The majority of patients who have cancer or are suspected of having cancer are not accessing healthcare services in the United Kingdom or the United States because of the COVID-19 pandemic, the first report of its kind estimates.

As a result, there will be an excess of deaths among patients who have cancer and multiple comorbidities in both countries during the current coronavirus emergency, the report warns.

The authors calculate that there will be 6,270 excess deaths among cancer patients 1 year from now in England and 33,890 excess deaths among cancer patients in the United States. (In the United States, the estimated excess number of deaths applies only to patients older than 40 years, they note.)

“The recorded underlying cause of these excess deaths may be cancer, COVID-19, or comorbidity (such as myocardial infarction),” Alvina Lai, PhD, University College London, United Kingdom, and colleagues observe.

“Our data have highlighted how cancer patients with multimorbidity are a particularly at-risk group during the current pandemic,” they emphasize.

The study was published on ResearchGate as a preprint and has not undergone peer review.

Commenting on the study on the UK Science Media Center, several experts emphasized the lack of peer review, noting that interpretation of these data needs to be further refined on the basis of that input. One expert suggested that there are “substantial uncertainties that this paper does not adequately communicate.” But others argued that this topic was important enough to warrant early release of the data.

Chris Bunce, PhD, University of Birmingham, United Kingdom, said this study represents “a highly valuable contribution.”

“It is universally accepted that early diagnosis and treatment and adherence to treatment regimens saves lives,” he pointed out.

“Therefore, these COVID-19-related impacts will cost lives,” Bunce said.

“And if this information is to influence cancer care and guide policy during the COVID-19 crisis, then it is important that the findings are disseminated and discussed immediately, warranting their release ahead of peer view,” he added.

In a Medscape UK commentary, oncologist Karol Sikora, MD, PhD, argues that “restarting cancer services can’t come soon enough.”
 

“Resonably Argued Numerical Estimate”

“It’s well known that there have been considerable changes in the provision of health care for many conditions, including cancers, as a result of all the measures to deal with the COVID-19 crisis,” said Kevin McConway, PhD, professor emeritus of applied statistics, the Open University, Milton Keynes, United Kingdom.

“It seems inevitable that there will be increased deaths in cancer patients if they are infected with the virus or because of changes in the health services available to them, and quite possibly also from socio-economic effects of the responses to the crisis,” he continued.

“This study is the first that I have seen that produces a reasonably argued numerical estimate of the number of excess deaths of people with cancer arising from these factors in the UK and the USA,” he added.

Declines in Urgent Referrals and Chemo Attendance

For the study, the team used DATA-CAN, the UK National Health Data Research Hub for Cancer, to assess weekly returns for urgent cancer referrals for early diagnosis and also chemotherapy attendances for hospitals in Leeds, London, and Northern Ireland going back to 2018.

The data revealed that there have been major declines in chemotherapy attendances. There has been, on average, a 60% decrease from prepandemic levels in eight hospitals in the three regions that were assessed.

Urgent cancer referrals have dropped by an average of 76% compared to prepandemic levels in the three regions.

On the conservative assumption that the COVID-19 pandemic will only affect patients with newly diagnosed cancer (incident cases), the researchers estimate that the proportion of the population affected by the emergency (PAE) is 40% and that the relative impact of the emergency (RIE) is 1.5.

PAE is a summary measure of exposure to the adverse health consequences of the emergency; RIE is a summary measure of the combined impact on mortality of infection, health service change, physical distancing, and economic downturn, the authors explain.

Comorbidities Common

“Comorbidities were common in people with cancer,” the study authors note. For example, more than one quarter of the study population had at least one comorbidity; more than 14% had two.

For incident cancers, the number of excess deaths steadily increased in conjunction with an increase in the number of comorbidities, such that more than 80% of deaths occurred in patients with one or more comorbidities.

“When considering both prevalent and incident cancers together with a COVID-19 PAE of 40%, we estimated 17,991 excess deaths at a RIE of 1.5; 78.1% of these deaths occur in patients with ≥1 comorbidities,” the authors report.

“The excess risk of death in people living with cancer during the COVID-19 emergency may be due not only to COVID-19 infection, but also to the unintended health consequences of changes in health service provision, the physical or psychological effects of social distancing, and economic upheaval,” they state.

“This is the first study demonstrating profound recent changes in cancer care delivery in multiple centers,” the authors observe.

Lai has disclosed no relevant financial relationships. Several coauthors have various relationships with industry, as listed in their article. The commentators have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

The majority of patients who have cancer or are suspected of having cancer are not accessing healthcare services in the United Kingdom or the United States because of the COVID-19 pandemic, the first report of its kind estimates.

As a result, there will be an excess of deaths among patients who have cancer and multiple comorbidities in both countries during the current coronavirus emergency, the report warns.

The authors calculate that there will be 6,270 excess deaths among cancer patients 1 year from now in England and 33,890 excess deaths among cancer patients in the United States. (In the United States, the estimated excess number of deaths applies only to patients older than 40 years, they note.)

“The recorded underlying cause of these excess deaths may be cancer, COVID-19, or comorbidity (such as myocardial infarction),” Alvina Lai, PhD, University College London, United Kingdom, and colleagues observe.

“Our data have highlighted how cancer patients with multimorbidity are a particularly at-risk group during the current pandemic,” they emphasize.

The study was published on ResearchGate as a preprint and has not undergone peer review.

Commenting on the study on the UK Science Media Center, several experts emphasized the lack of peer review, noting that interpretation of these data needs to be further refined on the basis of that input. One expert suggested that there are “substantial uncertainties that this paper does not adequately communicate.” But others argued that this topic was important enough to warrant early release of the data.

Chris Bunce, PhD, University of Birmingham, United Kingdom, said this study represents “a highly valuable contribution.”

“It is universally accepted that early diagnosis and treatment and adherence to treatment regimens saves lives,” he pointed out.

“Therefore, these COVID-19-related impacts will cost lives,” Bunce said.

“And if this information is to influence cancer care and guide policy during the COVID-19 crisis, then it is important that the findings are disseminated and discussed immediately, warranting their release ahead of peer view,” he added.

In a Medscape UK commentary, oncologist Karol Sikora, MD, PhD, argues that “restarting cancer services can’t come soon enough.”
 

“Resonably Argued Numerical Estimate”

“It’s well known that there have been considerable changes in the provision of health care for many conditions, including cancers, as a result of all the measures to deal with the COVID-19 crisis,” said Kevin McConway, PhD, professor emeritus of applied statistics, the Open University, Milton Keynes, United Kingdom.

“It seems inevitable that there will be increased deaths in cancer patients if they are infected with the virus or because of changes in the health services available to them, and quite possibly also from socio-economic effects of the responses to the crisis,” he continued.

“This study is the first that I have seen that produces a reasonably argued numerical estimate of the number of excess deaths of people with cancer arising from these factors in the UK and the USA,” he added.

Declines in Urgent Referrals and Chemo Attendance

For the study, the team used DATA-CAN, the UK National Health Data Research Hub for Cancer, to assess weekly returns for urgent cancer referrals for early diagnosis and also chemotherapy attendances for hospitals in Leeds, London, and Northern Ireland going back to 2018.

