MDedge Neurology

Thirty-eight percent of a large cohort of multiple sclerosis (MS) patients developed low IgM and 7.4% became hypogammaglobulinemic during a mean 30 months of follow-up on anti-CD20 therapy, Brandi L. Vollmer, MPH, reported online as part of the 2020 American Academy of Neurology Science Highlights.

The hypogammaglobulinemia was preceded by an IgM of 40 mg/dL or less in 35% of cases and was accompanied by concurrent development of low IgM in another 39%, added Ms. Vollmer, a professional research assistant at the Rocky Mountain Multiple Sclerosis Center at Anschutz Medical Campus, University of Colorado, Denver.

She presented a retrospective study of 527 randomly selected MS patients and another 17 with neuromyelitis optica spectrum disorder who averaged 44 years of age and a 9.2-year disease duration upon commencing rituximab (Rituxan) with close laboratory monitoring. Their mean cumulative rituximab dose during a mean 30.2 months of therapy was 3,312 mg. Ninety-six MS patients eventually switched to ocrelizumab (Ocrevus), accumulating a total dose of 1,175 mg of that anti-CD20 humanized monoclonal antibody.

Absolute lymphocyte count dropped to 500 cells/mm³ or lower in 10.4% of patients at a mean of 11.3 months into anti-CD20 therapy. Low immunoglobulins came later: The mean time to onset of low IgM in affected patients was 19.7 months, and hypogammaglobulinemia, as defined by an IgG of 500 mg/dL or less, occurred at a mean of 36.1 months. Higher cumulative doses of anti-CD20 agents were associated with increased likelihood of hypogammaglobulinemia.

Asked to comment on the research findings, neurologist Nida Laurin, MD, said the Colorado study provides helpful insights into the timing of onset of acquired immunodeficiency in patients on B-cell-targeted therapy.

“This paper informs us that we should monitor our patients much closer for signs of hypogammaglobulinemia and lymphopenia starting with year 2 on therapy, and switch treatment when the threshold is reached. I do expect production of gamma globulins and lymphocytes to recover with discontinuation of anti-CD20 therapy, maybe over a period of 6-10 months. It might also recover with lower-dose therapy because the effect on B cells is dose-dependent,” observed Dr. Laurin, an MS specialist at the Banner Health–University Medicine Neuroscience Institute in Phoenix and the University of Arizona in Tucson.

Her colleague Barry Hendin, MD, noted that there is no consensus regarding the best response to all these changes.

“Some clinicians add IVIG, some change therapies, and some observe only,” said Dr. Hendin, a neurologist at Banner Health–University Medical Center, Phoenix, and clinical professor of neurology at the University of Arizona in Tucson.

However, Dr. Laurin asserted that it would be a mistake for physicians and patients to shrug off anti-CD20 therapy–induced lymphopenia in light of studies demonstrating that lymphopenia and older age are two main risk factors for progressive multifocal leukoencephalopathy in patients on disease-modifying therapies.

“More cases of PML can be expected with continuous use of anti-CD20 therapies if lymphopenia is ignored,” she cautioned.

Depressed levels of IgM and IgG have been associated with increased risk of serious infections. In light of the COVID-19 pandemic and the eventual prospect of a vaccine, it is especially important to avoid putting patients with MS in harm’s way via treatment-induced acquired immunodeficiency, Dr. Laurin said.

Ms. Vollmer reported having no financial conflicts regarding her study. Dr. Laurin reported serving as a speaker or consultant for Alexion, Allergan, Biogen, Bristol-Myers Squibb, EMD Serono, Genentech, Lundbeck, and Sanofi Genzyme. Dr. Hendin serves as a consultant to Biogen, Genentech, Genzyme, EMD Serono, Novartis, and Bristol-Myers Squibb.

[email protected]

SOURCE: Vollmer BL et al. AAN 2020. Abstract S29.002.

Thirty-eight percent of a large cohort of multiple sclerosis (MS) patients developed low IgM and 7.4% became hypogammaglobulinemic during a mean 30 months of follow-up on anti-CD20 therapy, Brandi L. Vollmer, MPH, reported online as part of the 2020 American Academy of Neurology Science Highlights.

The hypogammaglobulinemia was preceded by an IgM of 40 mg/dL or less in 35% of cases and was accompanied by concurrent development of low IgM in another 39%, added Ms. Vollmer, a professional research assistant at the Rocky Mountain Multiple Sclerosis Center at Anschutz Medical Campus, University of Colorado, Denver.

She presented a retrospective study of 527 randomly selected MS patients and another 17 with neuromyelitis optica spectrum disorder who averaged 44 years of age and a 9.2-year disease duration upon commencing rituximab (Rituxan) with close laboratory monitoring. Their mean cumulative rituximab dose during a mean 30.2 months of therapy was 3,312 mg. Ninety-six MS patients eventually switched to ocrelizumab (Ocrevus), accumulating a total dose of 1,175 mg of that anti-CD20 humanized monoclonal antibody.

Absolute lymphocyte count dropped to 500 cells/mm³ or lower in 10.4% of patients at a mean of 11.3 months into anti-CD20 therapy. Low immunoglobulins came later: The mean time to onset of low IgM in affected patients was 19.7 months, and hypogammaglobulinemia, as defined by an IgG of 500 mg/dL or less, occurred at a mean of 36.1 months. Higher cumulative doses of anti-CD20 agents were associated with increased likelihood of hypogammaglobulinemia.

Asked to comment on the research findings, neurologist Nida Laurin, MD, said the Colorado study provides helpful insights into the timing of onset of acquired immunodeficiency in patients on B-cell-targeted therapy.

“This paper informs us that we should monitor our patients much closer for signs of hypogammaglobulinemia and lymphopenia starting with year 2 on therapy, and switch treatment when the threshold is reached. I do expect production of gamma globulins and lymphocytes to recover with discontinuation of anti-CD20 therapy, maybe over a period of 6-10 months. It might also recover with lower-dose therapy because the effect on B cells is dose-dependent,” observed Dr. Laurin, an MS specialist at the Banner Health–University Medicine Neuroscience Institute in Phoenix and the University of Arizona in Tucson.

Her colleague Barry Hendin, MD, noted that there is no consensus regarding the best response to all these changes.

“Some clinicians add IVIG, some change therapies, and some observe only,” said Dr. Hendin, a neurologist at Banner Health–University Medical Center, Phoenix, and clinical professor of neurology at the University of Arizona in Tucson.

However, Dr. Laurin asserted that it would be a mistake for physicians and patients to shrug off anti-CD20 therapy–induced lymphopenia in light of studies demonstrating that lymphopenia and older age are two main risk factors for progressive multifocal leukoencephalopathy in patients on disease-modifying therapies.

“More cases of PML can be expected with continuous use of anti-CD20 therapies if lymphopenia is ignored,” she cautioned.

Depressed levels of IgM and IgG have been associated with increased risk of serious infections. In light of the COVID-19 pandemic and the eventual prospect of a vaccine, it is especially important to avoid putting patients with MS in harm’s way via treatment-induced acquired immunodeficiency, Dr. Laurin said.

Ms. Vollmer reported having no financial conflicts regarding her study. Dr. Laurin reported serving as a speaker or consultant for Alexion, Allergan, Biogen, Bristol-Myers Squibb, EMD Serono, Genentech, Lundbeck, and Sanofi Genzyme. Dr. Hendin serves as a consultant to Biogen, Genentech, Genzyme, EMD Serono, Novartis, and Bristol-Myers Squibb.

[email protected]

SOURCE: Vollmer BL et al. AAN 2020. Abstract S29.002.

Thirty-eight percent of a large cohort of multiple sclerosis (MS) patients developed low IgM and 7.4% became hypogammaglobulinemic during a mean 30 months of follow-up on anti-CD20 therapy, Brandi L. Vollmer, MPH, reported online as part of the 2020 American Academy of Neurology Science Highlights.

The hypogammaglobulinemia was preceded by an IgM of 40 mg/dL or less in 35% of cases and was accompanied by concurrent development of low IgM in another 39%, added Ms. Vollmer, a professional research assistant at the Rocky Mountain Multiple Sclerosis Center at Anschutz Medical Campus, University of Colorado, Denver.

She presented a retrospective study of 527 randomly selected MS patients and another 17 with neuromyelitis optica spectrum disorder who averaged 44 years of age and a 9.2-year disease duration upon commencing rituximab (Rituxan) with close laboratory monitoring. Their mean cumulative rituximab dose during a mean 30.2 months of therapy was 3,312 mg. Ninety-six MS patients eventually switched to ocrelizumab (Ocrevus), accumulating a total dose of 1,175 mg of that anti-CD20 humanized monoclonal antibody.

Absolute lymphocyte count dropped to 500 cells/mm³ or lower in 10.4% of patients at a mean of 11.3 months into anti-CD20 therapy. Low immunoglobulins came later: The mean time to onset of low IgM in affected patients was 19.7 months, and hypogammaglobulinemia, as defined by an IgG of 500 mg/dL or less, occurred at a mean of 36.1 months. Higher cumulative doses of anti-CD20 agents were associated with increased likelihood of hypogammaglobulinemia.

Asked to comment on the research findings, neurologist Nida Laurin, MD, said the Colorado study provides helpful insights into the timing of onset of acquired immunodeficiency in patients on B-cell-targeted therapy.

“This paper informs us that we should monitor our patients much closer for signs of hypogammaglobulinemia and lymphopenia starting with year 2 on therapy, and switch treatment when the threshold is reached. I do expect production of gamma globulins and lymphocytes to recover with discontinuation of anti-CD20 therapy, maybe over a period of 6-10 months. It might also recover with lower-dose therapy because the effect on B cells is dose-dependent,” observed Dr. Laurin, an MS specialist at the Banner Health–University Medicine Neuroscience Institute in Phoenix and the University of Arizona in Tucson.

Her colleague Barry Hendin, MD, noted that there is no consensus regarding the best response to all these changes.

“Some clinicians add IVIG, some change therapies, and some observe only,” said Dr. Hendin, a neurologist at Banner Health–University Medical Center, Phoenix, and clinical professor of neurology at the University of Arizona in Tucson.

However, Dr. Laurin asserted that it would be a mistake for physicians and patients to shrug off anti-CD20 therapy–induced lymphopenia in light of studies demonstrating that lymphopenia and older age are two main risk factors for progressive multifocal leukoencephalopathy in patients on disease-modifying therapies.

“More cases of PML can be expected with continuous use of anti-CD20 therapies if lymphopenia is ignored,” she cautioned.

Depressed levels of IgM and IgG have been associated with increased risk of serious infections. In light of the COVID-19 pandemic and the eventual prospect of a vaccine, it is especially important to avoid putting patients with MS in harm’s way via treatment-induced acquired immunodeficiency, Dr. Laurin said.

Ms. Vollmer reported having no financial conflicts regarding her study. Dr. Laurin reported serving as a speaker or consultant for Alexion, Allergan, Biogen, Bristol-Myers Squibb, EMD Serono, Genentech, Lundbeck, and Sanofi Genzyme. Dr. Hendin serves as a consultant to Biogen, Genentech, Genzyme, EMD Serono, Novartis, and Bristol-Myers Squibb.

[email protected]

SOURCE: Vollmer BL et al. AAN 2020. Abstract S29.002.

Among patients with secondary progressive multiple sclerosis (MS) who received siponimod or placebo during a double-blind trial and entered an open-label extension, those who received siponimod throughout the study were less likely to experience disability progression and had a lower annualized relapse rate up to 5 years later, compared with patients who initially received placebo and switched to siponimod. This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.

Benefits of siponimod gained during the controlled period were “sustained for up to 5 years, suggesting a continuous effect of siponimod and underlining the advantages of early treatment initiation with siponimod,” the researchers said. Incidence rates of adverse events during the extension study were consistent with those during the controlled treatment period.

The results “highlight the critical importance of early treatment intervention ... to ensure the best possible long-term outcomes for patients with MS who are experiencing progression,” study investigator Bruce Cree, MD, PhD, said in a news release.

“It’s never too early to stay ahead of progression in MS, since the early identification of physical and cognitive changes – even subtle ones – can indicate MS disease progression and therefore allow for timely intervention.” said Dr. Cree, who is clinical research director and George A. Zimmermann Endowed Professor in Multiple Sclerosis at the University of California, San Francisco.

Siponimod, marketed as Mayzent, is a sphingosine 1-phosphate receptor modulator that selectively binds to S1P1 and S1P5 receptors. The oral drug was approved by the Food and Drug Administration in 2019 for the treatment of relapsing forms of MS, including clinically isolated syndrome, relapsing remitting disease, and active secondary progressive disease in adults.

To assess the long-term efficacy and safety of siponimod in patients with secondary progressive MS, Dr. Cree and colleagues analyzed data from patients in the controlled and extension parts of the EXPAND trial. Patients could have had been in the study for as long as 5 years at the data cutoff in April 2019. Efficacy analyses included time to 3-month confirmed disability progression on the Expanded Disability Status Scale (EDSS), time to 6-month confirmed disability progression, time to 6-month confirmed worsening of 4 or more points on the Symbol Digit Modalities Test (SDMT), and annualized relapse rate. In EXPAND, the researchers defined confirmed disability progression as a 1-point increase in EDSS if the baseline score was 3.0-5.0, or a 0.5-point increase if the baseline score was 5.5-6.5.

“Of the 1,224 (74% of 1,651 randomized) patients entering the extension, 878 (72%) were ongoing,” the researchers reported. Patients who received siponimod continuously were less likely to experience 3-month confirmed disability progression and 6-month confirmed disability progression, relative to patients who switched from placebo. In addition, patients who received continuous siponimod treatment had a prolonged time to 6-month confirmed disability progression, compared with patients who switched from placebo. For the 25th percentile of patients, continuous siponimod treatment corresponded to a delay of 54% (21 months vs. 13.6 months). Risk of worsening on the SDMT was reduced by 23% in the continuous siponimod–treatment group. For the 25th percentile of patients, this reduced risk corresponded to a delay of 62% (29.6 months vs. 18.3 months). ARR was 0.054 in the continuous-siponimod group, compared with 0.097 in the group that switched to siponimod from placebo, a reduction of 52%.

Dr. Cree has received personal compensation from Novartis, which markets siponimod, as well as Akili, Alexion, Atara, Biogen, EMD Serono, and TG Therapeutics. His coauthors reported receiving research support and personal compensation from Novartis and other pharmaceutical companies. Several coauthors were Novartis employees.

[email protected]

SOURCE: Kappos L et al. AAN 2020, Abstract S40.003.

Among patients with secondary progressive multiple sclerosis (MS) who received siponimod or placebo during a double-blind trial and entered an open-label extension, those who received siponimod throughout the study were less likely to experience disability progression and had a lower annualized relapse rate up to 5 years later, compared with patients who initially received placebo and switched to siponimod. This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.

Benefits of siponimod gained during the controlled period were “sustained for up to 5 years, suggesting a continuous effect of siponimod and underlining the advantages of early treatment initiation with siponimod,” the researchers said. Incidence rates of adverse events during the extension study were consistent with those during the controlled treatment period.

The results “highlight the critical importance of early treatment intervention ... to ensure the best possible long-term outcomes for patients with MS who are experiencing progression,” study investigator Bruce Cree, MD, PhD, said in a news release.

“It’s never too early to stay ahead of progression in MS, since the early identification of physical and cognitive changes – even subtle ones – can indicate MS disease progression and therefore allow for timely intervention.” said Dr. Cree, who is clinical research director and George A. Zimmermann Endowed Professor in Multiple Sclerosis at the University of California, San Francisco.

Siponimod, marketed as Mayzent, is a sphingosine 1-phosphate receptor modulator that selectively binds to S1P1 and S1P5 receptors. The oral drug was approved by the Food and Drug Administration in 2019 for the treatment of relapsing forms of MS, including clinically isolated syndrome, relapsing remitting disease, and active secondary progressive disease in adults.

