Social isolation is associated with an increased risk of a cardiovascular event of more than 40%, and of all-cause mortality approaching 50%, new research suggests. “These results are especially important in the current times of social isolation during the coronavirus crisis,” Janine Gronewold, PhD, University Hospital in Essen, Germany, told a press briefing.

The mechanism by which social isolation may boost risk for stroke, MI, or death is not clear, but other research has shown that loneliness or lack of contact with close friends and family can affect physical health, said Dr. Gronewold.

The findings were presented at the sixth Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual/online meeting because of the COVID-19 pandemic.

For this new study, researchers analyzed data from 4,139 participants, ranging in age from 45 to 75 years (mean 59.1 years), who were recruited into the large community-based Heinz Nixdorf Recall study. The randomly selected study group was representative of an industrial rural area of Germany, said Dr. Gronewold.

Study participants entered the study with no known cardiovascular disease and were followed for a mean of 13.4 years.
 

Social supports

Investigators collected information on three types of social support: instrumental (getting help with everyday activities such as buying food), emotional (provided with comfort), and financial (receiving monetary assistance when needed). They also looked at social integration (or social isolation) using an index with scores for marital status, number of contacts with family and friends, and membership in political, religious, community, sports, or professional associations.

Of the total, 501 participants reported a lack of instrumental support, 659 a lack of emotional support, and 907 a lack of financial support. A total of 309 lacked social integration, defined by the lowest level on the social integration index.

Participants were asked annually about new cardiovascular events, including stroke and MI. Over the follow-up period, there were 339 such events and 530 deaths.

After adjustment for age, sex, and social support, the analysis showed that social isolation was significantly associated with an increased risk of cardiovascular events (hazard ratio, 1.44; 95% confidence interval, 0.97-2.14) and all-cause mortality (HR, 1.47; 95% CI, 1.09-1.97).

The new research also showed that lack of financial support was significantly associated with increased risk for a cardiovascular event (HR, 1.30; 95% CI, 1.01-1.67).
 

Direct effect

Additional models that also adjusted for cardiovascular risk factors, health behaviors, depression, and socioeconomic factors, did not significantly change effect estimates.

“Social relationships protect us from cardiovascular events and mortality, not only via good mood, healthy behavior, and lower cardiovascular risk profile,” Dr. Gronewold said. “They seem to have a direct effect on these outcomes.”

Having strong social relationships is as important to cardiovascular health as classic protective factors such as controlling blood pressure and cholesterol levels, and maintaining a normal weight, said Dr. Gronewold.

The new results are worrying and are particularly important during the current COVID-19 pandemic, as social contact has been restricted in many areas, said Dr. Gronewold.

It is not yet clear why people who are socially isolated have such poor health outcomes, she added.

Dr. Gronewold has reported no relevant financial relationships.

This article first appeared on Medscape.com.

Social isolation is associated with an increased risk of a cardiovascular event of more than 40%, and of all-cause mortality approaching 50%, new research suggests. “These results are especially important in the current times of social isolation during the coronavirus crisis,” Janine Gronewold, PhD, University Hospital in Essen, Germany, told a press briefing.

The mechanism by which social isolation may boost risk for stroke, MI, or death is not clear, but other research has shown that loneliness or lack of contact with close friends and family can affect physical health, said Dr. Gronewold.

The findings were presented at the sixth Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual/online meeting because of the COVID-19 pandemic.

For this new study, researchers analyzed data from 4,139 participants, ranging in age from 45 to 75 years (mean 59.1 years), who were recruited into the large community-based Heinz Nixdorf Recall study. The randomly selected study group was representative of an industrial rural area of Germany, said Dr. Gronewold.

Study participants entered the study with no known cardiovascular disease and were followed for a mean of 13.4 years.
 

Social supports

Investigators collected information on three types of social support: instrumental (getting help with everyday activities such as buying food), emotional (provided with comfort), and financial (receiving monetary assistance when needed). They also looked at social integration (or social isolation) using an index with scores for marital status, number of contacts with family and friends, and membership in political, religious, community, sports, or professional associations.

Of the total, 501 participants reported a lack of instrumental support, 659 a lack of emotional support, and 907 a lack of financial support. A total of 309 lacked social integration, defined by the lowest level on the social integration index.

Participants were asked annually about new cardiovascular events, including stroke and MI. Over the follow-up period, there were 339 such events and 530 deaths.

After adjustment for age, sex, and social support, the analysis showed that social isolation was significantly associated with an increased risk of cardiovascular events (hazard ratio, 1.44; 95% confidence interval, 0.97-2.14) and all-cause mortality (HR, 1.47; 95% CI, 1.09-1.97).

The new research also showed that lack of financial support was significantly associated with increased risk for a cardiovascular event (HR, 1.30; 95% CI, 1.01-1.67).
 

Direct effect

Additional models that also adjusted for cardiovascular risk factors, health behaviors, depression, and socioeconomic factors, did not significantly change effect estimates.

“Social relationships protect us from cardiovascular events and mortality, not only via good mood, healthy behavior, and lower cardiovascular risk profile,” Dr. Gronewold said. “They seem to have a direct effect on these outcomes.”

Having strong social relationships is as important to cardiovascular health as classic protective factors such as controlling blood pressure and cholesterol levels, and maintaining a normal weight, said Dr. Gronewold.

The new results are worrying and are particularly important during the current COVID-19 pandemic, as social contact has been restricted in many areas, said Dr. Gronewold.

It is not yet clear why people who are socially isolated have such poor health outcomes, she added.

Dr. Gronewold has reported no relevant financial relationships.

This article first appeared on Medscape.com.

Social isolation is associated with an increased risk of a cardiovascular event of more than 40%, and of all-cause mortality approaching 50%, new research suggests. “These results are especially important in the current times of social isolation during the coronavirus crisis,” Janine Gronewold, PhD, University Hospital in Essen, Germany, told a press briefing.

The mechanism by which social isolation may boost risk for stroke, MI, or death is not clear, but other research has shown that loneliness or lack of contact with close friends and family can affect physical health, said Dr. Gronewold.

The findings were presented at the sixth Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual/online meeting because of the COVID-19 pandemic.

For this new study, researchers analyzed data from 4,139 participants, ranging in age from 45 to 75 years (mean 59.1 years), who were recruited into the large community-based Heinz Nixdorf Recall study. The randomly selected study group was representative of an industrial rural area of Germany, said Dr. Gronewold.

Study participants entered the study with no known cardiovascular disease and were followed for a mean of 13.4 years.
 

Social supports

Investigators collected information on three types of social support: instrumental (getting help with everyday activities such as buying food), emotional (provided with comfort), and financial (receiving monetary assistance when needed). They also looked at social integration (or social isolation) using an index with scores for marital status, number of contacts with family and friends, and membership in political, religious, community, sports, or professional associations.

Of the total, 501 participants reported a lack of instrumental support, 659 a lack of emotional support, and 907 a lack of financial support. A total of 309 lacked social integration, defined by the lowest level on the social integration index.

Participants were asked annually about new cardiovascular events, including stroke and MI. Over the follow-up period, there were 339 such events and 530 deaths.

After adjustment for age, sex, and social support, the analysis showed that social isolation was significantly associated with an increased risk of cardiovascular events (hazard ratio, 1.44; 95% confidence interval, 0.97-2.14) and all-cause mortality (HR, 1.47; 95% CI, 1.09-1.97).

The new research also showed that lack of financial support was significantly associated with increased risk for a cardiovascular event (HR, 1.30; 95% CI, 1.01-1.67).
 

Direct effect

Additional models that also adjusted for cardiovascular risk factors, health behaviors, depression, and socioeconomic factors, did not significantly change effect estimates.

“Social relationships protect us from cardiovascular events and mortality, not only via good mood, healthy behavior, and lower cardiovascular risk profile,” Dr. Gronewold said. “They seem to have a direct effect on these outcomes.”

Having strong social relationships is as important to cardiovascular health as classic protective factors such as controlling blood pressure and cholesterol levels, and maintaining a normal weight, said Dr. Gronewold.

The new results are worrying and are particularly important during the current COVID-19 pandemic, as social contact has been restricted in many areas, said Dr. Gronewold.

It is not yet clear why people who are socially isolated have such poor health outcomes, she added.

Dr. Gronewold has reported no relevant financial relationships.

This article first appeared on Medscape.com.

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

As an addiction psychiatrist specializing in the use of ketamine-assisted psychotherapy, both in patients with mood disorders and substance use disorders, I would like to offer some perspective about limits and possibilities of ketamine and esketamine.

Single infusions of ketamine targeting unipolar mood symptoms indeed yield initial 24-hour response rates of about 60%-70%, though those rates fall precipitously with time.¹ Where single treatments fall short in terms of durability of benefit, a series of multiple treatments – modeled around electroconvulsive therapy and pending a noninferiority study to compare the two² – provide for more robust and durable results.³

Esketamine nasal spray, recently approved by the Food and Drug Administration for treatment-resistant major depressive disorder, consists of one of the component stereoisomers of ketamine and is administered at first twice weekly and then less frequently with time. It now, like off-label ketamine,⁴ sees clinical use as monotherapy for MDD, as an alternative for patients who have intolerance or lack of response to first-line treatments such as SSRIs.

