Individuals who consumed more ultraprocessed foods had a significantly increased risk of developing inflammatory bowel disease (IBD) than those who consumed less, according to data from more than 100,000 adults.

“Diet alters the microbiome and modifies the intestinal immune response and so could play a role in the pathogenesis of IBD,” Neeraj Narula, MD, of McMaster University, Hamilton, Ont., and colleagues wrote. Although previous studies have investigated the impact of dietary risk factors on IBD, an association with ultraprocessed foods (defined as foods containing additives and preservatives) in particular has not been examined, they wrote.

In a study published in BMJ, the researchers examined data from 116,087 adults aged 35-70 years from 21 countries between 2003 and 2016 who were part of the large Prospective Urban Rural Epidemiology (PURE) Cohort. Participants completed baseline food frequency questionnaires and were followed at least every 3 years; the median follow-up time was 9.7 years. The primary outcome was the development of Crohn’s disease or ulcerative colitis. In this study, ultraprocessed food included all packaged and formulated foods and beverages that contained food additives, artificial flavors or colors, or other chemical ingredients.

The categories of ultraprocessed foods included processed meat, cold breakfast cereal, various sauces, soft drinks, and fruit drinks, and refined sweetened foods such as candy, chocolate, jam, jelly, and brownies.

Overall, 467 participants developed IBD, including 90 with Crohn’s disease and 377 with ulcerative colitis.

After controlling for confounding factors, the investigators found that increased consumption of ultraprocessed foods was significantly associated with an increased risk of incident IBD. Compared with individuals who consumed less than 1 serving per day of ultraprocessed foods, the hazard ratio was 1.82 for those who consumed 5 or more servings and 1.67 for those who consumed 1-4 servings daily (P = .006).

“The pattern of increased ultraprocessed food intake and higher risk of IBD persisted within each of the regions examined, and effect estimates were generally similar, with overlapping confidence intervals and no significant heterogeneity,” the researchers noted.

The risk of IBD increased among individuals who consumed 1 serving per week or more of processed meat, compared with those who consumed less than 1 serving per week, and the risk increased with the amount consumed (HR, 2.07 for 1 or more servings per day). Similarly, IBD risk was higher among individuals who consumed 100 g/day or more of refined sweetened foods compared with no intake of these foods (HR, 2.58).

Individuals who consumed at least one serving of fried foods per day had the highest risk of IBD (HR, 3.02), the researchers noted. The reason for the association is uncertain, but may occur not only because many fried foods are also processed but also because the action of frying food and the processing of oil, as well as type and quality of oil, might modify the nutrients.

In the subgroup analysis, higher consumption of salty snacks and soft drinks also was associated with higher risk for IBD. However, the researchers found no association between increased risk of IBD and consumption of white meat, unprocessed red meat, dairy, starchy foods, and fruit/vegetables/legumes.

The study findings were limited by several factors including the relatively small number of individuals with Crohn’s disease, potential lack of generalizability to those who develop IBD in childhood or young adulthood, and possible confounding from unmeasured variables. The study also did not account for dietary changes over time, the investigators reported. However, the longitudinal design allowed them “to focus on people with incident IBD and to use medical record review and central adjudication to validate a sample of the diagnoses.”

The results suggest that the way food is processed or ultraprocessed, rather than the food itself, may be what confers the risk for IBD, given the lack of association between IBD and other food categories such as unprocessed red meat and dairy, the researchers concluded.
 

Next steps: Pin down driving factors

“There is significant interest in the apparent increase in the incidence and prevalence of IBD, particularly in previously low incidence areas,” Edward L. Barnes, MD, MPH, of the University of North Carolina at Chapel Hill said in an interview.

“Many research groups and clinicians suspect that environmental exposures, including dietary exposures, may play a critical role in these trends,” said Dr. Barnes. “This study utilized a large, multinational prospective cohort design to assess the influence of diet on the risk of developing IBD,” which is particularly important considering the potential for processed foods and food additives to impact the gastrointestinal tract.

“The strong associations demonstrated by the authors were impressive, particularly given that the authors performed multiple subanalyses, including evaluations by participant age and evaluations of particular food groups/types [e.g., processed meat, soft drinks, and refined sweet foods],” he noted. Dr. Barnes also found the lack of association with intake of white meat and unprocessed red meat interesting. “In my opinion, these subanalyses strengthen the overall associations demonstrated by the authors given their prospective study design and their attention to evaluating all potential associations that may be driving the relationships present in this cohort.

“At this point, the take-home message for clinicians treating patients with Crohn’s disease and ulcerative colitis should be that this association exists,” said Dr. Barnes. “One question that remains is whether the same risk factors that are present for developing disease also influence the disease course, given that the primary outcome of this study was the development of IBD. Given that much of our data with regard to the interplay between diet and IBD are still emerging, physicians treating patients with IBD can make patients aware of these associations and the potential benefit of limiting ultraprocessed foods in their diet.”

For these important results to become actionable, “further research is likely necessary to identify the factors that are driving this association,” Dr. Barnes explained. “This would likely build on prior animal models that have demonstrated an association between food additives such as emulsifiers and changes in the gastrointestinal tract that could ultimately lead to increased inflammation and the development of IBD.” Such information about specific drivers “would then allow clinicians to determine which population would benefit most from dietary changes/recommendations.”

The overall PURE study was supported by the Population Health Research Institute, Hamilton Health Sciences Research Institute, Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, CIHR’s Strategy for Patient Oriented Research through the Ontario SPOR Support Unit, and the Ontario Ministry of Health and Long-term Care. PURE also was supported in part by unrestricted grants from several pharmaceutical companies, notably AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline. The researchers had no relevant financial conflicts to disclose. Dr. Barnes disclosed serving as a consultant for AbbVie, Gilead, Pfizer, Takeda, and Target RWE.

Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD. 

Individuals who consumed more ultraprocessed foods had a significantly increased risk of developing inflammatory bowel disease (IBD) than those who consumed less, according to data from more than 100,000 adults.

“Diet alters the microbiome and modifies the intestinal immune response and so could play a role in the pathogenesis of IBD,” Neeraj Narula, MD, of McMaster University, Hamilton, Ont., and colleagues wrote. Although previous studies have investigated the impact of dietary risk factors on IBD, an association with ultraprocessed foods (defined as foods containing additives and preservatives) in particular has not been examined, they wrote.

In a study published in BMJ, the researchers examined data from 116,087 adults aged 35-70 years from 21 countries between 2003 and 2016 who were part of the large Prospective Urban Rural Epidemiology (PURE) Cohort. Participants completed baseline food frequency questionnaires and were followed at least every 3 years; the median follow-up time was 9.7 years. The primary outcome was the development of Crohn’s disease or ulcerative colitis. In this study, ultraprocessed food included all packaged and formulated foods and beverages that contained food additives, artificial flavors or colors, or other chemical ingredients.

The categories of ultraprocessed foods included processed meat, cold breakfast cereal, various sauces, soft drinks, and fruit drinks, and refined sweetened foods such as candy, chocolate, jam, jelly, and brownies.

Overall, 467 participants developed IBD, including 90 with Crohn’s disease and 377 with ulcerative colitis.

After controlling for confounding factors, the investigators found that increased consumption of ultraprocessed foods was significantly associated with an increased risk of incident IBD. Compared with individuals who consumed less than 1 serving per day of ultraprocessed foods, the hazard ratio was 1.82 for those who consumed 5 or more servings and 1.67 for those who consumed 1-4 servings daily (P = .006).

“The pattern of increased ultraprocessed food intake and higher risk of IBD persisted within each of the regions examined, and effect estimates were generally similar, with overlapping confidence intervals and no significant heterogeneity,” the researchers noted.

The risk of IBD increased among individuals who consumed 1 serving per week or more of processed meat, compared with those who consumed less than 1 serving per week, and the risk increased with the amount consumed (HR, 2.07 for 1 or more servings per day). Similarly, IBD risk was higher among individuals who consumed 100 g/day or more of refined sweetened foods compared with no intake of these foods (HR, 2.58).

Individuals who consumed at least one serving of fried foods per day had the highest risk of IBD (HR, 3.02), the researchers noted. The reason for the association is uncertain, but may occur not only because many fried foods are also processed but also because the action of frying food and the processing of oil, as well as type and quality of oil, might modify the nutrients.

In the subgroup analysis, higher consumption of salty snacks and soft drinks also was associated with higher risk for IBD. However, the researchers found no association between increased risk of IBD and consumption of white meat, unprocessed red meat, dairy, starchy foods, and fruit/vegetables/legumes.

The study findings were limited by several factors including the relatively small number of individuals with Crohn’s disease, potential lack of generalizability to those who develop IBD in childhood or young adulthood, and possible confounding from unmeasured variables. The study also did not account for dietary changes over time, the investigators reported. However, the longitudinal design allowed them “to focus on people with incident IBD and to use medical record review and central adjudication to validate a sample of the diagnoses.”

The results suggest that the way food is processed or ultraprocessed, rather than the food itself, may be what confers the risk for IBD, given the lack of association between IBD and other food categories such as unprocessed red meat and dairy, the researchers concluded.
 

Next steps: Pin down driving factors

“There is significant interest in the apparent increase in the incidence and prevalence of IBD, particularly in previously low incidence areas,” Edward L. Barnes, MD, MPH, of the University of North Carolina at Chapel Hill said in an interview.

“Many research groups and clinicians suspect that environmental exposures, including dietary exposures, may play a critical role in these trends,” said Dr. Barnes. “This study utilized a large, multinational prospective cohort design to assess the influence of diet on the risk of developing IBD,” which is particularly important considering the potential for processed foods and food additives to impact the gastrointestinal tract.