To assess the long-term efficacy and safety of siponimod in patients with secondary progressive MS, Dr. Cree and colleagues analyzed data from patients in the controlled and extension parts of the EXPAND trial. Patients could have had been in the study for as long as 5 years at the data cutoff in April 2019. Efficacy analyses included time to 3-month confirmed disability progression on the Expanded Disability Status Scale (EDSS), time to 6-month confirmed disability progression, time to 6-month confirmed worsening of 4 or more points on the Symbol Digit Modalities Test (SDMT), and annualized relapse rate. In EXPAND, the researchers defined confirmed disability progression as a 1-point increase in EDSS if the baseline score was 3.0-5.0, or a 0.5-point increase if the baseline score was 5.5-6.5.

“Of the 1,224 (74% of 1,651 randomized) patients entering the extension, 878 (72%) were ongoing,” the researchers reported. Patients who received siponimod continuously were less likely to experience 3-month confirmed disability progression and 6-month confirmed disability progression, relative to patients who switched from placebo. In addition, patients who received continuous siponimod treatment had a prolonged time to 6-month confirmed disability progression, compared with patients who switched from placebo. For the 25th percentile of patients, continuous siponimod treatment corresponded to a delay of 54% (21 months vs. 13.6 months). Risk of worsening on the SDMT was reduced by 23% in the continuous siponimod–treatment group. For the 25th percentile of patients, this reduced risk corresponded to a delay of 62% (29.6 months vs. 18.3 months). ARR was 0.054 in the continuous-siponimod group, compared with 0.097 in the group that switched to siponimod from placebo, a reduction of 52%.

Dr. Cree has received personal compensation from Novartis, which markets siponimod, as well as Akili, Alexion, Atara, Biogen, EMD Serono, and TG Therapeutics. His coauthors reported receiving research support and personal compensation from Novartis and other pharmaceutical companies. Several coauthors were Novartis employees.

[email protected]

SOURCE: Kappos L et al. AAN 2020, Abstract S40.003.

Among patients with secondary progressive multiple sclerosis (MS) who received siponimod or placebo during a double-blind trial and entered an open-label extension, those who received siponimod throughout the study were less likely to experience disability progression and had a lower annualized relapse rate up to 5 years later, compared with patients who initially received placebo and switched to siponimod. This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.

Benefits of siponimod gained during the controlled period were “sustained for up to 5 years, suggesting a continuous effect of siponimod and underlining the advantages of early treatment initiation with siponimod,” the researchers said. Incidence rates of adverse events during the extension study were consistent with those during the controlled treatment period.

The results “highlight the critical importance of early treatment intervention ... to ensure the best possible long-term outcomes for patients with MS who are experiencing progression,” study investigator Bruce Cree, MD, PhD, said in a news release.

“It’s never too early to stay ahead of progression in MS, since the early identification of physical and cognitive changes – even subtle ones – can indicate MS disease progression and therefore allow for timely intervention.” said Dr. Cree, who is clinical research director and George A. Zimmermann Endowed Professor in Multiple Sclerosis at the University of California, San Francisco.

Siponimod, marketed as Mayzent, is a sphingosine 1-phosphate receptor modulator that selectively binds to S1P1 and S1P5 receptors. The oral drug was approved by the Food and Drug Administration in 2019 for the treatment of relapsing forms of MS, including clinically isolated syndrome, relapsing remitting disease, and active secondary progressive disease in adults.

To assess the long-term efficacy and safety of siponimod in patients with secondary progressive MS, Dr. Cree and colleagues analyzed data from patients in the controlled and extension parts of the EXPAND trial. Patients could have had been in the study for as long as 5 years at the data cutoff in April 2019. Efficacy analyses included time to 3-month confirmed disability progression on the Expanded Disability Status Scale (EDSS), time to 6-month confirmed disability progression, time to 6-month confirmed worsening of 4 or more points on the Symbol Digit Modalities Test (SDMT), and annualized relapse rate. In EXPAND, the researchers defined confirmed disability progression as a 1-point increase in EDSS if the baseline score was 3.0-5.0, or a 0.5-point increase if the baseline score was 5.5-6.5.

“Of the 1,224 (74% of 1,651 randomized) patients entering the extension, 878 (72%) were ongoing,” the researchers reported. Patients who received siponimod continuously were less likely to experience 3-month confirmed disability progression and 6-month confirmed disability progression, relative to patients who switched from placebo. In addition, patients who received continuous siponimod treatment had a prolonged time to 6-month confirmed disability progression, compared with patients who switched from placebo. For the 25th percentile of patients, continuous siponimod treatment corresponded to a delay of 54% (21 months vs. 13.6 months). Risk of worsening on the SDMT was reduced by 23% in the continuous siponimod–treatment group. For the 25th percentile of patients, this reduced risk corresponded to a delay of 62% (29.6 months vs. 18.3 months). ARR was 0.054 in the continuous-siponimod group, compared with 0.097 in the group that switched to siponimod from placebo, a reduction of 52%.

Dr. Cree has received personal compensation from Novartis, which markets siponimod, as well as Akili, Alexion, Atara, Biogen, EMD Serono, and TG Therapeutics. His coauthors reported receiving research support and personal compensation from Novartis and other pharmaceutical companies. Several coauthors were Novartis employees.

[email protected]

SOURCE: Kappos L et al. AAN 2020, Abstract S40.003.

The tragic death by suicide of an emergency department physician who had been caring for COVID-19 patients in New York City underscores the huge psychological impact of the pandemic – which will linger long after the virus is gone, experts say.

“For frontline responders, the trauma of witnessing so much illness and death will have lasting effects for many,” Bruce Schwartz, MD, president of the American Psychiatric Association (APA), said during the opening session of the annual meeting of the American Psychiatric Association, which was held as a virtual live event, replacing the organization’s canceled annual meeting.

“We will need the full workforce to cope with the psychiatric effects” of the pandemic, added Dr. Schwartz, deputy chairman and professor, department of psychiatry and behavioral sciences, Montefiore Medical Center and Albert Einstein College of Medicine, New York.

Joshua Morganstein, MD, chair of the APA’s Committee on the Psychiatric Dimensions of Disaster, led an afternoon session at the virtual meeting on “healthcare worker and organizational sustainment during COVID-19.”

The crisis is shaping up to be “a marathon, not a sprint; and self-care will remain a critical and ongoing issue. We are in this together,” he said.

Once the pandemic passes, “if history is any predictor, we should expect a significant ‘tail’ of mental health needs that extend for a considerable period of time,” Dr. Morganstein added.
 

Psychological first aid

It is important to realize that the psychological and behavioral effects of disasters are experienced by “more people, over a greater geography, across a much longer period of time than all other medical effects combined. This is important for disaster resource planning,” Dr. Morganstein told meeting attendees.

At times of crisis, many people will experience distress reactions and engage in behaviors that put their health at risk. Insomnia, increased alcohol and substance use, and family conflict are common and have a negative impact on functioning, he said.

In addition, pandemics result in unique responses. Protracted fear and uncertainty, elements of isolation, anger, misinformation, and faltering confidence in government/institutions may alter perceptions of risk.

“It’s the perception of risk, not the actual risk, that will ultimately determine how people behave,” Dr. Morganstein said.

“The ability to influence risk perception will alter the degree to which any group, community, or population ultimately chooses to engage in or reject recommended health behaviors,” he added.

In times of crisis, it’s also helpful to keep in mind and act upon the five essential elements of “psychological first aid,” he noted. These are safety, calming, self/community efficacy, social connectedness, and hope/optimism.

Psychological first aid is an evidence-based framework of supporting resilience in individuals, communities, and organizations, Dr. Morganstein said.

Individuals have a wide range of needs during times of crisis, and support should be tailored accordingly, he noted. As with many crises, instrumental support needs are significant and may be the primary need for many people. These include the need for food, clothing, rent/mortgage, financial relief, and child care.

Providing emotional support – empathy, validation, self-actualization, encouragement, and insight – will help individuals engage with instrumental supports.

“The reality is that it’s often difficult to talk about being sad when you feel hungry or worried you can’t pay the rent,” said Dr. Morganstein.

He also emphasized the importance of appropriate messaging and language during a crisis. These can have a profound impact on community well-being and the willingness of the public to engage in recommended health behaviors.

“As psychiatrists, we understand [that] the words we choose when we discuss this pandemic will have power. Communication is not only a means by which we deliver interventions, but it is, in and of itself, a behavioral health intervention. Good communication can serve to normalize experiences and function as an antidote to distress during times of uncertainty,” Dr. Morganstein said.

Importantly, “we need to remind people that eventually this will end and the vast majority of people, including those who have difficulties along the way, will ultimately be okay.”

The APA has provided a COVID-19 resource page on its website.

Dr. Morganstein and Dr. Schwartz have reported no relevant financial relationships.
 

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

The tragic death by suicide of an emergency department physician who had been caring for COVID-19 patients in New York City underscores the huge psychological impact of the pandemic – which will linger long after the virus is gone, experts say.

“For frontline responders, the trauma of witnessing so much illness and death will have lasting effects for many,” Bruce Schwartz, MD, president of the American Psychiatric Association (APA), said during the opening session of the annual meeting of the American Psychiatric Association, which was held as a virtual live event, replacing the organization’s canceled annual meeting.

“We will need the full workforce to cope with the psychiatric effects” of the pandemic, added Dr. Schwartz, deputy chairman and professor, department of psychiatry and behavioral sciences, Montefiore Medical Center and Albert Einstein College of Medicine, New York.

Joshua Morganstein, MD, chair of the APA’s Committee on the Psychiatric Dimensions of Disaster, led an afternoon session at the virtual meeting on “healthcare worker and organizational sustainment during COVID-19.”

The crisis is shaping up to be “a marathon, not a sprint; and self-care will remain a critical and ongoing issue. We are in this together,” he said.

Once the pandemic passes, “if history is any predictor, we should expect a significant ‘tail’ of mental health needs that extend for a considerable period of time,” Dr. Morganstein added.
 

Psychological first aid

It is important to realize that the psychological and behavioral effects of disasters are experienced by “more people, over a greater geography, across a much longer period of time than all other medical effects combined. This is important for disaster resource planning,” Dr. Morganstein told meeting attendees.

At times of crisis, many people will experience distress reactions and engage in behaviors that put their health at risk. Insomnia, increased alcohol and substance use, and family conflict are common and have a negative impact on functioning, he said.

In addition, pandemics result in unique responses. Protracted fear and uncertainty, elements of isolation, anger, misinformation, and faltering confidence in government/institutions may alter perceptions of risk.

“It’s the perception of risk, not the actual risk, that will ultimately determine how people behave,” Dr. Morganstein said.

“The ability to influence risk perception will alter the degree to which any group, community, or population ultimately chooses to engage in or reject recommended health behaviors,” he added.

In times of crisis, it’s also helpful to keep in mind and act upon the five essential elements of “psychological first aid,” he noted. These are safety, calming, self/community efficacy, social connectedness, and hope/optimism.

Psychological first aid is an evidence-based framework of supporting resilience in individuals, communities, and organizations, Dr. Morganstein said.

Individuals have a wide range of needs during times of crisis, and support should be tailored accordingly, he noted. As with many crises, instrumental support needs are significant and may be the primary need for many people. These include the need for food, clothing, rent/mortgage, financial relief, and child care.

Providing emotional support – empathy, validation, self-actualization, encouragement, and insight – will help individuals engage with instrumental supports.

“The reality is that it’s often difficult to talk about being sad when you feel hungry or worried you can’t pay the rent,” said Dr. Morganstein.

He also emphasized the importance of appropriate messaging and language during a crisis. These can have a profound impact on community well-being and the willingness of the public to engage in recommended health behaviors.

“As psychiatrists, we understand [that] the words we choose when we discuss this pandemic will have power. Communication is not only a means by which we deliver interventions, but it is, in and of itself, a behavioral health intervention. Good communication can serve to normalize experiences and function as an antidote to distress during times of uncertainty,” Dr. Morganstein said.

Importantly, “we need to remind people that eventually this will end and the vast majority of people, including those who have difficulties along the way, will ultimately be okay.”

The APA has provided a COVID-19 resource page on its website.

Dr. Morganstein and Dr. Schwartz have reported no relevant financial relationships.
 

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

The tragic death by suicide of an emergency department physician who had been caring for COVID-19 patients in New York City underscores the huge psychological impact of the pandemic – which will linger long after the virus is gone, experts say.

“For frontline responders, the trauma of witnessing so much illness and death will have lasting effects for many,” Bruce Schwartz, MD, president of the American Psychiatric Association (APA), said during the opening session of the annual meeting of the American Psychiatric Association, which was held as a virtual live event, replacing the organization’s canceled annual meeting.

“We will need the full workforce to cope with the psychiatric effects” of the pandemic, added Dr. Schwartz, deputy chairman and professor, department of psychiatry and behavioral sciences, Montefiore Medical Center and Albert Einstein College of Medicine, New York.

Joshua Morganstein, MD, chair of the APA’s Committee on the Psychiatric Dimensions of Disaster, led an afternoon session at the virtual meeting on “healthcare worker and organizational sustainment during COVID-19.”

The crisis is shaping up to be “a marathon, not a sprint; and self-care will remain a critical and ongoing issue. We are in this together,” he said.

Once the pandemic passes, “if history is any predictor, we should expect a significant ‘tail’ of mental health needs that extend for a considerable period of time,” Dr. Morganstein added.
 

Psychological first aid

It is important to realize that the psychological and behavioral effects of disasters are experienced by “more people, over a greater geography, across a much longer period of time than all other medical effects combined. This is important for disaster resource planning,” Dr. Morganstein told meeting attendees.

At times of crisis, many people will experience distress reactions and engage in behaviors that put their health at risk. Insomnia, increased alcohol and substance use, and family conflict are common and have a negative impact on functioning, he said.

In addition, pandemics result in unique responses. Protracted fear and uncertainty, elements of isolation, anger, misinformation, and faltering confidence in government/institutions may alter perceptions of risk.

“It’s the perception of risk, not the actual risk, that will ultimately determine how people behave,” Dr. Morganstein said.

“The ability to influence risk perception will alter the degree to which any group, community, or population ultimately chooses to engage in or reject recommended health behaviors,” he added.

In times of crisis, it’s also helpful to keep in mind and act upon the five essential elements of “psychological first aid,” he noted. These are safety, calming, self/community efficacy, social connectedness, and hope/optimism.

Psychological first aid is an evidence-based framework of supporting resilience in individuals, communities, and organizations, Dr. Morganstein said.

Individuals have a wide range of needs during times of crisis, and support should be tailored accordingly, he noted. As with many crises, instrumental support needs are significant and may be the primary need for many people. These include the need for food, clothing, rent/mortgage, financial relief, and child care.

Providing emotional support – empathy, validation, self-actualization, encouragement, and insight – will help individuals engage with instrumental supports.

“The reality is that it’s often difficult to talk about being sad when you feel hungry or worried you can’t pay the rent,” said Dr. Morganstein.

He also emphasized the importance of appropriate messaging and language during a crisis. These can have a profound impact on community well-being and the willingness of the public to engage in recommended health behaviors.

“As psychiatrists, we understand [that] the words we choose when we discuss this pandemic will have power. Communication is not only a means by which we deliver interventions, but it is, in and of itself, a behavioral health intervention. Good communication can serve to normalize experiences and function as an antidote to distress during times of uncertainty,” Dr. Morganstein said.

Importantly, “we need to remind people that eventually this will end and the vast majority of people, including those who have difficulties along the way, will ultimately be okay.”

The APA has provided a COVID-19 resource page on its website.

Dr. Morganstein and Dr. Schwartz have reported no relevant financial relationships.
 

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

A just-launched study of the type 2 diabetes agent dapagliflozin (Farxiga, AstraZeneca) in patients with mild to moderate COVID-19 is raising eyebrows, given that several expert groups have advised that drugs in this class – the sodium-glucose cotransporter 2 (SGLT2) inhibitors – be stopped in all patients hospitalized with COVID-19 because of the increased risk for diabetic ketoacidosis (DKA).

The randomized, double-blind, placebo-controlled, phase 3 Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19) study is sponsored by AstraZeneca and Saint Luke’s Mid America Heart Institute.

The trial will assess whether dapagliflozin reduces the risks of disease progression, clinical complications, and death because of COVID-19 in patients with type 2 diabetes, cardiovascular disease, and/or mild to moderate chronic kidney disease (CKD).