Ketamine, while perhaps less directly validated and more stigmatized for psychiatric use, recently has been demonstrated in a rigorous trial as noninferior in terms of antidepressant benefit at 24 hours,⁵ and a multitude of published case studies document maintenance of benefit with repeat doses over a period of months.⁶ Ketamine notably enjoys several advantages over esketamine as a treatment option: a cost one to two orders of magnitude lower⁷ (esketamine nasal spray sees a wholesale price of $600-$900 per dose), greater versatility in dose, and lack of a restrictive REMS program.⁸ The $1-$2 cost of a dose of ketamine means that the clinical barrier of prior authorizations is largely a nonissue and may in and of itself vastly improve access to this novel and efficacious treatment.

My clinical experience involves providing ketamine as an intramuscular bolus along with contemporaneous psychotherapy; such combination of medication and psychotherapy intervention may be more effective than ketamine alone⁹ and has seen impressive initial results in the treatment of alcohol use disorder, termed ketamine psychedelic therapy.¹⁰ I can affirm these hopeful initial findings in the treatment of both mood and substance use disorders, and have observed maintained response from mood symptoms for a period of 1-4 years in several patients, with such sessions provided approximately monthly.¹¹

I hope these preliminary data inform more rigorous study of long-term ketamine as a treatment for psychiatric indications.

Dr. Ryan is a board-certified psychiatrist and addiction psychiatrist who practices in Los Angeles. He has written several articles and a book chapter on ketamine. Dr. Ryan has no disclosures.

References

1. Murrough JW et al. Am J Psychiatry. 2013;170(10):1134-42.

2. Mathew SJ et al. Contemp Clin Trials. 2019;77:19-26.

3. Singh JB et al. Am J Psychiatry. 2016;173(8):816-26.

4. Calabrese L. Int J Psychiatr Res. 2019; 2(5):1-12.

5. Correia-Melo FS et al. J Affect Disord. 2020;264:527-34.

6. Ryan WC, Marta CJ, Koek RJ. Ketamine and depression, in “The Ketamine Papers: Science, Therapy, and Transformation.” Santa Cruz, Calif.: Multidisciplinary Association for Psychedelic Studies, 2016.

7. Institute for Clinical and Economic Review. “Esketamine for the Treatment of Treatment-Resistant Depression: Effectiveness and Value.” Final report. 2019 Jun 20.

8. Spravato package insert. Titusville, N.J.: Janssen Pharmaceuticals.

9. Dore J et al. J Psychoactive Drugs. 2019;51(2):189-98.

10. Krupitsky EM and Grinenko AY. J Psychoactive Drugs. 1997;29(2):165-83.

11. Ryan WC. Ketamine-assisted psychotherapy: Theory and chart review. KRIYA Ketamine Research Institute Conference. Hillsborough, Calif. 2019. Nov 9.

As an addiction psychiatrist specializing in the use of ketamine-assisted psychotherapy, both in patients with mood disorders and substance use disorders, I would like to offer some perspective about limits and possibilities of ketamine and esketamine.

Single infusions of ketamine targeting unipolar mood symptoms indeed yield initial 24-hour response rates of about 60%-70%, though those rates fall precipitously with time.¹ Where single treatments fall short in terms of durability of benefit, a series of multiple treatments – modeled around electroconvulsive therapy and pending a noninferiority study to compare the two² – provide for more robust and durable results.³

Esketamine nasal spray, recently approved by the Food and Drug Administration for treatment-resistant major depressive disorder, consists of one of the component stereoisomers of ketamine and is administered at first twice weekly and then less frequently with time. It now, like off-label ketamine,⁴ sees clinical use as monotherapy for MDD, as an alternative for patients who have intolerance or lack of response to first-line treatments such as SSRIs.

Ketamine, while perhaps less directly validated and more stigmatized for psychiatric use, recently has been demonstrated in a rigorous trial as noninferior in terms of antidepressant benefit at 24 hours,⁵ and a multitude of published case studies document maintenance of benefit with repeat doses over a period of months.⁶ Ketamine notably enjoys several advantages over esketamine as a treatment option: a cost one to two orders of magnitude lower⁷ (esketamine nasal spray sees a wholesale price of $600-$900 per dose), greater versatility in dose, and lack of a restrictive REMS program.⁸ The $1-$2 cost of a dose of ketamine means that the clinical barrier of prior authorizations is largely a nonissue and may in and of itself vastly improve access to this novel and efficacious treatment.

My clinical experience involves providing ketamine as an intramuscular bolus along with contemporaneous psychotherapy; such combination of medication and psychotherapy intervention may be more effective than ketamine alone⁹ and has seen impressive initial results in the treatment of alcohol use disorder, termed ketamine psychedelic therapy.¹⁰ I can affirm these hopeful initial findings in the treatment of both mood and substance use disorders, and have observed maintained response from mood symptoms for a period of 1-4 years in several patients, with such sessions provided approximately monthly.¹¹

I hope these preliminary data inform more rigorous study of long-term ketamine as a treatment for psychiatric indications.

Dr. Ryan is a board-certified psychiatrist and addiction psychiatrist who practices in Los Angeles. He has written several articles and a book chapter on ketamine. Dr. Ryan has no disclosures.

References

1. Murrough JW et al. Am J Psychiatry. 2013;170(10):1134-42.

2. Mathew SJ et al. Contemp Clin Trials. 2019;77:19-26.

3. Singh JB et al. Am J Psychiatry. 2016;173(8):816-26.

4. Calabrese L. Int J Psychiatr Res. 2019; 2(5):1-12.

5. Correia-Melo FS et al. J Affect Disord. 2020;264:527-34.

6. Ryan WC, Marta CJ, Koek RJ. Ketamine and depression, in “The Ketamine Papers: Science, Therapy, and Transformation.” Santa Cruz, Calif.: Multidisciplinary Association for Psychedelic Studies, 2016.

7. Institute for Clinical and Economic Review. “Esketamine for the Treatment of Treatment-Resistant Depression: Effectiveness and Value.” Final report. 2019 Jun 20.

8. Spravato package insert. Titusville, N.J.: Janssen Pharmaceuticals.

9. Dore J et al. J Psychoactive Drugs. 2019;51(2):189-98.

10. Krupitsky EM and Grinenko AY. J Psychoactive Drugs. 1997;29(2):165-83.

11. Ryan WC. Ketamine-assisted psychotherapy: Theory and chart review. KRIYA Ketamine Research Institute Conference. Hillsborough, Calif. 2019. Nov 9.

As an addiction psychiatrist specializing in the use of ketamine-assisted psychotherapy, both in patients with mood disorders and substance use disorders, I would like to offer some perspective about limits and possibilities of ketamine and esketamine.

Single infusions of ketamine targeting unipolar mood symptoms indeed yield initial 24-hour response rates of about 60%-70%, though those rates fall precipitously with time.¹ Where single treatments fall short in terms of durability of benefit, a series of multiple treatments – modeled around electroconvulsive therapy and pending a noninferiority study to compare the two² – provide for more robust and durable results.³

Esketamine nasal spray, recently approved by the Food and Drug Administration for treatment-resistant major depressive disorder, consists of one of the component stereoisomers of ketamine and is administered at first twice weekly and then less frequently with time. It now, like off-label ketamine,⁴ sees clinical use as monotherapy for MDD, as an alternative for patients who have intolerance or lack of response to first-line treatments such as SSRIs.

Ketamine, while perhaps less directly validated and more stigmatized for psychiatric use, recently has been demonstrated in a rigorous trial as noninferior in terms of antidepressant benefit at 24 hours,⁵ and a multitude of published case studies document maintenance of benefit with repeat doses over a period of months.⁶ Ketamine notably enjoys several advantages over esketamine as a treatment option: a cost one to two orders of magnitude lower⁷ (esketamine nasal spray sees a wholesale price of $600-$900 per dose), greater versatility in dose, and lack of a restrictive REMS program.⁸ The $1-$2 cost of a dose of ketamine means that the clinical barrier of prior authorizations is largely a nonissue and may in and of itself vastly improve access to this novel and efficacious treatment.

My clinical experience involves providing ketamine as an intramuscular bolus along with contemporaneous psychotherapy; such combination of medication and psychotherapy intervention may be more effective than ketamine alone⁹ and has seen impressive initial results in the treatment of alcohol use disorder, termed ketamine psychedelic therapy.¹⁰ I can affirm these hopeful initial findings in the treatment of both mood and substance use disorders, and have observed maintained response from mood symptoms for a period of 1-4 years in several patients, with such sessions provided approximately monthly.¹¹

I hope these preliminary data inform more rigorous study of long-term ketamine as a treatment for psychiatric indications.

Dr. Ryan is a board-certified psychiatrist and addiction psychiatrist who practices in Los Angeles. He has written several articles and a book chapter on ketamine. Dr. Ryan has no disclosures.

