblastoma to 40.0% of those with renal cell carcinoma.
The reason for this is not clear, said Dr. Quandt in an interview.
One possibility relates to other treatments patients with cancer also receive. In renal cell carcinoma, for example, patients also are treated with tyrosine kinase inhibitors, which can also cause thyroid dysfunction, so they may be more susceptible. Or there may be shared antigens activating the immune system.
“That’s definitely one of the questions we’re looking at,” she said.
Dr. Quandt and Dr. Lieb have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Immune checkpoint inhibitors have revolutionized the treatment of many different types of cancers, but can also trigger a variety of immune-related adverse effects. As these drugs become more widely used, rates of these events appear to be more common in the real-world compared with clinical trial settings.
In their new study, Zoe Quandt, MD, of the University of California, San Francisco (UCSF), and colleagues specifically looked at thyroid dysfunction in their own institution’s EHR data and found more than double the rate of hypothyroidism and more than triple the rate of hyperthyroidism, compared with rates in published trials.
Moreover, in contrast to previous studies that have found differences in thyroid dysfunction by checkpoint inhibitor type, Dr. Quandt and colleagues instead found significant differences by cancer type.
Dr. Quandt presented the findings during a virtual press briefing held March 31originally scheduled for ENDO 2020.
“Thyroid dysfunction following checkpoint inhibitor therapy appears to be much more common than was previously reported in clinical trials, and this is one of the first studies to show differences by cancer type rather than by checkpoint inhibitor type,” Dr. Quandt said during the presentation.
However, she also cautioned that there’s “a lot more research to be done to validate case definitions and validate these findings.”
Asked to comment, endocrinologist David C. Lieb, MD, associate professor of medicine at Eastern Virginia Medical School in Norfolk, said in an interview, “These drugs are becoming so much more commonly used, so it’s not surprising that we’re seeing more endocrine complications, especially thyroid disease.”
“Endocrinologists need to work closely with oncologists to make sure patients are being screened and followed appropriately.”
‘A much higher percentage than we were expecting’
Dr. Quandt’s study included 1,146 individuals treated with checkpoint inhibitors at UCSF during 2012-2018 who did not have thyroid cancer or preexisting thyroid dysfunction.
Pembrolizumab (Keytruda) was the most common treatment (45%), followed by nivolumab (Opdivo) (20%). Less than 10% of patients received atezolizumab (Tecentriq), durvalumab (Imfizi), ipilimumab (Yervoy) monotherapy, combined ipilimumab/nivolumab, or other combinations of checkpoint inhibitors.
A total of 19.1% developed thyroid disease, with 13.4% having hypothyroidism and 9.5% hyperthyroidism. These figures far exceed those found in a recent meta-analysis of 38 randomized clinical trials of checkpoint inhibitors that included 7551 patients.
“Using this approach, we found a much higher percentage of patients who developed thyroid dysfunction than we were expecting,” Dr. Quandt said.
In both cases, the two categories – hypothyroidism and hyperthyroidism – aren’t mutually exclusive as hypothyroidism can arise de novo or subsequent to hyperthyroidism.
Dr Lieb commented, “It would be interesting to see what the causes of hyperthyroidism are – thyroiditis or Graves disease.”
Dr. Quandt mentioned a possible reason for the large difference between clinical trial and real-world data.
“Once we’re actually using these drugs outside of clinical trials, some of the restrictions about using them in people with other autoimmune diseases have been lifted, so my guess is that as we give them to a broader population we’re seeing more of these [adverse effects],” she suggested.
Also, “In the initial trials, people weren’t quite as aware of the possibilities of these side effects, so now we’re doing many more labs. Patients get thyroid function tests with every infusion, so I think we’re probably catching more patients who develop disease.”
Differences by cancer type, not checkpoint inhibitor type
And in a new twist, Dr. Quandt found that, in contrast to the differences seen by checkpoint inhibitor type in randomized trials, “surprisingly, we found that this difference did not reach statistical significance.”
“Instead, we saw that cancer type was associated with development of thyroid dysfunction, even after taking checkpoint inhibitor type into account.”
The percentages of patients who developed thyroid dysfunction ranged from 9.7% of those with glioblastoma to 40.0% of those with renal cell carcinoma.
The reason for this is not clear, said Dr. Quandt in an interview.
One possibility relates to other treatments patients with cancer also receive. In renal cell carcinoma, for example, patients also are treated with tyrosine kinase inhibitors, which can also cause thyroid dysfunction, so they may be more susceptible. Or there may be shared antigens activating the immune system.
“That’s definitely one of the questions we’re looking at,” she said.
Dr. Quandt and Dr. Lieb have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Immune checkpoint inhibitors have revolutionized the treatment of many different types of cancers, but can also trigger a variety of immune-related adverse effects. As these drugs become more widely used, rates of these events appear to be more common in the real-world compared with clinical trial settings.
In their new study, Zoe Quandt, MD, of the University of California, San Francisco (UCSF), and colleagues specifically looked at thyroid dysfunction in their own institution’s EHR data and found more than double the rate of hypothyroidism and more than triple the rate of hyperthyroidism, compared with rates in published trials.
Moreover, in contrast to previous studies that have found differences in thyroid dysfunction by checkpoint inhibitor type, Dr. Quandt and colleagues instead found significant differences by cancer type.
Dr. Quandt presented the findings during a virtual press briefing held March 31originally scheduled for ENDO 2020.
“Thyroid dysfunction following checkpoint inhibitor therapy appears to be much more common than was previously reported in clinical trials, and this is one of the first studies to show differences by cancer type rather than by checkpoint inhibitor type,” Dr. Quandt said during the presentation.
However, she also cautioned that there’s “a lot more research to be done to validate case definitions and validate these findings.”
Asked to comment, endocrinologist David C. Lieb, MD, associate professor of medicine at Eastern Virginia Medical School in Norfolk, said in an interview, “These drugs are becoming so much more commonly used, so it’s not surprising that we’re seeing more endocrine complications, especially thyroid disease.”
“Endocrinologists need to work closely with oncologists to make sure patients are being screened and followed appropriately.”
‘A much higher percentage than we were expecting’
Dr. Quandt’s study included 1,146 individuals treated with checkpoint inhibitors at UCSF during 2012-2018 who did not have thyroid cancer or preexisting thyroid dysfunction.
Pembrolizumab (Keytruda) was the most common treatment (45%), followed by nivolumab (Opdivo) (20%). Less than 10% of patients received atezolizumab (Tecentriq), durvalumab (Imfizi), ipilimumab (Yervoy) monotherapy, combined ipilimumab/nivolumab, or other combinations of checkpoint inhibitors.
A total of 19.1% developed thyroid disease, with 13.4% having hypothyroidism and 9.5% hyperthyroidism. These figures far exceed those found in a recent meta-analysis of 38 randomized clinical trials of checkpoint inhibitors that included 7551 patients.
“Using this approach, we found a much higher percentage of patients who developed thyroid dysfunction than we were expecting,” Dr. Quandt said.
In both cases, the two categories – hypothyroidism and hyperthyroidism – aren’t mutually exclusive as hypothyroidism can arise de novo or subsequent to hyperthyroidism.
Dr Lieb commented, “It would be interesting to see what the causes of hyperthyroidism are – thyroiditis or Graves disease.”
Dr. Quandt mentioned a possible reason for the large difference between clinical trial and real-world data.
“Once we’re actually using these drugs outside of clinical trials, some of the restrictions about using them in people with other autoimmune diseases have been lifted, so my guess is that as we give them to a broader population we’re seeing more of these [adverse effects],” she suggested.
Also, “In the initial trials, people weren’t quite as aware of the possibilities of these side effects, so now we’re doing many more labs. Patients get thyroid function tests with every infusion, so I think we’re probably catching more patients who develop disease.”
Differences by cancer type, not checkpoint inhibitor type
And in a new twist, Dr. Quandt found that, in contrast to the differences seen by checkpoint inhibitor type in randomized trials, “surprisingly, we found that this difference did not reach statistical significance.”
“Instead, we saw that cancer type was associated with development of thyroid dysfunction, even after taking checkpoint inhibitor type into account.”
The percentages of patients who developed thyroid dysfunction ranged from 9.7% of those with glioblastoma to 40.0% of those with renal cell carcinoma.
The reason for this is not clear, said Dr. Quandt in an interview.
One possibility relates to other treatments patients with cancer also receive. In renal cell carcinoma, for example, patients also are treated with tyrosine kinase inhibitors, which can also cause thyroid dysfunction, so they may be more susceptible. Or there may be shared antigens activating the immune system.
“That’s definitely one of the questions we’re looking at,” she said.
Dr. Quandt and Dr. Lieb have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Neurologists navigate unknown territory during COVID-19 pandemic
Neurologic disorders are among the “underlying medical conditions that may increase the risk of serious COVID-19 for individuals of any age,” according to the Centers for Disease Control and Prevention.