The data revealed that there have been major declines in chemotherapy attendances. There has been, on average, a 60% decrease from prepandemic levels in eight hospitals in the three regions that were assessed.

Urgent cancer referrals have dropped by an average of 76% compared to prepandemic levels in the three regions.

On the conservative assumption that the COVID-19 pandemic will only affect patients with newly diagnosed cancer (incident cases), the researchers estimate that the proportion of the population affected by the emergency (PAE) is 40% and that the relative impact of the emergency (RIE) is 1.5.

PAE is a summary measure of exposure to the adverse health consequences of the emergency; RIE is a summary measure of the combined impact on mortality of infection, health service change, physical distancing, and economic downturn, the authors explain.

Comorbidities Common

“Comorbidities were common in people with cancer,” the study authors note. For example, more than one quarter of the study population had at least one comorbidity; more than 14% had two.

For incident cancers, the number of excess deaths steadily increased in conjunction with an increase in the number of comorbidities, such that more than 80% of deaths occurred in patients with one or more comorbidities.

“When considering both prevalent and incident cancers together with a COVID-19 PAE of 40%, we estimated 17,991 excess deaths at a RIE of 1.5; 78.1% of these deaths occur in patients with ≥1 comorbidities,” the authors report.

“The excess risk of death in people living with cancer during the COVID-19 emergency may be due not only to COVID-19 infection, but also to the unintended health consequences of changes in health service provision, the physical or psychological effects of social distancing, and economic upheaval,” they state.

“This is the first study demonstrating profound recent changes in cancer care delivery in multiple centers,” the authors observe.

Lai has disclosed no relevant financial relationships. Several coauthors have various relationships with industry, as listed in their article. The commentators have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

The majority of patients who have cancer or are suspected of having cancer are not accessing healthcare services in the United Kingdom or the United States because of the COVID-19 pandemic, the first report of its kind estimates.

As a result, there will be an excess of deaths among patients who have cancer and multiple comorbidities in both countries during the current coronavirus emergency, the report warns.

The authors calculate that there will be 6,270 excess deaths among cancer patients 1 year from now in England and 33,890 excess deaths among cancer patients in the United States. (In the United States, the estimated excess number of deaths applies only to patients older than 40 years, they note.)

“The recorded underlying cause of these excess deaths may be cancer, COVID-19, or comorbidity (such as myocardial infarction),” Alvina Lai, PhD, University College London, United Kingdom, and colleagues observe.

“Our data have highlighted how cancer patients with multimorbidity are a particularly at-risk group during the current pandemic,” they emphasize.

The study was published on ResearchGate as a preprint and has not undergone peer review.

Commenting on the study on the UK Science Media Center, several experts emphasized the lack of peer review, noting that interpretation of these data needs to be further refined on the basis of that input. One expert suggested that there are “substantial uncertainties that this paper does not adequately communicate.” But others argued that this topic was important enough to warrant early release of the data.

Chris Bunce, PhD, University of Birmingham, United Kingdom, said this study represents “a highly valuable contribution.”

“It is universally accepted that early diagnosis and treatment and adherence to treatment regimens saves lives,” he pointed out.

“Therefore, these COVID-19-related impacts will cost lives,” Bunce said.

“And if this information is to influence cancer care and guide policy during the COVID-19 crisis, then it is important that the findings are disseminated and discussed immediately, warranting their release ahead of peer view,” he added.

In a Medscape UK commentary, oncologist Karol Sikora, MD, PhD, argues that “restarting cancer services can’t come soon enough.”
 

“Resonably Argued Numerical Estimate”

“It’s well known that there have been considerable changes in the provision of health care for many conditions, including cancers, as a result of all the measures to deal with the COVID-19 crisis,” said Kevin McConway, PhD, professor emeritus of applied statistics, the Open University, Milton Keynes, United Kingdom.

“It seems inevitable that there will be increased deaths in cancer patients if they are infected with the virus or because of changes in the health services available to them, and quite possibly also from socio-economic effects of the responses to the crisis,” he continued.

“This study is the first that I have seen that produces a reasonably argued numerical estimate of the number of excess deaths of people with cancer arising from these factors in the UK and the USA,” he added.

Declines in Urgent Referrals and Chemo Attendance

For the study, the team used DATA-CAN, the UK National Health Data Research Hub for Cancer, to assess weekly returns for urgent cancer referrals for early diagnosis and also chemotherapy attendances for hospitals in Leeds, London, and Northern Ireland going back to 2018.

The data revealed that there have been major declines in chemotherapy attendances. There has been, on average, a 60% decrease from prepandemic levels in eight hospitals in the three regions that were assessed.

Urgent cancer referrals have dropped by an average of 76% compared to prepandemic levels in the three regions.

On the conservative assumption that the COVID-19 pandemic will only affect patients with newly diagnosed cancer (incident cases), the researchers estimate that the proportion of the population affected by the emergency (PAE) is 40% and that the relative impact of the emergency (RIE) is 1.5.

PAE is a summary measure of exposure to the adverse health consequences of the emergency; RIE is a summary measure of the combined impact on mortality of infection, health service change, physical distancing, and economic downturn, the authors explain.

Comorbidities Common

“Comorbidities were common in people with cancer,” the study authors note. For example, more than one quarter of the study population had at least one comorbidity; more than 14% had two.

For incident cancers, the number of excess deaths steadily increased in conjunction with an increase in the number of comorbidities, such that more than 80% of deaths occurred in patients with one or more comorbidities.

“When considering both prevalent and incident cancers together with a COVID-19 PAE of 40%, we estimated 17,991 excess deaths at a RIE of 1.5; 78.1% of these deaths occur in patients with ≥1 comorbidities,” the authors report.

“The excess risk of death in people living with cancer during the COVID-19 emergency may be due not only to COVID-19 infection, but also to the unintended health consequences of changes in health service provision, the physical or psychological effects of social distancing, and economic upheaval,” they state.

“This is the first study demonstrating profound recent changes in cancer care delivery in multiple centers,” the authors observe.

Lai has disclosed no relevant financial relationships. Several coauthors have various relationships with industry, as listed in their article. The commentators have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

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.

Background: Acute bacterial skin and skin-structure infections (ABSSSIs) continue to account for substantial morbidity and health care burden, with the emergence of drug-resistant pathogens further complicating their management. Omadacycline is a new once-daily tetracycline with in vitro activity against a wide range of causative agents of ABSSSI, including Streptococcus pyogenes, Staphylococcus aureus (including methicillin-resistant strains, or MRSA), and Enterococcus spp.

Omadacycline was noninferior to moxifloxacin with respect to early clinical response (84.8% vs. 85.5%, respectively) and posttreatment clinical response rates (86.1% vs. 83.6%). Efficacy was similar for methicillin-susceptible or methicillin-resistant Staphylococcus aureus, the most common isolated pathogens. Frequency of adverse events (primarily gastrointestinal) was also similar in the two groups. Mean duration of IV therapy was 4.4 days, and mean duration of oral therapy was 5.5 days in the omadacycline group.