“Dapagliflozin has demonstrated cardio- and renal-protective benefits and improved outcomes in high-risk patients with type 2 diabetes, heart failure with reduced ejection fraction, and CKD,” said the principal investigator of DARE-19, Mikhail N. Kosiborod, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

And “patients with COVID-19 and underlying cardiometabolic disease appear to be at the highest risk of morbid complications,” he explained in an AstraZeneca statement.

“Through DARE-19, we hope to decrease the severity of illness, and prevent cardiovascular, respiratory, and kidney decompensation, which are common in patients with COVID-19,” Dr. Kosiborod continued.

However, advice to stop SGLT2 inhibitors in patients hospitalized with COVID-19 because of its associated DKA risk has come from several channels.

These include initial guidance from Diabetes UK; experts who spoke during an American Diabetes Association webinar; and most recently, an international panel of diabetes experts.

Some clinicians went so far as to say that they view the trial as potentially dangerous, while others said they could see some logic to it, as long as it is carefully managed.
 

“A dangerous proposition – a DARE I would not take”

Partha Kar, MD, of Portsmouth Hospitals NHS Trust and national clinical director of diabetes at NHS England, said in an interview: “It’s interesting to see [AstraZeneca] embark on a study with a particular class of drug whereby ... [in] the UK we have said that if you get sent to hospital with COVID-19 you should stop [SGLT2 inhibitors] immediately.”

It “sounds like a risky proposition to go ahead with, [and it] definitely made me raise an eyebrow,” he added.

Nephrologist Bruce R. Leslie, MD, of Seventh Doctor Consulting in Princeton, N.J., agreed with Dr. Kar.

“Giving SGLT2 inhibitors to patients in the DARE-19 study is a dangerous proposition because these drugs can induce ketoacidosis during the stress of acute illness such as COVID-19. ... Moreover, ketoacidosis is associated with hypercoagulability which could be especially dangerous in COVID-19, given that it has been causing thrombophilia with large-vessel occlusive strokes in young patients,” he said in an interview.

“One wonders how these risks were assessed by the authorities that approved the DARE-19 study,” said Dr. Leslie, who formerly worked for Bristol-Myers Squibb.

“How does the sponsor intend to secure informed consent given the risks? This is a DARE I would not take,” he said.

Asked to address these concerns, Dr. Kosiborod said in an interview that “the DARE-19 trial will assess both the efficacy and the safety of dapagliflozin in this patient population in a closely monitored environment of a rigorously designed randomized clinical trial. The trial protocol excludes patients with type 1 diabetes or at high risk for DKA.

“Furthermore, the protocol includes detailed specific instructions to ensure careful monitoring for DKA, including frequent assessments of acid-base status in the hospital setting. The safety data will be closely monitored by an independent data-monitoring committee,” he continued.

Dr. Kosiborod also pointed out that there is “no systematically collected information on the use of dapagliflozin or any other SGLT2 inhibitor in patients being treated for COVID-19, including the associated potential benefits, possible risks such as DKA, and the balance of these potential benefits and risks.”

DARE-19 design: Several outcomes will be examined

The DARE-19 trial is designed to enroll 900 adults with confirmed SARS-CoV-2 infection and oxygen saturation of 94% or greater.

Inclusion criteria include a medical history of hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or stage 3-4 CKD. Exclusion criteria include current SGLT2 inhibitor treatment, type 1 diabetes, severe CKD, and severe COVID-19.

Dapagliflozin is approved in the EU for use in some patients with type 1 diabetes; this is not the case in the United States, although SGLT2 inhibitors in general are sometimes used off label in these patients.

Patients in DARE-19 will be randomized to 10 mg/day dapagliflozin or placebo for 30 days, in addition to standard care, in participating hospital. Primary outcomes are time to first occurrence of either death or new or worsened organ dysfunction, including respiratory decompensation, new or worsening heart failure, requirement for vasopressor therapy, ventricular tachycardia, and renal failure.

Secondary outcomes include a composite of time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30, and time to hospital discharge.

Rationale for the study

Irl B. Hirsch, MD, professor and diabetes treatment and teaching chair at the University of Washington, Seattle, said in an interview that he does see some logic to the trial.

Admitting that he doesn’t know much about “COVID-19 cardiomyopathy” – which would be one of the targets of dapagliflozin – other than it is quite common, he said that this, along with the potential renal benefits of dapagliflozin in the setting of COVID-19, make the study “intriguing.”

“Perhaps there is some rationale to it,” he said. However, “my concern is these sick COVID-19 patients are often acidemic, and besides the very complex acid-base challenges we see with intubated patients, these patients likely have combination lactic and ketoacidemia, the latter at least some from starvation.

“Still, if enough dextrose and insulin are provided to prevent ketoacid accumulation, my guess is it would do at least as well as hydroxychloroquine,” he said.

And Simon Heller, MD, professor of clinical diabetes at the University of Sheffield (England), said in an interview: “I think it is quite a brave study, mainly because of the increased risk of DKA.

“However, on the basis that these patients will be carefully monitored, the risk of DKA shouldn’t be great. I think it is important that patients with type 2 diabetes can participate whenever possible in such trials,” he said.

The estimated completion date for DARE-19 is December 2020.

Dr. Kosiborod has reported receiving grant support, honoraria, and/or research support from AstraZeneca, Boehringer Ingelheim, Sanofi, Amgen, Novo Nordisk, Merck, Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia Therapeutics, Novartis, Applied Therapeutics, Amarin, and Eli Lilly. Dr. Leslie has reported owning stock in Bristol-Myers Squibb, Pfizer, and Lilly. Dr. Hirsch has reported consulting for Abbott Diabetes Care, Roche, and Bigfoot Biomedical, conducting research for Medtronic, and is a diabetes editor for UpToDate. Dr. Heller has received advisory or consultation fees from Lilly, Novo Nordisk, Takeda, MSD, and Becton Dickinson; has served as a speaker for AstraZeneca, Lilly, Novo Nordisk, Boehringer Ingelheim, and Takeda; and has received research support from Medtronic UK. He is on the advisory board for Medscape. Dr. Kar has reported no relevant financial relationships.

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

A just-launched study of the type 2 diabetes agent dapagliflozin (Farxiga, AstraZeneca) in patients with mild to moderate COVID-19 is raising eyebrows, given that several expert groups have advised that drugs in this class – the sodium-glucose cotransporter 2 (SGLT2) inhibitors – be stopped in all patients hospitalized with COVID-19 because of the increased risk for diabetic ketoacidosis (DKA).

The randomized, double-blind, placebo-controlled, phase 3 Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19) study is sponsored by AstraZeneca and Saint Luke’s Mid America Heart Institute.

The trial will assess whether dapagliflozin reduces the risks of disease progression, clinical complications, and death because of COVID-19 in patients with type 2 diabetes, cardiovascular disease, and/or mild to moderate chronic kidney disease (CKD).

“Dapagliflozin has demonstrated cardio- and renal-protective benefits and improved outcomes in high-risk patients with type 2 diabetes, heart failure with reduced ejection fraction, and CKD,” said the principal investigator of DARE-19, Mikhail N. Kosiborod, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

And “patients with COVID-19 and underlying cardiometabolic disease appear to be at the highest risk of morbid complications,” he explained in an AstraZeneca statement.

“Through DARE-19, we hope to decrease the severity of illness, and prevent cardiovascular, respiratory, and kidney decompensation, which are common in patients with COVID-19,” Dr. Kosiborod continued.

However, advice to stop SGLT2 inhibitors in patients hospitalized with COVID-19 because of its associated DKA risk has come from several channels.

These include initial guidance from Diabetes UK; experts who spoke during an American Diabetes Association webinar; and most recently, an international panel of diabetes experts.

Some clinicians went so far as to say that they view the trial as potentially dangerous, while others said they could see some logic to it, as long as it is carefully managed.
 

“A dangerous proposition – a DARE I would not take”

Partha Kar, MD, of Portsmouth Hospitals NHS Trust and national clinical director of diabetes at NHS England, said in an interview: “It’s interesting to see [AstraZeneca] embark on a study with a particular class of drug whereby ... [in] the UK we have said that if you get sent to hospital with COVID-19 you should stop [SGLT2 inhibitors] immediately.”

It “sounds like a risky proposition to go ahead with, [and it] definitely made me raise an eyebrow,” he added.

Nephrologist Bruce R. Leslie, MD, of Seventh Doctor Consulting in Princeton, N.J., agreed with Dr. Kar.

“Giving SGLT2 inhibitors to patients in the DARE-19 study is a dangerous proposition because these drugs can induce ketoacidosis during the stress of acute illness such as COVID-19. ... Moreover, ketoacidosis is associated with hypercoagulability which could be especially dangerous in COVID-19, given that it has been causing thrombophilia with large-vessel occlusive strokes in young patients,” he said in an interview.

“One wonders how these risks were assessed by the authorities that approved the DARE-19 study,” said Dr. Leslie, who formerly worked for Bristol-Myers Squibb.

“How does the sponsor intend to secure informed consent given the risks? This is a DARE I would not take,” he said.

Asked to address these concerns, Dr. Kosiborod said in an interview that “the DARE-19 trial will assess both the efficacy and the safety of dapagliflozin in this patient population in a closely monitored environment of a rigorously designed randomized clinical trial. The trial protocol excludes patients with type 1 diabetes or at high risk for DKA.

“Furthermore, the protocol includes detailed specific instructions to ensure careful monitoring for DKA, including frequent assessments of acid-base status in the hospital setting. The safety data will be closely monitored by an independent data-monitoring committee,” he continued.

Dr. Kosiborod also pointed out that there is “no systematically collected information on the use of dapagliflozin or any other SGLT2 inhibitor in patients being treated for COVID-19, including the associated potential benefits, possible risks such as DKA, and the balance of these potential benefits and risks.”

DARE-19 design: Several outcomes will be examined

The DARE-19 trial is designed to enroll 900 adults with confirmed SARS-CoV-2 infection and oxygen saturation of 94% or greater.

Inclusion criteria include a medical history of hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or stage 3-4 CKD. Exclusion criteria include current SGLT2 inhibitor treatment, type 1 diabetes, severe CKD, and severe COVID-19.

Dapagliflozin is approved in the EU for use in some patients with type 1 diabetes; this is not the case in the United States, although SGLT2 inhibitors in general are sometimes used off label in these patients.

Patients in DARE-19 will be randomized to 10 mg/day dapagliflozin or placebo for 30 days, in addition to standard care, in participating hospital. Primary outcomes are time to first occurrence of either death or new or worsened organ dysfunction, including respiratory decompensation, new or worsening heart failure, requirement for vasopressor therapy, ventricular tachycardia, and renal failure.

Secondary outcomes include a composite of time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30, and time to hospital discharge.

Rationale for the study

Irl B. Hirsch, MD, professor and diabetes treatment and teaching chair at the University of Washington, Seattle, said in an interview that he does see some logic to the trial.

Admitting that he doesn’t know much about “COVID-19 cardiomyopathy” – which would be one of the targets of dapagliflozin – other than it is quite common, he said that this, along with the potential renal benefits of dapagliflozin in the setting of COVID-19, make the study “intriguing.”

“Perhaps there is some rationale to it,” he said. However, “my concern is these sick COVID-19 patients are often acidemic, and besides the very complex acid-base challenges we see with intubated patients, these patients likely have combination lactic and ketoacidemia, the latter at least some from starvation.

“Still, if enough dextrose and insulin are provided to prevent ketoacid accumulation, my guess is it would do at least as well as hydroxychloroquine,” he said.

And Simon Heller, MD, professor of clinical diabetes at the University of Sheffield (England), said in an interview: “I think it is quite a brave study, mainly because of the increased risk of DKA.

“However, on the basis that these patients will be carefully monitored, the risk of DKA shouldn’t be great. I think it is important that patients with type 2 diabetes can participate whenever possible in such trials,” he said.

The estimated completion date for DARE-19 is December 2020.

Dr. Kosiborod has reported receiving grant support, honoraria, and/or research support from AstraZeneca, Boehringer Ingelheim, Sanofi, Amgen, Novo Nordisk, Merck, Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia Therapeutics, Novartis, Applied Therapeutics, Amarin, and Eli Lilly. Dr. Leslie has reported owning stock in Bristol-Myers Squibb, Pfizer, and Lilly. Dr. Hirsch has reported consulting for Abbott Diabetes Care, Roche, and Bigfoot Biomedical, conducting research for Medtronic, and is a diabetes editor for UpToDate. Dr. Heller has received advisory or consultation fees from Lilly, Novo Nordisk, Takeda, MSD, and Becton Dickinson; has served as a speaker for AstraZeneca, Lilly, Novo Nordisk, Boehringer Ingelheim, and Takeda; and has received research support from Medtronic UK. He is on the advisory board for Medscape. Dr. Kar has reported no relevant financial relationships.

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

A just-launched study of the type 2 diabetes agent dapagliflozin (Farxiga, AstraZeneca) in patients with mild to moderate COVID-19 is raising eyebrows, given that several expert groups have advised that drugs in this class – the sodium-glucose cotransporter 2 (SGLT2) inhibitors – be stopped in all patients hospitalized with COVID-19 because of the increased risk for diabetic ketoacidosis (DKA).

The randomized, double-blind, placebo-controlled, phase 3 Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19) study is sponsored by AstraZeneca and Saint Luke’s Mid America Heart Institute.

The trial will assess whether dapagliflozin reduces the risks of disease progression, clinical complications, and death because of COVID-19 in patients with type 2 diabetes, cardiovascular disease, and/or mild to moderate chronic kidney disease (CKD).

“Dapagliflozin has demonstrated cardio- and renal-protective benefits and improved outcomes in high-risk patients with type 2 diabetes, heart failure with reduced ejection fraction, and CKD,” said the principal investigator of DARE-19, Mikhail N. Kosiborod, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

And “patients with COVID-19 and underlying cardiometabolic disease appear to be at the highest risk of morbid complications,” he explained in an AstraZeneca statement.

“Through DARE-19, we hope to decrease the severity of illness, and prevent cardiovascular, respiratory, and kidney decompensation, which are common in patients with COVID-19,” Dr. Kosiborod continued.

However, advice to stop SGLT2 inhibitors in patients hospitalized with COVID-19 because of its associated DKA risk has come from several channels.

These include initial guidance from Diabetes UK; experts who spoke during an American Diabetes Association webinar; and most recently, an international panel of diabetes experts.

Some clinicians went so far as to say that they view the trial as potentially dangerous, while others said they could see some logic to it, as long as it is carefully managed.
 

“A dangerous proposition – a DARE I would not take”

Partha Kar, MD, of Portsmouth Hospitals NHS Trust and national clinical director of diabetes at NHS England, said in an interview: “It’s interesting to see [AstraZeneca] embark on a study with a particular class of drug whereby ... [in] the UK we have said that if you get sent to hospital with COVID-19 you should stop [SGLT2 inhibitors] immediately.”

It “sounds like a risky proposition to go ahead with, [and it] definitely made me raise an eyebrow,” he added.

Nephrologist Bruce R. Leslie, MD, of Seventh Doctor Consulting in Princeton, N.J., agreed with Dr. Kar.

“Giving SGLT2 inhibitors to patients in the DARE-19 study is a dangerous proposition because these drugs can induce ketoacidosis during the stress of acute illness such as COVID-19. ... Moreover, ketoacidosis is associated with hypercoagulability which could be especially dangerous in COVID-19, given that it has been causing thrombophilia with large-vessel occlusive strokes in young patients,” he said in an interview.

“One wonders how these risks were assessed by the authorities that approved the DARE-19 study,” said Dr. Leslie, who formerly worked for Bristol-Myers Squibb.

“How does the sponsor intend to secure informed consent given the risks? This is a DARE I would not take,” he said.

Asked to address these concerns, Dr. Kosiborod said in an interview that “the DARE-19 trial will assess both the efficacy and the safety of dapagliflozin in this patient population in a closely monitored environment of a rigorously designed randomized clinical trial. The trial protocol excludes patients with type 1 diabetes or at high risk for DKA.

“Furthermore, the protocol includes detailed specific instructions to ensure careful monitoring for DKA, including frequent assessments of acid-base status in the hospital setting. The safety data will be closely monitored by an independent data-monitoring committee,” he continued.