Potentially relevant drug interactions, how immunosuppressive medications may influence the risk of COVID-19, and neurologic diseases that may be associated with greater risk are among the questions that experts and groups have addressed.
According to the CDC, neurologic conditions that may heighten the risk of severe COVID-19 include “disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy (seizure disorders), stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury.” Many patients, however, may not have substantially increased risks, neurologists suggest.
“Patients with conditions that do not affect their swallowing or breathing muscles and in whom the immune system is working normally are not considered to be at increased risk from COVID-19,” according to March 26 guidance from the Association of British Neurologists (ABN). “Milder or moderate forms of many of the commoner neurological disorders, such as Parkinson’s disease, multiple sclerosis, epilepsy, are not currently considered to confer increased risk, so long as the breathing and swallowing muscles are functioning well.”
Neurologists should tailor treatment decisions to individual patients, according to the ABN. “Although some neurological conditions or treatments increase the risk of complicated COVID-19, most patients in these groups will overcome the infection,” the association noted.
Interactions with potential COVID-19 treatments
Standard drugs in neurology may interact with potential COVID-19 treatments. For example, “preliminary experience suggests that there is a possible benefit from hydroxychloroquine and azithromycin treatment in COVID-19 infection,” but either of those drugs “may lead to a deterioration in myasthenia gravis,” the ABN notes. “Doctors will have to balance the risks from myasthenia and COVID-19 on a case-by-case basis.” The Liverpool Drug Interactions Group has published tables that describe interactions between potential COVID-19 treatments and anticonvulsants, analgesics, immunosuppressants, and other medication classes.
Many muscle diseases and neuromuscular junction diseases may entail higher risks of complicated COVID-19, the ABN suggested. For patients on immunotherapy, the medication may be a more important consideration for COVID-19 than the underlying disease. Other comorbidities such as hypertension, renal impairment, neutropenia, lymphopenia, liver disease, diabetes mellitus, ischemic heart disease, and lung disease may be important factors, according to the association.
Seizures may not worsen
After the CDC added epilepsy to its list of conditions that entail higher risk of severe COVID-19, M. Scott Perry, MD, medical director of neurology at Cook Children’s Medical Center in Fort Worth, Tex., commented on Twitter that “most healthy people with controlled epilepsy [are] probably at no more risk than others.”
“Those treated with steroids or other immunosuppressive drugs are likely higher risk,” Dr. Perry said. “Likewise, patients with other medical comorbidities such as muscle weakness, swallowing or breathing problems, and other complex cases of epilepsy are likely higher risk. Regardless: be responsible, avoid crowds, wash your hands, avoid sick contacts.”
Doctors in Italy, based on small numbers of cases, have found that seizures are not worse in patients with epilepsy and COVID-19, said Dr. Perry. A few children, including several patients with Dravet syndrome, “had uncomplicated illness and seizures were no worse,” he said. “That is reassuring.”
“Until now, there is no evidence of a direct effect of COVID-19 on seizures or epilepsy,” according to the International League Against Epilepsy (ILAE). “However, patients may experience worsening of seizures due to systemic illnesses, drug interactions, decreased access to antiseizure medications, and increased stress.”
“In younger children, the fever that accompanies COVID-19 may exacerbate seizures, as might any febrile illness,” according to an American Epilepsy Society (AES) resource for epilepsy clinicians. “The main known elevated risk factors related to COVID-19 are age, respiratory disease, and other chronic medical conditions not related to epilepsy. As for all, people with epilepsy should adhere to the CDC recommendations for reducing risk of infection.” Neurologists should review with patients the importance of treatment adherence, update plans for managing breakthrough seizures, and ensure necessary medications are on hand, according to the AES.
The Epilepsy Foundation created a page with information about COVID-19 for patients with epilepsy and recorded a discussion with epilepsy specialists. DEE-P (Developmental Epileptic Encephalopathy–Project) Connections recorded a webinar about protecting medically complex or immune-suppressed children with epilepsy from COVID-19.
MS DMTs and the coronavirus
The National Multiple Sclerosis (MS) Society has provided guidance on the use of disease-modifying therapies (DMTs) during the COVID-19 pandemic. “There are numerous recommendations circulating that attempt to provide clarity and guidance, however, differences among the recommendations have created confusion,” the society says. “DMT decision making varies significantly from country to country, ranging from highly provider-directed to a collaborative decision-making model. ... DMT decisions should be individualized and made collaboratively between the person with MS and his/her healthcare provider.”
Patients with MS and their physicians should weigh risks and benefits before starting cell-depleting DMTs such as alemtuzumab, cladribine, ocrelizumab, or rituximab, according the National MS Society. They also should consider the risks and benefits of DMTs that carry warnings of a potentially severe increase in disability after stopping therapy, such as fingolimod and natalizumab. “We endorse the global advice provided by the MS International Federation (MSIF) – but emphasize that DMT decision making must be individualized and based upon multiple factors,” the National MS Society said.
Neurologists currently lack evidence about how COVID-19 affects patients with MS, according to the MSIF, which based its DMT guidance on advice from MS neurologists and research experts from member organizations. Many DMTs suppress or modify the immune system, and “some MS medications might increase the likelihood of developing complications from a COVID-19 infection but this risk needs to be balanced with the risks of stopping treatment,” according to the federation.
Patients currently taking DMTs should continue treatment, and those who develop symptoms of COVID-19 or test positive for the infection should discuss their DMT with a health care professional familiar with their care, the MSIF recommends. Decisions about starting a DMT should take into account a patient’s disease course, disease activity, and regional COVID-19 risks, according to the federation. For patients due to start DMT, treatments that do not reduce lymphocytes, such as interferons, glatiramer acetate, or natalizumab, should be considered.
Fingolimod, dimethyl fumarate, teriflunomide, and siponimod “may reduce the ability of the immune system to respond to an infection,” and “people should carefully consider the risks and benefits of initiating these treatments during the COVID-19 pandemic,” according to the federation. “People with MS who are currently taking alemtuzumab, cladribine, ocrelizumab, rituximab, fingolimod, dimethyl fumarate, teriflunomide or siponimod and are living in a community with a COVID-19 outbreak should isolate as much as possible to reduce their risk of infection.”
Extended isolation during the COVID-19 outbreak may be warranted for patients with MS who have recently undergone autologous hematopoietic stem cell treatment, which entails intensive chemotherapy, the guidance says. In addition, postponement of this procedure should be considered.
Child neurology, migraine, movement disorders, and stroke
The Child Neurology Foundation (CNF) and Child Neurology Society (CNS) published a joint statement about COVID-19. “Most children who contract COVID-19 appear to exhibit only mild symptoms,” said Scott Pomeroy, MD, president of CNF’s board of directors and chair of the department of neurology at Boston Children’s Hospital, in the statement. “However, if your child is taking a medication such as steroids that can lower their immune system response, there could be an increased risk for more significant symptoms. In addition, children with lung disease, such as asthma, may also be at higher risk. Therefore, it is important to practice preventative precautions. We hope that this information will help to reduce some of the fears that families in our community may be experiencing.”
The American Migraine Foundation shared COVID-19 considerations for patients with migraine from Mia Minen, MD, associate professor of neurology and population health at NYU Langone in New York. Patients with migraine who are otherwise in good health are not expected to be at increased risk of severe COVID-19, according to Dr. Minen. Best practices include having an adequate supply of medicine, considering alternatives to in-person doctor visits, and being “mindful of routine and diet to reduce migraine triggers,” the foundation suggests. In addition, patients should try to limit stress and seek out “alternative methods of social interaction.”
“The relationship between COVID-19 and Parkinson’s disease or other movement disorders remains unknown,” the International Parkinson and Movement Disorder Society said. “In general, we recommend that our movement disorder patients do not assume they are at extreme risks, which for the time being are uncertain. Nevertheless, we strongly recommend following the standard measures strictly to avoid exposures to the virus.”
The American Heart Association (AHA) cautions that older patients with coronary heart disease or hypertension “may be more likely than others to be infected by the coronavirus that causes COVID-19 and to develop more severe symptoms.” In addition, people with a history of stroke “may face a higher risk of complications,” according to the AHA. “As a result, people who have heart disease or another underlying condition should stay home to limit their risk of contracting the virus.”
Several groups emphasized the importance of telemedicine as an option for patients with neurologic conditions during the pandemic. The American Headache Society has hosted discussions on conducting neurologic exams via telemedicine. The American Academy of Neurology also conducted a webinar on telemedicine and COVID-19 and created a page with COVID-19 resources. The journal Neurology is publishing invited commentaries about neurologic aspects of the COVID-19 pandemic.
Neurologic disorders are among the “underlying medical conditions that may increase the risk of serious COVID-19 for individuals of any age,” according to the Centers for Disease Control and Prevention.