Bottom line: Omadacycline provides similar clinical benefit as linezolid in the treatment of ABSSSIs.

Citation: O’Riordan W et al. Omadacycline for acute bacterial skin and skin-structure infections. N Eng J Med. 2019;380:528-38.

Dr. Manian is a core educator faculty member in the department of medicine at Massachusetts General Hospital and an associate professor of medicine at Harvard Medical School, Boston.

Background: Acute bacterial skin and skin-structure infections (ABSSSIs) continue to account for substantial morbidity and health care burden, with the emergence of drug-resistant pathogens further complicating their management. Omadacycline is a new once-daily tetracycline with in vitro activity against a wide range of causative agents of ABSSSI, including Streptococcus pyogenes, Staphylococcus aureus (including methicillin-resistant strains, or MRSA), and Enterococcus spp.

Omadacycline was noninferior to moxifloxacin with respect to early clinical response (84.8% vs. 85.5%, respectively) and posttreatment clinical response rates (86.1% vs. 83.6%). Efficacy was similar for methicillin-susceptible or methicillin-resistant Staphylococcus aureus, the most common isolated pathogens. Frequency of adverse events (primarily gastrointestinal) was also similar in the two groups. Mean duration of IV therapy was 4.4 days, and mean duration of oral therapy was 5.5 days in the omadacycline group.

Bottom line: Omadacycline provides similar clinical benefit as linezolid in the treatment of ABSSSIs.

Citation: O’Riordan W et al. Omadacycline for acute bacterial skin and skin-structure infections. N Eng J Med. 2019;380:528-38.

Dr. Manian is a core educator faculty member in the department of medicine at Massachusetts General Hospital and an associate professor of medicine at Harvard Medical School, Boston.

Background: Acute bacterial skin and skin-structure infections (ABSSSIs) continue to account for substantial morbidity and health care burden, with the emergence of drug-resistant pathogens further complicating their management. Omadacycline is a new once-daily tetracycline with in vitro activity against a wide range of causative agents of ABSSSI, including Streptococcus pyogenes, Staphylococcus aureus (including methicillin-resistant strains, or MRSA), and Enterococcus spp.

Omadacycline was noninferior to moxifloxacin with respect to early clinical response (84.8% vs. 85.5%, respectively) and posttreatment clinical response rates (86.1% vs. 83.6%). Efficacy was similar for methicillin-susceptible or methicillin-resistant Staphylococcus aureus, the most common isolated pathogens. Frequency of adverse events (primarily gastrointestinal) was also similar in the two groups. Mean duration of IV therapy was 4.4 days, and mean duration of oral therapy was 5.5 days in the omadacycline group.

Bottom line: Omadacycline provides similar clinical benefit as linezolid in the treatment of ABSSSIs.

Citation: O’Riordan W et al. Omadacycline for acute bacterial skin and skin-structure infections. N Eng J Med. 2019;380:528-38.

Dr. Manian is a core educator faculty member in the department of medicine at Massachusetts General Hospital and an associate professor of medicine at Harvard Medical School, Boston.

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.

As most 2020 medical conferences have, one by one, been canceled or rescheduled as virtual meetings in the time of a pandemic, some physicians and other healthcare professionals are wondering if this is the year that will change the scene forever.

Amid the choruses of resignation (“Unfortunately, it’s the right thing to do.”) and optimism (“See you next year!”), there have been plenty of voices describing another broad sentiment – that all was not well with medical meetings even before the coronavirus.

One dominant criticism is that there are too many meetings.

Indeed, there are many, many meetings. During 2005-2015, there were more than 30,000 medical meetings in the United States, according to a report from the Healthcare Convention and Exhibitors Association.

Most of those are of little value, tweeted Dhruv Khullar, MD, an internist at Weill Cornell Medicine, New York (@DhruvKhullar): “One possible consequence of cancelling so many meetings due to #COVID19 is that we realize we probably don’t need most of them.”

The tweet was liked 1.9K times, which is high for a medical post. Comments were mostly in agreement, with some skepticism.

Michaela West, MD, a surgeon at North Memorial Health, Minneapolis, Minnesota, responded (@MichaelaWst): “Agree. COVID-19 may forever change our perspective regarding medical professional meetings.”

Nwando Olayiwola, MD, chair of family medicine, Ohio State University, Columbus, strongly agreed (@DrNwando): “This is the tweet I wish I tweeted.”

However, Kelly Swords, MD, MPH, urologist, University of California, San Diego, in a dissenting opinion, stated the obvious (@k_dagger): “Except there is no substitute for human interaction.”
 

Worth the Effort?

The cancellation of medical meetings has given those who regularly attend an opportunity to reassess their value and to question the worth of the effort involved in attending in person.

David Steensma, MD, hematologist-oncologist, Harvard Medical School, Boston, (@DavidSteensma) tweeted that he would like to scale back: “The present crisis is an opportunity to reassess what is actually necessary and rebalance [in terms of meetings].”

Travel to meetings is often unpleasant, said others.

Chris Palatucci, life sciences executive recruiter, Coulter Partners, Boston, tweeted (@LifeSciRcruitr): “I will die a happy man if I never get on another plane. Glorified bus travel.” He also believes that once the coronavirus crisis is over, its “silver lining” will be the realization that “40% of all meetings are unnecessary.”

Many professionals have welcomed the announcements that major conferences have been canceled and will be conducted virtually.

The latest change is from the American Society of Clinical Oncology (ASCO), whose annual meeting was to be held in Chicago at the end of May but will now be held online.

Virtual ASCO will be more manageable – and comfy, said Fumiko Ladd Chino, MD, radiation oncologist, Memorial Sloan Kettering Cancer Center, New York.

She (@fumikochino) explained why in a recent tweet: “1) I will be finally able to see ALL OF THE PRESENTATIONS I wanted to see instead of wandering around feeling overwhelmed. 2) I will be able to FOCUS on the presentations and not searching for a power outlet. 3) PAJAMAS.”

Virtual meetings already beat real meetings, added Adriana Scheliga, MD, hematologist-oncologist, Brazilian National Cancer Institute (@linfopedia): “I’ve been saying this for a while. For me the best ASCO Meetings, for example, are the ‘virtual meetings!’ ”

However, meetings in place are also very much about professional community and mutual support, reminds Susan E. Sedory, MA, executive director, Society of Interventional Radiology, which canceled its meeting March 6 in a multifaceted process.
 

Is This the Time to Evaluate Meetings?

Coming up soon is the first major conference to go virtual after being canceled – the American College of Cardiology (ACC), which has been one of the top 20 largest meetings in the United States by attendance.

This meeting, which was to have taken place in Chicago on March 28–30, occurred online on those days. The ACC said it would stream all “live” sessions on demand and provide access to additional videos, abstracts, and slides for at least 90 days after the meeting. And it will be free to anyone with an Internet connection.

Medical meetings in distant locales may bounce back, as they have grown into a very big business. ASCO is illustrative.