Dr. Kosiborod also pointed out that there is “no systematically collected information on the use of dapagliflozin or any other SGLT2 inhibitor in patients being treated for COVID-19, including the associated potential benefits, possible risks such as DKA, and the balance of these potential benefits and risks.”

DARE-19 design: Several outcomes will be examined

The DARE-19 trial is designed to enroll 900 adults with confirmed SARS-CoV-2 infection and oxygen saturation of 94% or greater.

Inclusion criteria include a medical history of hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or stage 3-4 CKD. Exclusion criteria include current SGLT2 inhibitor treatment, type 1 diabetes, severe CKD, and severe COVID-19.

Dapagliflozin is approved in the EU for use in some patients with type 1 diabetes; this is not the case in the United States, although SGLT2 inhibitors in general are sometimes used off label in these patients.

Patients in DARE-19 will be randomized to 10 mg/day dapagliflozin or placebo for 30 days, in addition to standard care, in participating hospital. Primary outcomes are time to first occurrence of either death or new or worsened organ dysfunction, including respiratory decompensation, new or worsening heart failure, requirement for vasopressor therapy, ventricular tachycardia, and renal failure.

Secondary outcomes include a composite of time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30, and time to hospital discharge.

Rationale for the study

Irl B. Hirsch, MD, professor and diabetes treatment and teaching chair at the University of Washington, Seattle, said in an interview that he does see some logic to the trial.

Admitting that he doesn’t know much about “COVID-19 cardiomyopathy” – which would be one of the targets of dapagliflozin – other than it is quite common, he said that this, along with the potential renal benefits of dapagliflozin in the setting of COVID-19, make the study “intriguing.”

“Perhaps there is some rationale to it,” he said. However, “my concern is these sick COVID-19 patients are often acidemic, and besides the very complex acid-base challenges we see with intubated patients, these patients likely have combination lactic and ketoacidemia, the latter at least some from starvation.

“Still, if enough dextrose and insulin are provided to prevent ketoacid accumulation, my guess is it would do at least as well as hydroxychloroquine,” he said.

And Simon Heller, MD, professor of clinical diabetes at the University of Sheffield (England), said in an interview: “I think it is quite a brave study, mainly because of the increased risk of DKA.

“However, on the basis that these patients will be carefully monitored, the risk of DKA shouldn’t be great. I think it is important that patients with type 2 diabetes can participate whenever possible in such trials,” he said.

The estimated completion date for DARE-19 is December 2020.

Dr. Kosiborod has reported receiving grant support, honoraria, and/or research support from AstraZeneca, Boehringer Ingelheim, Sanofi, Amgen, Novo Nordisk, Merck, Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia Therapeutics, Novartis, Applied Therapeutics, Amarin, and Eli Lilly. Dr. Leslie has reported owning stock in Bristol-Myers Squibb, Pfizer, and Lilly. Dr. Hirsch has reported consulting for Abbott Diabetes Care, Roche, and Bigfoot Biomedical, conducting research for Medtronic, and is a diabetes editor for UpToDate. Dr. Heller has received advisory or consultation fees from Lilly, Novo Nordisk, Takeda, MSD, and Becton Dickinson; has served as a speaker for AstraZeneca, Lilly, Novo Nordisk, Boehringer Ingelheim, and Takeda; and has received research support from Medtronic UK. He is on the advisory board for Medscape. Dr. Kar has reported no relevant financial relationships.

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

Among patients with migraine, increase in the number of treatment failures is associated with increase in economic burden, researchers wrote. Utilization of health care resources and associated costs are greater among patients with three or more treatment failures, compared with patients with fewer treatment failures. This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.

Migraine entails a significant economic burden, including direct costs (e.g., medical costs) and indirect costs (e.g., lost productivity). Information about the burden associated with failed preventive treatments among migraineurs is limited, however. Lawrence C. Newman, MD, director of the division of headache at NYU Langone Health in New York, and colleagues conducted a study to characterize health care resource utilization (HCRU) and its associated costs among migraineurs, stratified by the number of preventive treatment failures.
 

About one quarter of patients had two treatment failures

Using data from the IBM MarketScan Commercial and Medicare Supplemental database, Dr. Newman and colleagues identified patients who received a new diagnosis of migraine between Jan. 1, 2011, and June 30, 2015. Next, they identified the number of treatment failures during the 2 years following the initial migraine diagnosis. They assessed HCRU and associated costs during the 12 months following an index event. The index was the date of initiation of the second preventive treatment for patients with one treatment failure, the date of initiation of the third treatment for patients with two treatment failures, and the date of initiation of the fourth treatment for patients with three or more treatment failures.

Dr. Newman’s group identified 44,181 patients with incident migraine who had failed preventive treatments. Of this population, 27,112 patients (61.4%) had one treatment failure, 10,583 (24%) had two treatment failures, and 6,486 (14.7%) had three or more treatment failures.

The total medical cost per patient, including emergency room (ER), inpatient (IP), and outpatient (OP) care, increased with increasing number of treatment failures ($10,329 for one, $13,774 for two, and $35,392 for three or more). When the investigators added prescription drug costs, the total health care costs also increased with number of treatment failures ($13,946 for one, $18,685 for two, and $41,864 for three or more).

Similarly, the per-patient annual health care provider visits increased with increasing numbers of treatment failures. The number of ER visits per year was 0.54, 0.69, and 1.02 for patients with one, two, and three or more treatment failures, respectively. The annual number of IP visits was 0.46, 0.59, and 0.97, for patients with one, two, and three or more treatment failures, respectively. OP visits showed a similar trend. The annual number of office visits was 9.47 for patients with one, 11.24 for patients with two, and 14.26 for patients with three or more treatment failures. The annual number of other visits was 13.15 for patients with one, 15.73 for patients with two, and 19.96 for patients with three or more treatment failures.
 

Guidelines could enable appropriate treatment

Reasons for treatment failure include misdiagnosis of the headache disorder, failure to identify and account for comorbidities, overlooking concurrent acute medication overuse, and inappropriate dose or formulation, said Dr. Newman. “Common pitfalls in prevention that lead to treatment failure include not using evidence-based treatments, starting at too low of a dose and not increasing, starting too high or increasing the dose too quickly, discontinuing the medication before an effect can be seen (before 8 weeks), patient nonadherence, and not establishing realistic expectations.”

Available resources could help clinicians treat migraine effectively. “The American Headache Society (AHS)/AAN preventive guidelines have been retired, yet they offered several levels of effectiveness of pharmacologic treatments that were evidence-based,” said Dr. Newman. “Furthermore, in 2019, the AHS published a consensus statement on integrating new migraine treatments into clinical practice. This statement offered advice about the new anti-CGRP agents, onabotulinum toxin, and neuromodulation devices. I think this is a good starting point for neurologists to be familiar with to choose appropriate therapeutic options for people living with migraine.”
 

Earlier treatment may reduce patients’ economic burden

The study’s weaknesses included its observational design and its reliance on diagnostic codes, which raised the possibility that comorbidities were inadequately recognized, said Dr. Newman. The reasons that patients changed medications are unknown, and the results are not generalizable to patients aged 65 years or older, he added.

Major strengths of Dr. Newman’s study are its large sample size and wealth of available data, said Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles. “The multiple subcategories suggest that this was a carefully organized and implemented study,” he added. If any diagnoses of migraine were provided by general practitioners with little knowledge of migraine, this would weaken the study, said Dr. Rapoport, editor-in-chief of Neurology Reviews.

“We can ease the economic burden of migraineurs by improving acute care therapy with better selection and earlier starting of effective preventive therapy,” he continued. “Going for migraine-specific acute care therapy is better than pain medications or other nonspecific therapies. If you do not stop a migraine attack with effective therapy, you increase the odds that the patient will go on to chronic migraine. It is always important to effectively teach doctors and nurses to improve their diagnostic skills and use the optimal acute and preventive therapy.” For their next trial, maximizing an accurate diagnosis and performing a prospective study measuring treatment outcomes will be particularly valuable, Dr. Rapoport concluded.

Dr. Newman’s study was supported by Novartis Pharma in Basel, Switzerland. Together with Amgen, Novartis developed erenumab. Dr. Newman has received compensation from Allergan, Alder, Amgen, Biohaven, Novartis, Teva, Supernus, and Theranica for consulting, serving on a scientific advisory board, speaking, or other activities. He has received compensation from Springer Scientific for editorial services.

[email protected]

SOURCE: Newman L et al. AAN 2020, Abstract S47.009.

Among patients with migraine, increase in the number of treatment failures is associated with increase in economic burden, researchers wrote. Utilization of health care resources and associated costs are greater among patients with three or more treatment failures, compared with patients with fewer treatment failures. This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.

Migraine entails a significant economic burden, including direct costs (e.g., medical costs) and indirect costs (e.g., lost productivity). Information about the burden associated with failed preventive treatments among migraineurs is limited, however. Lawrence C. Newman, MD, director of the division of headache at NYU Langone Health in New York, and colleagues conducted a study to characterize health care resource utilization (HCRU) and its associated costs among migraineurs, stratified by the number of preventive treatment failures.
 

About one quarter of patients had two treatment failures

Using data from the IBM MarketScan Commercial and Medicare Supplemental database, Dr. Newman and colleagues identified patients who received a new diagnosis of migraine between Jan. 1, 2011, and June 30, 2015. Next, they identified the number of treatment failures during the 2 years following the initial migraine diagnosis. They assessed HCRU and associated costs during the 12 months following an index event. The index was the date of initiation of the second preventive treatment for patients with one treatment failure, the date of initiation of the third treatment for patients with two treatment failures, and the date of initiation of the fourth treatment for patients with three or more treatment failures.

Dr. Newman’s group identified 44,181 patients with incident migraine who had failed preventive treatments. Of this population, 27,112 patients (61.4%) had one treatment failure, 10,583 (24%) had two treatment failures, and 6,486 (14.7%) had three or more treatment failures.

The total medical cost per patient, including emergency room (ER), inpatient (IP), and outpatient (OP) care, increased with increasing number of treatment failures ($10,329 for one, $13,774 for two, and $35,392 for three or more). When the investigators added prescription drug costs, the total health care costs also increased with number of treatment failures ($13,946 for one, $18,685 for two, and $41,864 for three or more).

Similarly, the per-patient annual health care provider visits increased with increasing numbers of treatment failures. The number of ER visits per year was 0.54, 0.69, and 1.02 for patients with one, two, and three or more treatment failures, respectively. The annual number of IP visits was 0.46, 0.59, and 0.97, for patients with one, two, and three or more treatment failures, respectively. OP visits showed a similar trend. The annual number of office visits was 9.47 for patients with one, 11.24 for patients with two, and 14.26 for patients with three or more treatment failures. The annual number of other visits was 13.15 for patients with one, 15.73 for patients with two, and 19.96 for patients with three or more treatment failures.
 

Guidelines could enable appropriate treatment

Reasons for treatment failure include misdiagnosis of the headache disorder, failure to identify and account for comorbidities, overlooking concurrent acute medication overuse, and inappropriate dose or formulation, said Dr. Newman. “Common pitfalls in prevention that lead to treatment failure include not using evidence-based treatments, starting at too low of a dose and not increasing, starting too high or increasing the dose too quickly, discontinuing the medication before an effect can be seen (before 8 weeks), patient nonadherence, and not establishing realistic expectations.”

Available resources could help clinicians treat migraine effectively. “The American Headache Society (AHS)/AAN preventive guidelines have been retired, yet they offered several levels of effectiveness of pharmacologic treatments that were evidence-based,” said Dr. Newman. “Furthermore, in 2019, the AHS published a consensus statement on integrating new migraine treatments into clinical practice. This statement offered advice about the new anti-CGRP agents, onabotulinum toxin, and neuromodulation devices. I think this is a good starting point for neurologists to be familiar with to choose appropriate therapeutic options for people living with migraine.”
 

Earlier treatment may reduce patients’ economic burden

The study’s weaknesses included its observational design and its reliance on diagnostic codes, which raised the possibility that comorbidities were inadequately recognized, said Dr. Newman. The reasons that patients changed medications are unknown, and the results are not generalizable to patients aged 65 years or older, he added.

Major strengths of Dr. Newman’s study are its large sample size and wealth of available data, said Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles. “The multiple subcategories suggest that this was a carefully organized and implemented study,” he added. If any diagnoses of migraine were provided by general practitioners with little knowledge of migraine, this would weaken the study, said Dr. Rapoport, editor-in-chief of Neurology Reviews.

“We can ease the economic burden of migraineurs by improving acute care therapy with better selection and earlier starting of effective preventive therapy,” he continued. “Going for migraine-specific acute care therapy is better than pain medications or other nonspecific therapies. If you do not stop a migraine attack with effective therapy, you increase the odds that the patient will go on to chronic migraine. It is always important to effectively teach doctors and nurses to improve their diagnostic skills and use the optimal acute and preventive therapy.” For their next trial, maximizing an accurate diagnosis and performing a prospective study measuring treatment outcomes will be particularly valuable, Dr. Rapoport concluded.

Dr. Newman’s study was supported by Novartis Pharma in Basel, Switzerland. Together with Amgen, Novartis developed erenumab. Dr. Newman has received compensation from Allergan, Alder, Amgen, Biohaven, Novartis, Teva, Supernus, and Theranica for consulting, serving on a scientific advisory board, speaking, or other activities. He has received compensation from Springer Scientific for editorial services.

[email protected]

SOURCE: Newman L et al. AAN 2020, Abstract S47.009.

Among patients with migraine, increase in the number of treatment failures is associated with increase in economic burden, researchers wrote. Utilization of health care resources and associated costs are greater among patients with three or more treatment failures, compared with patients with fewer treatment failures. This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.

Migraine entails a significant economic burden, including direct costs (e.g., medical costs) and indirect costs (e.g., lost productivity). Information about the burden associated with failed preventive treatments among migraineurs is limited, however. Lawrence C. Newman, MD, director of the division of headache at NYU Langone Health in New York, and colleagues conducted a study to characterize health care resource utilization (HCRU) and its associated costs among migraineurs, stratified by the number of preventive treatment failures.
 

About one quarter of patients had two treatment failures

Using data from the IBM MarketScan Commercial and Medicare Supplemental database, Dr. Newman and colleagues identified patients who received a new diagnosis of migraine between Jan. 1, 2011, and June 30, 2015. Next, they identified the number of treatment failures during the 2 years following the initial migraine diagnosis. They assessed HCRU and associated costs during the 12 months following an index event. The index was the date of initiation of the second preventive treatment for patients with one treatment failure, the date of initiation of the third treatment for patients with two treatment failures, and the date of initiation of the fourth treatment for patients with three or more treatment failures.

Dr. Newman’s group identified 44,181 patients with incident migraine who had failed preventive treatments. Of this population, 27,112 patients (61.4%) had one treatment failure, 10,583 (24%) had two treatment failures, and 6,486 (14.7%) had three or more treatment failures.

The total medical cost per patient, including emergency room (ER), inpatient (IP), and outpatient (OP) care, increased with increasing number of treatment failures ($10,329 for one, $13,774 for two, and $35,392 for three or more). When the investigators added prescription drug costs, the total health care costs also increased with number of treatment failures ($13,946 for one, $18,685 for two, and $41,864 for three or more).

Similarly, the per-patient annual health care provider visits increased with increasing numbers of treatment failures. The number of ER visits per year was 0.54, 0.69, and 1.02 for patients with one, two, and three or more treatment failures, respectively. The annual number of IP visits was 0.46, 0.59, and 0.97, for patients with one, two, and three or more treatment failures, respectively. OP visits showed a similar trend. The annual number of office visits was 9.47 for patients with one, 11.24 for patients with two, and 14.26 for patients with three or more treatment failures. The annual number of other visits was 13.15 for patients with one, 15.73 for patients with two, and 19.96 for patients with three or more treatment failures.
 

Guidelines could enable appropriate treatment

Reasons for treatment failure include misdiagnosis of the headache disorder, failure to identify and account for comorbidities, overlooking concurrent acute medication overuse, and inappropriate dose or formulation, said Dr. Newman. “Common pitfalls in prevention that lead to treatment failure include not using evidence-based treatments, starting at too low of a dose and not increasing, starting too high or increasing the dose too quickly, discontinuing the medication before an effect can be seen (before 8 weeks), patient nonadherence, and not establishing realistic expectations.”