References

1. Murrough JW et al. Am J Psychiatry. 2013;170(10):1134-42.

2. Mathew SJ et al. Contemp Clin Trials. 2019;77:19-26.

3. Singh JB et al. Am J Psychiatry. 2016;173(8):816-26.

4. Calabrese L. Int J Psychiatr Res. 2019; 2(5):1-12.

5. Correia-Melo FS et al. J Affect Disord. 2020;264:527-34.

6. Ryan WC, Marta CJ, Koek RJ. Ketamine and depression, in “The Ketamine Papers: Science, Therapy, and Transformation.” Santa Cruz, Calif.: Multidisciplinary Association for Psychedelic Studies, 2016.

7. Institute for Clinical and Economic Review. “Esketamine for the Treatment of Treatment-Resistant Depression: Effectiveness and Value.” Final report. 2019 Jun 20.

8. Spravato package insert. Titusville, N.J.: Janssen Pharmaceuticals.

9. Dore J et al. J Psychoactive Drugs. 2019;51(2):189-98.

10. Krupitsky EM and Grinenko AY. J Psychoactive Drugs. 1997;29(2):165-83.

11. Ryan WC. Ketamine-assisted psychotherapy: Theory and chart review. KRIYA Ketamine Research Institute Conference. Hillsborough, Calif. 2019. Nov 9.

According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”

Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m² (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.

Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.

“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”

They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”

Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”

The researchers and Dr. Goldberg reported having no disclosures.

dbrunk@mdedge.com

SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.

According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”

Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m² (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.

Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.

“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”

They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”

Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”

The researchers and Dr. Goldberg reported having no disclosures.

dbrunk@mdedge.com

SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.

According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”

Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m² (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.

Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.

“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”

They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”

Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”

The researchers and Dr. Goldberg reported having no disclosures.

dbrunk@mdedge.com

SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.

Here are the stories our MDedge editors across specialties think you need to know about today:

Remdesivir trial data published

Weeks after topline remdesivir data appeared in the press, investigators published their full experience using the drug to treat COVID-19 patients. The study, published in the New England Journal of Medicine, showed the drug reduced recovery time from 15 to 11 days, compared with placebo. Patients receiving oxygen seemed to fare best from treatment with remdesivir. “There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.” READ MORE.

FDA approves contraceptive gel

The Food and Drug Administration approved Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel to prevent pregnancy in women of reproductive potential. It’s the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5. READ MORE.

COVID-19 lessons from one cancer center

Physicians at Levine Cancer Institute in Charlotte, N.C., largely have been able to keep hematologic oncology patients on their treatment regimens and continue to care for inpatients during the early months of the COVID-19 pandemic. How have they kept the situation managable? Strict infection control, liberal testing, and a proactive plan to defer and temporarily replace infusion care when medically appropriate were all part of the strategy. “My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious, even before the coronavirus, using distancing, masking, and meticulous hand hygiene,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in Levine Cancer Institute’s Department of Hematologic Oncology and Blood Disorders. READ MORE.

Convalescent plasma: Hope or hype?

There are currently more than two dozen trials of convalescent plasma in the United States and elsewhere but most are single-arm trials to determine if one infusion can decrease the need for intubation or help patients on a ventilator to improve. Others researchers are investigating whether convalescent plasma might be used before severe disease sets in. Meanwhile, about 2,200 hospitals are participating in an expanded access program being led by the Mayo Clinic nationwide. The National Institutes of Health recently said that “there are insufficient clinical data to recommend either for or against” its use for COVID-19. READ MORE.

New rosacea treatment guidelines

Patients with rosacea should receive treatments based on their phenotype and specific symptoms, rather than being assigned into distinct subtype categories, according to updated guidance published in the Journal of the American Academy of Dermatology. The update comes from the National Rosacea Society Expert Committee and is based on a review of the evidence. Patients “shouldn’t be classified as having a certain subtype of rosacea” since “many patients have features that overlap more than one subtype,” said Diane Thiboutot, MD, lead author of the update and a professor of dermatology and associate dean of clinical and translational research education at Penn State University, Hershey. READ MORE.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Remdesivir trial data published

Weeks after topline remdesivir data appeared in the press, investigators published their full experience using the drug to treat COVID-19 patients. The study, published in the New England Journal of Medicine, showed the drug reduced recovery time from 15 to 11 days, compared with placebo. Patients receiving oxygen seemed to fare best from treatment with remdesivir. “There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.” READ MORE.

FDA approves contraceptive gel

The Food and Drug Administration approved Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel to prevent pregnancy in women of reproductive potential. It’s the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5. READ MORE.

COVID-19 lessons from one cancer center

Physicians at Levine Cancer Institute in Charlotte, N.C., largely have been able to keep hematologic oncology patients on their treatment regimens and continue to care for inpatients during the early months of the COVID-19 pandemic. How have they kept the situation managable? Strict infection control, liberal testing, and a proactive plan to defer and temporarily replace infusion care when medically appropriate were all part of the strategy. “My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious, even before the coronavirus, using distancing, masking, and meticulous hand hygiene,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in Levine Cancer Institute’s Department of Hematologic Oncology and Blood Disorders. READ MORE.

Convalescent plasma: Hope or hype?

There are currently more than two dozen trials of convalescent plasma in the United States and elsewhere but most are single-arm trials to determine if one infusion can decrease the need for intubation or help patients on a ventilator to improve. Others researchers are investigating whether convalescent plasma might be used before severe disease sets in. Meanwhile, about 2,200 hospitals are participating in an expanded access program being led by the Mayo Clinic nationwide. The National Institutes of Health recently said that “there are insufficient clinical data to recommend either for or against” its use for COVID-19. READ MORE.

New rosacea treatment guidelines

Patients with rosacea should receive treatments based on their phenotype and specific symptoms, rather than being assigned into distinct subtype categories, according to updated guidance published in the Journal of the American Academy of Dermatology. The update comes from the National Rosacea Society Expert Committee and is based on a review of the evidence. Patients “shouldn’t be classified as having a certain subtype of rosacea” since “many patients have features that overlap more than one subtype,” said Diane Thiboutot, MD, lead author of the update and a professor of dermatology and associate dean of clinical and translational research education at Penn State University, Hershey. READ MORE.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Remdesivir trial data published

Weeks after topline remdesivir data appeared in the press, investigators published their full experience using the drug to treat COVID-19 patients. The study, published in the New England Journal of Medicine, showed the drug reduced recovery time from 15 to 11 days, compared with placebo. Patients receiving oxygen seemed to fare best from treatment with remdesivir. “There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.” READ MORE.

FDA approves contraceptive gel

The Food and Drug Administration approved Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel to prevent pregnancy in women of reproductive potential. It’s the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5. READ MORE.

COVID-19 lessons from one cancer center

Physicians at Levine Cancer Institute in Charlotte, N.C., largely have been able to keep hematologic oncology patients on their treatment regimens and continue to care for inpatients during the early months of the COVID-19 pandemic. How have they kept the situation managable? Strict infection control, liberal testing, and a proactive plan to defer and temporarily replace infusion care when medically appropriate were all part of the strategy. “My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious, even before the coronavirus, using distancing, masking, and meticulous hand hygiene,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in Levine Cancer Institute’s Department of Hematologic Oncology and Blood Disorders. READ MORE.

Convalescent plasma: Hope or hype?

There are currently more than two dozen trials of convalescent plasma in the United States and elsewhere but most are single-arm trials to determine if one infusion can decrease the need for intubation or help patients on a ventilator to improve. Others researchers are investigating whether convalescent plasma might be used before severe disease sets in. Meanwhile, about 2,200 hospitals are participating in an expanded access program being led by the Mayo Clinic nationwide. The National Institutes of Health recently said that “there are insufficient clinical data to recommend either for or against” its use for COVID-19. READ MORE.

New rosacea treatment guidelines

Patients with rosacea should receive treatments based on their phenotype and specific symptoms, rather than being assigned into distinct subtype categories, according to updated guidance published in the Journal of the American Academy of Dermatology. The update comes from the National Rosacea Society Expert Committee and is based on a review of the evidence. Patients “shouldn’t be classified as having a certain subtype of rosacea” since “many patients have features that overlap more than one subtype,” said Diane Thiboutot, MD, lead author of the update and a professor of dermatology and associate dean of clinical and translational research education at Penn State University, Hershey. READ MORE.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Picky eating at age 4 years is stable over an approximately 4-year period, research published in Pediatrics suggests.

Yuki KONDO/Getty Images

In addition, picky eating is associated with lower body mass index (BMI). The stability of picky eating suggests that “interventions to prevent or modify picky eating may need to start before the preschool years,” said Carmen Fernandez, MPH, a researcher and medical student at University of Michigan in Ann Arbor, and colleagues.

Whether picky eating is a stable trait and how it relates to weight status has been unclear. Furthermore, “previous longitudinal studies have not focused on low-income children, who are at elevated risk for being both overweight and picky,” said Ms. Fernandez and associates.
 