Potentially relevant drug interactions, how immunosuppressive medications may influence the risk of COVID-19, and neurologic diseases that may be associated with greater risk are among the questions that experts and groups have addressed.
According to the CDC, neurologic conditions that may heighten the risk of severe COVID-19 include “disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy (seizure disorders), stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury.” Many patients, however, may not have substantially increased risks, neurologists suggest.
“Patients with conditions that do not affect their swallowing or breathing muscles and in whom the immune system is working normally are not considered to be at increased risk from COVID-19,” according to March 26 guidance from the Association of British Neurologists (ABN). “Milder or moderate forms of many of the commoner neurological disorders, such as Parkinson’s disease, multiple sclerosis, epilepsy, are not currently considered to confer increased risk, so long as the breathing and swallowing muscles are functioning well.”
Neurologists should tailor treatment decisions to individual patients, according to the ABN. “Although some neurological conditions or treatments increase the risk of complicated COVID-19, most patients in these groups will overcome the infection,” the association noted.
Interactions with potential COVID-19 treatments
Standard drugs in neurology may interact with potential COVID-19 treatments. For example, “preliminary experience suggests that there is a possible benefit from hydroxychloroquine and azithromycin treatment in COVID-19 infection,” but either of those drugs “may lead to a deterioration in myasthenia gravis,” the ABN notes. “Doctors will have to balance the risks from myasthenia and COVID-19 on a case-by-case basis.” The Liverpool Drug Interactions Group has published tables that describe interactions between potential COVID-19 treatments and anticonvulsants, analgesics, immunosuppressants, and other medication classes.
Many muscle diseases and neuromuscular junction diseases may entail higher risks of complicated COVID-19, the ABN suggested. For patients on immunotherapy, the medication may be a more important consideration for COVID-19 than the underlying disease. Other comorbidities such as hypertension, renal impairment, neutropenia, lymphopenia, liver disease, diabetes mellitus, ischemic heart disease, and lung disease may be important factors, according to the association.
Seizures may not worsen
After the CDC added epilepsy to its list of conditions that entail higher risk of severe COVID-19, M. Scott Perry, MD, medical director of neurology at Cook Children’s Medical Center in Fort Worth, Tex., commented on Twitter that “most healthy people with controlled epilepsy [are] probably at no more risk than others.”
“Those treated with steroids or other immunosuppressive drugs are likely higher risk,” Dr. Perry said. “Likewise, patients with other medical comorbidities such as muscle weakness, swallowing or breathing problems, and other complex cases of epilepsy are likely higher risk. Regardless: be responsible, avoid crowds, wash your hands, avoid sick contacts.”
Doctors in Italy, based on small numbers of cases, have found that seizures are not worse in patients with epilepsy and COVID-19, said Dr. Perry. A few children, including several patients with Dravet syndrome, “had uncomplicated illness and seizures were no worse,” he said. “That is reassuring.”
“Until now, there is no evidence of a direct effect of COVID-19 on seizures or epilepsy,” according to the International League Against Epilepsy (ILAE). “However, patients may experience worsening of seizures due to systemic illnesses, drug interactions, decreased access to antiseizure medications, and increased stress.”
“In younger children, the fever that accompanies COVID-19 may exacerbate seizures, as might any febrile illness,” according to an American Epilepsy Society (AES) resource for epilepsy clinicians. “The main known elevated risk factors related to COVID-19 are age, respiratory disease, and other chronic medical conditions not related to epilepsy. As for all, people with epilepsy should adhere to the CDC recommendations for reducing risk of infection.” Neurologists should review with patients the importance of treatment adherence, update plans for managing breakthrough seizures, and ensure necessary medications are on hand, according to the AES.
The Epilepsy Foundation created a page with information about COVID-19 for patients with epilepsy and recorded a discussion with epilepsy specialists. DEE-P (Developmental Epileptic Encephalopathy–Project) Connections recorded a webinar about protecting medically complex or immune-suppressed children with epilepsy from COVID-19.
MS DMTs and the coronavirus
The National Multiple Sclerosis (MS) Society has provided guidance on the use of disease-modifying therapies (DMTs) during the COVID-19 pandemic. “There are numerous recommendations circulating that attempt to provide clarity and guidance, however, differences among the recommendations have created confusion,” the society says. “DMT decision making varies significantly from country to country, ranging from highly provider-directed to a collaborative decision-making model. ... DMT decisions should be individualized and made collaboratively between the person with MS and his/her healthcare provider.”
Patients with MS and their physicians should weigh risks and benefits before starting cell-depleting DMTs such as alemtuzumab, cladribine, ocrelizumab, or rituximab, according the National MS Society. They also should consider the risks and benefits of DMTs that carry warnings of a potentially severe increase in disability after stopping therapy, such as fingolimod and natalizumab. “We endorse the global advice provided by the MS International Federation (MSIF) – but emphasize that DMT decision making must be individualized and based upon multiple factors,” the National MS Society said.
Neurologists currently lack evidence about how COVID-19 affects patients with MS, according to the MSIF, which based its DMT guidance on advice from MS neurologists and research experts from member organizations. Many DMTs suppress or modify the immune system, and “some MS medications might increase the likelihood of developing complications from a COVID-19 infection but this risk needs to be balanced with the risks of stopping treatment,” according to the federation.
Patients currently taking DMTs should continue treatment, and those who develop symptoms of COVID-19 or test positive for the infection should discuss their DMT with a health care professional familiar with their care, the MSIF recommends. Decisions about starting a DMT should take into account a patient’s disease course, disease activity, and regional COVID-19 risks, according to the federation. For patients due to start DMT, treatments that do not reduce lymphocytes, such as interferons, glatiramer acetate, or natalizumab, should be considered.
Fingolimod, dimethyl fumarate, teriflunomide, and siponimod “may reduce the ability of the immune system to respond to an infection,” and “people should carefully consider the risks and benefits of initiating these treatments during the COVID-19 pandemic,” according to the federation. “People with MS who are currently taking alemtuzumab, cladribine, ocrelizumab, rituximab, fingolimod, dimethyl fumarate, teriflunomide or siponimod and are living in a community with a COVID-19 outbreak should isolate as much as possible to reduce their risk of infection.”
Extended isolation during the COVID-19 outbreak may be warranted for patients with MS who have recently undergone autologous hematopoietic stem cell treatment, which entails intensive chemotherapy, the guidance says. In addition, postponement of this procedure should be considered.
Child neurology, migraine, movement disorders, and stroke
The Child Neurology Foundation (CNF) and Child Neurology Society (CNS) published a joint statement about COVID-19. “Most children who contract COVID-19 appear to exhibit only mild symptoms,” said Scott Pomeroy, MD, president of CNF’s board of directors and chair of the department of neurology at Boston Children’s Hospital, in the statement. “However, if your child is taking a medication such as steroids that can lower their immune system response, there could be an increased risk for more significant symptoms. In addition, children with lung disease, such as asthma, may also be at higher risk. Therefore, it is important to practice preventative precautions. We hope that this information will help to reduce some of the fears that families in our community may be experiencing.”
The American Migraine Foundation shared COVID-19 considerations for patients with migraine from Mia Minen, MD, associate professor of neurology and population health at NYU Langone in New York. Patients with migraine who are otherwise in good health are not expected to be at increased risk of severe COVID-19, according to Dr. Minen. Best practices include having an adequate supply of medicine, considering alternatives to in-person doctor visits, and being “mindful of routine and diet to reduce migraine triggers,” the foundation suggests. In addition, patients should try to limit stress and seek out “alternative methods of social interaction.”
“The relationship between COVID-19 and Parkinson’s disease or other movement disorders remains unknown,” the International Parkinson and Movement Disorder Society said. “In general, we recommend that our movement disorder patients do not assume they are at extreme risks, which for the time being are uncertain. Nevertheless, we strongly recommend following the standard measures strictly to avoid exposures to the virus.”
The American Heart Association (AHA) cautions that older patients with coronary heart disease or hypertension “may be more likely than others to be infected by the coronavirus that causes COVID-19 and to develop more severe symptoms.” In addition, people with a history of stroke “may face a higher risk of complications,” according to the AHA. “As a result, people who have heart disease or another underlying condition should stay home to limit their risk of contracting the virus.”
Several groups emphasized the importance of telemedicine as an option for patients with neurologic conditions during the pandemic. The American Headache Society has hosted discussions on conducting neurologic exams via telemedicine. The American Academy of Neurology also conducted a webinar on telemedicine and COVID-19 and created a page with COVID-19 resources. The journal Neurology is publishing invited commentaries about neurologic aspects of the COVID-19 pandemic.
Neurologic disorders are among the “underlying medical conditions that may increase the risk of serious COVID-19 for individuals of any age,” according to the Centers for Disease Control and Prevention.