“The strong associations demonstrated by the authors were impressive, particularly given that the authors performed multiple subanalyses, including evaluations by participant age and evaluations of particular food groups/types [e.g., processed meat, soft drinks, and refined sweet foods],” he noted. Dr. Barnes also found the lack of association with intake of white meat and unprocessed red meat interesting. “In my opinion, these subanalyses strengthen the overall associations demonstrated by the authors given their prospective study design and their attention to evaluating all potential associations that may be driving the relationships present in this cohort.

“At this point, the take-home message for clinicians treating patients with Crohn’s disease and ulcerative colitis should be that this association exists,” said Dr. Barnes. “One question that remains is whether the same risk factors that are present for developing disease also influence the disease course, given that the primary outcome of this study was the development of IBD. Given that much of our data with regard to the interplay between diet and IBD are still emerging, physicians treating patients with IBD can make patients aware of these associations and the potential benefit of limiting ultraprocessed foods in their diet.”

For these important results to become actionable, “further research is likely necessary to identify the factors that are driving this association,” Dr. Barnes explained. “This would likely build on prior animal models that have demonstrated an association between food additives such as emulsifiers and changes in the gastrointestinal tract that could ultimately lead to increased inflammation and the development of IBD.” Such information about specific drivers “would then allow clinicians to determine which population would benefit most from dietary changes/recommendations.”

The overall PURE study was supported by the Population Health Research Institute, Hamilton Health Sciences Research Institute, Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, CIHR’s Strategy for Patient Oriented Research through the Ontario SPOR Support Unit, and the Ontario Ministry of Health and Long-term Care. PURE also was supported in part by unrestricted grants from several pharmaceutical companies, notably AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline. The researchers had no relevant financial conflicts to disclose. Dr. Barnes disclosed serving as a consultant for AbbVie, Gilead, Pfizer, Takeda, and Target RWE.

Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD. 

Individuals who consumed more ultraprocessed foods had a significantly increased risk of developing inflammatory bowel disease (IBD) than those who consumed less, according to data from more than 100,000 adults.

“Diet alters the microbiome and modifies the intestinal immune response and so could play a role in the pathogenesis of IBD,” Neeraj Narula, MD, of McMaster University, Hamilton, Ont., and colleagues wrote. Although previous studies have investigated the impact of dietary risk factors on IBD, an association with ultraprocessed foods (defined as foods containing additives and preservatives) in particular has not been examined, they wrote.

In a study published in BMJ, the researchers examined data from 116,087 adults aged 35-70 years from 21 countries between 2003 and 2016 who were part of the large Prospective Urban Rural Epidemiology (PURE) Cohort. Participants completed baseline food frequency questionnaires and were followed at least every 3 years; the median follow-up time was 9.7 years. The primary outcome was the development of Crohn’s disease or ulcerative colitis. In this study, ultraprocessed food included all packaged and formulated foods and beverages that contained food additives, artificial flavors or colors, or other chemical ingredients.

The categories of ultraprocessed foods included processed meat, cold breakfast cereal, various sauces, soft drinks, and fruit drinks, and refined sweetened foods such as candy, chocolate, jam, jelly, and brownies.

Overall, 467 participants developed IBD, including 90 with Crohn’s disease and 377 with ulcerative colitis.

After controlling for confounding factors, the investigators found that increased consumption of ultraprocessed foods was significantly associated with an increased risk of incident IBD. Compared with individuals who consumed less than 1 serving per day of ultraprocessed foods, the hazard ratio was 1.82 for those who consumed 5 or more servings and 1.67 for those who consumed 1-4 servings daily (P = .006).

“The pattern of increased ultraprocessed food intake and higher risk of IBD persisted within each of the regions examined, and effect estimates were generally similar, with overlapping confidence intervals and no significant heterogeneity,” the researchers noted.

The risk of IBD increased among individuals who consumed 1 serving per week or more of processed meat, compared with those who consumed less than 1 serving per week, and the risk increased with the amount consumed (HR, 2.07 for 1 or more servings per day). Similarly, IBD risk was higher among individuals who consumed 100 g/day or more of refined sweetened foods compared with no intake of these foods (HR, 2.58).

Individuals who consumed at least one serving of fried foods per day had the highest risk of IBD (HR, 3.02), the researchers noted. The reason for the association is uncertain, but may occur not only because many fried foods are also processed but also because the action of frying food and the processing of oil, as well as type and quality of oil, might modify the nutrients.

In the subgroup analysis, higher consumption of salty snacks and soft drinks also was associated with higher risk for IBD. However, the researchers found no association between increased risk of IBD and consumption of white meat, unprocessed red meat, dairy, starchy foods, and fruit/vegetables/legumes.

The study findings were limited by several factors including the relatively small number of individuals with Crohn’s disease, potential lack of generalizability to those who develop IBD in childhood or young adulthood, and possible confounding from unmeasured variables. The study also did not account for dietary changes over time, the investigators reported. However, the longitudinal design allowed them “to focus on people with incident IBD and to use medical record review and central adjudication to validate a sample of the diagnoses.”

The results suggest that the way food is processed or ultraprocessed, rather than the food itself, may be what confers the risk for IBD, given the lack of association between IBD and other food categories such as unprocessed red meat and dairy, the researchers concluded.
 

Next steps: Pin down driving factors

“There is significant interest in the apparent increase in the incidence and prevalence of IBD, particularly in previously low incidence areas,” Edward L. Barnes, MD, MPH, of the University of North Carolina at Chapel Hill said in an interview.

“Many research groups and clinicians suspect that environmental exposures, including dietary exposures, may play a critical role in these trends,” said Dr. Barnes. “This study utilized a large, multinational prospective cohort design to assess the influence of diet on the risk of developing IBD,” which is particularly important considering the potential for processed foods and food additives to impact the gastrointestinal tract.

“The strong associations demonstrated by the authors were impressive, particularly given that the authors performed multiple subanalyses, including evaluations by participant age and evaluations of particular food groups/types [e.g., processed meat, soft drinks, and refined sweet foods],” he noted. Dr. Barnes also found the lack of association with intake of white meat and unprocessed red meat interesting. “In my opinion, these subanalyses strengthen the overall associations demonstrated by the authors given their prospective study design and their attention to evaluating all potential associations that may be driving the relationships present in this cohort.

“At this point, the take-home message for clinicians treating patients with Crohn’s disease and ulcerative colitis should be that this association exists,” said Dr. Barnes. “One question that remains is whether the same risk factors that are present for developing disease also influence the disease course, given that the primary outcome of this study was the development of IBD. Given that much of our data with regard to the interplay between diet and IBD are still emerging, physicians treating patients with IBD can make patients aware of these associations and the potential benefit of limiting ultraprocessed foods in their diet.”

For these important results to become actionable, “further research is likely necessary to identify the factors that are driving this association,” Dr. Barnes explained. “This would likely build on prior animal models that have demonstrated an association between food additives such as emulsifiers and changes in the gastrointestinal tract that could ultimately lead to increased inflammation and the development of IBD.” Such information about specific drivers “would then allow clinicians to determine which population would benefit most from dietary changes/recommendations.”

The overall PURE study was supported by the Population Health Research Institute, Hamilton Health Sciences Research Institute, Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, CIHR’s Strategy for Patient Oriented Research through the Ontario SPOR Support Unit, and the Ontario Ministry of Health and Long-term Care. PURE also was supported in part by unrestricted grants from several pharmaceutical companies, notably AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline. The researchers had no relevant financial conflicts to disclose. Dr. Barnes disclosed serving as a consultant for AbbVie, Gilead, Pfizer, Takeda, and Target RWE.

Help your patients better understand their IBD treatment options by sharing AGA’s patient education, “Living with IBD,” in the AGA GI Patient Center at www.gastro.org/IBD. 

Moderna says neutralizing antibodies generated by its COVID-19 vaccine against three variants of the virus that causes the disease waned substantially 6 months after the second dose.

Because of this, the company expects an increase in breakthrough infections with a need for boosters before winter.

In an experiment, a 50-mg dose of the vaccine, given as a third shot, boosted levels of antibodies in 20 previously vaccinated people by 32 times against the Beta variant, by 44 times against the Gamma variant, and by 42 times against Delta.

The new data was presented in an earnings call to investors and is based on a small study that hasn’t yet been published in medical literature.

The company also said its vaccine remained highly effective at preventing severe COVID outcomes through 6 months.

Last week, Pfizer released early data suggesting a similar drop in protection from its vaccine. The company also showed a third dose substantially boosted protection, including against the Delta variant.

The new results come just 1 day after the World Health Organization implored wealthy nations to hold off on third doses until more of the world’s population could get a first dose.

More than 80% of the 4 billion vaccine doses given around the world have been distributed to high-income countries.

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

Moderna says neutralizing antibodies generated by its COVID-19 vaccine against three variants of the virus that causes the disease waned substantially 6 months after the second dose.

Because of this, the company expects an increase in breakthrough infections with a need for boosters before winter.

In an experiment, a 50-mg dose of the vaccine, given as a third shot, boosted levels of antibodies in 20 previously vaccinated people by 32 times against the Beta variant, by 44 times against the Gamma variant, and by 42 times against Delta.

The new data was presented in an earnings call to investors and is based on a small study that hasn’t yet been published in medical literature.

The company also said its vaccine remained highly effective at preventing severe COVID outcomes through 6 months.

Last week, Pfizer released early data suggesting a similar drop in protection from its vaccine. The company also showed a third dose substantially boosted protection, including against the Delta variant.

The new results come just 1 day after the World Health Organization implored wealthy nations to hold off on third doses until more of the world’s population could get a first dose.

More than 80% of the 4 billion vaccine doses given around the world have been distributed to high-income countries.

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

Moderna says neutralizing antibodies generated by its COVID-19 vaccine against three variants of the virus that causes the disease waned substantially 6 months after the second dose.

Because of this, the company expects an increase in breakthrough infections with a need for boosters before winter.