Available resources could help clinicians treat migraine effectively. “The American Headache Society (AHS)/AAN preventive guidelines have been retired, yet they offered several levels of effectiveness of pharmacologic treatments that were evidence-based,” said Dr. Newman. “Furthermore, in 2019, the AHS published a consensus statement on integrating new migraine treatments into clinical practice. This statement offered advice about the new anti-CGRP agents, onabotulinum toxin, and neuromodulation devices. I think this is a good starting point for neurologists to be familiar with to choose appropriate therapeutic options for people living with migraine.”
 

Earlier treatment may reduce patients’ economic burden

The study’s weaknesses included its observational design and its reliance on diagnostic codes, which raised the possibility that comorbidities were inadequately recognized, said Dr. Newman. The reasons that patients changed medications are unknown, and the results are not generalizable to patients aged 65 years or older, he added.

Major strengths of Dr. Newman’s study are its large sample size and wealth of available data, said Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles. “The multiple subcategories suggest that this was a carefully organized and implemented study,” he added. If any diagnoses of migraine were provided by general practitioners with little knowledge of migraine, this would weaken the study, said Dr. Rapoport, editor-in-chief of Neurology Reviews.

“We can ease the economic burden of migraineurs by improving acute care therapy with better selection and earlier starting of effective preventive therapy,” he continued. “Going for migraine-specific acute care therapy is better than pain medications or other nonspecific therapies. If you do not stop a migraine attack with effective therapy, you increase the odds that the patient will go on to chronic migraine. It is always important to effectively teach doctors and nurses to improve their diagnostic skills and use the optimal acute and preventive therapy.” For their next trial, maximizing an accurate diagnosis and performing a prospective study measuring treatment outcomes will be particularly valuable, Dr. Rapoport concluded.

Dr. Newman’s study was supported by Novartis Pharma in Basel, Switzerland. Together with Amgen, Novartis developed erenumab. Dr. Newman has received compensation from Allergan, Alder, Amgen, Biohaven, Novartis, Teva, Supernus, and Theranica for consulting, serving on a scientific advisory board, speaking, or other activities. He has received compensation from Springer Scientific for editorial services.

[email protected]

SOURCE: Newman L et al. AAN 2020, Abstract S47.009.

Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.

“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.

There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.

Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.

Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.

A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.

Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.

Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.

Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).

It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.

Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.

Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.

The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.

As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”

There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.

[email protected]

SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.

Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.

“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.

There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.

Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.

Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.

A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.

Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.

Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.

Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).

It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.

Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.

Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.

The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.

As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”

There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.

[email protected]

SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.

Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.

“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.

There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.

Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.

Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.

A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.

Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.

Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.

Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).

It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.

Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.

Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.

The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.

As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”

There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.

[email protected]

SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.

Cancer patients who received antitumor treatment within 14 days of COVID-19 diagnosis had an increased risk of severe events, according to data from three hospitals in Wuhan.

Patients with patchy consolidation at hospital admission also had an increased risk of severe events, defined as ICU admission, mechanical ventilation, or death.

However, these findings are limited by the small number of patients studied and the retrospective nature of the analysis, according to researchers.

Li Zhang, MD, PhD, of Tongji Hospital in Wuhan, China, presented this research at the AACR virtual meeting I. Some of the data were previously published in Annals of Oncology.

The researchers studied 28 patients with cancer among 1,276 patients with COVID-19 treated at three hospitals in Wuhan. The most common cancer types were lung (n = 7), esophageal (n = 4), and breast (n = 3). Patients had other gastrointestinal, gynecologic, genitourinary, and head and neck cancers as well.

The patients’ median age was 65 years (range, 56-70 years), 60.9% were men, 35.7% had stage IV cancer, and 28.6% had hospital-acquired COVID-19. Antitumor treatments included chemotherapy (n = 22), surgery (n = 21), radiotherapy (n = 21), targeted therapy (n = 5), and immune checkpoint inhibitors (n = 2).
 

COVID-19 treatment

Most patients (n = 22) received oxygen as their only respiratory intervention, although 10 received mechanical ventilation.

For systemic therapy, patients received antibiotic treatment (n = 23), corticosteroids (n = 15), intravenous immunoglobulin (n = 10), and tocilizumab (n = 1).

Antiviral treatments included umifenovir (n = 14), lopinavir/ritonavir (n = 10), ganciclovir (n = 9), ribavirin (n = 1), or a combination of antiviral drugs (n = 9).

“No cancer patients were enrolled in clinical trials, so no one received hydroxychloroquine or remdesivir,” Dr. Zhang noted.
 

Outcomes

In all, 15 patients (53.6%) had severe events. The median time from COVID-19 diagnosis to severe events was 7 days (range, 5-15 days).

A total of eight patients (28.6%) died – three with lung cancer, two with prostate cancer, one with liver cancer, one with rectal cancer, and one with testicular cancer.

Causes of death were acute respiratory distress syndrome (n = 5), septic shock (n = 1), suspected pulmonary embolism (n = 1), and acute myocardial infarction (n = 1).

By April 4, 14 patients had been discharged from the hospital, and 6 were still hospitalized. The median duration of hospitalization was 18.4 days for discharged patients and 29.4 days for patients still in hospital.

Follow-up CT scans showed improvement in 13 patients, no changes in 5 patients, and deterioration in 6 patients.
 

Factors associated with severe events

In a multivariable analysis, receiving antitumor treatment within 14 days of COVID-19 diagnosis was associated with severe events (hazard ratio, 4.079; P = .037).

However, only seven patients received antitumor treatments within 14 days of COVID-19 diagnosis – three chemotherapy, two targeted therapy, one radiotherapy, and one immune checkpoint inhibitor. Five of these seven patients had severe events.

Another factor associated with severe events in multivariable analysis was patchy consolidation on CT scan at admission (HR, 5.438; P = .01). Age and gender were not significantly associated with severe events.
 

Immune checkpoint inhibitors

Dr. Zhang and colleagues also analyzed a second group of cancer patients and their family members to determine if patients on immune checkpoint inhibitors have an increased risk of COVID-19.

This group included 124 cancer patients treated with immune checkpoint inhibitors for at least 2 months. The patients had a median age of 59 years (range, 54-65 years), and 61.8% were men. Most patients (95.2%) had stage IV cancer, and the most common cancers were lung (54.0%), esophageal (18.6%), and head and neck (10.7%).

In this group, only one cancer patient developed COVID-19 (via nosocomial infection). In another case, a patient’s spouse developed COVID-19, but the patient did not.

Dr. Zhang said this “limited information did not suggest cancer patients treated with immune checkpoint inhibitors were more vulnerable to COVID infection.”

Dr. Zhang and colleagues reported no conflicts of interest. This research was funded by the National Natural Science Foundation of China and Huazhong University of Science and Technology COVID-19 Rapid Response Call China.

[email protected]

SOURCE: Zhang L et al. Ann Oncol. 2020 Mar 26. doi: 10.1016/j.annonc.2020.03.296.

Cancer patients who received antitumor treatment within 14 days of COVID-19 diagnosis had an increased risk of severe events, according to data from three hospitals in Wuhan.

Patients with patchy consolidation at hospital admission also had an increased risk of severe events, defined as ICU admission, mechanical ventilation, or death.

However, these findings are limited by the small number of patients studied and the retrospective nature of the analysis, according to researchers.

Li Zhang, MD, PhD, of Tongji Hospital in Wuhan, China, presented this research at the AACR virtual meeting I. Some of the data were previously published in Annals of Oncology.

The researchers studied 28 patients with cancer among 1,276 patients with COVID-19 treated at three hospitals in Wuhan. The most common cancer types were lung (n = 7), esophageal (n = 4), and breast (n = 3). Patients had other gastrointestinal, gynecologic, genitourinary, and head and neck cancers as well.

The patients’ median age was 65 years (range, 56-70 years), 60.9% were men, 35.7% had stage IV cancer, and 28.6% had hospital-acquired COVID-19. Antitumor treatments included chemotherapy (n = 22), surgery (n = 21), radiotherapy (n = 21), targeted therapy (n = 5), and immune checkpoint inhibitors (n = 2).
 

COVID-19 treatment

Most patients (n = 22) received oxygen as their only respiratory intervention, although 10 received mechanical ventilation.

For systemic therapy, patients received antibiotic treatment (n = 23), corticosteroids (n = 15), intravenous immunoglobulin (n = 10), and tocilizumab (n = 1).

Antiviral treatments included umifenovir (n = 14), lopinavir/ritonavir (n = 10), ganciclovir (n = 9), ribavirin (n = 1), or a combination of antiviral drugs (n = 9).

“No cancer patients were enrolled in clinical trials, so no one received hydroxychloroquine or remdesivir,” Dr. Zhang noted.
 

Outcomes

In all, 15 patients (53.6%) had severe events. The median time from COVID-19 diagnosis to severe events was 7 days (range, 5-15 days).

A total of eight patients (28.6%) died – three with lung cancer, two with prostate cancer, one with liver cancer, one with rectal cancer, and one with testicular cancer.

Causes of death were acute respiratory distress syndrome (n = 5), septic shock (n = 1), suspected pulmonary embolism (n = 1), and acute myocardial infarction (n = 1).

By April 4, 14 patients had been discharged from the hospital, and 6 were still hospitalized. The median duration of hospitalization was 18.4 days for discharged patients and 29.4 days for patients still in hospital.

Follow-up CT scans showed improvement in 13 patients, no changes in 5 patients, and deterioration in 6 patients.
 

Factors associated with severe events

In a multivariable analysis, receiving antitumor treatment within 14 days of COVID-19 diagnosis was associated with severe events (hazard ratio, 4.079; P = .037).

However, only seven patients received antitumor treatments within 14 days of COVID-19 diagnosis – three chemotherapy, two targeted therapy, one radiotherapy, and one immune checkpoint inhibitor. Five of these seven patients had severe events.

Another factor associated with severe events in multivariable analysis was patchy consolidation on CT scan at admission (HR, 5.438; P = .01). Age and gender were not significantly associated with severe events.
 

Immune checkpoint inhibitors

Dr. Zhang and colleagues also analyzed a second group of cancer patients and their family members to determine if patients on immune checkpoint inhibitors have an increased risk of COVID-19.

This group included 124 cancer patients treated with immune checkpoint inhibitors for at least 2 months. The patients had a median age of 59 years (range, 54-65 years), and 61.8% were men. Most patients (95.2%) had stage IV cancer, and the most common cancers were lung (54.0%), esophageal (18.6%), and head and neck (10.7%).

In this group, only one cancer patient developed COVID-19 (via nosocomial infection). In another case, a patient’s spouse developed COVID-19, but the patient did not.

Dr. Zhang said this “limited information did not suggest cancer patients treated with immune checkpoint inhibitors were more vulnerable to COVID infection.”

Dr. Zhang and colleagues reported no conflicts of interest. This research was funded by the National Natural Science Foundation of China and Huazhong University of Science and Technology COVID-19 Rapid Response Call China.

[email protected]

SOURCE: Zhang L et al. Ann Oncol. 2020 Mar 26. doi: 10.1016/j.annonc.2020.03.296.

Cancer patients who received antitumor treatment within 14 days of COVID-19 diagnosis had an increased risk of severe events, according to data from three hospitals in Wuhan.

Patients with patchy consolidation at hospital admission also had an increased risk of severe events, defined as ICU admission, mechanical ventilation, or death.

However, these findings are limited by the small number of patients studied and the retrospective nature of the analysis, according to researchers.

Li Zhang, MD, PhD, of Tongji Hospital in Wuhan, China, presented this research at the AACR virtual meeting I. Some of the data were previously published in Annals of Oncology.

The researchers studied 28 patients with cancer among 1,276 patients with COVID-19 treated at three hospitals in Wuhan. The most common cancer types were lung (n = 7), esophageal (n = 4), and breast (n = 3). Patients had other gastrointestinal, gynecologic, genitourinary, and head and neck cancers as well.

The patients’ median age was 65 years (range, 56-70 years), 60.9% were men, 35.7% had stage IV cancer, and 28.6% had hospital-acquired COVID-19. Antitumor treatments included chemotherapy (n = 22), surgery (n = 21), radiotherapy (n = 21), targeted therapy (n = 5), and immune checkpoint inhibitors (n = 2).
 

COVID-19 treatment

Most patients (n = 22) received oxygen as their only respiratory intervention, although 10 received mechanical ventilation.

For systemic therapy, patients received antibiotic treatment (n = 23), corticosteroids (n = 15), intravenous immunoglobulin (n = 10), and tocilizumab (n = 1).

Antiviral treatments included umifenovir (n = 14), lopinavir/ritonavir (n = 10), ganciclovir (n = 9), ribavirin (n = 1), or a combination of antiviral drugs (n = 9).

“No cancer patients were enrolled in clinical trials, so no one received hydroxychloroquine or remdesivir,” Dr. Zhang noted.
 

Outcomes

In all, 15 patients (53.6%) had severe events. The median time from COVID-19 diagnosis to severe events was 7 days (range, 5-15 days).

A total of eight patients (28.6%) died – three with lung cancer, two with prostate cancer, one with liver cancer, one with rectal cancer, and one with testicular cancer.

Causes of death were acute respiratory distress syndrome (n = 5), septic shock (n = 1), suspected pulmonary embolism (n = 1), and acute myocardial infarction (n = 1).

By April 4, 14 patients had been discharged from the hospital, and 6 were still hospitalized. The median duration of hospitalization was 18.4 days for discharged patients and 29.4 days for patients still in hospital.

Follow-up CT scans showed improvement in 13 patients, no changes in 5 patients, and deterioration in 6 patients.
 

Factors associated with severe events

In a multivariable analysis, receiving antitumor treatment within 14 days of COVID-19 diagnosis was associated with severe events (hazard ratio, 4.079; P = .037).

However, only seven patients received antitumor treatments within 14 days of COVID-19 diagnosis – three chemotherapy, two targeted therapy, one radiotherapy, and one immune checkpoint inhibitor. Five of these seven patients had severe events.

Another factor associated with severe events in multivariable analysis was patchy consolidation on CT scan at admission (HR, 5.438; P = .01). Age and gender were not significantly associated with severe events.
 

Immune checkpoint inhibitors

Dr. Zhang and colleagues also analyzed a second group of cancer patients and their family members to determine if patients on immune checkpoint inhibitors have an increased risk of COVID-19.

This group included 124 cancer patients treated with immune checkpoint inhibitors for at least 2 months. The patients had a median age of 59 years (range, 54-65 years), and 61.8% were men. Most patients (95.2%) had stage IV cancer, and the most common cancers were lung (54.0%), esophageal (18.6%), and head and neck (10.7%).

In this group, only one cancer patient developed COVID-19 (via nosocomial infection). In another case, a patient’s spouse developed COVID-19, but the patient did not.

Dr. Zhang said this “limited information did not suggest cancer patients treated with immune checkpoint inhibitors were more vulnerable to COVID infection.”

Dr. Zhang and colleagues reported no conflicts of interest. This research was funded by the National Natural Science Foundation of China and Huazhong University of Science and Technology COVID-19 Rapid Response Call China.

[email protected]

SOURCE: Zhang L et al. Ann Oncol. 2020 Mar 26. doi: 10.1016/j.annonc.2020.03.296.

As U.S. health care systems prepare for inpatient surges linked to hospitalizations of critically ill COVID-19 patients, two hospitalists with med-peds training (combined training in internal medicine and pediatrics) have launched an innovative solution to help facilities deal with the challenge.

The Pediatric Overflow Planning Contingency Response Network (POPCoRN network) has quickly linked almost 400 physicians and other health professionals, including hospitalists, attending physicians, residents, medical students, and nurses. The network wants to help provide more information about how pediatric-focused institutions can safely gear up to admit adult patients in children’s hospitals, in order to offset the predicted demand for hospital beds for patients with COVID-19.

According to the POPCoRN network website (www.popcornetwork.org), the majority of providers who have contacted the network say they have already started or are committed to planning for their pediatric facilities to be used for adult overflow. The Children’s Hospital Association has issued a guidance on this kind of community collaboration for children’s hospitals partnering with adult hospitals in their community and with policy makers.