Potentially relevant drug interactions, how immunosuppressive medications may influence the risk of COVID-19, and neurologic diseases that may be associated with greater risk are among the questions that experts and groups have addressed.
According to the CDC, neurologic conditions that may heighten the risk of severe COVID-19 include “disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy (seizure disorders), stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury.” Many patients, however, may not have substantially increased risks, neurologists suggest.
“Patients with conditions that do not affect their swallowing or breathing muscles and in whom the immune system is working normally are not considered to be at increased risk from COVID-19,” according to March 26 guidance from the Association of British Neurologists (ABN). “Milder or moderate forms of many of the commoner neurological disorders, such as Parkinson’s disease, multiple sclerosis, epilepsy, are not currently considered to confer increased risk, so long as the breathing and swallowing muscles are functioning well.”
Neurologists should tailor treatment decisions to individual patients, according to the ABN. “Although some neurological conditions or treatments increase the risk of complicated COVID-19, most patients in these groups will overcome the infection,” the association noted.
Interactions with potential COVID-19 treatments
Standard drugs in neurology may interact with potential COVID-19 treatments. For example, “preliminary experience suggests that there is a possible benefit from hydroxychloroquine and azithromycin treatment in COVID-19 infection,” but either of those drugs “may lead to a deterioration in myasthenia gravis,” the ABN notes. “Doctors will have to balance the risks from myasthenia and COVID-19 on a case-by-case basis.” The Liverpool Drug Interactions Group has published tables that describe interactions between potential COVID-19 treatments and anticonvulsants, analgesics, immunosuppressants, and other medication classes.
Many muscle diseases and neuromuscular junction diseases may entail higher risks of complicated COVID-19, the ABN suggested. For patients on immunotherapy, the medication may be a more important consideration for COVID-19 than the underlying disease. Other comorbidities such as hypertension, renal impairment, neutropenia, lymphopenia, liver disease, diabetes mellitus, ischemic heart disease, and lung disease may be important factors, according to the association.
Seizures may not worsen
After the CDC added epilepsy to its list of conditions that entail higher risk of severe COVID-19, M. Scott Perry, MD, medical director of neurology at Cook Children’s Medical Center in Fort Worth, Tex., commented on Twitter that “most healthy people with controlled epilepsy [are] probably at no more risk than others.”
“Those treated with steroids or other immunosuppressive drugs are likely higher risk,” Dr. Perry said. “Likewise, patients with other medical comorbidities such as muscle weakness, swallowing or breathing problems, and other complex cases of epilepsy are likely higher risk. Regardless: be responsible, avoid crowds, wash your hands, avoid sick contacts.”
Doctors in Italy, based on small numbers of cases, have found that seizures are not worse in patients with epilepsy and COVID-19, said Dr. Perry. A few children, including several patients with Dravet syndrome, “had uncomplicated illness and seizures were no worse,” he said. “That is reassuring.”
“Until now, there is no evidence of a direct effect of COVID-19 on seizures or epilepsy,” according to the International League Against Epilepsy (ILAE). “However, patients may experience worsening of seizures due to systemic illnesses, drug interactions, decreased access to antiseizure medications, and increased stress.”
“In younger children, the fever that accompanies COVID-19 may exacerbate seizures, as might any febrile illness,” according to an American Epilepsy Society (AES) resource for epilepsy clinicians. “The main known elevated risk factors related to COVID-19 are age, respiratory disease, and other chronic medical conditions not related to epilepsy. As for all, people with epilepsy should adhere to the CDC recommendations for reducing risk of infection.” Neurologists should review with patients the importance of treatment adherence, update plans for managing breakthrough seizures, and ensure necessary medications are on hand, according to the AES.
The Epilepsy Foundation created a page with information about COVID-19 for patients with epilepsy and recorded a discussion with epilepsy specialists. DEE-P (Developmental Epileptic Encephalopathy–Project) Connections recorded a webinar about protecting medically complex or immune-suppressed children with epilepsy from COVID-19.
MS DMTs and the coronavirus
The National Multiple Sclerosis (MS) Society has provided guidance on the use of disease-modifying therapies (DMTs) during the COVID-19 pandemic. “There are numerous recommendations circulating that attempt to provide clarity and guidance, however, differences among the recommendations have created confusion,” the society says. “DMT decision making varies significantly from country to country, ranging from highly provider-directed to a collaborative decision-making model. ... DMT decisions should be individualized and made collaboratively between the person with MS and his/her healthcare provider.”
Patients with MS and their physicians should weigh risks and benefits before starting cell-depleting DMTs such as alemtuzumab, cladribine, ocrelizumab, or rituximab, according the National MS Society. They also should consider the risks and benefits of DMTs that carry warnings of a potentially severe increase in disability after stopping therapy, such as fingolimod and natalizumab. “We endorse the global advice provided by the MS International Federation (MSIF) – but emphasize that DMT decision making must be individualized and based upon multiple factors,” the National MS Society said.
Neurologists currently lack evidence about how COVID-19 affects patients with MS, according to the MSIF, which based its DMT guidance on advice from MS neurologists and research experts from member organizations. Many DMTs suppress or modify the immune system, and “some MS medications might increase the likelihood of developing complications from a COVID-19 infection but this risk needs to be balanced with the risks of stopping treatment,” according to the federation.
Patients currently taking DMTs should continue treatment, and those who develop symptoms of COVID-19 or test positive for the infection should discuss their DMT with a health care professional familiar with their care, the MSIF recommends. Decisions about starting a DMT should take into account a patient’s disease course, disease activity, and regional COVID-19 risks, according to the federation. For patients due to start DMT, treatments that do not reduce lymphocytes, such as interferons, glatiramer acetate, or natalizumab, should be considered.
Fingolimod, dimethyl fumarate, teriflunomide, and siponimod “may reduce the ability of the immune system to respond to an infection,” and “people should carefully consider the risks and benefits of initiating these treatments during the COVID-19 pandemic,” according to the federation. “People with MS who are currently taking alemtuzumab, cladribine, ocrelizumab, rituximab, fingolimod, dimethyl fumarate, teriflunomide or siponimod and are living in a community with a COVID-19 outbreak should isolate as much as possible to reduce their risk of infection.”
Extended isolation during the COVID-19 outbreak may be warranted for patients with MS who have recently undergone autologous hematopoietic stem cell treatment, which entails intensive chemotherapy, the guidance says. In addition, postponement of this procedure should be considered.
Child neurology, migraine, movement disorders, and stroke
The Child Neurology Foundation (CNF) and Child Neurology Society (CNS) published a joint statement about COVID-19. “Most children who contract COVID-19 appear to exhibit only mild symptoms,” said Scott Pomeroy, MD, president of CNF’s board of directors and chair of the department of neurology at Boston Children’s Hospital, in the statement. “However, if your child is taking a medication such as steroids that can lower their immune system response, there could be an increased risk for more significant symptoms. In addition, children with lung disease, such as asthma, may also be at higher risk. Therefore, it is important to practice preventative precautions. We hope that this information will help to reduce some of the fears that families in our community may be experiencing.”
The American Migraine Foundation shared COVID-19 considerations for patients with migraine from Mia Minen, MD, associate professor of neurology and population health at NYU Langone in New York. Patients with migraine who are otherwise in good health are not expected to be at increased risk of severe COVID-19, according to Dr. Minen. Best practices include having an adequate supply of medicine, considering alternatives to in-person doctor visits, and being “mindful of routine and diet to reduce migraine triggers,” the foundation suggests. In addition, patients should try to limit stress and seek out “alternative methods of social interaction.”
“The relationship between COVID-19 and Parkinson’s disease or other movement disorders remains unknown,” the International Parkinson and Movement Disorder Society said. “In general, we recommend that our movement disorder patients do not assume they are at extreme risks, which for the time being are uncertain. Nevertheless, we strongly recommend following the standard measures strictly to avoid exposures to the virus.”
The American Heart Association (AHA) cautions that older patients with coronary heart disease or hypertension “may be more likely than others to be infected by the coronavirus that causes COVID-19 and to develop more severe symptoms.” In addition, people with a history of stroke “may face a higher risk of complications,” according to the AHA. “As a result, people who have heart disease or another underlying condition should stay home to limit their risk of contracting the virus.”
Several groups emphasized the importance of telemedicine as an option for patients with neurologic conditions during the pandemic. The American Headache Society has hosted discussions on conducting neurologic exams via telemedicine. The American Academy of Neurology also conducted a webinar on telemedicine and COVID-19 and created a page with COVID-19 resources. The journal Neurology is publishing invited commentaries about neurologic aspects of the COVID-19 pandemic.
Cognitive reserve may play protective role in MS-related cognitive dysfunction
Key clinical point: Cognitive reserve (CR) is strongly associated with cognitive function in patients with multiple sclerosis (MS); CR along with disability and depressive symptoms explained up to roughly 23.7% of the cognitive performance.