In an experiment, a 50-mg dose of the vaccine, given as a third shot, boosted levels of antibodies in 20 previously vaccinated people by 32 times against the Beta variant, by 44 times against the Gamma variant, and by 42 times against Delta.

The new data was presented in an earnings call to investors and is based on a small study that hasn’t yet been published in medical literature.

The company also said its vaccine remained highly effective at preventing severe COVID outcomes through 6 months.

Last week, Pfizer released early data suggesting a similar drop in protection from its vaccine. The company also showed a third dose substantially boosted protection, including against the Delta variant.

The new results come just 1 day after the World Health Organization implored wealthy nations to hold off on third doses until more of the world’s population could get a first dose.

More than 80% of the 4 billion vaccine doses given around the world have been distributed to high-income countries.

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

A retracted study on the safety of blood pressure medications in patients with COVID-19 continues to be cited nearly a year later, new research shows.

Floaria Bicher/iStock/Getty Images Plus

The study in question, published on May 1, 2020, in the New England Journal of Medicine, showed no increased risk for in-hospital death with the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) in hospitalized patients with COVID-19.

Concerns about the veracity of the Surgisphere database used for the study, however, led to a June 4 retraction and to the June 13 retraction of a second study, published in the Lancet, that focused on hydroxychloroquine as a COVID-19 treatment.

Although the Surgisphere scandal caused a global reckoning of COVID-19 scientific studies, the new analysis identified 652 citations of the NEJM article as of May 31.

More than a third of the citations occurred in the first 2 months after the retraction, 54% were at least 3 months later, and 2.8% at least 6 months later. In May, 11 months after the article was retracted, it was cited 21 times, senior author Emily G. McDonald, MD, MSc, McGill University, Montreal, and colleagues reported in a research letter in JAMA Internal Medicine.

“In early May and June there were already more than 200 citations in one of the world’s leading scientific journals, so I do believe it was a highly influential article early on and had an impact on different types of studies or research taking place,” she said in an interview.

Dr. McDonald said she’s also “certain that it impacted patient care,” observing that when there are no guidelines available on how to manage patients, physicians will turn to the most recent evidence in the most reputable journals.

“In the case of ACE [inhibitors] and ARBs, although the study was based on fraudulent data, we were lucky that the overall message was in the end probably correct, but that might not have been the case for another study or dataset,” she said.

Early in the pandemic, concerns existed that ACE inhibitors and ARBs could be harmful, increasing the expression of ACE2 receptors, which the SARS-CoV-2 virus uses to gain entry into cells. The first randomized trial to examine the issue, BRACE CORONA, showed no clinical benefit to interrupting use of the agents in hospitalized patients. An observational study suggested ACE inhibitors may even be protective.

Of two high-profile retractions, McDonald said they chose to bypass the hydroxychloroquine study, which had an eye-popping Altmetric attention score of 23,084, compared with 3,727 for the NEJM paper, because it may have been cited for “other” reasons. “We wanted to focus less on the politics and more on the problem of retracted work.”

The team found that researchers across the globe were citing the retracted ACE/ARB paper (18.7% in the United States, 8.1% in Italy, and 44% other countries). Most citations were used to support a statement in the main text of a study, but in nearly 3% of cases, the data were incorporated into new analyses.

Just 17.6% of the studies cited or noted the retraction. “For sure, that was surprising to us. We suspected it, but our study confirmed it,” Dr. McDonald said.

Although retracted articles can be identified by a watermark or line of text, in some cases that can be easily missed, she noted. What’s more, not all citation software points out when a study has been retracted, a fate shared by the copyediting process.

“There are a lot of mechanisms in place and, in general, what’s happening is rare but there isn’t a perfect automated system solution to absolutely prevent this from happening,” she said. “It’s still subject to human error.”

The findings also have to be taken in the context of a rapidly emerging pandemic and the unprecedented torrent of scientific papers released over the past year.

“That might have contributed to why this happened, but the takeaway message is that this can happen despite our best efforts, and we need to challenge ourselves to come up with a system solution to prevent this from happening in the future,” Dr. McDonald said. “Current mechanisms are probably capturing 95% of it, but we need to do better.”

Limitations of the present analysis are that it was limited to the single retracted study; used only a single search engine, Google Scholar, to identify the citing works; and that additional citations may have been missed, the authors noted.

McDonald and coauthor Todd C. Lee, MD, report being signatories on a public letter calling for the retraction of the Surgisphere papers. Dr. Lee also reported receiving research support from Fonds De Recherche du Quebec-Sante during the conduct of the study.

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

A retracted study on the safety of blood pressure medications in patients with COVID-19 continues to be cited nearly a year later, new research shows.

Floaria Bicher/iStock/Getty Images Plus

The study in question, published on May 1, 2020, in the New England Journal of Medicine, showed no increased risk for in-hospital death with the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) in hospitalized patients with COVID-19.

Concerns about the veracity of the Surgisphere database used for the study, however, led to a June 4 retraction and to the June 13 retraction of a second study, published in the Lancet, that focused on hydroxychloroquine as a COVID-19 treatment.

Although the Surgisphere scandal caused a global reckoning of COVID-19 scientific studies, the new analysis identified 652 citations of the NEJM article as of May 31.

More than a third of the citations occurred in the first 2 months after the retraction, 54% were at least 3 months later, and 2.8% at least 6 months later. In May, 11 months after the article was retracted, it was cited 21 times, senior author Emily G. McDonald, MD, MSc, McGill University, Montreal, and colleagues reported in a research letter in JAMA Internal Medicine.

“In early May and June there were already more than 200 citations in one of the world’s leading scientific journals, so I do believe it was a highly influential article early on and had an impact on different types of studies or research taking place,” she said in an interview.

Dr. McDonald said she’s also “certain that it impacted patient care,” observing that when there are no guidelines available on how to manage patients, physicians will turn to the most recent evidence in the most reputable journals.

“In the case of ACE [inhibitors] and ARBs, although the study was based on fraudulent data, we were lucky that the overall message was in the end probably correct, but that might not have been the case for another study or dataset,” she said.

Early in the pandemic, concerns existed that ACE inhibitors and ARBs could be harmful, increasing the expression of ACE2 receptors, which the SARS-CoV-2 virus uses to gain entry into cells. The first randomized trial to examine the issue, BRACE CORONA, showed no clinical benefit to interrupting use of the agents in hospitalized patients. An observational study suggested ACE inhibitors may even be protective.

Of two high-profile retractions, McDonald said they chose to bypass the hydroxychloroquine study, which had an eye-popping Altmetric attention score of 23,084, compared with 3,727 for the NEJM paper, because it may have been cited for “other” reasons. “We wanted to focus less on the politics and more on the problem of retracted work.”

The team found that researchers across the globe were citing the retracted ACE/ARB paper (18.7% in the United States, 8.1% in Italy, and 44% other countries). Most citations were used to support a statement in the main text of a study, but in nearly 3% of cases, the data were incorporated into new analyses.

Just 17.6% of the studies cited or noted the retraction. “For sure, that was surprising to us. We suspected it, but our study confirmed it,” Dr. McDonald said.

Although retracted articles can be identified by a watermark or line of text, in some cases that can be easily missed, she noted. What’s more, not all citation software points out when a study has been retracted, a fate shared by the copyediting process.

“There are a lot of mechanisms in place and, in general, what’s happening is rare but there isn’t a perfect automated system solution to absolutely prevent this from happening,” she said. “It’s still subject to human error.”

The findings also have to be taken in the context of a rapidly emerging pandemic and the unprecedented torrent of scientific papers released over the past year.

“That might have contributed to why this happened, but the takeaway message is that this can happen despite our best efforts, and we need to challenge ourselves to come up with a system solution to prevent this from happening in the future,” Dr. McDonald said. “Current mechanisms are probably capturing 95% of it, but we need to do better.”

Limitations of the present analysis are that it was limited to the single retracted study; used only a single search engine, Google Scholar, to identify the citing works; and that additional citations may have been missed, the authors noted.

McDonald and coauthor Todd C. Lee, MD, report being signatories on a public letter calling for the retraction of the Surgisphere papers. Dr. Lee also reported receiving research support from Fonds De Recherche du Quebec-Sante during the conduct of the study.

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

A retracted study on the safety of blood pressure medications in patients with COVID-19 continues to be cited nearly a year later, new research shows.

Floaria Bicher/iStock/Getty Images Plus

The study in question, published on May 1, 2020, in the New England Journal of Medicine, showed no increased risk for in-hospital death with the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) in hospitalized patients with COVID-19.

Concerns about the veracity of the Surgisphere database used for the study, however, led to a June 4 retraction and to the June 13 retraction of a second study, published in the Lancet, that focused on hydroxychloroquine as a COVID-19 treatment.

Although the Surgisphere scandal caused a global reckoning of COVID-19 scientific studies, the new analysis identified 652 citations of the NEJM article as of May 31.

More than a third of the citations occurred in the first 2 months after the retraction, 54% were at least 3 months later, and 2.8% at least 6 months later. In May, 11 months after the article was retracted, it was cited 21 times, senior author Emily G. McDonald, MD, MSc, McGill University, Montreal, and colleagues reported in a research letter in JAMA Internal Medicine.

“In early May and June there were already more than 200 citations in one of the world’s leading scientific journals, so I do believe it was a highly influential article early on and had an impact on different types of studies or research taking place,” she said in an interview.

Dr. McDonald said she’s also “certain that it impacted patient care,” observing that when there are no guidelines available on how to manage patients, physicians will turn to the most recent evidence in the most reputable journals.

“In the case of ACE [inhibitors] and ARBs, although the study was based on fraudulent data, we were lucky that the overall message was in the end probably correct, but that might not have been the case for another study or dataset,” she said.