“We are a network of folks from different institutions, many med-peds–trained hospitalists but quickly growing,” said Leah Ratner, MD, a second-year fellow in the Global Pediatrics Program at Boston Children’s Hospital and cofounder of the POPCoRN network. “We came together to think about how to increase capacity – both in the work force and for actual hospital space – by helping to train pediatric hospitalists and pediatrics-trained nurses to care for adult patients.”

A web-based platform filled with a rapidly expanding list of resources, an active Twitter account, and utilization of Zoom networking software for webinars and working group meetings have facilitated the network’s growth. “Social media has helped us,” Dr. Ratner said. But equally important are personal connections.

“It all started just a few weeks ago,” added cofounder Ashley Jenkins, MD, a med-peds hospital medicine and general academics research fellow in the division of hospital medicine at Cincinnati Children’s Hospital Medical Center. “I sent out some emails in mid-March, asking what other people were doing about these issues. Leah and I met as a result of these initial emails. We immediately started connecting with other health systems and it just expanded from there. Once we knew that enough other systems were thinking about it and trying to build capacity, we started pulling the people and information together.”
 

High-yield one-pagers

A third or more of those on the POPCoRN contact list are also participating as volunteers on its varied working groups, including health system operation groups exploring the needs of three distinct hospital models: freestanding children’s hospitals; community hospitals, which may see small numbers of children; and integrated mixed hospitals, which often means a pediatric hospital or pediatric units located within an adult hospital.

An immediate goal is to develop high-yield informational “one-pagers,” culling essential clinical facts on a variety of topics in adult inpatient medicine that may no longer be familiar to working pediatric hospitalists. These one-pagers, designed with the help of network members with graphic design skills, address topics such as syncope or chest pain or managing exacerbation of COPD in adults. They draw upon existing informational sources, encapsulating practical information tips that can be used at the bedside, including test workups, differential diagnoses, treatment approaches, and other pearls for providers. Drafts are reviewed for content by specialists, and then by pediatricians to make sure the information covers what they need.

Also under development are educational materials for nurses trained in pediatrics, a section for outpatient providers redeployed to triage or telehealth, and information for other team members including occupational, physical, and respiratory therapists. Another section offers critical care lectures for the nonintensivist. A metrics and outcomes working group is looking for ways to evaluate how the network is doing and who is being reached without having to ask frontline providers to fill out surveys.

Dr. Ratner and Dr. Jenkins have created an intentional structure for encouraging mentoring. They also call on their own mentors – Ahmet Uluer, DO, director of Weitzman Family Bridges Adult Transition Program at Boston Children’s Hospital, and Brian Herbst Jr., MD, medical director of the Hospital Medicine Adult Care Service at Cincinnati Children’s – for advice.
 

Beyond the silos

Pediatric hospitalists may have been doing similar things, working on similar projects, but not necessarily reaching out to each other across a system that tends to promote staying within administrative silos, Dr. Uluer said. “Through our personal contacts in POPCoRN, we’ve been able to reach beyond the silos. This network has worked like medical crowd sourcing, and the founders have been inspirational.”

Dr. Herbst added, “How do we expand bandwidth and safely expand services to take young patients and adults from other hospitals? What other populations do we need to expand to take? This network is a workplace of ideas. It’s amazing to see what has been built in a few weeks and how useful it can be.”

Med-peds hospitalists are an important resource for bridging the two specialties. Their experience with transitioning young adults with long-standing chronic conditions of childhood, who have received most of their care at a children’s hospital before reaching adulthood, offers a helpful model. “We’ve also tried to target junior physicians who could step up into leadership roles and to pull in medical students – who are the backbone of this network through their administrative support,” Dr. Jenkins said.

Marie Pfarr, MD, also a med-peds trained hospital medicine fellow at Cincinnati Children’s, was contacted in March by Dr. Jenkins. “She said they had this brainstorm, and they were getting feedback that it would be helpful to provide educational materials for pediatric providers. Because I have an interest in medical education, she asked if I wanted to help. I was at home struggling with what I could contribute during this crazy time, so I said yes.”

Dr. Pfarr leads POPCoRN’s educational working group, which came up with a list of 50 topics in need of one-pagers and people willing to create them, mostly still under development. The aim for the one-pagers is to offer a good starting point for pediatricians, helping them, for example, to ask the right questions during history and physical exams. “We also want to offer additional resources for those who want to do a deeper dive.”

Dr. Pfarr said she has enjoyed working closely with medical students, who really want to help. “That’s been great to see. We are all working toward the same goal, and we help to keep each other in check. I think there’s a future for this kind of mobilization through collaborations to connect pediatric to adult providers. A lot of good things will come out of the network, which is an example of how folks can talk to each other. It’s very dynamic and changing every day.”

One of those medical students is Chinma Onyewuenyi, finishing her fourth year at Baylor College of Medicine. Scheduled to start a med-peds residency at Geisinger Health on July 1, she had completed all of her rotations and was looking for ways to get involved in the pandemic response while respecting the shelter-in-place order. “I had heard about the network, which was recruiting medical students to play administrative roles for the working groups. I said, ‘If you have anything else you need help with, I have time on my hands.’”

Ms. Onyewuenyi says she fell into the role of a lead administrative volunteer, and her responsibilities grew from there, eventually taking charge of all the medical students’ recruiting, screening, and assignments, freeing up the project’s physician leaders from administrative tasks. “I wanted something active to do to contribute, and I appreciate all that I’m learning. With a master’s degree in public health, I have researched how health care is delivered,” she said.

“This experience has really opened my eyes to what’s required to deliver care, and just the level of collaboration that needs to go on with something like this. Even as a medical student, I felt glad to have an opportunity to contribute beyond the administrative tasks. At meetings, they ask for my opinion.”


 

Equitable access to resources

Another major focus for the network is promoting health equity – giving pediatric providers and health systems equitable access to information that meets their needs, Dr. Ratner said. “We’ve made a particular effort to reach out to hospitals that are the most vulnerable, including rural hospitals, and to those serving the most vulnerable patients,” she noted. These also include the homeless and refugees.

“We’ve been trying to be mindful of avoiding the sometimes-intimidating power structure that has been traditional in medicine,” Dr. Ratner said. The network’s equity working group is trying to provide content with structural competency and cultural humility. “We’re learning a lot about the ways the health care system is broken,” she added. “We all agree that we have a fragmented health care system, but there are ways to make it less fragmented and learn from each other.”

In the tragedy of the COVID epidemic, there are also unique opportunities to learn to work collaboratively and make the health care system stronger for those in greatest need, Dr. Ratner added. “What we hope is that our network becomes an example of that, even as it is moving so quickly.”

Audrey Uong, MD, an attending physician in the division of hospital medicine at Children’s Hospital at Montefiore Medical Center in New York, connected with POPCoRN for an educational presentation reviewing resuscitation in adult patients. She wanted to talk with peers about what’s going on, so as not to feel alone in her practice. She has also found the network’s website useful for identifying educational resources.

“As pediatricians, we have been asked to care for adult patients. One of our units has been admitting mostly patients under age 30, and we are accepting older patients in another unit on the pediatric wing.” This kind of thing is also happening in a lot of other places, Dr. Uong said. Keeping up with these changes in her own practice has been challenging.

She tries to take one day at a time. “Everyone at this institution feels the same – that we’re locked in on meeting the need. Even our child life specialists, when they’re not working with younger patients, have created this amazing support room for staff, with snacks and soothing music. There’s been a lot of attention paid to making us feel supported in this work.”

As U.S. health care systems prepare for inpatient surges linked to hospitalizations of critically ill COVID-19 patients, two hospitalists with med-peds training (combined training in internal medicine and pediatrics) have launched an innovative solution to help facilities deal with the challenge.

The Pediatric Overflow Planning Contingency Response Network (POPCoRN network) has quickly linked almost 400 physicians and other health professionals, including hospitalists, attending physicians, residents, medical students, and nurses. The network wants to help provide more information about how pediatric-focused institutions can safely gear up to admit adult patients in children’s hospitals, in order to offset the predicted demand for hospital beds for patients with COVID-19.

According to the POPCoRN network website (www.popcornetwork.org), the majority of providers who have contacted the network say they have already started or are committed to planning for their pediatric facilities to be used for adult overflow. The Children’s Hospital Association has issued a guidance on this kind of community collaboration for children’s hospitals partnering with adult hospitals in their community and with policy makers.

“We are a network of folks from different institutions, many med-peds–trained hospitalists but quickly growing,” said Leah Ratner, MD, a second-year fellow in the Global Pediatrics Program at Boston Children’s Hospital and cofounder of the POPCoRN network. “We came together to think about how to increase capacity – both in the work force and for actual hospital space – by helping to train pediatric hospitalists and pediatrics-trained nurses to care for adult patients.”

A web-based platform filled with a rapidly expanding list of resources, an active Twitter account, and utilization of Zoom networking software for webinars and working group meetings have facilitated the network’s growth. “Social media has helped us,” Dr. Ratner said. But equally important are personal connections.

“It all started just a few weeks ago,” added cofounder Ashley Jenkins, MD, a med-peds hospital medicine and general academics research fellow in the division of hospital medicine at Cincinnati Children’s Hospital Medical Center. “I sent out some emails in mid-March, asking what other people were doing about these issues. Leah and I met as a result of these initial emails. We immediately started connecting with other health systems and it just expanded from there. Once we knew that enough other systems were thinking about it and trying to build capacity, we started pulling the people and information together.”
 

High-yield one-pagers

A third or more of those on the POPCoRN contact list are also participating as volunteers on its varied working groups, including health system operation groups exploring the needs of three distinct hospital models: freestanding children’s hospitals; community hospitals, which may see small numbers of children; and integrated mixed hospitals, which often means a pediatric hospital or pediatric units located within an adult hospital.

An immediate goal is to develop high-yield informational “one-pagers,” culling essential clinical facts on a variety of topics in adult inpatient medicine that may no longer be familiar to working pediatric hospitalists. These one-pagers, designed with the help of network members with graphic design skills, address topics such as syncope or chest pain or managing exacerbation of COPD in adults. They draw upon existing informational sources, encapsulating practical information tips that can be used at the bedside, including test workups, differential diagnoses, treatment approaches, and other pearls for providers. Drafts are reviewed for content by specialists, and then by pediatricians to make sure the information covers what they need.

Also under development are educational materials for nurses trained in pediatrics, a section for outpatient providers redeployed to triage or telehealth, and information for other team members including occupational, physical, and respiratory therapists. Another section offers critical care lectures for the nonintensivist. A metrics and outcomes working group is looking for ways to evaluate how the network is doing and who is being reached without having to ask frontline providers to fill out surveys.

Dr. Ratner and Dr. Jenkins have created an intentional structure for encouraging mentoring. They also call on their own mentors – Ahmet Uluer, DO, director of Weitzman Family Bridges Adult Transition Program at Boston Children’s Hospital, and Brian Herbst Jr., MD, medical director of the Hospital Medicine Adult Care Service at Cincinnati Children’s – for advice.
 

Beyond the silos

Pediatric hospitalists may have been doing similar things, working on similar projects, but not necessarily reaching out to each other across a system that tends to promote staying within administrative silos, Dr. Uluer said. “Through our personal contacts in POPCoRN, we’ve been able to reach beyond the silos. This network has worked like medical crowd sourcing, and the founders have been inspirational.”

Dr. Herbst added, “How do we expand bandwidth and safely expand services to take young patients and adults from other hospitals? What other populations do we need to expand to take? This network is a workplace of ideas. It’s amazing to see what has been built in a few weeks and how useful it can be.”

Med-peds hospitalists are an important resource for bridging the two specialties. Their experience with transitioning young adults with long-standing chronic conditions of childhood, who have received most of their care at a children’s hospital before reaching adulthood, offers a helpful model. “We’ve also tried to target junior physicians who could step up into leadership roles and to pull in medical students – who are the backbone of this network through their administrative support,” Dr. Jenkins said.

Marie Pfarr, MD, also a med-peds trained hospital medicine fellow at Cincinnati Children’s, was contacted in March by Dr. Jenkins. “She said they had this brainstorm, and they were getting feedback that it would be helpful to provide educational materials for pediatric providers. Because I have an interest in medical education, she asked if I wanted to help. I was at home struggling with what I could contribute during this crazy time, so I said yes.”

Dr. Pfarr leads POPCoRN’s educational working group, which came up with a list of 50 topics in need of one-pagers and people willing to create them, mostly still under development. The aim for the one-pagers is to offer a good starting point for pediatricians, helping them, for example, to ask the right questions during history and physical exams. “We also want to offer additional resources for those who want to do a deeper dive.”

Dr. Pfarr said she has enjoyed working closely with medical students, who really want to help. “That’s been great to see. We are all working toward the same goal, and we help to keep each other in check. I think there’s a future for this kind of mobilization through collaborations to connect pediatric to adult providers. A lot of good things will come out of the network, which is an example of how folks can talk to each other. It’s very dynamic and changing every day.”

One of those medical students is Chinma Onyewuenyi, finishing her fourth year at Baylor College of Medicine. Scheduled to start a med-peds residency at Geisinger Health on July 1, she had completed all of her rotations and was looking for ways to get involved in the pandemic response while respecting the shelter-in-place order. “I had heard about the network, which was recruiting medical students to play administrative roles for the working groups. I said, ‘If you have anything else you need help with, I have time on my hands.’”

Ms. Onyewuenyi says she fell into the role of a lead administrative volunteer, and her responsibilities grew from there, eventually taking charge of all the medical students’ recruiting, screening, and assignments, freeing up the project’s physician leaders from administrative tasks. “I wanted something active to do to contribute, and I appreciate all that I’m learning. With a master’s degree in public health, I have researched how health care is delivered,” she said.

“This experience has really opened my eyes to what’s required to deliver care, and just the level of collaboration that needs to go on with something like this. Even as a medical student, I felt glad to have an opportunity to contribute beyond the administrative tasks. At meetings, they ask for my opinion.”


 

Equitable access to resources

Another major focus for the network is promoting health equity – giving pediatric providers and health systems equitable access to information that meets their needs, Dr. Ratner said. “We’ve made a particular effort to reach out to hospitals that are the most vulnerable, including rural hospitals, and to those serving the most vulnerable patients,” she noted. These also include the homeless and refugees.

“We’ve been trying to be mindful of avoiding the sometimes-intimidating power structure that has been traditional in medicine,” Dr. Ratner said. The network’s equity working group is trying to provide content with structural competency and cultural humility. “We’re learning a lot about the ways the health care system is broken,” she added. “We all agree that we have a fragmented health care system, but there are ways to make it less fragmented and learn from each other.”

In the tragedy of the COVID epidemic, there are also unique opportunities to learn to work collaboratively and make the health care system stronger for those in greatest need, Dr. Ratner added. “What we hope is that our network becomes an example of that, even as it is moving so quickly.”

Audrey Uong, MD, an attending physician in the division of hospital medicine at Children’s Hospital at Montefiore Medical Center in New York, connected with POPCoRN for an educational presentation reviewing resuscitation in adult patients. She wanted to talk with peers about what’s going on, so as not to feel alone in her practice. She has also found the network’s website useful for identifying educational resources.

“As pediatricians, we have been asked to care for adult patients. One of our units has been admitting mostly patients under age 30, and we are accepting older patients in another unit on the pediatric wing.” This kind of thing is also happening in a lot of other places, Dr. Uong said. Keeping up with these changes in her own practice has been challenging.

She tries to take one day at a time. “Everyone at this institution feels the same – that we’re locked in on meeting the need. Even our child life specialists, when they’re not working with younger patients, have created this amazing support room for staff, with snacks and soothing music. There’s been a lot of attention paid to making us feel supported in this work.”

As U.S. health care systems prepare for inpatient surges linked to hospitalizations of critically ill COVID-19 patients, two hospitalists with med-peds training (combined training in internal medicine and pediatrics) have launched an innovative solution to help facilities deal with the challenge.

The Pediatric Overflow Planning Contingency Response Network (POPCoRN network) has quickly linked almost 400 physicians and other health professionals, including hospitalists, attending physicians, residents, medical students, and nurses. The network wants to help provide more information about how pediatric-focused institutions can safely gear up to admit adult patients in children’s hospitals, in order to offset the predicted demand for hospital beds for patients with COVID-19.