Major finding: Cognitive impairment (CI) was detected in 202 (38.4%) patients. The CR Index questionnaire (CRIq) score was lower in patients with CI vs. those without (94.8±11.6 vs. 102.2±14.1; P less than .001). CRIq score significantly correlated with information-processing speed, verbal memory, and visuospatial memory (P less than .001 for all). Higher CRIq was associated with lower disability and depressive symptoms (P less than .001 for both).
Study details: Cross-sectional study of 526 MS outpatients (70.9% female patients; mean age, 41.7±11.1 years); CR was assessed by the CRIq.
Disclosures: No study sponsor was identified. Dr. Bakirtzis and Prof. Grigoriadis reported receiving research funding and/or honoraria from multiple pharmaceutical companies. The remaining authors reported no conflict of interest.
Citation: Artemiadis A et al. Mult Scler Relat Disord. 2020 Mar 7. doi: 10.1016/j.msard.2020.102047.
Key clinical point: Cognitive reserve (CR) is strongly associated with cognitive function in patients with multiple sclerosis (MS); CR along with disability and depressive symptoms explained up to roughly 23.7% of the cognitive performance.
Major finding: Cognitive impairment (CI) was detected in 202 (38.4%) patients. The CR Index questionnaire (CRIq) score was lower in patients with CI vs. those without (94.8±11.6 vs. 102.2±14.1; P less than .001). CRIq score significantly correlated with information-processing speed, verbal memory, and visuospatial memory (P less than .001 for all). Higher CRIq was associated with lower disability and depressive symptoms (P less than .001 for both).
Study details: Cross-sectional study of 526 MS outpatients (70.9% female patients; mean age, 41.7±11.1 years); CR was assessed by the CRIq.
Disclosures: No study sponsor was identified. Dr. Bakirtzis and Prof. Grigoriadis reported receiving research funding and/or honoraria from multiple pharmaceutical companies. The remaining authors reported no conflict of interest.
Citation: Artemiadis A et al. Mult Scler Relat Disord. 2020 Mar 7. doi: 10.1016/j.msard.2020.102047.
Key clinical point: Cognitive reserve (CR) is strongly associated with cognitive function in patients with multiple sclerosis (MS); CR along with disability and depressive symptoms explained up to roughly 23.7% of the cognitive performance.
Major finding: Cognitive impairment (CI) was detected in 202 (38.4%) patients. The CR Index questionnaire (CRIq) score was lower in patients with CI vs. those without (94.8±11.6 vs. 102.2±14.1; P less than .001). CRIq score significantly correlated with information-processing speed, verbal memory, and visuospatial memory (P less than .001 for all). Higher CRIq was associated with lower disability and depressive symptoms (P less than .001 for both).
Study details: Cross-sectional study of 526 MS outpatients (70.9% female patients; mean age, 41.7±11.1 years); CR was assessed by the CRIq.
Disclosures: No study sponsor was identified. Dr. Bakirtzis and Prof. Grigoriadis reported receiving research funding and/or honoraria from multiple pharmaceutical companies. The remaining authors reported no conflict of interest.
Citation: Artemiadis A et al. Mult Scler Relat Disord. 2020 Mar 7. doi: 10.1016/j.msard.2020.102047.
Higher incidence of trigeminal neuralgia in patients with MS
Key clinical point: The incidence of trigeminal neuralgia (TN) is 15-fold higher in patients with multiple sclerosis (MS) compared with the general neurological outpatient population.
Major finding: Concomitant diagnoses of MS and TN were verified in 55 patients, giving a prevalence of 2.1% for TN in patients with MS. Patients with MS had a significantly higher incidence of TN vs. general neurological outpatient population (149 vs. 9.9 per 100,000 person-years). A demyelinating lesion in the proximity of the trigeminal ganglia was observed in 26 (63%) of the 41 patients with a concomitant MS diagnosis and with magnetic resonance imaging scans available.
Study details: Single-center retrospective study included 2,575 patients with MS and 2,008 patients with a diagnosis of TN using data from the Finnish MS register.
Disclosures: The presenting author received fee for lecture from Merck; congress expenses from Roche, Merck. Funding for building the Finnish MS registry was received from Biogen Idec, Merck, Novartis, Sanofi-Genzyme, Roche, Teva, and Business Finland.
Citation: Laakso SM et al. Acta Neurol Scand. 2020 Mar 18. doi: 10.1111/ane.13243.
Key clinical point: The incidence of trigeminal neuralgia (TN) is 15-fold higher in patients with multiple sclerosis (MS) compared with the general neurological outpatient population.
Major finding: Concomitant diagnoses of MS and TN were verified in 55 patients, giving a prevalence of 2.1% for TN in patients with MS. Patients with MS had a significantly higher incidence of TN vs. general neurological outpatient population (149 vs. 9.9 per 100,000 person-years). A demyelinating lesion in the proximity of the trigeminal ganglia was observed in 26 (63%) of the 41 patients with a concomitant MS diagnosis and with magnetic resonance imaging scans available.
Study details: Single-center retrospective study included 2,575 patients with MS and 2,008 patients with a diagnosis of TN using data from the Finnish MS register.
Disclosures: The presenting author received fee for lecture from Merck; congress expenses from Roche, Merck. Funding for building the Finnish MS registry was received from Biogen Idec, Merck, Novartis, Sanofi-Genzyme, Roche, Teva, and Business Finland.
Citation: Laakso SM et al. Acta Neurol Scand. 2020 Mar 18. doi: 10.1111/ane.13243.
Key clinical point: The incidence of trigeminal neuralgia (TN) is 15-fold higher in patients with multiple sclerosis (MS) compared with the general neurological outpatient population.
Major finding: Concomitant diagnoses of MS and TN were verified in 55 patients, giving a prevalence of 2.1% for TN in patients with MS. Patients with MS had a significantly higher incidence of TN vs. general neurological outpatient population (149 vs. 9.9 per 100,000 person-years). A demyelinating lesion in the proximity of the trigeminal ganglia was observed in 26 (63%) of the 41 patients with a concomitant MS diagnosis and with magnetic resonance imaging scans available.
Study details: Single-center retrospective study included 2,575 patients with MS and 2,008 patients with a diagnosis of TN using data from the Finnish MS register.
Disclosures: The presenting author received fee for lecture from Merck; congress expenses from Roche, Merck. Funding for building the Finnish MS registry was received from Biogen Idec, Merck, Novartis, Sanofi-Genzyme, Roche, Teva, and Business Finland.
Citation: Laakso SM et al. Acta Neurol Scand. 2020 Mar 18. doi: 10.1111/ane.13243.
Exposure to passive smoking during adolescence tied to MS risk
Key clinical point: Exposure to passive smoking during adolescence is a strong risk factor for developing multiple sclerosis (MS) in later life.
Major finding: Among never smokers, female patients with MS more often than healthy control participants reported exposure to passive smoking between the age of 10 and 19 years (women: odds ratio [OR], 1.432; P = .037 and men: OR, 1.232; P = .390). Among active smokers aged 19 years or older, male MS patients more often than male control participants reported with passive smoking (men: OR, 1.593; P = .022 and women: OR, 1.102; P = .440).
Study details: The data come from a case-control study of 919 MS cases and 3,419 controls (never active smokers: 342/822 cases/controls; active smokers aged 19 years or older: 577/2,597 cases/controls).
Disclosures: This study was supported by grants from the Danish Multiple Sclerosis Society, the Danish Council for Strategic Research, Novartis, Biogen (Denmark), the Sofus Carl Emil Friis og Hustru Olga Doris Friis foundation, the Foundation for Research in Neurology, and the Director Einar Jonasson (Johnsen) and Wife foundation. Some of the authors reported receiving research support from various pharmaceutical companies.
Citation: Oturai DB et al. Mult Scler. 2020 Mar 23. doi: 10.1177/1352458520912500.
Key clinical point: Exposure to passive smoking during adolescence is a strong risk factor for developing multiple sclerosis (MS) in later life.
Major finding: Among never smokers, female patients with MS more often than healthy control participants reported exposure to passive smoking between the age of 10 and 19 years (women: odds ratio [OR], 1.432; P = .037 and men: OR, 1.232; P = .390). Among active smokers aged 19 years or older, male MS patients more often than male control participants reported with passive smoking (men: OR, 1.593; P = .022 and women: OR, 1.102; P = .440).
Study details: The data come from a case-control study of 919 MS cases and 3,419 controls (never active smokers: 342/822 cases/controls; active smokers aged 19 years or older: 577/2,597 cases/controls).
Disclosures: This study was supported by grants from the Danish Multiple Sclerosis Society, the Danish Council for Strategic Research, Novartis, Biogen (Denmark), the Sofus Carl Emil Friis og Hustru Olga Doris Friis foundation, the Foundation for Research in Neurology, and the Director Einar Jonasson (Johnsen) and Wife foundation. Some of the authors reported receiving research support from various pharmaceutical companies.