Early in the pandemic, concerns existed that ACE inhibitors and ARBs could be harmful, increasing the expression of ACE2 receptors, which the SARS-CoV-2 virus uses to gain entry into cells. The first randomized trial to examine the issue, BRACE CORONA, showed no clinical benefit to interrupting use of the agents in hospitalized patients. An observational study suggested ACE inhibitors may even be protective.

Of two high-profile retractions, McDonald said they chose to bypass the hydroxychloroquine study, which had an eye-popping Altmetric attention score of 23,084, compared with 3,727 for the NEJM paper, because it may have been cited for “other” reasons. “We wanted to focus less on the politics and more on the problem of retracted work.”

The team found that researchers across the globe were citing the retracted ACE/ARB paper (18.7% in the United States, 8.1% in Italy, and 44% other countries). Most citations were used to support a statement in the main text of a study, but in nearly 3% of cases, the data were incorporated into new analyses.

Just 17.6% of the studies cited or noted the retraction. “For sure, that was surprising to us. We suspected it, but our study confirmed it,” Dr. McDonald said.

Although retracted articles can be identified by a watermark or line of text, in some cases that can be easily missed, she noted. What’s more, not all citation software points out when a study has been retracted, a fate shared by the copyediting process.

“There are a lot of mechanisms in place and, in general, what’s happening is rare but there isn’t a perfect automated system solution to absolutely prevent this from happening,” she said. “It’s still subject to human error.”

The findings also have to be taken in the context of a rapidly emerging pandemic and the unprecedented torrent of scientific papers released over the past year.

“That might have contributed to why this happened, but the takeaway message is that this can happen despite our best efforts, and we need to challenge ourselves to come up with a system solution to prevent this from happening in the future,” Dr. McDonald said. “Current mechanisms are probably capturing 95% of it, but we need to do better.”

Limitations of the present analysis are that it was limited to the single retracted study; used only a single search engine, Google Scholar, to identify the citing works; and that additional citations may have been missed, the authors noted.

McDonald and coauthor Todd C. Lee, MD, report being signatories on a public letter calling for the retraction of the Surgisphere papers. Dr. Lee also reported receiving research support from Fonds De Recherche du Quebec-Sante during the conduct of the study.

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

While cases of pericarditis or myocarditis temporally linked to COVID-19 vaccination remain rare, they may happen more often than reported, according to a large review of electronic medical records (EMRs).

peterschreiber_media/iStock/Getty Images

They also appear to represent two “distinct syndromes,” George Diaz, MD, Providence Regional Medical Center Everett (Washington), said in an interview.

Myocarditis typically occurs soon after vaccination in younger patients and mostly after the second dose, while pericarditis occurs later in older patients, after the first or second dose.

Dr. Diaz and colleagues reported their analysis in a research letter published online August 4 in JAMA.

They reviewed the records of 2,000,287 people who received at least one COVID-19 vaccination at 40 hospitals in Washington, Oregon, Montana, and California that are part of the Providence health care system and use the same EMRs.

The median age of the cohort was 57 years and 59% were women.

A little more than three quarters (77%) received more than one dose; most received the mRNA vaccines made by Pfizer (53%) and Moderna (44%); 3% received the Johnson & Johnson vaccine.

The records showed that 20 people had vaccine-related myocarditis (1.0 per 100,000) and 37 had pericarditis (1.8 per 100,000).

A recent report, based on data from the Centers for Disease Control and Prevention’s Vaccine Adverse Events Reporting System, suggested an incidence of myocarditis of about 4.8 cases per 1 million following receipt of mRNA COVID-19 vaccine.

The new study shows a “similar pattern, although at higher incidence, suggesting vaccine adverse event underreporting. In addition, pericarditis may be more common than myocarditis among older patients,” the study team wrote.

“Our study resulted in higher numbers of cases probably because we searched the EMR, and VAERS requires doctors to report suspected cases voluntarily,” Dr. Diaz said in an interview.

Also, in the governments’ statistics, pericarditis and myocarditis were “lumped together,” he noted.
 

Myocarditis cases

The 20 myocarditis cases occurred a median of 3.5 days after vaccination (11 after the Moderna vaccine and 9 after the Pfizer vaccine), 15 of the patients (75%) were men, and the median age was 36 years.

Four individuals (20%) developed myocarditis symptoms after the first vaccination and 16 (80%) after the second dose. Nineteen of the patients (95%) were admitted to the hospital and all were discharged after a median of 2 days.

None of the 20 patients were readmitted or died. Two received a second vaccination after onset of myocarditis; neither had worsening of symptoms. At last available follow-up (median, 23.5 days after symptom onset), 13 patients (65%) had a resolution of their myocarditis symptoms and seven (35%) were improving.
 

Pericarditis cases

The 37 pericarditis cases occurred a median of 20 days after the most recent COVID-19 vaccination: 23 (62%) with Pfizer, 12 (32%) with Moderna, and 2 (5%) with the J&J vaccine. Fifteen developed pericarditis after the first vaccine dose (41%) and 22 (59%) after the second.

Twenty-seven (73%) of the cases occurred in men; the median age was 59 years.

Thirteen patients (35%) were admitted to the hospital, none to intensive care. The median hospital stay was 1 day. Seven patients with pericarditis received a second vaccination. No patient died.

At last available follow-up (median, 28 days), 7 patients (19%) had resolved symptoms and 23 (62%) were improving.

The researchers also calculate that the average monthly number of cases of myocarditis or myopericarditis during the prevaccine period of January 2019 through January 2021 was 16.9 (95% confidence interval, 15.3-18.6) compared with 27.3 (95% CI, 22.4-32.9) during the vaccine period of February through May 2021 (P < .001).

The mean numbers of pericarditis cases during the same periods were 49.1 (95% CI, 46.4-51.9) and 78.8 (95% CI, 70.3-87.9), respectively (P < .001).

The authors say limitations of their analysis include potential missed cases outside care settings and missed diagnoses of myocarditis or pericarditis, which would underestimate the incidence, as well as inaccurate EMR vaccination information.

“Temporal association does not prove causation, although the short span between vaccination and myocarditis onset and the elevated incidence of myocarditis and pericarditis in the study hospitals lend support to a possible relationship,” they wrote.

In late June, the Food and Drug Administration added a warning to the fact sheets accompanying the Pfizer and Moderna mRNA COVID-19 vaccines, flagging the rare risk of heart inflammation after their use.  

Dr. Diaz cautioned that myocarditis and pericarditis events remain “a rare occurrence” after COVID-19 vaccination.

“When discussing vaccination with patients, [health care providers] can advise them that patients generally recover in the rare event they get pericarditis or myocarditis and no deaths were found, and that the vaccines are safe and effective,” Dr. Diaz said.

The study had no specific funding. Dr. Diaz reported receipt of clinical trial research support from Gilead Sciences, Regeneron, Roche, Boehringer Ingelheim, and Edesa Biotech and scientific advisory board membership for Safeology.

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

While cases of pericarditis or myocarditis temporally linked to COVID-19 vaccination remain rare, they may happen more often than reported, according to a large review of electronic medical records (EMRs).

peterschreiber_media/iStock/Getty Images

They also appear to represent two “distinct syndromes,” George Diaz, MD, Providence Regional Medical Center Everett (Washington), said in an interview.

Myocarditis typically occurs soon after vaccination in younger patients and mostly after the second dose, while pericarditis occurs later in older patients, after the first or second dose.

Dr. Diaz and colleagues reported their analysis in a research letter published online August 4 in JAMA.

They reviewed the records of 2,000,287 people who received at least one COVID-19 vaccination at 40 hospitals in Washington, Oregon, Montana, and California that are part of the Providence health care system and use the same EMRs.

The median age of the cohort was 57 years and 59% were women.

A little more than three quarters (77%) received more than one dose; most received the mRNA vaccines made by Pfizer (53%) and Moderna (44%); 3% received the Johnson & Johnson vaccine.

The records showed that 20 people had vaccine-related myocarditis (1.0 per 100,000) and 37 had pericarditis (1.8 per 100,000).

A recent report, based on data from the Centers for Disease Control and Prevention’s Vaccine Adverse Events Reporting System, suggested an incidence of myocarditis of about 4.8 cases per 1 million following receipt of mRNA COVID-19 vaccine.

The new study shows a “similar pattern, although at higher incidence, suggesting vaccine adverse event underreporting. In addition, pericarditis may be more common than myocarditis among older patients,” the study team wrote.

“Our study resulted in higher numbers of cases probably because we searched the EMR, and VAERS requires doctors to report suspected cases voluntarily,” Dr. Diaz said in an interview.

Also, in the governments’ statistics, pericarditis and myocarditis were “lumped together,” he noted.
 

Myocarditis cases

The 20 myocarditis cases occurred a median of 3.5 days after vaccination (11 after the Moderna vaccine and 9 after the Pfizer vaccine), 15 of the patients (75%) were men, and the median age was 36 years.

Four individuals (20%) developed myocarditis symptoms after the first vaccination and 16 (80%) after the second dose. Nineteen of the patients (95%) were admitted to the hospital and all were discharged after a median of 2 days.

None of the 20 patients were readmitted or died. Two received a second vaccination after onset of myocarditis; neither had worsening of symptoms. At last available follow-up (median, 23.5 days after symptom onset), 13 patients (65%) had a resolution of their myocarditis symptoms and seven (35%) were improving.
 

Pericarditis cases

The 37 pericarditis cases occurred a median of 20 days after the most recent COVID-19 vaccination: 23 (62%) with Pfizer, 12 (32%) with Moderna, and 2 (5%) with the J&J vaccine. Fifteen developed pericarditis after the first vaccine dose (41%) and 22 (59%) after the second.

Twenty-seven (73%) of the cases occurred in men; the median age was 59 years.