A stable trait

To examine trajectories of picky eating in a low-income population of children and how picky eating relates to BMI z score (BMIz) and maternal behavior, the researchers conducted a longitudinal cohort study. They recruited more than 300 mother-child dyads from Head Start programs in Southeastern Michigan between 2009 and 2011. Children were 3-4 years old at recruitment, and researchers collected data at five time points. Children had an average age of 4 years at the first time point and 9 years at the fifth time point. Investigators collected child BMIz scores at all time points, Children’s Eating Behavior Questionnaire (CEBQ) scores at four time points, and Child Feeding Questionnaire and Caregiver’s Feeding Styles Questionnaire scores at three time points. Mothers completed the Emotion Regulation Checklist at baseline.

Among 317 children, an analysis identified three trajectories of picky eating severity as measured by the CEBQ Food Fussiness subscale: persistently low (29% of the children), persistently medium (57%), and persistently high (14%). “Maternal feeding behaviors characterized by restriction and demandingness were associated with picky eating,” the authors said. In post hoc analyses, emotional regulation was higher and emotional lability was lower among children with low levels of picky eating, compared with children with medium and high levels of picky eating.

“High and medium picky eating was associated with lower average BMIz, in the healthy BMIz range, suggesting that picky eating could be protective against overweight and obesity, as others have proposed,” Ms. Fernandez and colleagues said. “We did not find evidence that picky eating was associated with being underweight, which is consistent with previous studies. ... Little is known, however, about the long-term weight gain trajectories of picky eaters into adulthood, and this is an important area for future research.”

The results from this cohort may not apply to other populations, the authors noted.
 

What to do about picky eating

“Health providers, researchers, and parents do not yet have a handle on the management and messaging of picky eating in children,” said Nancy L. Zucker, PhD, and Sheryl O. Hughes, PhD, in an accompanying editorial. “When a parent describes a child as often or always selective, it is beyond normative. … Roughly only 14% were described this way.”

The results suggest a need for early intervention, and age 24 months and younger may be when “children are more receptive to the exploration of new tastes,” said Dr. Zucker of the department of psychiatry and behavioral sciences and the department of psychology and neuroscience at Duke University in Durham, NC., and Dr. Hughes of the Children’s Nutrition Research Center at Baylor College of Medicine in Houston.

Researchers should examine the impact of an authoritative feeding style, which combines elements of authoritarian and indulgent feeding styles, on a child’s willingness to explore foods, said Dr. Zucker and Dr. Hughes. This feeding style incorporates “structure and guidance while being sensitive to the child’s needs without being punitive,” they said. “According to theories of inhibitory learning ... we can think of children with elevated picky eating as having thousands of negative memories about food (e.g., conflict, unexpected tastes, discomfort). Thus, caregivers can work to create positive memories and experiences around food (e.g., cooking, gardening) to help picky eaters expand their preferences. However, in doing so, it is critical that caregivers let go of their need for a child to taste something and instead focus on accumulating pleasant experiences.”

Whether this approach reduces pickiness is unknown, but it may improve shared eating experiences, Dr. Zucker and Dr. Hughes said.

Ms. Fernandez and coauthors had no relevant financial disclosures. The study was supported by the American Heart Association, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institutes of Health. Dr. Zucker received funding from the National Science Foundation and National Institute of Mental Health; Dr. Hughes had no relevant financial disclosures. The editorial was funded by the National Institutes of Health.

jremaly@mdedge.com

SOURCES: Fernandez C et al. Pediatrics. 2020 May 26. doi: 10.1542/peds.2019-2018; Zucker NL and Hughes SO. Pediatrics. 2020 May 26. doi: 10.1542/peds.2020-0893.
 

Picky eating at age 4 years is stable over an approximately 4-year period, research published in Pediatrics suggests.

Yuki KONDO/Getty Images

In addition, picky eating is associated with lower body mass index (BMI). The stability of picky eating suggests that “interventions to prevent or modify picky eating may need to start before the preschool years,” said Carmen Fernandez, MPH, a researcher and medical student at University of Michigan in Ann Arbor, and colleagues.

Whether picky eating is a stable trait and how it relates to weight status has been unclear. Furthermore, “previous longitudinal studies have not focused on low-income children, who are at elevated risk for being both overweight and picky,” said Ms. Fernandez and associates.
 

A stable trait

To examine trajectories of picky eating in a low-income population of children and how picky eating relates to BMI z score (BMIz) and maternal behavior, the researchers conducted a longitudinal cohort study. They recruited more than 300 mother-child dyads from Head Start programs in Southeastern Michigan between 2009 and 2011. Children were 3-4 years old at recruitment, and researchers collected data at five time points. Children had an average age of 4 years at the first time point and 9 years at the fifth time point. Investigators collected child BMIz scores at all time points, Children’s Eating Behavior Questionnaire (CEBQ) scores at four time points, and Child Feeding Questionnaire and Caregiver’s Feeding Styles Questionnaire scores at three time points. Mothers completed the Emotion Regulation Checklist at baseline.

Among 317 children, an analysis identified three trajectories of picky eating severity as measured by the CEBQ Food Fussiness subscale: persistently low (29% of the children), persistently medium (57%), and persistently high (14%). “Maternal feeding behaviors characterized by restriction and demandingness were associated with picky eating,” the authors said. In post hoc analyses, emotional regulation was higher and emotional lability was lower among children with low levels of picky eating, compared with children with medium and high levels of picky eating.

“High and medium picky eating was associated with lower average BMIz, in the healthy BMIz range, suggesting that picky eating could be protective against overweight and obesity, as others have proposed,” Ms. Fernandez and colleagues said. “We did not find evidence that picky eating was associated with being underweight, which is consistent with previous studies. ... Little is known, however, about the long-term weight gain trajectories of picky eaters into adulthood, and this is an important area for future research.”

The results from this cohort may not apply to other populations, the authors noted.
 

What to do about picky eating

“Health providers, researchers, and parents do not yet have a handle on the management and messaging of picky eating in children,” said Nancy L. Zucker, PhD, and Sheryl O. Hughes, PhD, in an accompanying editorial. “When a parent describes a child as often or always selective, it is beyond normative. … Roughly only 14% were described this way.”

The results suggest a need for early intervention, and age 24 months and younger may be when “children are more receptive to the exploration of new tastes,” said Dr. Zucker of the department of psychiatry and behavioral sciences and the department of psychology and neuroscience at Duke University in Durham, NC., and Dr. Hughes of the Children’s Nutrition Research Center at Baylor College of Medicine in Houston.

Researchers should examine the impact of an authoritative feeding style, which combines elements of authoritarian and indulgent feeding styles, on a child’s willingness to explore foods, said Dr. Zucker and Dr. Hughes. This feeding style incorporates “structure and guidance while being sensitive to the child’s needs without being punitive,” they said. “According to theories of inhibitory learning ... we can think of children with elevated picky eating as having thousands of negative memories about food (e.g., conflict, unexpected tastes, discomfort). Thus, caregivers can work to create positive memories and experiences around food (e.g., cooking, gardening) to help picky eaters expand their preferences. However, in doing so, it is critical that caregivers let go of their need for a child to taste something and instead focus on accumulating pleasant experiences.”

Whether this approach reduces pickiness is unknown, but it may improve shared eating experiences, Dr. Zucker and Dr. Hughes said.

Ms. Fernandez and coauthors had no relevant financial disclosures. The study was supported by the American Heart Association, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institutes of Health. Dr. Zucker received funding from the National Science Foundation and National Institute of Mental Health; Dr. Hughes had no relevant financial disclosures. The editorial was funded by the National Institutes of Health.

jremaly@mdedge.com

SOURCES: Fernandez C et al. Pediatrics. 2020 May 26. doi: 10.1542/peds.2019-2018; Zucker NL and Hughes SO. Pediatrics. 2020 May 26. doi: 10.1542/peds.2020-0893.
 

Picky eating at age 4 years is stable over an approximately 4-year period, research published in Pediatrics suggests.

Yuki KONDO/Getty Images

In addition, picky eating is associated with lower body mass index (BMI). The stability of picky eating suggests that “interventions to prevent or modify picky eating may need to start before the preschool years,” said Carmen Fernandez, MPH, a researcher and medical student at University of Michigan in Ann Arbor, and colleagues.

Whether picky eating is a stable trait and how it relates to weight status has been unclear. Furthermore, “previous longitudinal studies have not focused on low-income children, who are at elevated risk for being both overweight and picky,” said Ms. Fernandez and associates.
 

A stable trait

To examine trajectories of picky eating in a low-income population of children and how picky eating relates to BMI z score (BMIz) and maternal behavior, the researchers conducted a longitudinal cohort study. They recruited more than 300 mother-child dyads from Head Start programs in Southeastern Michigan between 2009 and 2011. Children were 3-4 years old at recruitment, and researchers collected data at five time points. Children had an average age of 4 years at the first time point and 9 years at the fifth time point. Investigators collected child BMIz scores at all time points, Children’s Eating Behavior Questionnaire (CEBQ) scores at four time points, and Child Feeding Questionnaire and Caregiver’s Feeding Styles Questionnaire scores at three time points. Mothers completed the Emotion Regulation Checklist at baseline.