Citation: Oturai DB et al. Mult Scler. 2020 Mar 23. doi: 10.1177/1352458520912500.
Key clinical point: Exposure to passive smoking during adolescence is a strong risk factor for developing multiple sclerosis (MS) in later life.
Major finding: Among never smokers, female patients with MS more often than healthy control participants reported exposure to passive smoking between the age of 10 and 19 years (women: odds ratio [OR], 1.432; P = .037 and men: OR, 1.232; P = .390). Among active smokers aged 19 years or older, male MS patients more often than male control participants reported with passive smoking (men: OR, 1.593; P = .022 and women: OR, 1.102; P = .440).
Study details: The data come from a case-control study of 919 MS cases and 3,419 controls (never active smokers: 342/822 cases/controls; active smokers aged 19 years or older: 577/2,597 cases/controls).
Disclosures: This study was supported by grants from the Danish Multiple Sclerosis Society, the Danish Council for Strategic Research, Novartis, Biogen (Denmark), the Sofus Carl Emil Friis og Hustru Olga Doris Friis foundation, the Foundation for Research in Neurology, and the Director Einar Jonasson (Johnsen) and Wife foundation. Some of the authors reported receiving research support from various pharmaceutical companies.
Citation: Oturai DB et al. Mult Scler. 2020 Mar 23. doi: 10.1177/1352458520912500.
Genome study examines heritability of psoriatic disease subtypes
Genetic variation plays a greater role in the phenotype of cutaneous psoriasis, compared with psoriatic arthritis or psoriasis vulgaris, according to a study published in Scientific Reports.
Psoriatic disease is known to have a strong genetic basis, but understanding variations in the heritability of different forms of psoriasis is important for research into new genes, risk factors, and potential treatments, wrote Quan Li, PhD, of the faculty of medicine at Memorial University, St. John’s, Nfld., and coauthors.
“Heritability essentially refers to how much variation in a trait is due to variation in genetic factors,” the authors wrote. “Better approximation of the heritability of PsC [cutaneous psoriasis], PsV [psoriasis vulgaris], and PsA [psoriatic arthritis] will culminate in more efficient genetic profiling of psoriatic disease and facilitate gene identification studies by providing more accurate estimates of sample sizes needed based on the heritability of different subsets of psoriatic disease.”
The analysis used data from a previous genome-wide association study that looked at single nucleotide polymorphisms – a variation in the DNA sequence of a particular gene – in 2,938 people with PsV, 1,155 with PsC, 715 with PsA, and 3,117 unaffected controls.
The authors used two different modeling approaches to estimate the contribution these genetic variations made to each condition. These both revealed that PsC had a greater heritability than both PsV and PsA.
“This is the first study to quantify the additive heritability of three subsets of psoriatic disease that is attributable to common susceptibility [single nucleotide polymorphisms] from large-scale genotyping arrays,” the authors wrote.
The authors wrote that this finding differed from other population-based genetic epidemiologic studies, which had pointed to much greater heritability for PsA than for PsV. However, these earlier results could be attributed to common environmental factors.
Given these heritability estimates previously made for PsA, the authors commented on the surprising absence of PsA-specific genes that reach significance in genome-wide association studies.
“This is partly explained by the much larger number of patients in the PsC or PsV [genome-wide association] studies to date, compared with PsA,” they wrote, also suggesting that this may be because of the greater disease heterogeneity seen with PsA, compared with psoriasis.
“Considerably increasing the number of PsA patients in [genome-wide association] studies will help clarify the heritability estimate question for PsA,” they wrote, but acknowledged that lower heritability or greater environmental influence could also be an explanation for this finding.
The study was supported by the Atlantic Innovation Fund. The authors reported having no conflicts of interest.
SOURCE: Li Q et al. Sci Rep. 2020 Mar 18. doi: 10.1038/s41598-020-61981-5
Genetic variation plays a greater role in the phenotype of cutaneous psoriasis, compared with psoriatic arthritis or psoriasis vulgaris, according to a study published in Scientific Reports.
Psoriatic disease is known to have a strong genetic basis, but understanding variations in the heritability of different forms of psoriasis is important for research into new genes, risk factors, and potential treatments, wrote Quan Li, PhD, of the faculty of medicine at Memorial University, St. John’s, Nfld., and coauthors.
“Heritability essentially refers to how much variation in a trait is due to variation in genetic factors,” the authors wrote. “Better approximation of the heritability of PsC [cutaneous psoriasis], PsV [psoriasis vulgaris], and PsA [psoriatic arthritis] will culminate in more efficient genetic profiling of psoriatic disease and facilitate gene identification studies by providing more accurate estimates of sample sizes needed based on the heritability of different subsets of psoriatic disease.”
The analysis used data from a previous genome-wide association study that looked at single nucleotide polymorphisms – a variation in the DNA sequence of a particular gene – in 2,938 people with PsV, 1,155 with PsC, 715 with PsA, and 3,117 unaffected controls.
The authors used two different modeling approaches to estimate the contribution these genetic variations made to each condition. These both revealed that PsC had a greater heritability than both PsV and PsA.
“This is the first study to quantify the additive heritability of three subsets of psoriatic disease that is attributable to common susceptibility [single nucleotide polymorphisms] from large-scale genotyping arrays,” the authors wrote.
The authors wrote that this finding differed from other population-based genetic epidemiologic studies, which had pointed to much greater heritability for PsA than for PsV. However, these earlier results could be attributed to common environmental factors.
Given these heritability estimates previously made for PsA, the authors commented on the surprising absence of PsA-specific genes that reach significance in genome-wide association studies.
“This is partly explained by the much larger number of patients in the PsC or PsV [genome-wide association] studies to date, compared with PsA,” they wrote, also suggesting that this may be because of the greater disease heterogeneity seen with PsA, compared with psoriasis.
“Considerably increasing the number of PsA patients in [genome-wide association] studies will help clarify the heritability estimate question for PsA,” they wrote, but acknowledged that lower heritability or greater environmental influence could also be an explanation for this finding.
The study was supported by the Atlantic Innovation Fund. The authors reported having no conflicts of interest.
SOURCE: Li Q et al. Sci Rep. 2020 Mar 18. doi: 10.1038/s41598-020-61981-5
Genetic variation plays a greater role in the phenotype of cutaneous psoriasis, compared with psoriatic arthritis or psoriasis vulgaris, according to a study published in Scientific Reports.
Psoriatic disease is known to have a strong genetic basis, but understanding variations in the heritability of different forms of psoriasis is important for research into new genes, risk factors, and potential treatments, wrote Quan Li, PhD, of the faculty of medicine at Memorial University, St. John’s, Nfld., and coauthors.
“Heritability essentially refers to how much variation in a trait is due to variation in genetic factors,” the authors wrote. “Better approximation of the heritability of PsC [cutaneous psoriasis], PsV [psoriasis vulgaris], and PsA [psoriatic arthritis] will culminate in more efficient genetic profiling of psoriatic disease and facilitate gene identification studies by providing more accurate estimates of sample sizes needed based on the heritability of different subsets of psoriatic disease.”
The analysis used data from a previous genome-wide association study that looked at single nucleotide polymorphisms – a variation in the DNA sequence of a particular gene – in 2,938 people with PsV, 1,155 with PsC, 715 with PsA, and 3,117 unaffected controls.
The authors used two different modeling approaches to estimate the contribution these genetic variations made to each condition. These both revealed that PsC had a greater heritability than both PsV and PsA.
“This is the first study to quantify the additive heritability of three subsets of psoriatic disease that is attributable to common susceptibility [single nucleotide polymorphisms] from large-scale genotyping arrays,” the authors wrote.
The authors wrote that this finding differed from other population-based genetic epidemiologic studies, which had pointed to much greater heritability for PsA than for PsV. However, these earlier results could be attributed to common environmental factors.
Given these heritability estimates previously made for PsA, the authors commented on the surprising absence of PsA-specific genes that reach significance in genome-wide association studies.
“This is partly explained by the much larger number of patients in the PsC or PsV [genome-wide association] studies to date, compared with PsA,” they wrote, also suggesting that this may be because of the greater disease heterogeneity seen with PsA, compared with psoriasis.
“Considerably increasing the number of PsA patients in [genome-wide association] studies will help clarify the heritability estimate question for PsA,” they wrote, but acknowledged that lower heritability or greater environmental influence could also be an explanation for this finding.
The study was supported by the Atlantic Innovation Fund. The authors reported having no conflicts of interest.
SOURCE: Li Q et al. Sci Rep. 2020 Mar 18. doi: 10.1038/s41598-020-61981-5
FROM SCIENTIFIC REPORTS
Physical exercise reduces fatigue in patients with MS
Key clinical point: Physical exercise significantly reduces fatigue in patients with multiple sclerosis (MS).