Thirteen patients (35%) were admitted to the hospital, none to intensive care. The median hospital stay was 1 day. Seven patients with pericarditis received a second vaccination. No patient died.

At last available follow-up (median, 28 days), 7 patients (19%) had resolved symptoms and 23 (62%) were improving.

The researchers also calculate that the average monthly number of cases of myocarditis or myopericarditis during the prevaccine period of January 2019 through January 2021 was 16.9 (95% confidence interval, 15.3-18.6) compared with 27.3 (95% CI, 22.4-32.9) during the vaccine period of February through May 2021 (P < .001).

The mean numbers of pericarditis cases during the same periods were 49.1 (95% CI, 46.4-51.9) and 78.8 (95% CI, 70.3-87.9), respectively (P < .001).

The authors say limitations of their analysis include potential missed cases outside care settings and missed diagnoses of myocarditis or pericarditis, which would underestimate the incidence, as well as inaccurate EMR vaccination information.

“Temporal association does not prove causation, although the short span between vaccination and myocarditis onset and the elevated incidence of myocarditis and pericarditis in the study hospitals lend support to a possible relationship,” they wrote.

In late June, the Food and Drug Administration added a warning to the fact sheets accompanying the Pfizer and Moderna mRNA COVID-19 vaccines, flagging the rare risk of heart inflammation after their use.  

Dr. Diaz cautioned that myocarditis and pericarditis events remain “a rare occurrence” after COVID-19 vaccination.

“When discussing vaccination with patients, [health care providers] can advise them that patients generally recover in the rare event they get pericarditis or myocarditis and no deaths were found, and that the vaccines are safe and effective,” Dr. Diaz said.

The study had no specific funding. Dr. Diaz reported receipt of clinical trial research support from Gilead Sciences, Regeneron, Roche, Boehringer Ingelheim, and Edesa Biotech and scientific advisory board membership for Safeology.

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

While cases of pericarditis or myocarditis temporally linked to COVID-19 vaccination remain rare, they may happen more often than reported, according to a large review of electronic medical records (EMRs).

peterschreiber_media/iStock/Getty Images

They also appear to represent two “distinct syndromes,” George Diaz, MD, Providence Regional Medical Center Everett (Washington), said in an interview.

Myocarditis typically occurs soon after vaccination in younger patients and mostly after the second dose, while pericarditis occurs later in older patients, after the first or second dose.

Dr. Diaz and colleagues reported their analysis in a research letter published online August 4 in JAMA.

They reviewed the records of 2,000,287 people who received at least one COVID-19 vaccination at 40 hospitals in Washington, Oregon, Montana, and California that are part of the Providence health care system and use the same EMRs.

The median age of the cohort was 57 years and 59% were women.

A little more than three quarters (77%) received more than one dose; most received the mRNA vaccines made by Pfizer (53%) and Moderna (44%); 3% received the Johnson & Johnson vaccine.

The records showed that 20 people had vaccine-related myocarditis (1.0 per 100,000) and 37 had pericarditis (1.8 per 100,000).

A recent report, based on data from the Centers for Disease Control and Prevention’s Vaccine Adverse Events Reporting System, suggested an incidence of myocarditis of about 4.8 cases per 1 million following receipt of mRNA COVID-19 vaccine.

The new study shows a “similar pattern, although at higher incidence, suggesting vaccine adverse event underreporting. In addition, pericarditis may be more common than myocarditis among older patients,” the study team wrote.

“Our study resulted in higher numbers of cases probably because we searched the EMR, and VAERS requires doctors to report suspected cases voluntarily,” Dr. Diaz said in an interview.

Also, in the governments’ statistics, pericarditis and myocarditis were “lumped together,” he noted.
 

Myocarditis cases

The 20 myocarditis cases occurred a median of 3.5 days after vaccination (11 after the Moderna vaccine and 9 after the Pfizer vaccine), 15 of the patients (75%) were men, and the median age was 36 years.

Four individuals (20%) developed myocarditis symptoms after the first vaccination and 16 (80%) after the second dose. Nineteen of the patients (95%) were admitted to the hospital and all were discharged after a median of 2 days.

None of the 20 patients were readmitted or died. Two received a second vaccination after onset of myocarditis; neither had worsening of symptoms. At last available follow-up (median, 23.5 days after symptom onset), 13 patients (65%) had a resolution of their myocarditis symptoms and seven (35%) were improving.
 

Pericarditis cases

The 37 pericarditis cases occurred a median of 20 days after the most recent COVID-19 vaccination: 23 (62%) with Pfizer, 12 (32%) with Moderna, and 2 (5%) with the J&J vaccine. Fifteen developed pericarditis after the first vaccine dose (41%) and 22 (59%) after the second.

Twenty-seven (73%) of the cases occurred in men; the median age was 59 years.

Thirteen patients (35%) were admitted to the hospital, none to intensive care. The median hospital stay was 1 day. Seven patients with pericarditis received a second vaccination. No patient died.

At last available follow-up (median, 28 days), 7 patients (19%) had resolved symptoms and 23 (62%) were improving.

The researchers also calculate that the average monthly number of cases of myocarditis or myopericarditis during the prevaccine period of January 2019 through January 2021 was 16.9 (95% confidence interval, 15.3-18.6) compared with 27.3 (95% CI, 22.4-32.9) during the vaccine period of February through May 2021 (P < .001).

The mean numbers of pericarditis cases during the same periods were 49.1 (95% CI, 46.4-51.9) and 78.8 (95% CI, 70.3-87.9), respectively (P < .001).

The authors say limitations of their analysis include potential missed cases outside care settings and missed diagnoses of myocarditis or pericarditis, which would underestimate the incidence, as well as inaccurate EMR vaccination information.

“Temporal association does not prove causation, although the short span between vaccination and myocarditis onset and the elevated incidence of myocarditis and pericarditis in the study hospitals lend support to a possible relationship,” they wrote.

In late June, the Food and Drug Administration added a warning to the fact sheets accompanying the Pfizer and Moderna mRNA COVID-19 vaccines, flagging the rare risk of heart inflammation after their use.  

Dr. Diaz cautioned that myocarditis and pericarditis events remain “a rare occurrence” after COVID-19 vaccination.

“When discussing vaccination with patients, [health care providers] can advise them that patients generally recover in the rare event they get pericarditis or myocarditis and no deaths were found, and that the vaccines are safe and effective,” Dr. Diaz said.

The study had no specific funding. Dr. Diaz reported receipt of clinical trial research support from Gilead Sciences, Regeneron, Roche, Boehringer Ingelheim, and Edesa Biotech and scientific advisory board membership for Safeology.

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

The Food and Drug Administration has cleared the FreeStyle Libre 2 iOS application for use with compatible iPhones.

The new app works with the FreeStyle Libre 2 with optional glucose alarms, which was approved in the United States in June 2020 for people with diabetes aged 4 years and older.

Until now, it was only a reader device with no app compatibility. The older FreeStyle Libre 14-day, available in the United States since July 2018, has both a reader and an app, but not optional alarms.

The new app, which will soon be available for download from the App Store, enables users to view glucose readings on their iPhones and allows for caregivers or other individuals to remotely monitor the patient’s glucose levels and receive real-time alarms via the LibreLinkUp app.

Worn for 14 days before replacement is needed, the FreeStyle Libre 2 is the longest-lasting integrated continuous glucose monitoring (iCGM) sensor currently on the market. The first iCGM, the Dexcom G6, is worn for 10 days.

The Libre 2 is available at pharmacies, typically at a lower cost than other CGM systems based on a list price comparison. The actual cost for patients varies depending on insurance coverage.

Abbott has secured partial or full reimbursement for the FreeStyle Libre system in 38 countries, including Canada, France, Germany, Japan, the United Kingdom, and the United States.

The FreeStyle Libre 3 is approved for use in the European Union.

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

The Food and Drug Administration has cleared the FreeStyle Libre 2 iOS application for use with compatible iPhones.

The new app works with the FreeStyle Libre 2 with optional glucose alarms, which was approved in the United States in June 2020 for people with diabetes aged 4 years and older.

Until now, it was only a reader device with no app compatibility. The older FreeStyle Libre 14-day, available in the United States since July 2018, has both a reader and an app, but not optional alarms.

The new app, which will soon be available for download from the App Store, enables users to view glucose readings on their iPhones and allows for caregivers or other individuals to remotely monitor the patient’s glucose levels and receive real-time alarms via the LibreLinkUp app.

Worn for 14 days before replacement is needed, the FreeStyle Libre 2 is the longest-lasting integrated continuous glucose monitoring (iCGM) sensor currently on the market. The first iCGM, the Dexcom G6, is worn for 10 days.

The Libre 2 is available at pharmacies, typically at a lower cost than other CGM systems based on a list price comparison. The actual cost for patients varies depending on insurance coverage.

Abbott has secured partial or full reimbursement for the FreeStyle Libre system in 38 countries, including Canada, France, Germany, Japan, the United Kingdom, and the United States.

The FreeStyle Libre 3 is approved for use in the European Union.

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

The Food and Drug Administration has cleared the FreeStyle Libre 2 iOS application for use with compatible iPhones.

The new app works with the FreeStyle Libre 2 with optional glucose alarms, which was approved in the United States in June 2020 for people with diabetes aged 4 years and older.

Until now, it was only a reader device with no app compatibility. The older FreeStyle Libre 14-day, available in the United States since July 2018, has both a reader and an app, but not optional alarms.

The new app, which will soon be available for download from the App Store, enables users to view glucose readings on their iPhones and allows for caregivers or other individuals to remotely monitor the patient’s glucose levels and receive real-time alarms via the LibreLinkUp app.

Worn for 14 days before replacement is needed, the FreeStyle Libre 2 is the longest-lasting integrated continuous glucose monitoring (iCGM) sensor currently on the market. The first iCGM, the Dexcom G6, is worn for 10 days.