Among 317 children, an analysis identified three trajectories of picky eating severity as measured by the CEBQ Food Fussiness subscale: persistently low (29% of the children), persistently medium (57%), and persistently high (14%). “Maternal feeding behaviors characterized by restriction and demandingness were associated with picky eating,” the authors said. In post hoc analyses, emotional regulation was higher and emotional lability was lower among children with low levels of picky eating, compared with children with medium and high levels of picky eating.

“High and medium picky eating was associated with lower average BMIz, in the healthy BMIz range, suggesting that picky eating could be protective against overweight and obesity, as others have proposed,” Ms. Fernandez and colleagues said. “We did not find evidence that picky eating was associated with being underweight, which is consistent with previous studies. ... Little is known, however, about the long-term weight gain trajectories of picky eaters into adulthood, and this is an important area for future research.”

The results from this cohort may not apply to other populations, the authors noted.
 

What to do about picky eating

“Health providers, researchers, and parents do not yet have a handle on the management and messaging of picky eating in children,” said Nancy L. Zucker, PhD, and Sheryl O. Hughes, PhD, in an accompanying editorial. “When a parent describes a child as often or always selective, it is beyond normative. … Roughly only 14% were described this way.”

The results suggest a need for early intervention, and age 24 months and younger may be when “children are more receptive to the exploration of new tastes,” said Dr. Zucker of the department of psychiatry and behavioral sciences and the department of psychology and neuroscience at Duke University in Durham, NC., and Dr. Hughes of the Children’s Nutrition Research Center at Baylor College of Medicine in Houston.

Researchers should examine the impact of an authoritative feeding style, which combines elements of authoritarian and indulgent feeding styles, on a child’s willingness to explore foods, said Dr. Zucker and Dr. Hughes. This feeding style incorporates “structure and guidance while being sensitive to the child’s needs without being punitive,” they said. “According to theories of inhibitory learning ... we can think of children with elevated picky eating as having thousands of negative memories about food (e.g., conflict, unexpected tastes, discomfort). Thus, caregivers can work to create positive memories and experiences around food (e.g., cooking, gardening) to help picky eaters expand their preferences. However, in doing so, it is critical that caregivers let go of their need for a child to taste something and instead focus on accumulating pleasant experiences.”

Whether this approach reduces pickiness is unknown, but it may improve shared eating experiences, Dr. Zucker and Dr. Hughes said.

Ms. Fernandez and coauthors had no relevant financial disclosures. The study was supported by the American Heart Association, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institutes of Health. Dr. Zucker received funding from the National Science Foundation and National Institute of Mental Health; Dr. Hughes had no relevant financial disclosures. The editorial was funded by the National Institutes of Health.

jremaly@mdedge.com

SOURCES: Fernandez C et al. Pediatrics. 2020 May 26. doi: 10.1542/peds.2019-2018; Zucker NL and Hughes SO. Pediatrics. 2020 May 26. doi: 10.1542/peds.2020-0893.
 

I am SO done with telemedicine.

In mid-March, as quarantine restrictions began, I embraced it. I frantically learned which insurances would and wouldn’t allow it, what billing codes had to be used (which varied wildly between plans), and what communication systems were and weren’t allowed.

For most of us it was a way to continue caring for patients and at least keep a trickle of revenue coming in. We could still go over test results face to face, see how a treatment plan was working, and check in with established patients before sending in refills. It seemed like a great solution. For the first 2-3 weeks I was thinking this was the way to go even after the pandemic calmed down.

Then it became increasingly problematic. New patients wanted to be seen remotely. No, I wasn’t doing that. It upset some, but I didn’t care. A neurologic exam is still a critical part of me assessing someone for the first time.

The next problem that came up was in routine check-ins with established patients. Headaches had recently gotten worse, but now I couldn’t do a fundoscopic exam. A stable seizure patient mentioned he’d had a month of worsening lumbar pain and right-leg weakness, but I can’t really check strength, reflexes, or sensation remotely. A lady I saw last year for a diabetic neuropathy is now being referred back to me for possible Parkinson’s disease. While hypomimia or shuffling gait can be seen on camera, you can’t check for rigidity and cogwheeling that way.

So my use of telemedicine has begun to decrease, and as the pandemic fades will hopefully stop entirely. Currently I’m only using it for recently seen patients to review test results or for established patients doing routine check-ins for stable issues. My secretary asks if they have any new issues to discuss with me when she sets up the appointment, and if they say yes she tells them it has to be in person.

This isn’t, as some will claim, a matter of my trying to increase revenue. It’s about practicing good medicine.

Neurology is a contact sport. We spend years learning to recognize minutiae from the moment we first see a patient. The way they speak, and walk, and move. The details of the exam. These are not, for the most part, things you can do with a camera. Other specialties may be less exam dependent, but not mine, and definitely not me. I’d be practicing substandard care if I did otherwise.

Not only that, but it becomes a liability issue. In a legal action you won’t get a pass if you miss something via remote appointment because it was a pandemic. The daily practice of medicine is full of minefields as it is. I don’t want to add another one.

When things return to normal – whatever the new normal is – I’m hoping to put my webcam away for good. It seemed like a good idea at the time, but in reality is only useful in a handful of cases. For all others, my patients deserve better neurologic care than it lets me provide.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I am SO done with telemedicine.

In mid-March, as quarantine restrictions began, I embraced it. I frantically learned which insurances would and wouldn’t allow it, what billing codes had to be used (which varied wildly between plans), and what communication systems were and weren’t allowed.

For most of us it was a way to continue caring for patients and at least keep a trickle of revenue coming in. We could still go over test results face to face, see how a treatment plan was working, and check in with established patients before sending in refills. It seemed like a great solution. For the first 2-3 weeks I was thinking this was the way to go even after the pandemic calmed down.

Then it became increasingly problematic. New patients wanted to be seen remotely. No, I wasn’t doing that. It upset some, but I didn’t care. A neurologic exam is still a critical part of me assessing someone for the first time.

The next problem that came up was in routine check-ins with established patients. Headaches had recently gotten worse, but now I couldn’t do a fundoscopic exam. A stable seizure patient mentioned he’d had a month of worsening lumbar pain and right-leg weakness, but I can’t really check strength, reflexes, or sensation remotely. A lady I saw last year for a diabetic neuropathy is now being referred back to me for possible Parkinson’s disease. While hypomimia or shuffling gait can be seen on camera, you can’t check for rigidity and cogwheeling that way.

So my use of telemedicine has begun to decrease, and as the pandemic fades will hopefully stop entirely. Currently I’m only using it for recently seen patients to review test results or for established patients doing routine check-ins for stable issues. My secretary asks if they have any new issues to discuss with me when she sets up the appointment, and if they say yes she tells them it has to be in person.

This isn’t, as some will claim, a matter of my trying to increase revenue. It’s about practicing good medicine.

Neurology is a contact sport. We spend years learning to recognize minutiae from the moment we first see a patient. The way they speak, and walk, and move. The details of the exam. These are not, for the most part, things you can do with a camera. Other specialties may be less exam dependent, but not mine, and definitely not me. I’d be practicing substandard care if I did otherwise.

Not only that, but it becomes a liability issue. In a legal action you won’t get a pass if you miss something via remote appointment because it was a pandemic. The daily practice of medicine is full of minefields as it is. I don’t want to add another one.

When things return to normal – whatever the new normal is – I’m hoping to put my webcam away for good. It seemed like a good idea at the time, but in reality is only useful in a handful of cases. For all others, my patients deserve better neurologic care than it lets me provide.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I am SO done with telemedicine.

In mid-March, as quarantine restrictions began, I embraced it. I frantically learned which insurances would and wouldn’t allow it, what billing codes had to be used (which varied wildly between plans), and what communication systems were and weren’t allowed.

For most of us it was a way to continue caring for patients and at least keep a trickle of revenue coming in. We could still go over test results face to face, see how a treatment plan was working, and check in with established patients before sending in refills. It seemed like a great solution. For the first 2-3 weeks I was thinking this was the way to go even after the pandemic calmed down.

Then it became increasingly problematic. New patients wanted to be seen remotely. No, I wasn’t doing that. It upset some, but I didn’t care. A neurologic exam is still a critical part of me assessing someone for the first time.

The next problem that came up was in routine check-ins with established patients. Headaches had recently gotten worse, but now I couldn’t do a fundoscopic exam. A stable seizure patient mentioned he’d had a month of worsening lumbar pain and right-leg weakness, but I can’t really check strength, reflexes, or sensation remotely. A lady I saw last year for a diabetic neuropathy is now being referred back to me for possible Parkinson’s disease. While hypomimia or shuffling gait can be seen on camera, you can’t check for rigidity and cogwheeling that way.

So my use of telemedicine has begun to decrease, and as the pandemic fades will hopefully stop entirely. Currently I’m only using it for recently seen patients to review test results or for established patients doing routine check-ins for stable issues. My secretary asks if they have any new issues to discuss with me when she sets up the appointment, and if they say yes she tells them it has to be in person.