According to the POPCoRN network website (www.popcornetwork.org), the majority of providers who have contacted the network say they have already started or are committed to planning for their pediatric facilities to be used for adult overflow. The Children’s Hospital Association has issued a guidance on this kind of community collaboration for children’s hospitals partnering with adult hospitals in their community and with policy makers.

“We are a network of folks from different institutions, many med-peds–trained hospitalists but quickly growing,” said Leah Ratner, MD, a second-year fellow in the Global Pediatrics Program at Boston Children’s Hospital and cofounder of the POPCoRN network. “We came together to think about how to increase capacity – both in the work force and for actual hospital space – by helping to train pediatric hospitalists and pediatrics-trained nurses to care for adult patients.”

A web-based platform filled with a rapidly expanding list of resources, an active Twitter account, and utilization of Zoom networking software for webinars and working group meetings have facilitated the network’s growth. “Social media has helped us,” Dr. Ratner said. But equally important are personal connections.

“It all started just a few weeks ago,” added cofounder Ashley Jenkins, MD, a med-peds hospital medicine and general academics research fellow in the division of hospital medicine at Cincinnati Children’s Hospital Medical Center. “I sent out some emails in mid-March, asking what other people were doing about these issues. Leah and I met as a result of these initial emails. We immediately started connecting with other health systems and it just expanded from there. Once we knew that enough other systems were thinking about it and trying to build capacity, we started pulling the people and information together.”
 

High-yield one-pagers

A third or more of those on the POPCoRN contact list are also participating as volunteers on its varied working groups, including health system operation groups exploring the needs of three distinct hospital models: freestanding children’s hospitals; community hospitals, which may see small numbers of children; and integrated mixed hospitals, which often means a pediatric hospital or pediatric units located within an adult hospital.

An immediate goal is to develop high-yield informational “one-pagers,” culling essential clinical facts on a variety of topics in adult inpatient medicine that may no longer be familiar to working pediatric hospitalists. These one-pagers, designed with the help of network members with graphic design skills, address topics such as syncope or chest pain or managing exacerbation of COPD in adults. They draw upon existing informational sources, encapsulating practical information tips that can be used at the bedside, including test workups, differential diagnoses, treatment approaches, and other pearls for providers. Drafts are reviewed for content by specialists, and then by pediatricians to make sure the information covers what they need.

Also under development are educational materials for nurses trained in pediatrics, a section for outpatient providers redeployed to triage or telehealth, and information for other team members including occupational, physical, and respiratory therapists. Another section offers critical care lectures for the nonintensivist. A metrics and outcomes working group is looking for ways to evaluate how the network is doing and who is being reached without having to ask frontline providers to fill out surveys.

Dr. Ratner and Dr. Jenkins have created an intentional structure for encouraging mentoring. They also call on their own mentors – Ahmet Uluer, DO, director of Weitzman Family Bridges Adult Transition Program at Boston Children’s Hospital, and Brian Herbst Jr., MD, medical director of the Hospital Medicine Adult Care Service at Cincinnati Children’s – for advice.
 

Beyond the silos

Pediatric hospitalists may have been doing similar things, working on similar projects, but not necessarily reaching out to each other across a system that tends to promote staying within administrative silos, Dr. Uluer said. “Through our personal contacts in POPCoRN, we’ve been able to reach beyond the silos. This network has worked like medical crowd sourcing, and the founders have been inspirational.”

Dr. Herbst added, “How do we expand bandwidth and safely expand services to take young patients and adults from other hospitals? What other populations do we need to expand to take? This network is a workplace of ideas. It’s amazing to see what has been built in a few weeks and how useful it can be.”

Med-peds hospitalists are an important resource for bridging the two specialties. Their experience with transitioning young adults with long-standing chronic conditions of childhood, who have received most of their care at a children’s hospital before reaching adulthood, offers a helpful model. “We’ve also tried to target junior physicians who could step up into leadership roles and to pull in medical students – who are the backbone of this network through their administrative support,” Dr. Jenkins said.

Marie Pfarr, MD, also a med-peds trained hospital medicine fellow at Cincinnati Children’s, was contacted in March by Dr. Jenkins. “She said they had this brainstorm, and they were getting feedback that it would be helpful to provide educational materials for pediatric providers. Because I have an interest in medical education, she asked if I wanted to help. I was at home struggling with what I could contribute during this crazy time, so I said yes.”

Dr. Pfarr leads POPCoRN’s educational working group, which came up with a list of 50 topics in need of one-pagers and people willing to create them, mostly still under development. The aim for the one-pagers is to offer a good starting point for pediatricians, helping them, for example, to ask the right questions during history and physical exams. “We also want to offer additional resources for those who want to do a deeper dive.”

Dr. Pfarr said she has enjoyed working closely with medical students, who really want to help. “That’s been great to see. We are all working toward the same goal, and we help to keep each other in check. I think there’s a future for this kind of mobilization through collaborations to connect pediatric to adult providers. A lot of good things will come out of the network, which is an example of how folks can talk to each other. It’s very dynamic and changing every day.”

One of those medical students is Chinma Onyewuenyi, finishing her fourth year at Baylor College of Medicine. Scheduled to start a med-peds residency at Geisinger Health on July 1, she had completed all of her rotations and was looking for ways to get involved in the pandemic response while respecting the shelter-in-place order. “I had heard about the network, which was recruiting medical students to play administrative roles for the working groups. I said, ‘If you have anything else you need help with, I have time on my hands.’”

Ms. Onyewuenyi says she fell into the role of a lead administrative volunteer, and her responsibilities grew from there, eventually taking charge of all the medical students’ recruiting, screening, and assignments, freeing up the project’s physician leaders from administrative tasks. “I wanted something active to do to contribute, and I appreciate all that I’m learning. With a master’s degree in public health, I have researched how health care is delivered,” she said.

“This experience has really opened my eyes to what’s required to deliver care, and just the level of collaboration that needs to go on with something like this. Even as a medical student, I felt glad to have an opportunity to contribute beyond the administrative tasks. At meetings, they ask for my opinion.”


 

Equitable access to resources

Another major focus for the network is promoting health equity – giving pediatric providers and health systems equitable access to information that meets their needs, Dr. Ratner said. “We’ve made a particular effort to reach out to hospitals that are the most vulnerable, including rural hospitals, and to those serving the most vulnerable patients,” she noted. These also include the homeless and refugees.

“We’ve been trying to be mindful of avoiding the sometimes-intimidating power structure that has been traditional in medicine,” Dr. Ratner said. The network’s equity working group is trying to provide content with structural competency and cultural humility. “We’re learning a lot about the ways the health care system is broken,” she added. “We all agree that we have a fragmented health care system, but there are ways to make it less fragmented and learn from each other.”

In the tragedy of the COVID epidemic, there are also unique opportunities to learn to work collaboratively and make the health care system stronger for those in greatest need, Dr. Ratner added. “What we hope is that our network becomes an example of that, even as it is moving so quickly.”

Audrey Uong, MD, an attending physician in the division of hospital medicine at Children’s Hospital at Montefiore Medical Center in New York, connected with POPCoRN for an educational presentation reviewing resuscitation in adult patients. She wanted to talk with peers about what’s going on, so as not to feel alone in her practice. She has also found the network’s website useful for identifying educational resources.

“As pediatricians, we have been asked to care for adult patients. One of our units has been admitting mostly patients under age 30, and we are accepting older patients in another unit on the pediatric wing.” This kind of thing is also happening in a lot of other places, Dr. Uong said. Keeping up with these changes in her own practice has been challenging.

She tries to take one day at a time. “Everyone at this institution feels the same – that we’re locked in on meeting the need. Even our child life specialists, when they’re not working with younger patients, have created this amazing support room for staff, with snacks and soothing music. There’s been a lot of attention paid to making us feel supported in this work.”

Head injury before the onset of Parkinson’s disease is associated with more severe motor and nonmotor phenotypes, according to research presented online as part of the 2020 American Academy of Neurology Science Highlights.

Neurologists have identified various phenotypes among patients with Parkinson’s disease; however, the factors that determine these phenotypes, which may include genetic and environmental variables, are poorly understood. Ethan G. Brown, MD, assistant professor of neurology at the University of California, San Francisco, and colleagues hypothesized that head injury, which is a risk factor for Parkinson’s disease, would be associated with a more severe phenotype.

“Head injury is a risk factor for other conditions that involve cognitive impairment,” said Dr. Brown. “The mechanisms of how head injury contributes to neurodegenerative disease are not clear, but may be related to the initiation of an inflammatory cascade that can have a long-term, chronic effect. We hypothesized that these long-term sequelae may contribute to symptoms in Parkinson’s disease.”
 

An analysis of data from two cohorts

The researchers examined the relationship between head injury and clinical features by analyzing data for two cohorts of patients with Parkinson’s disease. Through an online survey, the investigators elicited information about head injury and other exposures from participants in the Parkinson’s Progression Markers Initiative (PPMI) and the Fox Insight (FI) study. Dr. Brown and colleagues determined disease phenotypes for participants in PPMI using baseline Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) score and 5-year change in Montreal Cognitive Assessment score. For participants in FI, the researchers determined phenotypes using baseline self-reported MDS-UPDRS-II score and self-reported cognitive impairment. They used parametric and nonparametric tests as appropriate and adjusted the results for age, sex, and smoking history.

In all, 267 participants with Parkinson’s disease in PPMI and 25,308 in FI submitted information about head injury. In the PPMI cohort, head injury before Parkinson’s disease diagnosis was associated with greater nonmotor symptom burden at enrollment. The mean MDS-UPDRS-I score was 7.73 among participants with any injury, compared with 6.19 among participants with no injury. Similarly, the mean MDS-UPDRS-I score was 8.29 among participants with severe head injury, compared with 6.19 among participants with no injury. Motor symptoms were worse among participants with severe injury (MDS-UPDRS-II score, 8.35). Among 110 participants who were followed for 5 years, patients who reported severe head injury before diagnosis had a decline in cognitive function. The mean change in Montreal Cognitive Assessment score was –0.60 for patients with severe head injury and 0.76 in those with no head injury.

“The improvement from baseline in the participants with Parkinson’s disease but without head injury was small and not statistically significant,” said Dr. Brown. The increase could have resulted from practice effect, although it is not certain, he added. “We are continuing to evaluate other, more sensitive tests of cognitive impairment to try to understand these results more completely in this population.”

In the FI cohort, participants who reported a prior head injury had more motor symptoms (MDS-UPDRS-II, 14.4), compared with those without head injury (MDS-UPDRS-II, 12.1). Also, the risk of self-reported cognitive impairment was elevated in participants who reported head injury (odds ratio, 1.58).

“The results most affected by the self-reported nature of [the] FI [data] are the cognitive impairment results,” said Dr. Brown. “Subjective cognitive impairment ... is very different from objective cognitive impairment, which could be measured through in-person testing in the PPMI cohort. Many factors may contribute to noticing cognitive decline, some of which can be measured and controlled for, but some cannot. There may be a correlation between subjective cognitive decline and true cognitive impairment, but this has not been fully studied in Parkinson’s disease.”
 

The search for the underlying mechanism

Clarifying whether the relationship between head injury and Parkinson’s disease phenotype is causal or whether falling is an early indication of worse symptoms will require more longitudinal data. “We would like to further characterize the differences between people with Parkinson’s disease with and without a history of head injury,” said Dr. Brown. “More detailed understanding of these phenotypic differences could point to an underlying mechanism, or whether or not other comorbid conditions are involved. We would also like to understand whether genetics plays a role.”

The PPMI and FI studies are funded by the Michael J. Fox Foundation. Dr. Brown has received compensation from HiOscar, NEJM Knowledge Plus, and Rune Labs and has received research support from Gateway Institute for Brain Research.

[email protected]

SOURCE: Brown EG et al. AAN 2020, Abstract S17.002.

Head injury before the onset of Parkinson’s disease is associated with more severe motor and nonmotor phenotypes, according to research presented online as part of the 2020 American Academy of Neurology Science Highlights.

Neurologists have identified various phenotypes among patients with Parkinson’s disease; however, the factors that determine these phenotypes, which may include genetic and environmental variables, are poorly understood. Ethan G. Brown, MD, assistant professor of neurology at the University of California, San Francisco, and colleagues hypothesized that head injury, which is a risk factor for Parkinson’s disease, would be associated with a more severe phenotype.

“Head injury is a risk factor for other conditions that involve cognitive impairment,” said Dr. Brown. “The mechanisms of how head injury contributes to neurodegenerative disease are not clear, but may be related to the initiation of an inflammatory cascade that can have a long-term, chronic effect. We hypothesized that these long-term sequelae may contribute to symptoms in Parkinson’s disease.”
 

An analysis of data from two cohorts

The researchers examined the relationship between head injury and clinical features by analyzing data for two cohorts of patients with Parkinson’s disease. Through an online survey, the investigators elicited information about head injury and other exposures from participants in the Parkinson’s Progression Markers Initiative (PPMI) and the Fox Insight (FI) study. Dr. Brown and colleagues determined disease phenotypes for participants in PPMI using baseline Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) score and 5-year change in Montreal Cognitive Assessment score. For participants in FI, the researchers determined phenotypes using baseline self-reported MDS-UPDRS-II score and self-reported cognitive impairment. They used parametric and nonparametric tests as appropriate and adjusted the results for age, sex, and smoking history.

In all, 267 participants with Parkinson’s disease in PPMI and 25,308 in FI submitted information about head injury. In the PPMI cohort, head injury before Parkinson’s disease diagnosis was associated with greater nonmotor symptom burden at enrollment. The mean MDS-UPDRS-I score was 7.73 among participants with any injury, compared with 6.19 among participants with no injury. Similarly, the mean MDS-UPDRS-I score was 8.29 among participants with severe head injury, compared with 6.19 among participants with no injury. Motor symptoms were worse among participants with severe injury (MDS-UPDRS-II score, 8.35). Among 110 participants who were followed for 5 years, patients who reported severe head injury before diagnosis had a decline in cognitive function. The mean change in Montreal Cognitive Assessment score was –0.60 for patients with severe head injury and 0.76 in those with no head injury.

“The improvement from baseline in the participants with Parkinson’s disease but without head injury was small and not statistically significant,” said Dr. Brown. The increase could have resulted from practice effect, although it is not certain, he added. “We are continuing to evaluate other, more sensitive tests of cognitive impairment to try to understand these results more completely in this population.”

In the FI cohort, participants who reported a prior head injury had more motor symptoms (MDS-UPDRS-II, 14.4), compared with those without head injury (MDS-UPDRS-II, 12.1). Also, the risk of self-reported cognitive impairment was elevated in participants who reported head injury (odds ratio, 1.58).

“The results most affected by the self-reported nature of [the] FI [data] are the cognitive impairment results,” said Dr. Brown. “Subjective cognitive impairment ... is very different from objective cognitive impairment, which could be measured through in-person testing in the PPMI cohort. Many factors may contribute to noticing cognitive decline, some of which can be measured and controlled for, but some cannot. There may be a correlation between subjective cognitive decline and true cognitive impairment, but this has not been fully studied in Parkinson’s disease.”
 

The search for the underlying mechanism

Clarifying whether the relationship between head injury and Parkinson’s disease phenotype is causal or whether falling is an early indication of worse symptoms will require more longitudinal data. “We would like to further characterize the differences between people with Parkinson’s disease with and without a history of head injury,” said Dr. Brown. “More detailed understanding of these phenotypic differences could point to an underlying mechanism, or whether or not other comorbid conditions are involved. We would also like to understand whether genetics plays a role.”

The PPMI and FI studies are funded by the Michael J. Fox Foundation. Dr. Brown has received compensation from HiOscar, NEJM Knowledge Plus, and Rune Labs and has received research support from Gateway Institute for Brain Research.

[email protected]

SOURCE: Brown EG et al. AAN 2020, Abstract S17.002.

Head injury before the onset of Parkinson’s disease is associated with more severe motor and nonmotor phenotypes, according to research presented online as part of the 2020 American Academy of Neurology Science Highlights.

Neurologists have identified various phenotypes among patients with Parkinson’s disease; however, the factors that determine these phenotypes, which may include genetic and environmental variables, are poorly understood. Ethan G. Brown, MD, assistant professor of neurology at the University of California, San Francisco, and colleagues hypothesized that head injury, which is a risk factor for Parkinson’s disease, would be associated with a more severe phenotype.