The Libre 2 is available at pharmacies, typically at a lower cost than other CGM systems based on a list price comparison. The actual cost for patients varies depending on insurance coverage.

Abbott has secured partial or full reimbursement for the FreeStyle Libre system in 38 countries, including Canada, France, Germany, Japan, the United Kingdom, and the United States.

The FreeStyle Libre 3 is approved for use in the European Union.

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

Certain plasma biomarkers of neuronal damage and neuroinflammation are markedly elevated in hospitalized COVID-19 patients with neurologic symptoms compared with hospitalized COVID-19 patients without such symptoms, a new study shows.

These results suggest that COVID-19 may accelerate Alzheimer’s disease symptoms and pathology, said study investigator Thomas Wisniewski, MD, professor of neurology, pathology, and psychiatry at New York University.

The findings were presented here at the Alzheimer’s Association International Conference (AAIC) 2021.
 

Strong correlation

There’s a clear association between SARS-CoV-2 infection and Alzheimer’s disease-related dementia. Patients with Alzheimer’s disease are at threefold higher risk for the infection and have a twofold higher risk for death, Dr. Wisniewski told meeting delegates.

He and his colleagues conducted a prospective study of patients who had tested positive for SARS-CoV-2 and who experienced neurologic sequelae and SARS-CoV-2 patients who were without neurologic sequelae. All patients were hospitalized from March 10 to May 20, 2020. This was during a period when New York City was overwhelmed by COVID: About 35% of hospitalized patients had COVID.

Of those who experienced neurologic events, the most common “by far and away” (51%) was toxic metabolic encephalopathy (TME), said Dr. Wisniewski. Other associations included seizures, hypoxic/anoxic injury, and ischemic stroke.

The most common TMEs were septic and hypoxic ischemia. In most patients (78%), TME had more than one cause.

Researchers followed 196 patients with COVID and neurologic complications (case patients) and 186 matched control patients who had no neurologic complications over a period of 6 months.

“Unfortunately, both groups had poor outcomes,” said Dr. Wisniewski. About 50% had impaired cognition, and 56% experienced limitations in activities of daily living.

However, those patients with COVID-19 who had neurologic sequelae “fared even worse,” said Dr. Wisniewski. Compared with control patients, they had twofold worse Modified Rankin Scale scores and worse scores on activity of daily living, and they were much less likely to return to work.

Mechanisms by which COVID-19 affects longer-term cognitive dysfunction are unclear, but inflammation likely plays a role.

The research team compared a number of Alzheimer’s disease plasma biomarkers in 158 patients with COVID-19 who had neurologic symptoms and 152 COVID patients with COVID but no neurologic symptoms. They found marked elevations of neurofilament light, a marker of neuronal injury, in those with symptoms (P = .0003) as well as increased glial fibrillary acid protein, a marker of neuroinflammation (P = .0098).

Ubiquitin carboxyl-terminal hydrolase L1, another marker of neuronal injury, was also elevated in those with neurologic symptoms. Regarding Alzheimer’s disease pathology, total tau (t-tau) and phosphorylated tau “also tracked with neurological sequelae,” said Dr. Wisniewski.

There was no difference in levels of amyloid beta 40 (A beta 40) between groups. However, A beta 42 plasma levels were significantly lower in those with neurologic effects, suggesting higher levels in the brain. In addition, the ratio of t-tau to A beta 42 “clearly differentiated the two groups,” he said.

“Serum biomarkers of neuroinflammation and neuronal injury and Alzheimer’s disease correlate strongly, perhaps suggesting that folks with COVID infection and neurological sequelae may have an acceleration of Alzheimer’s disease symptoms and pathology,” he said. “That’s something that needs longer follow-up.”
 

Important differentiation

Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said the study provides important information. The inclusion of plasma biomarkers in this research is “really critical to tease out what’s the impact of COVID itself on the brain,” said Dr. Edelmayer.

“We’re in an era of biomarkers when it comes to Alzheimer’s disease and other dementias, and being able to define those changes that are happening in the brain over time is going to be really critical and aid in early detection and accurate diagnoses,” she said.

What is still to be learned is what these biomarkers reveal long term, said Dr. Edelmayer. “Do those biological markers change? Do they go back to normal? A lot of that is still unknown,” she said.

She noted that many diseases that are linked to inflammation produce similar biomarkers in the brain – for example, neurofilament light.

With other viral infections, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), similar associations between the infection and cognition have been reported, said Dr. Edelmayer.

“But there are still a lot of questions around cause and effect. Is it really a direct effect of the virus on the brain itself? Is it an effect of having an enormous amount of inflammation going on in the body? A lot of that still needs to be teased out,” she commented.

The study was supported by the National Institutes of Health, the Alzheimer’s Association, and the State of New York. Dr. Wisniewski has consulted for Grifols, Amylon Pharmaceuticals, and Alzamed Neuro; 30 NYU patents are related to AD therapeutics.

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

Certain plasma biomarkers of neuronal damage and neuroinflammation are markedly elevated in hospitalized COVID-19 patients with neurologic symptoms compared with hospitalized COVID-19 patients without such symptoms, a new study shows.

These results suggest that COVID-19 may accelerate Alzheimer’s disease symptoms and pathology, said study investigator Thomas Wisniewski, MD, professor of neurology, pathology, and psychiatry at New York University.

The findings were presented here at the Alzheimer’s Association International Conference (AAIC) 2021.
 

Strong correlation

There’s a clear association between SARS-CoV-2 infection and Alzheimer’s disease-related dementia. Patients with Alzheimer’s disease are at threefold higher risk for the infection and have a twofold higher risk for death, Dr. Wisniewski told meeting delegates.

He and his colleagues conducted a prospective study of patients who had tested positive for SARS-CoV-2 and who experienced neurologic sequelae and SARS-CoV-2 patients who were without neurologic sequelae. All patients were hospitalized from March 10 to May 20, 2020. This was during a period when New York City was overwhelmed by COVID: About 35% of hospitalized patients had COVID.

Of those who experienced neurologic events, the most common “by far and away” (51%) was toxic metabolic encephalopathy (TME), said Dr. Wisniewski. Other associations included seizures, hypoxic/anoxic injury, and ischemic stroke.

The most common TMEs were septic and hypoxic ischemia. In most patients (78%), TME had more than one cause.

Researchers followed 196 patients with COVID and neurologic complications (case patients) and 186 matched control patients who had no neurologic complications over a period of 6 months.

“Unfortunately, both groups had poor outcomes,” said Dr. Wisniewski. About 50% had impaired cognition, and 56% experienced limitations in activities of daily living.

However, those patients with COVID-19 who had neurologic sequelae “fared even worse,” said Dr. Wisniewski. Compared with control patients, they had twofold worse Modified Rankin Scale scores and worse scores on activity of daily living, and they were much less likely to return to work.

Mechanisms by which COVID-19 affects longer-term cognitive dysfunction are unclear, but inflammation likely plays a role.

The research team compared a number of Alzheimer’s disease plasma biomarkers in 158 patients with COVID-19 who had neurologic symptoms and 152 COVID patients with COVID but no neurologic symptoms. They found marked elevations of neurofilament light, a marker of neuronal injury, in those with symptoms (P = .0003) as well as increased glial fibrillary acid protein, a marker of neuroinflammation (P = .0098).

Ubiquitin carboxyl-terminal hydrolase L1, another marker of neuronal injury, was also elevated in those with neurologic symptoms. Regarding Alzheimer’s disease pathology, total tau (t-tau) and phosphorylated tau “also tracked with neurological sequelae,” said Dr. Wisniewski.

There was no difference in levels of amyloid beta 40 (A beta 40) between groups. However, A beta 42 plasma levels were significantly lower in those with neurologic effects, suggesting higher levels in the brain. In addition, the ratio of t-tau to A beta 42 “clearly differentiated the two groups,” he said.

“Serum biomarkers of neuroinflammation and neuronal injury and Alzheimer’s disease correlate strongly, perhaps suggesting that folks with COVID infection and neurological sequelae may have an acceleration of Alzheimer’s disease symptoms and pathology,” he said. “That’s something that needs longer follow-up.”
 

Important differentiation

Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said the study provides important information. The inclusion of plasma biomarkers in this research is “really critical to tease out what’s the impact of COVID itself on the brain,” said Dr. Edelmayer.

“We’re in an era of biomarkers when it comes to Alzheimer’s disease and other dementias, and being able to define those changes that are happening in the brain over time is going to be really critical and aid in early detection and accurate diagnoses,” she said.

What is still to be learned is what these biomarkers reveal long term, said Dr. Edelmayer. “Do those biological markers change? Do they go back to normal? A lot of that is still unknown,” she said.

She noted that many diseases that are linked to inflammation produce similar biomarkers in the brain – for example, neurofilament light.

With other viral infections, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), similar associations between the infection and cognition have been reported, said Dr. Edelmayer.

“But there are still a lot of questions around cause and effect. Is it really a direct effect of the virus on the brain itself? Is it an effect of having an enormous amount of inflammation going on in the body? A lot of that still needs to be teased out,” she commented.

The study was supported by the National Institutes of Health, the Alzheimer’s Association, and the State of New York. Dr. Wisniewski has consulted for Grifols, Amylon Pharmaceuticals, and Alzamed Neuro; 30 NYU patents are related to AD therapeutics.

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

Certain plasma biomarkers of neuronal damage and neuroinflammation are markedly elevated in hospitalized COVID-19 patients with neurologic symptoms compared with hospitalized COVID-19 patients without such symptoms, a new study shows.

These results suggest that COVID-19 may accelerate Alzheimer’s disease symptoms and pathology, said study investigator Thomas Wisniewski, MD, professor of neurology, pathology, and psychiatry at New York University.