Major finding: The standardized mean difference between the intervention groups before and after the intervention was estimated to be 23.8±6.2 and 16.9±3.2, respectively.
Study details: Meta-analysis of 31 studies including 1,434 participants (714 in the intervention group; 720 in the control group).
Disclosures: This study was funded by the Student Research Committee of Kermanshah University of Medical Sciences, Deputy for Research and Technology, Kermanshah University of Medical Sciences. The authors declared no conflict of interest.
Citation: Razazian N et al. BMC Neurol. 2020 Mar 13. doi: 10.1186/s12883-020-01654-y.
Key clinical point: Physical exercise significantly reduces fatigue in patients with multiple sclerosis (MS).
Major finding: The standardized mean difference between the intervention groups before and after the intervention was estimated to be 23.8±6.2 and 16.9±3.2, respectively.
Study details: Meta-analysis of 31 studies including 1,434 participants (714 in the intervention group; 720 in the control group).
Disclosures: This study was funded by the Student Research Committee of Kermanshah University of Medical Sciences, Deputy for Research and Technology, Kermanshah University of Medical Sciences. The authors declared no conflict of interest.
Citation: Razazian N et al. BMC Neurol. 2020 Mar 13. doi: 10.1186/s12883-020-01654-y.
Key clinical point: Physical exercise significantly reduces fatigue in patients with multiple sclerosis (MS).
Major finding: The standardized mean difference between the intervention groups before and after the intervention was estimated to be 23.8±6.2 and 16.9±3.2, respectively.
Study details: Meta-analysis of 31 studies including 1,434 participants (714 in the intervention group; 720 in the control group).
Disclosures: This study was funded by the Student Research Committee of Kermanshah University of Medical Sciences, Deputy for Research and Technology, Kermanshah University of Medical Sciences. The authors declared no conflict of interest.
Citation: Razazian N et al. BMC Neurol. 2020 Mar 13. doi: 10.1186/s12883-020-01654-y.
Fingolimod vs. natalizumab as second-line therapy for RRMS
Key clinical point: In patients with relapsing-remitting multiple sclerosis (RRMS), both fingolimod (FIN) and natalizumab (NTZ) reduce the annualized relapse rate (ARR), but ARR percent reduction is significantly higher with NTZ after 12 months of treatment.
Major finding: ARR reduction during the first year of treatment was statistically significant in both the groups, from 1.67±0.98 to 0.28±0.62 in the FIN group and from 1.71±1.37 to 0.12±0.33 in the NTZ group (P less than .0001 for both). Nevertheless, the ARR percent reduction was significantly higher in the NTZ group vs. FIN group during the first year of treatment (92.3% vs. 81.8%; P = .0064).
Study details: Retrospective, observational study compared the ARR over the first year in 314 patients with RRMS after the treatment with FIN (n = 184) or NTZ (n = 130) as a second-line therapy in routine clinical practice in Spain.
Disclosures: This study was funding by Novartis Farmaceutica, S.A. The authors declared no conflicts of interest.
Citation: Meca-Lallana J et al. Eur Neurol. 2020 Mar 18. doi: 10.1159/000505778.
Key clinical point: In patients with relapsing-remitting multiple sclerosis (RRMS), both fingolimod (FIN) and natalizumab (NTZ) reduce the annualized relapse rate (ARR), but ARR percent reduction is significantly higher with NTZ after 12 months of treatment.
Major finding: ARR reduction during the first year of treatment was statistically significant in both the groups, from 1.67±0.98 to 0.28±0.62 in the FIN group and from 1.71±1.37 to 0.12±0.33 in the NTZ group (P less than .0001 for both). Nevertheless, the ARR percent reduction was significantly higher in the NTZ group vs. FIN group during the first year of treatment (92.3% vs. 81.8%; P = .0064).
Study details: Retrospective, observational study compared the ARR over the first year in 314 patients with RRMS after the treatment with FIN (n = 184) or NTZ (n = 130) as a second-line therapy in routine clinical practice in Spain.
Disclosures: This study was funding by Novartis Farmaceutica, S.A. The authors declared no conflicts of interest.
Citation: Meca-Lallana J et al. Eur Neurol. 2020 Mar 18. doi: 10.1159/000505778.
Key clinical point: In patients with relapsing-remitting multiple sclerosis (RRMS), both fingolimod (FIN) and natalizumab (NTZ) reduce the annualized relapse rate (ARR), but ARR percent reduction is significantly higher with NTZ after 12 months of treatment.
Major finding: ARR reduction during the first year of treatment was statistically significant in both the groups, from 1.67±0.98 to 0.28±0.62 in the FIN group and from 1.71±1.37 to 0.12±0.33 in the NTZ group (P less than .0001 for both). Nevertheless, the ARR percent reduction was significantly higher in the NTZ group vs. FIN group during the first year of treatment (92.3% vs. 81.8%; P = .0064).
Study details: Retrospective, observational study compared the ARR over the first year in 314 patients with RRMS after the treatment with FIN (n = 184) or NTZ (n = 130) as a second-line therapy in routine clinical practice in Spain.
Disclosures: This study was funding by Novartis Farmaceutica, S.A. The authors declared no conflicts of interest.
Citation: Meca-Lallana J et al. Eur Neurol. 2020 Mar 18. doi: 10.1159/000505778.
Surge in firearm sales tied to COVID-19 fears, uncertainty presents risks
Use gentle assumptions and focus on home access to elicit positive answers.
In the wake of the 2012 shooting at Sandy Hook Elementary, in Newtown, Conn., after 20 children and seven adults were murdered, American gun sales surged on fears of new restrictions.
In the ensuing months, 20 more children and 40 more adults died from unintentional shootings believed to be tied to that surge in gun purchases.1 More recently, American gun sales surged in response to the COVID-19 pandemic with heated legal battles brewing over whether gun sales are essential.2,3 The results of this surge in sales are yet to fully manifest, but I would like to discuss several risks.
The public health risks of firearm access are well established: Nearly every measure of harm, from suicide to negligent injury and death to homicide to shootings of police, increase along with access to firearms.4 That firearms in the home are associated with greater likelihoods of suicide, negligent injury and death, and intrafamilial homicide has been recognized for decades as has the substantially heightened risk in the immediate period after a firearm is brought into the home.5,6 Defensive gun use is rare despite this being the nominal reason for firearm ownership among many.7 Even prior to recent events, there had been concerns of increased unsafe carrying and handling of firearms.8 It seems reasonable to expect such trends not to be diminished by recent events.
Added to this are several stressors, which one can reasonably expect to be associated with increased risks for unsafe use. There are new, broad social stressors from fear and uncertainty about COVID-19. Unemployment rates have skyrocketed, clinical care has been disrupted, and basic necessities have become scant. Children are home from school, unable to play with friends and unable to access mental health services as easily as before; risks of negligent and suicidal injuries and death may ensue. Couples and families are isolated in homes together for longer periods and with fewer avenues for relief; previously peaceful homes may see conflicts increase and homes with abuse have now trapped victims with their assailants. Social isolation is difficult for any person and may be even more traumatic for people with underlying vulnerabilities, including mental illness. The risks of being isolated in a home – struggling with worsening symptoms – with ready access to a firearm are self-evident.
- Consider reassessing for firearm access. Patients may be in new homes, or there may be new firearms in their homes. Use gentle assumptions and focus on home access over personal access to elicit the most true, positive answers, for example: “I understand there have been a lot of changes recently; how many guns are in the home now?”
- Reinforce safer storage practices. Simple measures, such as storing ammunition separately and using trigger locks or safes, can make a substantial difference in injury risks.
- Do not forget aging clients; suicide risk increases with age, and there may be substantial risks among the geriatric population for suicide and murder-suicide. If using telepsychiatry, realize that the abuser might be in the home or within earshot of any clinical encounter, and this might put the client at heightened risk, during and after telesessions.
- Highlight access to local and national resources, including the Disaster Distress Hotline (800-985-5990) and the National Suicide Prevention Lifeline (800-273-TALK). Promote both numbers, and note that some people may be more comfortable reaching out for help for “distress” than for “suicide.”
References
1. Levine PB and McKnight R. Science. 2017 Dec 8;358(6368):1324-8.
2. Levin D. “Coronavirus and firearms: Are gun shops essential businesses?” The New York Times. 2020 Mar 25.
3. Robertson L. “Neither hurricanes nor 9/11 caused as big a surge in gun sales as coronavirus.” Miami Herald. 2020 Mar 25.