The group’s first scientific annual meeting was held in 1965 in Philadelphia, with about 70 members and invited guests in attendance. Fast-forward more than 50 years later to 2019: There were 42,500 attendees, a 4.4% increase from 2018. Notably, the top countries in attendance in 2019 were the United States and China.

Not everyone is happy that canceled meetings are being held online in the middle of a pandemic.

“In a COVID-19 world, the brain cannot focus on nonviral topics,” said commentator John Mandrola, MD, Baptist Health, Louisville, Ky., in a regular column.

The virtual ACC meeting should be canceled or delayed – to mirror what is happening in the world, he argued. “In hospitals, we have postponed the elective to make room for the coming surge. Shouldn’t ACC do the same? After the crisis passes, we can have a virtual meeting with a proper discussion of the science,” he wrote.

But #MedTwitter, with its collective constructive criticism of medical meetings, is perhaps proof that the brain can function – and arrive at clarity – when under pandemic duress.

“Am I the only one experiencing a certain relief at the cancellation of multiple trips and meetings, and vowing to let this revelation affect my decision making in the future,” tweeted Steven Joffe, MD, University of Pennsylvania, Philadelphia (@Steve Joffe).

Louise Perkins King, MD, a bioethicist at Harvard Medical School, responded to Joffe. Hoping not to “belittle” the suffering from the COVID-19 pandemic, she (@louise_p_king) addressed her health care colleagues: “... there is potential for us all to learn what is essential travel and burden and what is not from this. I hope it leads to lasting change.”
 

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

Editor’s note: For information on the impending virtual DDW^®  meeting, please go to https://ddw.org/attendee-planning/covid-19-update/.

As most 2020 medical conferences have, one by one, been canceled or rescheduled as virtual meetings in the time of a pandemic, some physicians and other healthcare professionals are wondering if this is the year that will change the scene forever.

Amid the choruses of resignation (“Unfortunately, it’s the right thing to do.”) and optimism (“See you next year!”), there have been plenty of voices describing another broad sentiment – that all was not well with medical meetings even before the coronavirus.

One dominant criticism is that there are too many meetings.

Indeed, there are many, many meetings. During 2005-2015, there were more than 30,000 medical meetings in the United States, according to a report from the Healthcare Convention and Exhibitors Association.

Most of those are of little value, tweeted Dhruv Khullar, MD, an internist at Weill Cornell Medicine, New York (@DhruvKhullar): “One possible consequence of cancelling so many meetings due to #COVID19 is that we realize we probably don’t need most of them.”

The tweet was liked 1.9K times, which is high for a medical post. Comments were mostly in agreement, with some skepticism.

Michaela West, MD, a surgeon at North Memorial Health, Minneapolis, Minnesota, responded (@MichaelaWst): “Agree. COVID-19 may forever change our perspective regarding medical professional meetings.”

Nwando Olayiwola, MD, chair of family medicine, Ohio State University, Columbus, strongly agreed (@DrNwando): “This is the tweet I wish I tweeted.”

However, Kelly Swords, MD, MPH, urologist, University of California, San Diego, in a dissenting opinion, stated the obvious (@k_dagger): “Except there is no substitute for human interaction.”
 

Worth the Effort?

The cancellation of medical meetings has given those who regularly attend an opportunity to reassess their value and to question the worth of the effort involved in attending in person.

David Steensma, MD, hematologist-oncologist, Harvard Medical School, Boston, (@DavidSteensma) tweeted that he would like to scale back: “The present crisis is an opportunity to reassess what is actually necessary and rebalance [in terms of meetings].”

Travel to meetings is often unpleasant, said others.

Chris Palatucci, life sciences executive recruiter, Coulter Partners, Boston, tweeted (@LifeSciRcruitr): “I will die a happy man if I never get on another plane. Glorified bus travel.” He also believes that once the coronavirus crisis is over, its “silver lining” will be the realization that “40% of all meetings are unnecessary.”

Many professionals have welcomed the announcements that major conferences have been canceled and will be conducted virtually.

The latest change is from the American Society of Clinical Oncology (ASCO), whose annual meeting was to be held in Chicago at the end of May but will now be held online.

Virtual ASCO will be more manageable – and comfy, said Fumiko Ladd Chino, MD, radiation oncologist, Memorial Sloan Kettering Cancer Center, New York.

She (@fumikochino) explained why in a recent tweet: “1) I will be finally able to see ALL OF THE PRESENTATIONS I wanted to see instead of wandering around feeling overwhelmed. 2) I will be able to FOCUS on the presentations and not searching for a power outlet. 3) PAJAMAS.”

Virtual meetings already beat real meetings, added Adriana Scheliga, MD, hematologist-oncologist, Brazilian National Cancer Institute (@linfopedia): “I’ve been saying this for a while. For me the best ASCO Meetings, for example, are the ‘virtual meetings!’ ”

However, meetings in place are also very much about professional community and mutual support, reminds Susan E. Sedory, MA, executive director, Society of Interventional Radiology, which canceled its meeting March 6 in a multifaceted process.
 

Is This the Time to Evaluate Meetings?

Coming up soon is the first major conference to go virtual after being canceled – the American College of Cardiology (ACC), which has been one of the top 20 largest meetings in the United States by attendance.

This meeting, which was to have taken place in Chicago on March 28–30, occurred online on those days. The ACC said it would stream all “live” sessions on demand and provide access to additional videos, abstracts, and slides for at least 90 days after the meeting. And it will be free to anyone with an Internet connection.

Medical meetings in distant locales may bounce back, as they have grown into a very big business. ASCO is illustrative.

The group’s first scientific annual meeting was held in 1965 in Philadelphia, with about 70 members and invited guests in attendance. Fast-forward more than 50 years later to 2019: There were 42,500 attendees, a 4.4% increase from 2018. Notably, the top countries in attendance in 2019 were the United States and China.

Not everyone is happy that canceled meetings are being held online in the middle of a pandemic.

“In a COVID-19 world, the brain cannot focus on nonviral topics,” said commentator John Mandrola, MD, Baptist Health, Louisville, Ky., in a regular column.

The virtual ACC meeting should be canceled or delayed – to mirror what is happening in the world, he argued. “In hospitals, we have postponed the elective to make room for the coming surge. Shouldn’t ACC do the same? After the crisis passes, we can have a virtual meeting with a proper discussion of the science,” he wrote.

But #MedTwitter, with its collective constructive criticism of medical meetings, is perhaps proof that the brain can function – and arrive at clarity – when under pandemic duress.

“Am I the only one experiencing a certain relief at the cancellation of multiple trips and meetings, and vowing to let this revelation affect my decision making in the future,” tweeted Steven Joffe, MD, University of Pennsylvania, Philadelphia (@Steve Joffe).

Louise Perkins King, MD, a bioethicist at Harvard Medical School, responded to Joffe. Hoping not to “belittle” the suffering from the COVID-19 pandemic, she (@louise_p_king) addressed her health care colleagues: “... there is potential for us all to learn what is essential travel and burden and what is not from this. I hope it leads to lasting change.”
 