This isn’t, as some will claim, a matter of my trying to increase revenue. It’s about practicing good medicine.

Neurology is a contact sport. We spend years learning to recognize minutiae from the moment we first see a patient. The way they speak, and walk, and move. The details of the exam. These are not, for the most part, things you can do with a camera. Other specialties may be less exam dependent, but not mine, and definitely not me. I’d be practicing substandard care if I did otherwise.

Not only that, but it becomes a liability issue. In a legal action you won’t get a pass if you miss something via remote appointment because it was a pandemic. The daily practice of medicine is full of minefields as it is. I don’t want to add another one.

When things return to normal – whatever the new normal is – I’m hoping to put my webcam away for good. It seemed like a good idea at the time, but in reality is only useful in a handful of cases. For all others, my patients deserve better neurologic care than it lets me provide.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

In December 1917, a large part of Halifax was destroyed when an ammunition ship exploded.

In the wake of the explosion large parts of the city were burning. Surrounding communities’ fire departments raced to the scene, only to find their efforts thwarted by a lack of uniform standards for hydrant-hose-nozzle connectors. With no way to tap into Halifax’s water supply, their hoses were worthless.

In the aftermath of WWI, this led to a standardization of fire hose connectors across multiple countries, to ensure it wouldn’t happen again. Sometimes it takes a disaster to bring such problems to the forefront so they can be fixed.

One issue that has come up repeatedly in talking to other physicians is the complete lack of uniformity in telemedicine billing codes. While not a new issue, the coronavirus pandemic has brought it into focus here, and it’s time to fix it.

Here’s an example of information I’ve found about telemedicine billing codes (Note: I have no idea if any of this is correct, so don’t rely on it in your own billing).

• Aetna: Point of service 02
• Cigna: Point of service 02 with modifier 95.
• BCBS Anthem Point of Service 02 with modifier GT.
• Medicare: Point of service 02 OR Point of service 11 with modifier 95 (I’ve seen conflicting reports).

And that’s just a sample. BCBS, for example, seems to vary by state and sub-network.

This is ridiculous. Even with different plans, the CPT and ICD10 codes are standardized, so why not things such as POS codes and modifiers? The only ones benefiting from this are insurance companies, who get to deny claims on grounds that they weren’t billed correctly.

This is, allegedly, the Internet age. Medical bills are submitted electronically, and often paid the same way. If such a complicated system can be made to work in so many other ways, it should be standardized to benefit all involved. Including those doing our best to care for patients in this challenging time – and at all times.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

In December 1917, a large part of Halifax was destroyed when an ammunition ship exploded.

In the wake of the explosion large parts of the city were burning. Surrounding communities’ fire departments raced to the scene, only to find their efforts thwarted by a lack of uniform standards for hydrant-hose-nozzle connectors. With no way to tap into Halifax’s water supply, their hoses were worthless.

In the aftermath of WWI, this led to a standardization of fire hose connectors across multiple countries, to ensure it wouldn’t happen again. Sometimes it takes a disaster to bring such problems to the forefront so they can be fixed.

One issue that has come up repeatedly in talking to other physicians is the complete lack of uniformity in telemedicine billing codes. While not a new issue, the coronavirus pandemic has brought it into focus here, and it’s time to fix it.

Here’s an example of information I’ve found about telemedicine billing codes (Note: I have no idea if any of this is correct, so don’t rely on it in your own billing).

• Aetna: Point of service 02
• Cigna: Point of service 02 with modifier 95.
• BCBS Anthem Point of Service 02 with modifier GT.
• Medicare: Point of service 02 OR Point of service 11 with modifier 95 (I’ve seen conflicting reports).

And that’s just a sample. BCBS, for example, seems to vary by state and sub-network.

This is ridiculous. Even with different plans, the CPT and ICD10 codes are standardized, so why not things such as POS codes and modifiers? The only ones benefiting from this are insurance companies, who get to deny claims on grounds that they weren’t billed correctly.

This is, allegedly, the Internet age. Medical bills are submitted electronically, and often paid the same way. If such a complicated system can be made to work in so many other ways, it should be standardized to benefit all involved. Including those doing our best to care for patients in this challenging time – and at all times.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

In December 1917, a large part of Halifax was destroyed when an ammunition ship exploded.

In the wake of the explosion large parts of the city were burning. Surrounding communities’ fire departments raced to the scene, only to find their efforts thwarted by a lack of uniform standards for hydrant-hose-nozzle connectors. With no way to tap into Halifax’s water supply, their hoses were worthless.

In the aftermath of WWI, this led to a standardization of fire hose connectors across multiple countries, to ensure it wouldn’t happen again. Sometimes it takes a disaster to bring such problems to the forefront so they can be fixed.

One issue that has come up repeatedly in talking to other physicians is the complete lack of uniformity in telemedicine billing codes. While not a new issue, the coronavirus pandemic has brought it into focus here, and it’s time to fix it.

Here’s an example of information I’ve found about telemedicine billing codes (Note: I have no idea if any of this is correct, so don’t rely on it in your own billing).

• Aetna: Point of service 02
• Cigna: Point of service 02 with modifier 95.
• BCBS Anthem Point of Service 02 with modifier GT.
• Medicare: Point of service 02 OR Point of service 11 with modifier 95 (I’ve seen conflicting reports).

And that’s just a sample. BCBS, for example, seems to vary by state and sub-network.

This is ridiculous. Even with different plans, the CPT and ICD10 codes are standardized, so why not things such as POS codes and modifiers? The only ones benefiting from this are insurance companies, who get to deny claims on grounds that they weren’t billed correctly.

This is, allegedly, the Internet age. Medical bills are submitted electronically, and often paid the same way. If such a complicated system can be made to work in so many other ways, it should be standardized to benefit all involved. Including those doing our best to care for patients in this challenging time – and at all times.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

For patients with inflammatory bowel disease (IBD) who develop coronavirus disease of 2019 (COVID-19), corticosteroid use may significantly increase risk of severe disease, according to data from more than 500 patients.

Use of sulfasalazine or 5-aminosalicylates (5-ASAs) also increased risk of severe COVID-19, albeit to a lesser degree, reported co-lead authors Erica J. Brenner, MD, of University of North Carolina Children’s Hospital, Chapel Hill, and Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

In contrast, tumor necrosis factor (TNF) blockers were not an independent risk factor for severe COVID-19.

“As TNF antagonists are the most commonly prescribed biologic therapy for patients with IBD, these initial findings should be reassuring to the large number of patients receiving TNF antagonist therapy and support their continued use during this current pandemic,” the investigators wrote in Gastroenterology.

These conclusions were drawn from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, a large registry actively collecting data from clinicians around the world.

In the present analysis, which involved 525 patients from 33 countries, the investigators searched for independent risk factors for severe COVID-19. Various factors were tested through multivariable regression, including age, comorbidities, usage of specific medications, and more.

The primary outcome was defined by a composite of hospitalization, ventilator use, or death, while secondary outcomes included a composite of hospitalization or death, as well as death alone.

The analysis revealed that patients receiving corticosteroids had an adjusted odds ratio of 6.87 (95% confidence interval, 2.30-20.51) for severe COVID-19, with increased risks also detected for both secondary outcomes. In contrast, TNF antagonist use was not significantly associated with the primary outcome; in fact, a possible protective effect was detected for hospitalization or death (aOR, 0.60; 95% CI, 0.38-0.96).

The investigators noted that the above findings aligned with extensive literature concerning infectious complications with corticosteroid use and “more recent commentary” surrounding TNF antagonists. Similarly, increased age and the presence of at least two comorbidities were each independently associated with increased risk of severe COVID-19, both of which are correlations that have been previously described.

But the threefold increased risk of severe COVID-19 associated with use of sulfasalazine or 5-ASAs (aOR, 3.14; 95% CI, 1.28-7.71) was a “surprising” finding, the investigators noted.

“In a direct comparison, we observed that 5-ASA/sulfasalazine–treated patients fared worse than those treated with TNF inhibitors,” the investigators wrote. “Although we cannot exclude unmeasured confounding, further exploration of biological mechanisms is warranted.”

David T. Rubin, MD, of the University of Chicago agreed that the finding deserves further investigation, particularly since sulfasalazine and 5-ASAs represent the second most commonly prescribed medication class for IBD.

“The risk with 5-ASAs is of interest but not well explained by what we know about the safety or the mechanism of these therapies,” Dr. Rubin said. “Clearly, more work is needed.”

The risks associated with corticosteroids were particularly concerning, Dr. Rubin said, because 10%-20% of patients with IBD may be taking corticosteroids at any given time.

“Steroids are still the number one prescribed therapy for Crohn’s and colitis,” he said.

Still, Dr. Rubin advised against abrupt changes to drug regimens, especially if they are effectively controlling IBD.

“Patients should stay on their existing therapies and stay in remission,” Dr. Rubin said. “If you stop your therapies … you are more likely to relapse. When you relapse, you’re more likely to need steroids as a rescue therapy … or end up in the hospital, and those are not places we want you to be.”