“Head injury is a risk factor for other conditions that involve cognitive impairment,” said Dr. Brown. “The mechanisms of how head injury contributes to neurodegenerative disease are not clear, but may be related to the initiation of an inflammatory cascade that can have a long-term, chronic effect. We hypothesized that these long-term sequelae may contribute to symptoms in Parkinson’s disease.”
 

An analysis of data from two cohorts

The researchers examined the relationship between head injury and clinical features by analyzing data for two cohorts of patients with Parkinson’s disease. Through an online survey, the investigators elicited information about head injury and other exposures from participants in the Parkinson’s Progression Markers Initiative (PPMI) and the Fox Insight (FI) study. Dr. Brown and colleagues determined disease phenotypes for participants in PPMI using baseline Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) score and 5-year change in Montreal Cognitive Assessment score. For participants in FI, the researchers determined phenotypes using baseline self-reported MDS-UPDRS-II score and self-reported cognitive impairment. They used parametric and nonparametric tests as appropriate and adjusted the results for age, sex, and smoking history.

In all, 267 participants with Parkinson’s disease in PPMI and 25,308 in FI submitted information about head injury. In the PPMI cohort, head injury before Parkinson’s disease diagnosis was associated with greater nonmotor symptom burden at enrollment. The mean MDS-UPDRS-I score was 7.73 among participants with any injury, compared with 6.19 among participants with no injury. Similarly, the mean MDS-UPDRS-I score was 8.29 among participants with severe head injury, compared with 6.19 among participants with no injury. Motor symptoms were worse among participants with severe injury (MDS-UPDRS-II score, 8.35). Among 110 participants who were followed for 5 years, patients who reported severe head injury before diagnosis had a decline in cognitive function. The mean change in Montreal Cognitive Assessment score was –0.60 for patients with severe head injury and 0.76 in those with no head injury.

“The improvement from baseline in the participants with Parkinson’s disease but without head injury was small and not statistically significant,” said Dr. Brown. The increase could have resulted from practice effect, although it is not certain, he added. “We are continuing to evaluate other, more sensitive tests of cognitive impairment to try to understand these results more completely in this population.”

In the FI cohort, participants who reported a prior head injury had more motor symptoms (MDS-UPDRS-II, 14.4), compared with those without head injury (MDS-UPDRS-II, 12.1). Also, the risk of self-reported cognitive impairment was elevated in participants who reported head injury (odds ratio, 1.58).

“The results most affected by the self-reported nature of [the] FI [data] are the cognitive impairment results,” said Dr. Brown. “Subjective cognitive impairment ... is very different from objective cognitive impairment, which could be measured through in-person testing in the PPMI cohort. Many factors may contribute to noticing cognitive decline, some of which can be measured and controlled for, but some cannot. There may be a correlation between subjective cognitive decline and true cognitive impairment, but this has not been fully studied in Parkinson’s disease.”
 

The search for the underlying mechanism

Clarifying whether the relationship between head injury and Parkinson’s disease phenotype is causal or whether falling is an early indication of worse symptoms will require more longitudinal data. “We would like to further characterize the differences between people with Parkinson’s disease with and without a history of head injury,” said Dr. Brown. “More detailed understanding of these phenotypic differences could point to an underlying mechanism, or whether or not other comorbid conditions are involved. We would also like to understand whether genetics plays a role.”

The PPMI and FI studies are funded by the Michael J. Fox Foundation. Dr. Brown has received compensation from HiOscar, NEJM Knowledge Plus, and Rune Labs and has received research support from Gateway Institute for Brain Research.

[email protected]

SOURCE: Brown EG et al. AAN 2020, Abstract S17.002.

A clinical score may help clinicians predict which patients undergoing mechanical thrombectomy up to 24 hours after a stroke are at higher risk of developing symptomatic intracranial hemorrhage (ICH), new research suggests. In a study of nearly 600 patients undergoing thrombectomy, investigators combined a modified Thrombolysis in Cerebral Ischemia (TICI) score, an Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and glucose levels (the “TAG score”) to predict risk. Results showed that each unit increase in the combination score was associated with a significant, nearly twofold greater likelihood of symptomatic ICH.

“It is very easy” to calculate the new score in a clinical setting, lead author Mayra Johana Montalvo Perero, MD, Department of Neurology, Brown University and Rhode Island Hospital, Providence, said. “You just need three variables.”

The findings were presented online as part of the 2020 American Academy of Neurology Science Highlights.
 

Limited data

High TAG scores are associated with symptomatic ICH in patients receiving mechanical thrombectomy, Dr. Montalvo Perero and colleagues said.

Although clinical predictors of symptomatic ICH are well established, “there is limited data in patients who underwent mechanical thrombectomy,” the researchers noted.

To learn more, they assessed 578 patients (52% women; mean age, 73 years) who had mechanical thrombectomy for acute ischemic stroke at a comprehensive stroke center. Within this cohort, 19 patients (3.3%) developed symptomatic ICH.

The investigators compared clinical and radiographic findings between patients who experienced symptomatic ICH and those who did not.

The TICI score emerged as a predictor when each unit decrease in this score was associated with greater risk for symptomatic ICH (odds ratio, 5.13; 95% confidence interval, 1.84-14.29; P = .002).

Each one-point decrease in the ASPECTS score also predicted increased risk (OR, 1.52; 95% CI, 1.1-2.0; P = .003).

“The main driver is the size of the stroke core, which is correlated with the ASPECTS score,” Dr. Montalvo Perero said.

Each 10 mg/dL increase in glucose level also correlated with increased risk (OR, 1.07; 95% CI, 1.01-1.13; P = .018).
 

Twice the risk

The investigators then combined these three independent variables into a weighted TAG score based on a multivariate analysis. Each unit increase in this composite score was associated with increased risk of symptomatic ICH (OR, 1.98; 95% CI, 1.48-2.66; P < .001).

A step in the right direction?

Commenting on the study, Jeremy Payne, MD, PhD, director of the Stroke Center at Banner Health’s University Medicine Neuroscience Institute in Phoenix, Arizona, noted the importance of predicting which patients might have secondary bleeding after interventional treatment of a large vessel occlusion stroke

“In aggregate, the role of endovascular thrombectomy is quite clear, but we still struggle to predict at the individual patient level who will benefit,” said Dr. Payne, who was not involved with the research.

Transfer and treatment of these patients also carries an economic cost. “Just getting patients to our center, where about 80% of the complex stroke patients come by helicopter, costs upwards of $30,000,” Dr. Payne said. “The financial argument isn’t one we like to talk much about, but we’re committing to spending probably $100,000-$200,000 on each person’s care.”

This study “attempts to address an important issue,” he said.

Predicting who is more likely to benefit leads to the assumption that if that were to happen, “we could skip all the rigamarole of helicopters and procedures, avoid the extra expense and particularly not make things worse than they already are,” explained Dr. Payne.

Potential limitations include that this is a single-center study and is based on an analysis of 19 patients out of 578. As a result, it is not clear that these findings will necessarily be generalizable to other centers, said Dr. Payne.

The TICI and ASPECTS “are pretty obvious markers of risk,” he noted. “The glucose levels, however, are more subtly interesting.”

He also pointed out that an association between diabetes and worse stroke outcomes is well established.

“The mechanisms are poorly understood, but the role of glucose keeps popping up as a potential marker of risk, and so it’s interesting that it bubbles up in their work too,” Dr. Payne said.

Furthermore, unlike TICI and ASPECTS, glucose levels are modifiable.

“Overall, then, we will continue to study this,” Dr. Payne said. “It’s very important to refine our ability to predict which patients may receive benefit versus harm from such procedures, and this is a step in the right direction.”

Some findings were also published December 2019 in the Journal of Neurology, Neurosurgery & Psychiatry.

Montalvo Perero and Payne have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

SOURCE: Motalvo Perero MJ et al. AAN 2020, Abstract S20.001.

A clinical score may help clinicians predict which patients undergoing mechanical thrombectomy up to 24 hours after a stroke are at higher risk of developing symptomatic intracranial hemorrhage (ICH), new research suggests. In a study of nearly 600 patients undergoing thrombectomy, investigators combined a modified Thrombolysis in Cerebral Ischemia (TICI) score, an Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and glucose levels (the “TAG score”) to predict risk. Results showed that each unit increase in the combination score was associated with a significant, nearly twofold greater likelihood of symptomatic ICH.

“It is very easy” to calculate the new score in a clinical setting, lead author Mayra Johana Montalvo Perero, MD, Department of Neurology, Brown University and Rhode Island Hospital, Providence, said. “You just need three variables.”

The findings were presented online as part of the 2020 American Academy of Neurology Science Highlights.
 

Limited data

High TAG scores are associated with symptomatic ICH in patients receiving mechanical thrombectomy, Dr. Montalvo Perero and colleagues said.

Although clinical predictors of symptomatic ICH are well established, “there is limited data in patients who underwent mechanical thrombectomy,” the researchers noted.

To learn more, they assessed 578 patients (52% women; mean age, 73 years) who had mechanical thrombectomy for acute ischemic stroke at a comprehensive stroke center. Within this cohort, 19 patients (3.3%) developed symptomatic ICH.

The investigators compared clinical and radiographic findings between patients who experienced symptomatic ICH and those who did not.

The TICI score emerged as a predictor when each unit decrease in this score was associated with greater risk for symptomatic ICH (odds ratio, 5.13; 95% confidence interval, 1.84-14.29; P = .002).

Each one-point decrease in the ASPECTS score also predicted increased risk (OR, 1.52; 95% CI, 1.1-2.0; P = .003).

“The main driver is the size of the stroke core, which is correlated with the ASPECTS score,” Dr. Montalvo Perero said.

Each 10 mg/dL increase in glucose level also correlated with increased risk (OR, 1.07; 95% CI, 1.01-1.13; P = .018).
 

Twice the risk

The investigators then combined these three independent variables into a weighted TAG score based on a multivariate analysis. Each unit increase in this composite score was associated with increased risk of symptomatic ICH (OR, 1.98; 95% CI, 1.48-2.66; P < .001).

A step in the right direction?

Commenting on the study, Jeremy Payne, MD, PhD, director of the Stroke Center at Banner Health’s University Medicine Neuroscience Institute in Phoenix, Arizona, noted the importance of predicting which patients might have secondary bleeding after interventional treatment of a large vessel occlusion stroke

“In aggregate, the role of endovascular thrombectomy is quite clear, but we still struggle to predict at the individual patient level who will benefit,” said Dr. Payne, who was not involved with the research.

Transfer and treatment of these patients also carries an economic cost. “Just getting patients to our center, where about 80% of the complex stroke patients come by helicopter, costs upwards of $30,000,” Dr. Payne said. “The financial argument isn’t one we like to talk much about, but we’re committing to spending probably $100,000-$200,000 on each person’s care.”

This study “attempts to address an important issue,” he said.

Predicting who is more likely to benefit leads to the assumption that if that were to happen, “we could skip all the rigamarole of helicopters and procedures, avoid the extra expense and particularly not make things worse than they already are,” explained Dr. Payne.

Potential limitations include that this is a single-center study and is based on an analysis of 19 patients out of 578. As a result, it is not clear that these findings will necessarily be generalizable to other centers, said Dr. Payne.

The TICI and ASPECTS “are pretty obvious markers of risk,” he noted. “The glucose levels, however, are more subtly interesting.”

He also pointed out that an association between diabetes and worse stroke outcomes is well established.

“The mechanisms are poorly understood, but the role of glucose keeps popping up as a potential marker of risk, and so it’s interesting that it bubbles up in their work too,” Dr. Payne said.

Furthermore, unlike TICI and ASPECTS, glucose levels are modifiable.

“Overall, then, we will continue to study this,” Dr. Payne said. “It’s very important to refine our ability to predict which patients may receive benefit versus harm from such procedures, and this is a step in the right direction.”

Some findings were also published December 2019 in the Journal of Neurology, Neurosurgery & Psychiatry.

Montalvo Perero and Payne have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

SOURCE: Motalvo Perero MJ et al. AAN 2020, Abstract S20.001.

A clinical score may help clinicians predict which patients undergoing mechanical thrombectomy up to 24 hours after a stroke are at higher risk of developing symptomatic intracranial hemorrhage (ICH), new research suggests. In a study of nearly 600 patients undergoing thrombectomy, investigators combined a modified Thrombolysis in Cerebral Ischemia (TICI) score, an Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and glucose levels (the “TAG score”) to predict risk. Results showed that each unit increase in the combination score was associated with a significant, nearly twofold greater likelihood of symptomatic ICH.

“It is very easy” to calculate the new score in a clinical setting, lead author Mayra Johana Montalvo Perero, MD, Department of Neurology, Brown University and Rhode Island Hospital, Providence, said. “You just need three variables.”

The findings were presented online as part of the 2020 American Academy of Neurology Science Highlights.
 

Limited data

High TAG scores are associated with symptomatic ICH in patients receiving mechanical thrombectomy, Dr. Montalvo Perero and colleagues said.

Although clinical predictors of symptomatic ICH are well established, “there is limited data in patients who underwent mechanical thrombectomy,” the researchers noted.

To learn more, they assessed 578 patients (52% women; mean age, 73 years) who had mechanical thrombectomy for acute ischemic stroke at a comprehensive stroke center. Within this cohort, 19 patients (3.3%) developed symptomatic ICH.

The investigators compared clinical and radiographic findings between patients who experienced symptomatic ICH and those who did not.

The TICI score emerged as a predictor when each unit decrease in this score was associated with greater risk for symptomatic ICH (odds ratio, 5.13; 95% confidence interval, 1.84-14.29; P = .002).

Each one-point decrease in the ASPECTS score also predicted increased risk (OR, 1.52; 95% CI, 1.1-2.0; P = .003).

“The main driver is the size of the stroke core, which is correlated with the ASPECTS score,” Dr. Montalvo Perero said.

Each 10 mg/dL increase in glucose level also correlated with increased risk (OR, 1.07; 95% CI, 1.01-1.13; P = .018).
 

Twice the risk

The investigators then combined these three independent variables into a weighted TAG score based on a multivariate analysis. Each unit increase in this composite score was associated with increased risk of symptomatic ICH (OR, 1.98; 95% CI, 1.48-2.66; P < .001).

A step in the right direction?

Commenting on the study, Jeremy Payne, MD, PhD, director of the Stroke Center at Banner Health’s University Medicine Neuroscience Institute in Phoenix, Arizona, noted the importance of predicting which patients might have secondary bleeding after interventional treatment of a large vessel occlusion stroke

“In aggregate, the role of endovascular thrombectomy is quite clear, but we still struggle to predict at the individual patient level who will benefit,” said Dr. Payne, who was not involved with the research.

Transfer and treatment of these patients also carries an economic cost. “Just getting patients to our center, where about 80% of the complex stroke patients come by helicopter, costs upwards of $30,000,” Dr. Payne said. “The financial argument isn’t one we like to talk much about, but we’re committing to spending probably $100,000-$200,000 on each person’s care.”

This study “attempts to address an important issue,” he said.

Predicting who is more likely to benefit leads to the assumption that if that were to happen, “we could skip all the rigamarole of helicopters and procedures, avoid the extra expense and particularly not make things worse than they already are,” explained Dr. Payne.

Potential limitations include that this is a single-center study and is based on an analysis of 19 patients out of 578. As a result, it is not clear that these findings will necessarily be generalizable to other centers, said Dr. Payne.

The TICI and ASPECTS “are pretty obvious markers of risk,” he noted. “The glucose levels, however, are more subtly interesting.”

He also pointed out that an association between diabetes and worse stroke outcomes is well established.

“The mechanisms are poorly understood, but the role of glucose keeps popping up as a potential marker of risk, and so it’s interesting that it bubbles up in their work too,” Dr. Payne said.

Furthermore, unlike TICI and ASPECTS, glucose levels are modifiable.

“Overall, then, we will continue to study this,” Dr. Payne said. “It’s very important to refine our ability to predict which patients may receive benefit versus harm from such procedures, and this is a step in the right direction.”

Some findings were also published December 2019 in the Journal of Neurology, Neurosurgery & Psychiatry.

Montalvo Perero and Payne have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

SOURCE: Motalvo Perero MJ et al. AAN 2020, Abstract S20.001.