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

Editor’s note: For information on the impending virtual DDW^®  meeting, please go to https://ddw.org/attendee-planning/covid-19-update/.

As most 2020 medical conferences have, one by one, been canceled or rescheduled as virtual meetings in the time of a pandemic, some physicians and other healthcare professionals are wondering if this is the year that will change the scene forever.

Amid the choruses of resignation (“Unfortunately, it’s the right thing to do.”) and optimism (“See you next year!”), there have been plenty of voices describing another broad sentiment – that all was not well with medical meetings even before the coronavirus.

One dominant criticism is that there are too many meetings.

Indeed, there are many, many meetings. During 2005-2015, there were more than 30,000 medical meetings in the United States, according to a report from the Healthcare Convention and Exhibitors Association.

Most of those are of little value, tweeted Dhruv Khullar, MD, an internist at Weill Cornell Medicine, New York (@DhruvKhullar): “One possible consequence of cancelling so many meetings due to #COVID19 is that we realize we probably don’t need most of them.”

The tweet was liked 1.9K times, which is high for a medical post. Comments were mostly in agreement, with some skepticism.

Michaela West, MD, a surgeon at North Memorial Health, Minneapolis, Minnesota, responded (@MichaelaWst): “Agree. COVID-19 may forever change our perspective regarding medical professional meetings.”

Nwando Olayiwola, MD, chair of family medicine, Ohio State University, Columbus, strongly agreed (@DrNwando): “This is the tweet I wish I tweeted.”

However, Kelly Swords, MD, MPH, urologist, University of California, San Diego, in a dissenting opinion, stated the obvious (@k_dagger): “Except there is no substitute for human interaction.”
 

Worth the Effort?

The cancellation of medical meetings has given those who regularly attend an opportunity to reassess their value and to question the worth of the effort involved in attending in person.

David Steensma, MD, hematologist-oncologist, Harvard Medical School, Boston, (@DavidSteensma) tweeted that he would like to scale back: “The present crisis is an opportunity to reassess what is actually necessary and rebalance [in terms of meetings].”

Travel to meetings is often unpleasant, said others.

Chris Palatucci, life sciences executive recruiter, Coulter Partners, Boston, tweeted (@LifeSciRcruitr): “I will die a happy man if I never get on another plane. Glorified bus travel.” He also believes that once the coronavirus crisis is over, its “silver lining” will be the realization that “40% of all meetings are unnecessary.”

Many professionals have welcomed the announcements that major conferences have been canceled and will be conducted virtually.

The latest change is from the American Society of Clinical Oncology (ASCO), whose annual meeting was to be held in Chicago at the end of May but will now be held online.

Virtual ASCO will be more manageable – and comfy, said Fumiko Ladd Chino, MD, radiation oncologist, Memorial Sloan Kettering Cancer Center, New York.

She (@fumikochino) explained why in a recent tweet: “1) I will be finally able to see ALL OF THE PRESENTATIONS I wanted to see instead of wandering around feeling overwhelmed. 2) I will be able to FOCUS on the presentations and not searching for a power outlet. 3) PAJAMAS.”

Virtual meetings already beat real meetings, added Adriana Scheliga, MD, hematologist-oncologist, Brazilian National Cancer Institute (@linfopedia): “I’ve been saying this for a while. For me the best ASCO Meetings, for example, are the ‘virtual meetings!’ ”

However, meetings in place are also very much about professional community and mutual support, reminds Susan E. Sedory, MA, executive director, Society of Interventional Radiology, which canceled its meeting March 6 in a multifaceted process.
 

Is This the Time to Evaluate Meetings?

Coming up soon is the first major conference to go virtual after being canceled – the American College of Cardiology (ACC), which has been one of the top 20 largest meetings in the United States by attendance.

This meeting, which was to have taken place in Chicago on March 28–30, occurred online on those days. The ACC said it would stream all “live” sessions on demand and provide access to additional videos, abstracts, and slides for at least 90 days after the meeting. And it will be free to anyone with an Internet connection.

Medical meetings in distant locales may bounce back, as they have grown into a very big business. ASCO is illustrative.

The group’s first scientific annual meeting was held in 1965 in Philadelphia, with about 70 members and invited guests in attendance. Fast-forward more than 50 years later to 2019: There were 42,500 attendees, a 4.4% increase from 2018. Notably, the top countries in attendance in 2019 were the United States and China.

Not everyone is happy that canceled meetings are being held online in the middle of a pandemic.

“In a COVID-19 world, the brain cannot focus on nonviral topics,” said commentator John Mandrola, MD, Baptist Health, Louisville, Ky., in a regular column.

The virtual ACC meeting should be canceled or delayed – to mirror what is happening in the world, he argued. “In hospitals, we have postponed the elective to make room for the coming surge. Shouldn’t ACC do the same? After the crisis passes, we can have a virtual meeting with a proper discussion of the science,” he wrote.

But #MedTwitter, with its collective constructive criticism of medical meetings, is perhaps proof that the brain can function – and arrive at clarity – when under pandemic duress.

“Am I the only one experiencing a certain relief at the cancellation of multiple trips and meetings, and vowing to let this revelation affect my decision making in the future,” tweeted Steven Joffe, MD, University of Pennsylvania, Philadelphia (@Steve Joffe).

Louise Perkins King, MD, a bioethicist at Harvard Medical School, responded to Joffe. Hoping not to “belittle” the suffering from the COVID-19 pandemic, she (@louise_p_king) addressed her health care colleagues: “... there is potential for us all to learn what is essential travel and burden and what is not from this. I hope it leads to lasting change.”
 

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

Editor’s note: For information on the impending virtual DDW^®  meeting, please go to https://ddw.org/attendee-planning/covid-19-update/.

A novel biomarker may predict early responses to anti–tumor necrosis factor (TNF) therapy in patients with Crohn’s disease, according to investigators.

After 1 week of therapy with adalimumab, serum levels of citrullinated and matrix metalloproteinase-degraded vimentin (VICM) predicted early responses to treatment with an odds ratio of 42.5, reported lead author Joachim H. Mortensen, PhD, of Nordic Bioscience, Herlev, Denmark, and colleagues.

“VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients,” the investigators wrote in the Journal of Clinical Gastroenterology.This is an area of particular need, the investigators explained because 10%-40% of patients with Crohn’s disease have an inadequate response to anti-TNF therapy, yet early detection of treatment failure remains challenging.

According to the investigators, C-reactive protein (CRP) may serve as a reliable biomarker for acute inflammation, but intestinal tissue remodeling in Crohn’s disease is largely caused by chronic inflammation, which is driven by proteases. As these proteases degrade intestinal tissue, protein fragments called neo-epitopes are released into circulation, offering a potential biomarker of disease activity. Previous research showed that VICM, a neo-epitope that correlates with macrophage activity, was highly associated with Crohn’s disease.

“Because anti-TNF reduces the number of activated macrophages, we hypothesized that changes in VICM levels can be applied to monitor the outcome of early response to anti-TNF treatment in Crohn’s disease,” the investigators wrote.