Despite the risks associated with steroids and sulfasalazine/5-ASAs, Dr. Rubin had an optimistic take on the study, calling the findings “very reassuring” because they support continued usage of TNF inhibitors and other biologic agents during the pandemic. He also noted that the SECURE-IBD registry, which he has contributed to, represents “an extraordinary effort” from around the world.

“[This is] an unprecedented collaboration across a scale and timeframe that has really never been seen before in our field, and I would hazard a guess that it’s probably never been seen in most other fields right now,” he said.

Clinicians seeking more information about managing patients with IBD during the COVID-19 pandemic can find guidance in the recent AGA practice update, of which Dr. Rubin was the lead author. Clinicians who would like to contribute to the SECURE-IBD registry may do so at covidibd.org. The registry now includes more than 1,000 patients.

The study was funded by Clinical and Translational Science Award grants through Dr. Ungaro. The investigators disclosed relationships with Takeda, Janssen, Pfizer, and others. Dr. Rubin disclosed relationships with Gilead, Eli Lilly, Shire, and others.

SOURCE: Brenner EJ et al. Gastroenterology. 2020 May 18. doi: 10.1053/j.gastro.2020.05.032.

For patients with inflammatory bowel disease (IBD) who develop coronavirus disease of 2019 (COVID-19), corticosteroid use may significantly increase risk of severe disease, according to data from more than 500 patients.

Use of sulfasalazine or 5-aminosalicylates (5-ASAs) also increased risk of severe COVID-19, albeit to a lesser degree, reported co-lead authors Erica J. Brenner, MD, of University of North Carolina Children’s Hospital, Chapel Hill, and Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

In contrast, tumor necrosis factor (TNF) blockers were not an independent risk factor for severe COVID-19.

“As TNF antagonists are the most commonly prescribed biologic therapy for patients with IBD, these initial findings should be reassuring to the large number of patients receiving TNF antagonist therapy and support their continued use during this current pandemic,” the investigators wrote in Gastroenterology.

These conclusions were drawn from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, a large registry actively collecting data from clinicians around the world.

In the present analysis, which involved 525 patients from 33 countries, the investigators searched for independent risk factors for severe COVID-19. Various factors were tested through multivariable regression, including age, comorbidities, usage of specific medications, and more.

The primary outcome was defined by a composite of hospitalization, ventilator use, or death, while secondary outcomes included a composite of hospitalization or death, as well as death alone.

The analysis revealed that patients receiving corticosteroids had an adjusted odds ratio of 6.87 (95% confidence interval, 2.30-20.51) for severe COVID-19, with increased risks also detected for both secondary outcomes. In contrast, TNF antagonist use was not significantly associated with the primary outcome; in fact, a possible protective effect was detected for hospitalization or death (aOR, 0.60; 95% CI, 0.38-0.96).

The investigators noted that the above findings aligned with extensive literature concerning infectious complications with corticosteroid use and “more recent commentary” surrounding TNF antagonists. Similarly, increased age and the presence of at least two comorbidities were each independently associated with increased risk of severe COVID-19, both of which are correlations that have been previously described.

But the threefold increased risk of severe COVID-19 associated with use of sulfasalazine or 5-ASAs (aOR, 3.14; 95% CI, 1.28-7.71) was a “surprising” finding, the investigators noted.

“In a direct comparison, we observed that 5-ASA/sulfasalazine–treated patients fared worse than those treated with TNF inhibitors,” the investigators wrote. “Although we cannot exclude unmeasured confounding, further exploration of biological mechanisms is warranted.”

David T. Rubin, MD, of the University of Chicago agreed that the finding deserves further investigation, particularly since sulfasalazine and 5-ASAs represent the second most commonly prescribed medication class for IBD.

“The risk with 5-ASAs is of interest but not well explained by what we know about the safety or the mechanism of these therapies,” Dr. Rubin said. “Clearly, more work is needed.”

The risks associated with corticosteroids were particularly concerning, Dr. Rubin said, because 10%-20% of patients with IBD may be taking corticosteroids at any given time.

“Steroids are still the number one prescribed therapy for Crohn’s and colitis,” he said.

Still, Dr. Rubin advised against abrupt changes to drug regimens, especially if they are effectively controlling IBD.

“Patients should stay on their existing therapies and stay in remission,” Dr. Rubin said. “If you stop your therapies … you are more likely to relapse. When you relapse, you’re more likely to need steroids as a rescue therapy … or end up in the hospital, and those are not places we want you to be.”

Despite the risks associated with steroids and sulfasalazine/5-ASAs, Dr. Rubin had an optimistic take on the study, calling the findings “very reassuring” because they support continued usage of TNF inhibitors and other biologic agents during the pandemic. He also noted that the SECURE-IBD registry, which he has contributed to, represents “an extraordinary effort” from around the world.

“[This is] an unprecedented collaboration across a scale and timeframe that has really never been seen before in our field, and I would hazard a guess that it’s probably never been seen in most other fields right now,” he said.

Clinicians seeking more information about managing patients with IBD during the COVID-19 pandemic can find guidance in the recent AGA practice update, of which Dr. Rubin was the lead author. Clinicians who would like to contribute to the SECURE-IBD registry may do so at covidibd.org. The registry now includes more than 1,000 patients.

The study was funded by Clinical and Translational Science Award grants through Dr. Ungaro. The investigators disclosed relationships with Takeda, Janssen, Pfizer, and others. Dr. Rubin disclosed relationships with Gilead, Eli Lilly, Shire, and others.

SOURCE: Brenner EJ et al. Gastroenterology. 2020 May 18. doi: 10.1053/j.gastro.2020.05.032.

For patients with inflammatory bowel disease (IBD) who develop coronavirus disease of 2019 (COVID-19), corticosteroid use may significantly increase risk of severe disease, according to data from more than 500 patients.

Use of sulfasalazine or 5-aminosalicylates (5-ASAs) also increased risk of severe COVID-19, albeit to a lesser degree, reported co-lead authors Erica J. Brenner, MD, of University of North Carolina Children’s Hospital, Chapel Hill, and Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

In contrast, tumor necrosis factor (TNF) blockers were not an independent risk factor for severe COVID-19.

“As TNF antagonists are the most commonly prescribed biologic therapy for patients with IBD, these initial findings should be reassuring to the large number of patients receiving TNF antagonist therapy and support their continued use during this current pandemic,” the investigators wrote in Gastroenterology.

These conclusions were drawn from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, a large registry actively collecting data from clinicians around the world.

In the present analysis, which involved 525 patients from 33 countries, the investigators searched for independent risk factors for severe COVID-19. Various factors were tested through multivariable regression, including age, comorbidities, usage of specific medications, and more.

The primary outcome was defined by a composite of hospitalization, ventilator use, or death, while secondary outcomes included a composite of hospitalization or death, as well as death alone.

The analysis revealed that patients receiving corticosteroids had an adjusted odds ratio of 6.87 (95% confidence interval, 2.30-20.51) for severe COVID-19, with increased risks also detected for both secondary outcomes. In contrast, TNF antagonist use was not significantly associated with the primary outcome; in fact, a possible protective effect was detected for hospitalization or death (aOR, 0.60; 95% CI, 0.38-0.96).

The investigators noted that the above findings aligned with extensive literature concerning infectious complications with corticosteroid use and “more recent commentary” surrounding TNF antagonists. Similarly, increased age and the presence of at least two comorbidities were each independently associated with increased risk of severe COVID-19, both of which are correlations that have been previously described.

But the threefold increased risk of severe COVID-19 associated with use of sulfasalazine or 5-ASAs (aOR, 3.14; 95% CI, 1.28-7.71) was a “surprising” finding, the investigators noted.

“In a direct comparison, we observed that 5-ASA/sulfasalazine–treated patients fared worse than those treated with TNF inhibitors,” the investigators wrote. “Although we cannot exclude unmeasured confounding, further exploration of biological mechanisms is warranted.”

David T. Rubin, MD, of the University of Chicago agreed that the finding deserves further investigation, particularly since sulfasalazine and 5-ASAs represent the second most commonly prescribed medication class for IBD.

“The risk with 5-ASAs is of interest but not well explained by what we know about the safety or the mechanism of these therapies,” Dr. Rubin said. “Clearly, more work is needed.”

The risks associated with corticosteroids were particularly concerning, Dr. Rubin said, because 10%-20% of patients with IBD may be taking corticosteroids at any given time.

“Steroids are still the number one prescribed therapy for Crohn’s and colitis,” he said.

Still, Dr. Rubin advised against abrupt changes to drug regimens, especially if they are effectively controlling IBD.

“Patients should stay on their existing therapies and stay in remission,” Dr. Rubin said. “If you stop your therapies … you are more likely to relapse. When you relapse, you’re more likely to need steroids as a rescue therapy … or end up in the hospital, and those are not places we want you to be.”

Despite the risks associated with steroids and sulfasalazine/5-ASAs, Dr. Rubin had an optimistic take on the study, calling the findings “very reassuring” because they support continued usage of TNF inhibitors and other biologic agents during the pandemic. He also noted that the SECURE-IBD registry, which he has contributed to, represents “an extraordinary effort” from around the world.