The findings were presented here at the Alzheimer’s Association International Conference (AAIC) 2021.
 

Strong correlation

There’s a clear association between SARS-CoV-2 infection and Alzheimer’s disease-related dementia. Patients with Alzheimer’s disease are at threefold higher risk for the infection and have a twofold higher risk for death, Dr. Wisniewski told meeting delegates.

He and his colleagues conducted a prospective study of patients who had tested positive for SARS-CoV-2 and who experienced neurologic sequelae and SARS-CoV-2 patients who were without neurologic sequelae. All patients were hospitalized from March 10 to May 20, 2020. This was during a period when New York City was overwhelmed by COVID: About 35% of hospitalized patients had COVID.

Of those who experienced neurologic events, the most common “by far and away” (51%) was toxic metabolic encephalopathy (TME), said Dr. Wisniewski. Other associations included seizures, hypoxic/anoxic injury, and ischemic stroke.

The most common TMEs were septic and hypoxic ischemia. In most patients (78%), TME had more than one cause.

Researchers followed 196 patients with COVID and neurologic complications (case patients) and 186 matched control patients who had no neurologic complications over a period of 6 months.

“Unfortunately, both groups had poor outcomes,” said Dr. Wisniewski. About 50% had impaired cognition, and 56% experienced limitations in activities of daily living.

However, those patients with COVID-19 who had neurologic sequelae “fared even worse,” said Dr. Wisniewski. Compared with control patients, they had twofold worse Modified Rankin Scale scores and worse scores on activity of daily living, and they were much less likely to return to work.

Mechanisms by which COVID-19 affects longer-term cognitive dysfunction are unclear, but inflammation likely plays a role.

The research team compared a number of Alzheimer’s disease plasma biomarkers in 158 patients with COVID-19 who had neurologic symptoms and 152 COVID patients with COVID but no neurologic symptoms. They found marked elevations of neurofilament light, a marker of neuronal injury, in those with symptoms (P = .0003) as well as increased glial fibrillary acid protein, a marker of neuroinflammation (P = .0098).

Ubiquitin carboxyl-terminal hydrolase L1, another marker of neuronal injury, was also elevated in those with neurologic symptoms. Regarding Alzheimer’s disease pathology, total tau (t-tau) and phosphorylated tau “also tracked with neurological sequelae,” said Dr. Wisniewski.

There was no difference in levels of amyloid beta 40 (A beta 40) between groups. However, A beta 42 plasma levels were significantly lower in those with neurologic effects, suggesting higher levels in the brain. In addition, the ratio of t-tau to A beta 42 “clearly differentiated the two groups,” he said.

“Serum biomarkers of neuroinflammation and neuronal injury and Alzheimer’s disease correlate strongly, perhaps suggesting that folks with COVID infection and neurological sequelae may have an acceleration of Alzheimer’s disease symptoms and pathology,” he said. “That’s something that needs longer follow-up.”
 

Important differentiation

Commenting on the research, Rebecca Edelmayer, PhD, senior director of scientific engagement, Alzheimer’s Association, said the study provides important information. The inclusion of plasma biomarkers in this research is “really critical to tease out what’s the impact of COVID itself on the brain,” said Dr. Edelmayer.

“We’re in an era of biomarkers when it comes to Alzheimer’s disease and other dementias, and being able to define those changes that are happening in the brain over time is going to be really critical and aid in early detection and accurate diagnoses,” she said.

What is still to be learned is what these biomarkers reveal long term, said Dr. Edelmayer. “Do those biological markers change? Do they go back to normal? A lot of that is still unknown,” she said.

She noted that many diseases that are linked to inflammation produce similar biomarkers in the brain – for example, neurofilament light.

With other viral infections, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), similar associations between the infection and cognition have been reported, said Dr. Edelmayer.

“But there are still a lot of questions around cause and effect. Is it really a direct effect of the virus on the brain itself? Is it an effect of having an enormous amount of inflammation going on in the body? A lot of that still needs to be teased out,” she commented.

The study was supported by the National Institutes of Health, the Alzheimer’s Association, and the State of New York. Dr. Wisniewski has consulted for Grifols, Amylon Pharmaceuticals, and Alzamed Neuro; 30 NYU patents are related to AD therapeutics.

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

Transgender adults are more likely to experience subjective cognitive decline (SCD) than their cisgender peers, and at an earlier age, new research shows.

Investigators found transgender adults – individuals who identify with a gender different than the one assigned to them at birth – were nearly twice as likely to report subjective cognitive decline and more than twice as likely to report SCD-related functional limitations – such as reduced ability to work, volunteer, or be social – than cisgender adults.

‘Alarming’ finding

SCD is a self-reported experience of worsening memory or thinking and is one of the first clinical manifestations of Alzheimer’s disease and related dementia (ADRD). Yet there is limited research into cognitive impairment among transgender adults.

The researchers examined SCD and associated functional limitations among transgender and cisgender adults older than age 45 years who provided health and health behavior data as part of the Behavioral Risk Factor Surveillance System (BRFSS) surveys (2015-2019). 

The sample included 386,529 adults of whom 1,302 identified as transgender and 385,227 as cisgender.

Roughly 17% of transgender adults reported SCD, which is significantly higher than the 10.6% rate for cisgender adults (P < .001).

Compared with cisgender adults reporting SCD, transgender adults reporting SCD were younger (mean age 61.9 vs. 65.2 years, P = .0005), more likely to be in a racial/ethnic minority group (37.3% vs. 19.5%, P < .0001), have a high school degree or less (59.6% vs. 43.4%, P = .0003), be uninsured (17% vs. 5.5%, P = .0007) and have a depressive disorder (58.8% vs. 45.7%, P = .0028).

The fact that transgender people who reported SCD were about 3 years younger than cisgender people who reported SCD is “somewhat alarming and a red flag to ask middle-aged trans adults about their brain health and not just older or elderly trans adults,” said Dr. Cicero.

The study also showed that transgender adults reporting SCD were 2.3 times more likely to report related social and self-care limitations when compared with cisgender adults reporting SCD.

The findings align with a study reported at AAIC 2019, which showed that sexual or gender minorities (SGM) are almost 30% more likely to report subjective cognitive decline compared with the non-SGM population.
 

Cause unclear

“We are not certain what may be causing the elevated subjective cognitive decline rates among transgender adults. We postulate that it may be in part due to anti-transgender stigma and prejudice that expose transgender people to high rates of mistreatment and discrimination where they live, work, learn, seek health care, and age,” Dr. Cicero said.

“More research is needed to identify and target preventive intervention strategies, develop culturally relevant screenings, and shape policies to improve the health and well-being of the transgender population,” he added.

Weighing in on the study, Rebecca Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said “researchers have only just started to explore the experiences of dementia within the lesbian, gay, and bisexual community, but this is the first time we are seeing some specific research that’s looking at cognition in transgender individuals and gender nonbinary individuals.”

“We don’t know exactly why transgender and gender nonbinary individuals experience greater rates of subjective cognitive decline, but we do know that they have greater rates of health disparities that are considered risk factors for dementia, including higher rates of cardiovascular disease, depression, diabetes, tobacco and alcohol use, and obesity,” Dr. Edelmayer said. 

“Alzheimer’s and dementia do not discriminate. Neither can we,” Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said in a statement.

“The Alzheimer’s Association advocates for more research to better understand the cognitive and emotional needs of transgender and nonbinary individuals so that our nation’s health care providers can offer them culturally sensitive care,” said Dr. Carrillo.

The study had no specific funding. Dr. Cicero, Dr. Carrillo, and Dr. Edelmayer have disclosed no relevant financial relationships.

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

Transgender adults are more likely to experience subjective cognitive decline (SCD) than their cisgender peers, and at an earlier age, new research shows.

Investigators found transgender adults – individuals who identify with a gender different than the one assigned to them at birth – were nearly twice as likely to report subjective cognitive decline and more than twice as likely to report SCD-related functional limitations – such as reduced ability to work, volunteer, or be social – than cisgender adults.

‘Alarming’ finding

SCD is a self-reported experience of worsening memory or thinking and is one of the first clinical manifestations of Alzheimer’s disease and related dementia (ADRD). Yet there is limited research into cognitive impairment among transgender adults.

The researchers examined SCD and associated functional limitations among transgender and cisgender adults older than age 45 years who provided health and health behavior data as part of the Behavioral Risk Factor Surveillance System (BRFSS) surveys (2015-2019). 

The sample included 386,529 adults of whom 1,302 identified as transgender and 385,227 as cisgender.

Roughly 17% of transgender adults reported SCD, which is significantly higher than the 10.6% rate for cisgender adults (P < .001).

Compared with cisgender adults reporting SCD, transgender adults reporting SCD were younger (mean age 61.9 vs. 65.2 years, P = .0005), more likely to be in a racial/ethnic minority group (37.3% vs. 19.5%, P < .0001), have a high school degree or less (59.6% vs. 43.4%, P = .0003), be uninsured (17% vs. 5.5%, P = .0007) and have a depressive disorder (58.8% vs. 45.7%, P = .0028).

The fact that transgender people who reported SCD were about 3 years younger than cisgender people who reported SCD is “somewhat alarming and a red flag to ask middle-aged trans adults about their brain health and not just older or elderly trans adults,” said Dr. Cicero.

The study also showed that transgender adults reporting SCD were 2.3 times more likely to report related social and self-care limitations when compared with cisgender adults reporting SCD.

The findings align with a study reported at AAIC 2019, which showed that sexual or gender minorities (SGM) are almost 30% more likely to report subjective cognitive decline compared with the non-SGM population.
 

Cause unclear

“We are not certain what may be causing the elevated subjective cognitive decline rates among transgender adults. We postulate that it may be in part due to anti-transgender stigma and prejudice that expose transgender people to high rates of mistreatment and discrimination where they live, work, learn, seek health care, and age,” Dr. Cicero said.