To test this hypothesis, the investigators retrospectively analyzed clinical data and serum samples from 42 patients with Crohn’s disease, of whom 21 were treated with adalimumab at University Medical Center Groningen (the Netherlands) and 21 were treated with infliximab at Aarhus (Denmark) University Hospital. In both cohorts, disease activity was measured by the Harvey-Bradshaw Index, with responders defined by a score of less than 5, which indicates clinical remission. Harvey-Bradshaw Index scores were evaluated at week 8 and week 14 for the adalimumab and infliximab groups, respectively. In the adalimumab group, serum VICM and CRP levels were evaluated at baseline, then at weeks 1 and 8. In the infliximab group, VICM and CRP were measured at baseline, then at weeks 2, 6, and 14.

Patients responding to adalimumab had significantly lower levels of VICM than did nonresponders at week 1 (P = .007) and week 8 (P = .048). Although infliximab responders showed numerical differences in VICM, compared with nonresponders, at week 2 (P = .48), these differences lacked statistical significance until week 6 (P = .046), then lost significance again at week 14 (P = .23). No significant differences in CRP levels between responders and nonresponders were detected at any timepoints.

Using a receiver operating characteristic–curve analysis, the investigators identified a clinically relevant cutoff value for VICM at 12.5 ng/mL. With this cutoff, responders were identifiable as early as week 6 in the infliximab group with an area under the curve (AUC) of 0.89 (specificity, 75%; sensitivity, 88%; P less than .01). In the adalimumab group, responders were identifiable as early as week 1, with an AUC of 0.91 (specificity, 87%; sensitivity, 100%; P less than .01).

In the infliximab group, patients with a serum VICM level less than 12.5 ng/mL at week 6 were 22.5 times more likely to be responders (odds ratio, 22.5). Patients treated with adalimumab were 42 times more likely to be responders if their VICM level fell below the cutoff at week 1. A similar analysis involving CRP had no predictive value.

“In conclusion, the reduction in VICM serum levels, but not reduction in CRP levels, was associated with early response to [anti–TNF-alpha] treatment in patients with Crohn’s disease,” the investigators concluded. “Thus, VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients.”

The study was funded by the Danish Research Foundation. The investigators disclosed additional relationships with Nordic Bioscience.

SOURCE: Mortensen JH et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001341.

Help your patients understand their Crohn’s disease treatment options by sharing AGA patient education content at https://www.gastro.org/practice-guidance/gi-patient-center/topic/crohn-s-disease.  

A novel biomarker may predict early responses to anti–tumor necrosis factor (TNF) therapy in patients with Crohn’s disease, according to investigators.

After 1 week of therapy with adalimumab, serum levels of citrullinated and matrix metalloproteinase-degraded vimentin (VICM) predicted early responses to treatment with an odds ratio of 42.5, reported lead author Joachim H. Mortensen, PhD, of Nordic Bioscience, Herlev, Denmark, and colleagues.

“VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients,” the investigators wrote in the Journal of Clinical Gastroenterology.This is an area of particular need, the investigators explained because 10%-40% of patients with Crohn’s disease have an inadequate response to anti-TNF therapy, yet early detection of treatment failure remains challenging.

According to the investigators, C-reactive protein (CRP) may serve as a reliable biomarker for acute inflammation, but intestinal tissue remodeling in Crohn’s disease is largely caused by chronic inflammation, which is driven by proteases. As these proteases degrade intestinal tissue, protein fragments called neo-epitopes are released into circulation, offering a potential biomarker of disease activity. Previous research showed that VICM, a neo-epitope that correlates with macrophage activity, was highly associated with Crohn’s disease.

“Because anti-TNF reduces the number of activated macrophages, we hypothesized that changes in VICM levels can be applied to monitor the outcome of early response to anti-TNF treatment in Crohn’s disease,” the investigators wrote.

To test this hypothesis, the investigators retrospectively analyzed clinical data and serum samples from 42 patients with Crohn’s disease, of whom 21 were treated with adalimumab at University Medical Center Groningen (the Netherlands) and 21 were treated with infliximab at Aarhus (Denmark) University Hospital. In both cohorts, disease activity was measured by the Harvey-Bradshaw Index, with responders defined by a score of less than 5, which indicates clinical remission. Harvey-Bradshaw Index scores were evaluated at week 8 and week 14 for the adalimumab and infliximab groups, respectively. In the adalimumab group, serum VICM and CRP levels were evaluated at baseline, then at weeks 1 and 8. In the infliximab group, VICM and CRP were measured at baseline, then at weeks 2, 6, and 14.

Patients responding to adalimumab had significantly lower levels of VICM than did nonresponders at week 1 (P = .007) and week 8 (P = .048). Although infliximab responders showed numerical differences in VICM, compared with nonresponders, at week 2 (P = .48), these differences lacked statistical significance until week 6 (P = .046), then lost significance again at week 14 (P = .23). No significant differences in CRP levels between responders and nonresponders were detected at any timepoints.

Using a receiver operating characteristic–curve analysis, the investigators identified a clinically relevant cutoff value for VICM at 12.5 ng/mL. With this cutoff, responders were identifiable as early as week 6 in the infliximab group with an area under the curve (AUC) of 0.89 (specificity, 75%; sensitivity, 88%; P less than .01). In the adalimumab group, responders were identifiable as early as week 1, with an AUC of 0.91 (specificity, 87%; sensitivity, 100%; P less than .01).

In the infliximab group, patients with a serum VICM level less than 12.5 ng/mL at week 6 were 22.5 times more likely to be responders (odds ratio, 22.5). Patients treated with adalimumab were 42 times more likely to be responders if their VICM level fell below the cutoff at week 1. A similar analysis involving CRP had no predictive value.

“In conclusion, the reduction in VICM serum levels, but not reduction in CRP levels, was associated with early response to [anti–TNF-alpha] treatment in patients with Crohn’s disease,” the investigators concluded. “Thus, VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients.”

The study was funded by the Danish Research Foundation. The investigators disclosed additional relationships with Nordic Bioscience.

SOURCE: Mortensen JH et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001341.

Help your patients understand their Crohn’s disease treatment options by sharing AGA patient education content at https://www.gastro.org/practice-guidance/gi-patient-center/topic/crohn-s-disease.  

A novel biomarker may predict early responses to anti–tumor necrosis factor (TNF) therapy in patients with Crohn’s disease, according to investigators.

After 1 week of therapy with adalimumab, serum levels of citrullinated and matrix metalloproteinase-degraded vimentin (VICM) predicted early responses to treatment with an odds ratio of 42.5, reported lead author Joachim H. Mortensen, PhD, of Nordic Bioscience, Herlev, Denmark, and colleagues.

“VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients,” the investigators wrote in the Journal of Clinical Gastroenterology.This is an area of particular need, the investigators explained because 10%-40% of patients with Crohn’s disease have an inadequate response to anti-TNF therapy, yet early detection of treatment failure remains challenging.