“[This is] an unprecedented collaboration across a scale and timeframe that has really never been seen before in our field, and I would hazard a guess that it’s probably never been seen in most other fields right now,” he said.

Clinicians seeking more information about managing patients with IBD during the COVID-19 pandemic can find guidance in the recent AGA practice update, of which Dr. Rubin was the lead author. Clinicians who would like to contribute to the SECURE-IBD registry may do so at covidibd.org. The registry now includes more than 1,000 patients.

The study was funded by Clinical and Translational Science Award grants through Dr. Ungaro. The investigators disclosed relationships with Takeda, Janssen, Pfizer, and others. Dr. Rubin disclosed relationships with Gilead, Eli Lilly, Shire, and others.

SOURCE: Brenner EJ et al. Gastroenterology. 2020 May 18. doi: 10.1053/j.gastro.2020.05.032.

Ignorance may be bliss for some. But as I sit here in my scenic social isolation on the Maine coast I find that, like most people, what I don’t know unsettles me. How is the COVID-19 virus spread? Does my wife’s wipe down of the doorknobs after I return from the grocery store really make us any less likely to contract the virus? Is wearing my homemade bandana face mask doing anything to protect me? I suspect not, but I wear it as a statement of courtesy and solidarity to my fellow community members.

zimmytws/Thinkstock

Does the 6-foot rule make any sense? I’ve read that it is based on a study dating back to the 1930s. I’ve seen images of the 25-foot droplet plume blasting out from a sneeze and understand that, as a bicyclist, I may be generating a shower of droplets in my wake. But, are those droplets a threat to anyone I pedal by if I am symptom free? What does being a carrier mean when we are talking about COVID-19?

What makes me more vulnerable to this particular virus as an apparently healthy septuagenarian? What collection of misfortunes have fallen on those younger victims of the pandemic? How often was it genetic?

Of course, none of us has the information yet that can provide us answers. This vacuum has attracted scores of “experts” bold enough or careless enough to venture an opinion. They may have also issued a caveat, but how often have the media failed to include it in the report or buried it in the fine print at the end of the story?

My discomfort with this information void has left me and you and everyone else to our imaginations to craft our own explanations. So, I try to piece together a construct based on what I can glean from what I read and see in the news because like most people I fortunately have no first-hand information about even a single case. The number of deaths is horrifying, but may not have hit close to home and given most of us a real personal sense of the illness and its character.

Maine is a small state with just over a million inhabitants, and most of us have some connection to one another. It may be that a person is the second cousin of someone who used to live 2 miles down the road. But, there is some feeling of familiarity. We have had deaths related to COVID-19, but very scanty information other than the county about where they occurred and whether the victim was a resident of an extended care facility. We are told very little if any details about exposure as officials invoke HIPAA regulations that leave us in the dark. Other than one vague reference to a “traveling salesman” who may have introduced the virus to several nursing homes, there has been very little information about how the virus may have been spread here in Maine. Even national reports of the deaths of high-profile entertainers and retired athletes are usually draped in the same haze of privacy.

Most of us don’t need to know the names and street addresses of the victims but a few anonymous narratives that include some general information on how epidemiologists believe clusters began and propagated would help us understand our risks with just a glimmer of clarity.

Of course the epidemiologists may not have the answers we are seeking because they too are struggling to untangle connections hampered by concerns of privacy. There is no question that privacy must remain an important part of the physician-patient relationship. But a pandemic has thrown us into a situation where common sense demands that HIPAA be interpreted with an emphasis on the greater good. Finding that balance between privacy and public knowledge will continue to be one of our greatest challenges.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

Ignorance may be bliss for some. But as I sit here in my scenic social isolation on the Maine coast I find that, like most people, what I don’t know unsettles me. How is the COVID-19 virus spread? Does my wife’s wipe down of the doorknobs after I return from the grocery store really make us any less likely to contract the virus? Is wearing my homemade bandana face mask doing anything to protect me? I suspect not, but I wear it as a statement of courtesy and solidarity to my fellow community members.

zimmytws/Thinkstock

Does the 6-foot rule make any sense? I’ve read that it is based on a study dating back to the 1930s. I’ve seen images of the 25-foot droplet plume blasting out from a sneeze and understand that, as a bicyclist, I may be generating a shower of droplets in my wake. But, are those droplets a threat to anyone I pedal by if I am symptom free? What does being a carrier mean when we are talking about COVID-19?

What makes me more vulnerable to this particular virus as an apparently healthy septuagenarian? What collection of misfortunes have fallen on those younger victims of the pandemic? How often was it genetic?

Of course, none of us has the information yet that can provide us answers. This vacuum has attracted scores of “experts” bold enough or careless enough to venture an opinion. They may have also issued a caveat, but how often have the media failed to include it in the report or buried it in the fine print at the end of the story?

My discomfort with this information void has left me and you and everyone else to our imaginations to craft our own explanations. So, I try to piece together a construct based on what I can glean from what I read and see in the news because like most people I fortunately have no first-hand information about even a single case. The number of deaths is horrifying, but may not have hit close to home and given most of us a real personal sense of the illness and its character.

Maine is a small state with just over a million inhabitants, and most of us have some connection to one another. It may be that a person is the second cousin of someone who used to live 2 miles down the road. But, there is some feeling of familiarity. We have had deaths related to COVID-19, but very scanty information other than the county about where they occurred and whether the victim was a resident of an extended care facility. We are told very little if any details about exposure as officials invoke HIPAA regulations that leave us in the dark. Other than one vague reference to a “traveling salesman” who may have introduced the virus to several nursing homes, there has been very little information about how the virus may have been spread here in Maine. Even national reports of the deaths of high-profile entertainers and retired athletes are usually draped in the same haze of privacy.

Most of us don’t need to know the names and street addresses of the victims but a few anonymous narratives that include some general information on how epidemiologists believe clusters began and propagated would help us understand our risks with just a glimmer of clarity.

Of course the epidemiologists may not have the answers we are seeking because they too are struggling to untangle connections hampered by concerns of privacy. There is no question that privacy must remain an important part of the physician-patient relationship. But a pandemic has thrown us into a situation where common sense demands that HIPAA be interpreted with an emphasis on the greater good. Finding that balance between privacy and public knowledge will continue to be one of our greatest challenges.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

Ignorance may be bliss for some. But as I sit here in my scenic social isolation on the Maine coast I find that, like most people, what I don’t know unsettles me. How is the COVID-19 virus spread? Does my wife’s wipe down of the doorknobs after I return from the grocery store really make us any less likely to contract the virus? Is wearing my homemade bandana face mask doing anything to protect me? I suspect not, but I wear it as a statement of courtesy and solidarity to my fellow community members.

zimmytws/Thinkstock

Does the 6-foot rule make any sense? I’ve read that it is based on a study dating back to the 1930s. I’ve seen images of the 25-foot droplet plume blasting out from a sneeze and understand that, as a bicyclist, I may be generating a shower of droplets in my wake. But, are those droplets a threat to anyone I pedal by if I am symptom free? What does being a carrier mean when we are talking about COVID-19?

What makes me more vulnerable to this particular virus as an apparently healthy septuagenarian? What collection of misfortunes have fallen on those younger victims of the pandemic? How often was it genetic?

Of course, none of us has the information yet that can provide us answers. This vacuum has attracted scores of “experts” bold enough or careless enough to venture an opinion. They may have also issued a caveat, but how often have the media failed to include it in the report or buried it in the fine print at the end of the story?

My discomfort with this information void has left me and you and everyone else to our imaginations to craft our own explanations. So, I try to piece together a construct based on what I can glean from what I read and see in the news because like most people I fortunately have no first-hand information about even a single case. The number of deaths is horrifying, but may not have hit close to home and given most of us a real personal sense of the illness and its character.

Maine is a small state with just over a million inhabitants, and most of us have some connection to one another. It may be that a person is the second cousin of someone who used to live 2 miles down the road. But, there is some feeling of familiarity. We have had deaths related to COVID-19, but very scanty information other than the county about where they occurred and whether the victim was a resident of an extended care facility. We are told very little if any details about exposure as officials invoke HIPAA regulations that leave us in the dark. Other than one vague reference to a “traveling salesman” who may have introduced the virus to several nursing homes, there has been very little information about how the virus may have been spread here in Maine. Even national reports of the deaths of high-profile entertainers and retired athletes are usually draped in the same haze of privacy.

Most of us don’t need to know the names and street addresses of the victims but a few anonymous narratives that include some general information on how epidemiologists believe clusters began and propagated would help us understand our risks with just a glimmer of clarity.

Of course the epidemiologists may not have the answers we are seeking because they too are struggling to untangle connections hampered by concerns of privacy. There is no question that privacy must remain an important part of the physician-patient relationship. But a pandemic has thrown us into a situation where common sense demands that HIPAA be interpreted with an emphasis on the greater good. Finding that balance between privacy and public knowledge will continue to be one of our greatest challenges.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.