4. Moyer MW. Scientific American. 2017 Oct;317(4):54-63.
5. Kellermann AL et al. J Trauma. 1998 Aug;45(2):263-7.
6. Wintemute GJ et al. New Engl J Med. 1999 Nov 18;341(21):1583-9.
7. Firearm Justifiable Homicides and Non-Fatal Self-Defense Gun Use: An Analysis of Federal Bureau of Investigation and National Crime Victimization Survey Data. Washington: Violence Policy Center; 2019 Jul.
8. Towers S et al. bioRxiv. 2019 Apr 18;613687.
Dr. Rozel is the medical director of resolve Crisis Services at UPMC Western Psychiatric Hospital and president of the American Association for Emergency Psychiatry. He also is associate professor of psychiatry and an adjunct professor of law at the University of Pittsburgh. He has no conflicts of interest but has worked for a gun dealer to teach sales staff how to recognize people in crisis (rather than sell a gun).
Use gentle assumptions and focus on home access to elicit positive answers.
Use gentle assumptions and focus on home access to elicit positive answers.
In the wake of the 2012 shooting at Sandy Hook Elementary, in Newtown, Conn., after 20 children and seven adults were murdered, American gun sales surged on fears of new restrictions.
In the ensuing months, 20 more children and 40 more adults died from unintentional shootings believed to be tied to that surge in gun purchases.1 More recently, American gun sales surged in response to the COVID-19 pandemic with heated legal battles brewing over whether gun sales are essential.2,3 The results of this surge in sales are yet to fully manifest, but I would like to discuss several risks.
The public health risks of firearm access are well established: Nearly every measure of harm, from suicide to negligent injury and death to homicide to shootings of police, increase along with access to firearms.4 That firearms in the home are associated with greater likelihoods of suicide, negligent injury and death, and intrafamilial homicide has been recognized for decades as has the substantially heightened risk in the immediate period after a firearm is brought into the home.5,6 Defensive gun use is rare despite this being the nominal reason for firearm ownership among many.7 Even prior to recent events, there had been concerns of increased unsafe carrying and handling of firearms.8 It seems reasonable to expect such trends not to be diminished by recent events.
Added to this are several stressors, which one can reasonably expect to be associated with increased risks for unsafe use. There are new, broad social stressors from fear and uncertainty about COVID-19. Unemployment rates have skyrocketed, clinical care has been disrupted, and basic necessities have become scant. Children are home from school, unable to play with friends and unable to access mental health services as easily as before; risks of negligent and suicidal injuries and death may ensue. Couples and families are isolated in homes together for longer periods and with fewer avenues for relief; previously peaceful homes may see conflicts increase and homes with abuse have now trapped victims with their assailants. Social isolation is difficult for any person and may be even more traumatic for people with underlying vulnerabilities, including mental illness. The risks of being isolated in a home – struggling with worsening symptoms – with ready access to a firearm are self-evident.
- Consider reassessing for firearm access. Patients may be in new homes, or there may be new firearms in their homes. Use gentle assumptions and focus on home access over personal access to elicit the most true, positive answers, for example: “I understand there have been a lot of changes recently; how many guns are in the home now?”
- Reinforce safer storage practices. Simple measures, such as storing ammunition separately and using trigger locks or safes, can make a substantial difference in injury risks.
- Do not forget aging clients; suicide risk increases with age, and there may be substantial risks among the geriatric population for suicide and murder-suicide. If using telepsychiatry, realize that the abuser might be in the home or within earshot of any clinical encounter, and this might put the client at heightened risk, during and after telesessions.
- Highlight access to local and national resources, including the Disaster Distress Hotline (800-985-5990) and the National Suicide Prevention Lifeline (800-273-TALK). Promote both numbers, and note that some people may be more comfortable reaching out for help for “distress” than for “suicide.”
References
1. Levine PB and McKnight R. Science. 2017 Dec 8;358(6368):1324-8.
2. Levin D. “Coronavirus and firearms: Are gun shops essential businesses?” The New York Times. 2020 Mar 25.
3. Robertson L. “Neither hurricanes nor 9/11 caused as big a surge in gun sales as coronavirus.” Miami Herald. 2020 Mar 25.
4. Moyer MW. Scientific American. 2017 Oct;317(4):54-63.
5. Kellermann AL et al. J Trauma. 1998 Aug;45(2):263-7.
6. Wintemute GJ et al. New Engl J Med. 1999 Nov 18;341(21):1583-9.
7. Firearm Justifiable Homicides and Non-Fatal Self-Defense Gun Use: An Analysis of Federal Bureau of Investigation and National Crime Victimization Survey Data. Washington: Violence Policy Center; 2019 Jul.
8. Towers S et al. bioRxiv. 2019 Apr 18;613687.
Dr. Rozel is the medical director of resolve Crisis Services at UPMC Western Psychiatric Hospital and president of the American Association for Emergency Psychiatry. He also is associate professor of psychiatry and an adjunct professor of law at the University of Pittsburgh. He has no conflicts of interest but has worked for a gun dealer to teach sales staff how to recognize people in crisis (rather than sell a gun).
In the wake of the 2012 shooting at Sandy Hook Elementary, in Newtown, Conn., after 20 children and seven adults were murdered, American gun sales surged on fears of new restrictions.
In the ensuing months, 20 more children and 40 more adults died from unintentional shootings believed to be tied to that surge in gun purchases.1 More recently, American gun sales surged in response to the COVID-19 pandemic with heated legal battles brewing over whether gun sales are essential.2,3 The results of this surge in sales are yet to fully manifest, but I would like to discuss several risks.
The public health risks of firearm access are well established: Nearly every measure of harm, from suicide to negligent injury and death to homicide to shootings of police, increase along with access to firearms.4 That firearms in the home are associated with greater likelihoods of suicide, negligent injury and death, and intrafamilial homicide has been recognized for decades as has the substantially heightened risk in the immediate period after a firearm is brought into the home.5,6 Defensive gun use is rare despite this being the nominal reason for firearm ownership among many.7 Even prior to recent events, there had been concerns of increased unsafe carrying and handling of firearms.8 It seems reasonable to expect such trends not to be diminished by recent events.
Added to this are several stressors, which one can reasonably expect to be associated with increased risks for unsafe use. There are new, broad social stressors from fear and uncertainty about COVID-19. Unemployment rates have skyrocketed, clinical care has been disrupted, and basic necessities have become scant. Children are home from school, unable to play with friends and unable to access mental health services as easily as before; risks of negligent and suicidal injuries and death may ensue. Couples and families are isolated in homes together for longer periods and with fewer avenues for relief; previously peaceful homes may see conflicts increase and homes with abuse have now trapped victims with their assailants. Social isolation is difficult for any person and may be even more traumatic for people with underlying vulnerabilities, including mental illness. The risks of being isolated in a home – struggling with worsening symptoms – with ready access to a firearm are self-evident.
- Consider reassessing for firearm access. Patients may be in new homes, or there may be new firearms in their homes. Use gentle assumptions and focus on home access over personal access to elicit the most true, positive answers, for example: “I understand there have been a lot of changes recently; how many guns are in the home now?”
- Reinforce safer storage practices. Simple measures, such as storing ammunition separately and using trigger locks or safes, can make a substantial difference in injury risks.
- Do not forget aging clients; suicide risk increases with age, and there may be substantial risks among the geriatric population for suicide and murder-suicide. If using telepsychiatry, realize that the abuser might be in the home or within earshot of any clinical encounter, and this might put the client at heightened risk, during and after telesessions.
- Highlight access to local and national resources, including the Disaster Distress Hotline (800-985-5990) and the National Suicide Prevention Lifeline (800-273-TALK). Promote both numbers, and note that some people may be more comfortable reaching out for help for “distress” than for “suicide.”
References
1. Levine PB and McKnight R. Science. 2017 Dec 8;358(6368):1324-8.
2. Levin D. “Coronavirus and firearms: Are gun shops essential businesses?” The New York Times. 2020 Mar 25.
3. Robertson L. “Neither hurricanes nor 9/11 caused as big a surge in gun sales as coronavirus.” Miami Herald. 2020 Mar 25.
4. Moyer MW. Scientific American. 2017 Oct;317(4):54-63.
5. Kellermann AL et al. J Trauma. 1998 Aug;45(2):263-7.
6. Wintemute GJ et al. New Engl J Med. 1999 Nov 18;341(21):1583-9.
7. Firearm Justifiable Homicides and Non-Fatal Self-Defense Gun Use: An Analysis of Federal Bureau of Investigation and National Crime Victimization Survey Data. Washington: Violence Policy Center; 2019 Jul.
8. Towers S et al. bioRxiv. 2019 Apr 18;613687.
Dr. Rozel is the medical director of resolve Crisis Services at UPMC Western Psychiatric Hospital and president of the American Association for Emergency Psychiatry. He also is associate professor of psychiatry and an adjunct professor of law at the University of Pittsburgh. He has no conflicts of interest but has worked for a gun dealer to teach sales staff how to recognize people in crisis (rather than sell a gun).