According to the investigators, C-reactive protein (CRP) may serve as a reliable biomarker for acute inflammation, but intestinal tissue remodeling in Crohn’s disease is largely caused by chronic inflammation, which is driven by proteases. As these proteases degrade intestinal tissue, protein fragments called neo-epitopes are released into circulation, offering a potential biomarker of disease activity. Previous research showed that VICM, a neo-epitope that correlates with macrophage activity, was highly associated with Crohn’s disease.

“Because anti-TNF reduces the number of activated macrophages, we hypothesized that changes in VICM levels can be applied to monitor the outcome of early response to anti-TNF treatment in Crohn’s disease,” the investigators wrote.

To test this hypothesis, the investigators retrospectively analyzed clinical data and serum samples from 42 patients with Crohn’s disease, of whom 21 were treated with adalimumab at University Medical Center Groningen (the Netherlands) and 21 were treated with infliximab at Aarhus (Denmark) University Hospital. In both cohorts, disease activity was measured by the Harvey-Bradshaw Index, with responders defined by a score of less than 5, which indicates clinical remission. Harvey-Bradshaw Index scores were evaluated at week 8 and week 14 for the adalimumab and infliximab groups, respectively. In the adalimumab group, serum VICM and CRP levels were evaluated at baseline, then at weeks 1 and 8. In the infliximab group, VICM and CRP were measured at baseline, then at weeks 2, 6, and 14.

Patients responding to adalimumab had significantly lower levels of VICM than did nonresponders at week 1 (P = .007) and week 8 (P = .048). Although infliximab responders showed numerical differences in VICM, compared with nonresponders, at week 2 (P = .48), these differences lacked statistical significance until week 6 (P = .046), then lost significance again at week 14 (P = .23). No significant differences in CRP levels between responders and nonresponders were detected at any timepoints.

Using a receiver operating characteristic–curve analysis, the investigators identified a clinically relevant cutoff value for VICM at 12.5 ng/mL. With this cutoff, responders were identifiable as early as week 6 in the infliximab group with an area under the curve (AUC) of 0.89 (specificity, 75%; sensitivity, 88%; P less than .01). In the adalimumab group, responders were identifiable as early as week 1, with an AUC of 0.91 (specificity, 87%; sensitivity, 100%; P less than .01).

In the infliximab group, patients with a serum VICM level less than 12.5 ng/mL at week 6 were 22.5 times more likely to be responders (odds ratio, 22.5). Patients treated with adalimumab were 42 times more likely to be responders if their VICM level fell below the cutoff at week 1. A similar analysis involving CRP had no predictive value.

“In conclusion, the reduction in VICM serum levels, but not reduction in CRP levels, was associated with early response to [anti–TNF-alpha] treatment in patients with Crohn’s disease,” the investigators concluded. “Thus, VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients.”

The study was funded by the Danish Research Foundation. The investigators disclosed additional relationships with Nordic Bioscience.

SOURCE: Mortensen JH et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001341.

Help your patients understand their Crohn’s disease treatment options by sharing AGA patient education content at https://www.gastro.org/practice-guidance/gi-patient-center/topic/crohn-s-disease.  

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.

From 2006 to 2015, suicide attempts in the United States became more common and more lethal in certain subgroups of the population, new data from the Centers for Disease Control and Prevention show.

Investigators found the incidence of suicidal acts increased in females, adolescents, and older adults aged 65-74 years, whereas suicidal acts became more lethal in both sexes and in those between the ages of 20 and 64 years.

“Effective suicide prevention efforts must be informed by an understanding of whether increased suicide rates are associated with more suicidal acts, greater lethality of suicidal acts, or a combination of both,” wrote Jing Wang, MD, MPH, and colleagues at the CDC’s National Center for Injury Prevention and Control.

The study was published online April 22 in JAMA Psychiatry.

Prior U.S. studies show a greater incidence of suicide attempts among some adult subgroups and young people, as well as changing patterns in suicide methods over time.

Between 2000 and 2010, for example, the rate of suicide by suffocation jumped 52% compared with a 19% increase in suicide by poisoning and a 3% increase in firearm-related suicides.

However, until now, there’s been no research examining the trends in both incidence and lethality of suicidal acts.

Dr. Wang and colleagues analyzed data on more than 1.2 million suicidal acts (suicides and nonfatal suicide attempts) from 2006 to 2015 among people aged 10-74 years.

Medically treated nonfatal suicide attempts were identified via the Nationwide Inpatient Sample and Nationwide Emergency Department Sample databases, and suicide deaths were identified via the National Vital Statistics System.

The incidence rate of total suicidal acts rose 10% during the study period (annual percentage change [APC] 0.8%; 95% confidence interval [CI], 0.3%-1.3%). The case fatality rate (CFR) increased 13% (APC, 2.3%; 95% CI, 1.3%-3.3%).

In subgroup analyses, the incidence rate of suicidal acts increased 1.1% (95% CI, 0.6%-1.6%) per year for women but held stable for men. The CFR increased for women and men, with APCs of 5% (95% CI, 3.1%-6.9%) since 2010 for women and 1.6% (95% CI, 0.6%-2.5%) since 2009 for men.

The data show an increase in incidence rate of suicidal acts among adults aged 65-74 years throughout the study period, and among adolescents from 2011 to 2015. The CFR increased since 2009 among those aged 20-44 years (APC, 3.7%; 95% CI, 2.5%-5.0%) and since 2012 for individuals 45-64 years (APC, 2.7%; 95% CI, 0%-5.4%).

Among males and females aged 20-64 years, suicidal acts involving guns and suffocation (methods of greater lethality) increased, but suicidal acts by poisoning (a method of lesser lethality) decreased or flattened, “which may explain the observed increases in lethality,” the CDC researchers said.

“Adolescents and older adults aged 65-74 years experienced general increases in suicide attempts by all means, including poisoning, which was associated with stable or declining lethality for these subgroups,” they reported.

Dr. Wang and colleagues said their findings on population-level epidemiologic patterns may help with efforts to develop comprehensive suicide prevention strategies.

In particular, they said, reducing access to lethal means of suicide among those at risk, “which include not only firearms but also medications and other potentially dangerous household products, may be a helpful approach for reducing suicide rates.

“Ultimately, upstream prevention approaches, including teaching coping and problem-solving skills early in life, promoting connectedness, and developing and implementing policies that strengthen economic supports, may mitigate the risk of suicidal behavior for all age groups,” they concluded.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

From 2006 to 2015, suicide attempts in the United States became more common and more lethal in certain subgroups of the population, new data from the Centers for Disease Control and Prevention show.

Investigators found the incidence of suicidal acts increased in females, adolescents, and older adults aged 65-74 years, whereas suicidal acts became more lethal in both sexes and in those between the ages of 20 and 64 years.

“Effective suicide prevention efforts must be informed by an understanding of whether increased suicide rates are associated with more suicidal acts, greater lethality of suicidal acts, or a combination of both,” wrote Jing Wang, MD, MPH, and colleagues at the CDC’s National Center for Injury Prevention and Control.

The study was published online April 22 in JAMA Psychiatry.

Prior U.S. studies show a greater incidence of suicide attempts among some adult subgroups and young people, as well as changing patterns in suicide methods over time.

Between 2000 and 2010, for example, the rate of suicide by suffocation jumped 52% compared with a 19% increase in suicide by poisoning and a 3% increase in firearm-related suicides.

However, until now, there’s been no research examining the trends in both incidence and lethality of suicidal acts.

Dr. Wang and colleagues analyzed data on more than 1.2 million suicidal acts (suicides and nonfatal suicide attempts) from 2006 to 2015 among people aged 10-74 years.

Medically treated nonfatal suicide attempts were identified via the Nationwide Inpatient Sample and Nationwide Emergency Department Sample databases, and suicide deaths were identified via the National Vital Statistics System.

The incidence rate of total suicidal acts rose 10% during the study period (annual percentage change [APC] 0.8%; 95% confidence interval [CI], 0.3%-1.3%). The case fatality rate (CFR) increased 13% (APC, 2.3%; 95% CI, 1.3%-3.3%).

In subgroup analyses, the incidence rate of suicidal acts increased 1.1% (95% CI, 0.6%-1.6%) per year for women but held stable for men. The CFR increased for women and men, with APCs of 5% (95% CI, 3.1%-6.9%) since 2010 for women and 1.6% (95% CI, 0.6%-2.5%) since 2009 for men.

The data show an increase in incidence rate of suicidal acts among adults aged 65-74 years throughout the study period, and among adolescents from 2011 to 2015. The CFR increased since 2009 among those aged 20-44 years (APC, 3.7%; 95% CI, 2.5%-5.0%) and since 2012 for individuals 45-64 years (APC, 2.7%; 95% CI, 0%-5.4%).

Among males and females aged 20-64 years, suicidal acts involving guns and suffocation (methods of greater lethality) increased, but suicidal acts by poisoning (a method of lesser lethality) decreased or flattened, “which may explain the observed increases in lethality,” the CDC researchers said.

“Adolescents and older adults aged 65-74 years experienced general increases in suicide attempts by all means, including poisoning, which was associated with stable or declining lethality for these subgroups,” they reported.

Dr. Wang and colleagues said their findings on population-level epidemiologic patterns may help with efforts to develop comprehensive suicide prevention strategies.

In particular, they said, reducing access to lethal means of suicide among those at risk, “which include not only firearms but also medications and other potentially dangerous household products, may be a helpful approach for reducing suicide rates.

“Ultimately, upstream prevention approaches, including teaching coping and problem-solving skills early in life, promoting connectedness, and developing and implementing policies that strengthen economic supports, may mitigate the risk of suicidal behavior for all age groups,” they concluded.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

From 2006 to 2015, suicide attempts in the United States became more common and more lethal in certain subgroups of the population, new data from the Centers for Disease Control and Prevention show.

Investigators found the incidence of suicidal acts increased in females, adolescents, and older adults aged 65-74 years, whereas suicidal acts became more lethal in both sexes and in those between the ages of 20 and 64 years.

“Effective suicide prevention efforts must be informed by an understanding of whether increased suicide rates are associated with more suicidal acts, greater lethality of suicidal acts, or a combination of both,” wrote Jing Wang, MD, MPH, and colleagues at the CDC’s National Center for Injury Prevention and Control.

The study was published online April 22 in JAMA Psychiatry.

Prior U.S. studies show a greater incidence of suicide attempts among some adult subgroups and young people, as well as changing patterns in suicide methods over time.

Between 2000 and 2010, for example, the rate of suicide by suffocation jumped 52% compared with a 19% increase in suicide by poisoning and a 3% increase in firearm-related suicides.

However, until now, there’s been no research examining the trends in both incidence and lethality of suicidal acts.

Dr. Wang and colleagues analyzed data on more than 1.2 million suicidal acts (suicides and nonfatal suicide attempts) from 2006 to 2015 among people aged 10-74 years.

Medically treated nonfatal suicide attempts were identified via the Nationwide Inpatient Sample and Nationwide Emergency Department Sample databases, and suicide deaths were identified via the National Vital Statistics System.

The incidence rate of total suicidal acts rose 10% during the study period (annual percentage change [APC] 0.8%; 95% confidence interval [CI], 0.3%-1.3%). The case fatality rate (CFR) increased 13% (APC, 2.3%; 95% CI, 1.3%-3.3%).

In subgroup analyses, the incidence rate of suicidal acts increased 1.1% (95% CI, 0.6%-1.6%) per year for women but held stable for men. The CFR increased for women and men, with APCs of 5% (95% CI, 3.1%-6.9%) since 2010 for women and 1.6% (95% CI, 0.6%-2.5%) since 2009 for men.

The data show an increase in incidence rate of suicidal acts among adults aged 65-74 years throughout the study period, and among adolescents from 2011 to 2015. The CFR increased since 2009 among those aged 20-44 years (APC, 3.7%; 95% CI, 2.5%-5.0%) and since 2012 for individuals 45-64 years (APC, 2.7%; 95% CI, 0%-5.4%).

Among males and females aged 20-64 years, suicidal acts involving guns and suffocation (methods of greater lethality) increased, but suicidal acts by poisoning (a method of lesser lethality) decreased or flattened, “which may explain the observed increases in lethality,” the CDC researchers said.

“Adolescents and older adults aged 65-74 years experienced general increases in suicide attempts by all means, including poisoning, which was associated with stable or declining lethality for these subgroups,” they reported.

Dr. Wang and colleagues said their findings on population-level epidemiologic patterns may help with efforts to develop comprehensive suicide prevention strategies.

In particular, they said, reducing access to lethal means of suicide among those at risk, “which include not only firearms but also medications and other potentially dangerous household products, may be a helpful approach for reducing suicide rates.

“Ultimately, upstream prevention approaches, including teaching coping and problem-solving skills early in life, promoting connectedness, and developing and implementing policies that strengthen economic supports, may mitigate the risk of suicidal behavior for all age groups,” they concluded.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

Worldwide cases of neonatal tetanus fell by 90% from 2000 to 2018, deaths dropped by 85%, and 45 countries achieved elimination of maternal and neonatal tetanus (MNT), according to the Centers for Disease Control and Prevention.

[email protected]

SOURCE: Njuguna HN et al. MMWR. 2020 May 1;69(17):515-20.

Worldwide cases of neonatal tetanus fell by 90% from 2000 to 2018, deaths dropped by 85%, and 45 countries achieved elimination of maternal and neonatal tetanus (MNT), according to the Centers for Disease Control and Prevention.

[email protected]

SOURCE: Njuguna HN et al. MMWR. 2020 May 1;69(17):515-20.

Worldwide cases of neonatal tetanus fell by 90% from 2000 to 2018, deaths dropped by 85%, and 45 countries achieved elimination of maternal and neonatal tetanus (MNT), according to the Centers for Disease Control and Prevention.

[email protected]

SOURCE: Njuguna HN et al. MMWR. 2020 May 1;69(17):515-20.

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.