“More research is needed to identify and target preventive intervention strategies, develop culturally relevant screenings, and shape policies to improve the health and well-being of the transgender population,” he added.

Weighing in on the study, Rebecca Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said “researchers have only just started to explore the experiences of dementia within the lesbian, gay, and bisexual community, but this is the first time we are seeing some specific research that’s looking at cognition in transgender individuals and gender nonbinary individuals.”

“We don’t know exactly why transgender and gender nonbinary individuals experience greater rates of subjective cognitive decline, but we do know that they have greater rates of health disparities that are considered risk factors for dementia, including higher rates of cardiovascular disease, depression, diabetes, tobacco and alcohol use, and obesity,” Dr. Edelmayer said. 

“Alzheimer’s and dementia do not discriminate. Neither can we,” Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said in a statement.

“The Alzheimer’s Association advocates for more research to better understand the cognitive and emotional needs of transgender and nonbinary individuals so that our nation’s health care providers can offer them culturally sensitive care,” said Dr. Carrillo.

The study had no specific funding. Dr. Cicero, Dr. Carrillo, and Dr. Edelmayer have disclosed no relevant financial relationships.

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

Transgender adults are more likely to experience subjective cognitive decline (SCD) than their cisgender peers, and at an earlier age, new research shows.

Investigators found transgender adults – individuals who identify with a gender different than the one assigned to them at birth – were nearly twice as likely to report subjective cognitive decline and more than twice as likely to report SCD-related functional limitations – such as reduced ability to work, volunteer, or be social – than cisgender adults.

‘Alarming’ finding

SCD is a self-reported experience of worsening memory or thinking and is one of the first clinical manifestations of Alzheimer’s disease and related dementia (ADRD). Yet there is limited research into cognitive impairment among transgender adults.

The researchers examined SCD and associated functional limitations among transgender and cisgender adults older than age 45 years who provided health and health behavior data as part of the Behavioral Risk Factor Surveillance System (BRFSS) surveys (2015-2019). 

The sample included 386,529 adults of whom 1,302 identified as transgender and 385,227 as cisgender.

Roughly 17% of transgender adults reported SCD, which is significantly higher than the 10.6% rate for cisgender adults (P < .001).

Compared with cisgender adults reporting SCD, transgender adults reporting SCD were younger (mean age 61.9 vs. 65.2 years, P = .0005), more likely to be in a racial/ethnic minority group (37.3% vs. 19.5%, P < .0001), have a high school degree or less (59.6% vs. 43.4%, P = .0003), be uninsured (17% vs. 5.5%, P = .0007) and have a depressive disorder (58.8% vs. 45.7%, P = .0028).

The fact that transgender people who reported SCD were about 3 years younger than cisgender people who reported SCD is “somewhat alarming and a red flag to ask middle-aged trans adults about their brain health and not just older or elderly trans adults,” said Dr. Cicero.

The study also showed that transgender adults reporting SCD were 2.3 times more likely to report related social and self-care limitations when compared with cisgender adults reporting SCD.

The findings align with a study reported at AAIC 2019, which showed that sexual or gender minorities (SGM) are almost 30% more likely to report subjective cognitive decline compared with the non-SGM population.
 

Cause unclear

“We are not certain what may be causing the elevated subjective cognitive decline rates among transgender adults. We postulate that it may be in part due to anti-transgender stigma and prejudice that expose transgender people to high rates of mistreatment and discrimination where they live, work, learn, seek health care, and age,” Dr. Cicero said.

“More research is needed to identify and target preventive intervention strategies, develop culturally relevant screenings, and shape policies to improve the health and well-being of the transgender population,” he added.

Weighing in on the study, Rebecca Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said “researchers have only just started to explore the experiences of dementia within the lesbian, gay, and bisexual community, but this is the first time we are seeing some specific research that’s looking at cognition in transgender individuals and gender nonbinary individuals.”

“We don’t know exactly why transgender and gender nonbinary individuals experience greater rates of subjective cognitive decline, but we do know that they have greater rates of health disparities that are considered risk factors for dementia, including higher rates of cardiovascular disease, depression, diabetes, tobacco and alcohol use, and obesity,” Dr. Edelmayer said. 

“Alzheimer’s and dementia do not discriminate. Neither can we,” Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said in a statement.

“The Alzheimer’s Association advocates for more research to better understand the cognitive and emotional needs of transgender and nonbinary individuals so that our nation’s health care providers can offer them culturally sensitive care,” said Dr. Carrillo.

The study had no specific funding. Dr. Cicero, Dr. Carrillo, and Dr. Edelmayer have disclosed no relevant financial relationships.

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

A new study documents a handful of cases of women with Munchausen syndrome by Internet who targeted doulas in the United Kingdom during the COVID-19 lockdown. The women pretended to have a variety of dramatic perinatal crises that garnered them significant attention from birth support professionals.

The five cases were investigated by Kathryn Newns, MSc, DClinPsy, a clinical psychologist in Cambridge, England, who said the cases were brought to her attention by a doula she herself had used for the birth of her own child a decade earlier.

Dr. Newns said she believes these are not isolated cases – either geographically or in terms of the specialty involved.

“I don’t think it is likely that this is only happening in the United Kingdom. And I’m sure it’s not just happening in the doula world,” Dr. Newns told this news organization.

Coinvestigator Marc Feldman, MD, a clinical professor of psychiatry at the University of Alabama, Tuscaloosa, coined the term “Munchausen by Internet” in a 2000 article. The expression refers to use of electronic media to perpetrate hoaxes that reward posers with sympathy, control, or emotional gratification. The hoaxers do not seek financial gain.

“The ease of carrying out Munchausen behaviors makes me think that it must be much more common than it ever was,” Dr. Feldman said in an interview.

He noted that the new DSM-5 will eliminate the terms “Munchausen” and “Munchausen by Internet” and will clarify that “factitious disorder” can be partly or wholly carried out online.

The study was published in the May issue of the Annals of Clinical Psychiatry.
 

A warning for others

In the past, those with factitious disorder had to go to medical libraries to study up on the ailment they wanted to feign. They would then present to an emergency department or a doctor’s office and act convincingly, Dr. Feldman said.

“Now all you have to do is go to Wikipedia and you can become an expert on a medical ailment within a few minutes,” he added.

In the five cases described in the study, the hoaxers created rich stories, especially in cases 1 and 2. In those cases, the perpetrator turned out to be the same person. Subterfuge “obviously made it much harder to know she wasn’t who she purported to be,” said Dr. Newns.

Dr. Feldman noted that in Munchausen by Internet, there may be some element of truth within the stories.

For health care professionals, “it takes a considerable leap to assume that somebody who’s talking about some dreaded ailment is in fact exaggerating or outright lying,” he said.

In the five cases described in the study, persons contacted doulas, then related traumatic stories and described dramatic, immediate needs. All of the doulas were working remotely because of the COVID-19 pandemic. This likely made it easier for the perpetrators to pull off the hoaxes. The health care professionals agreed to share their experiences in the hopes of warning others.
 

Elaborate scenarios

The first two cases were ultimately determined to involve one person who had created elaborate scenarios.

In case 1, the hoaxer, who called herself “Jessica,” texted the doula “Charlotte” when she was allegedly 39 weeks’ pregnant. She said she was unable to go to the hospital because of the COVID-19 risks to her husband, who had cystic fibrosis and had recently undergone a heart and lung transplant.

The husband “Jordan” took over communications, using the same WhatsApp number as Jessica, as Jessica went into labor.

Ostensibly, a midwife team had come to Jessica’s and Jordan’s house. When the doula was on the phone with Jordan, she heard Jessica crying, grunting, and screaming, and then, at 2:00 a.m., she heard the sound of a baby crying. A photo of the baby was texted to Charlotte.

Soon, there were many problems. Jessica allegedly had a postpartum hemorrhage, and mother and baby were taken to separate hospitals. The baby was then diagnosed with congenital heart disease.

Over the next week, “midwives” started texting back and forth with Charlotte. The doula began to have doubts and asked a midwife to share a visual communication.

After receiving no response, Charlotte used a video call, got Jessica on screen, and told her she thought there was no baby. Jessica said the baby was real and showed a “growth chart” as proof of the 5-day-old baby’s existence. The birth and baby noises were later determined to be recordings.
 

Child deaths

After sharing information among themselves on a private Facebook group, the doulas determined that the person in case 2, “Dakota,” was the same woman who was involved in case 1.

In case 2, a doula had spent 2 years supporting Dakota through the deaths of a parent and her baby, who had a congenital defect. A baby-loss charity had also worked with Dakota but could not confirm the baby’s existence.

Dakota had gone so far as to make a video for the doula that showed a hospital room. In a voice-over, Dakota thanks everyone for the support she received as the baby died.

In case 3, “Hannah” texted a doula seeking emotional but not birth support. The doula, Nikki Barrow, has recounted the case on her own blog.

Hannah became desperate when she went into labor. Ms. Barrow remained close via texts, phone, and video calls, even as the baby supposedly died after 3 days. The doula lit a candle for the baby and cried with Hannah.

Ms. Barrow was eventually able to break away from Hannah, saying she was not a bereavement specialist. However, days later, Hannah tracked her down and claimed she had an infection in her heart and did not have much time to live. At that point, Ms. Barrow stopped all contact.

She determined from other doulas that Hannah had been hoaxing doulas for 4 or 5 years. Some had offered to get her help, but she refused and ended all contact.
 

Multiple COVID crises?

In case 4, a woman sought support on a doula-centered Facebook page and said her partner “Jack” would be in touch. Jack sent the doula hundreds of emails, texts, and WhatsApp messages and then said he was hospitalized with COVID. The woman, “Hayley,” was also soon diagnosed with COVID.

Hayley refused video contact and did not share photos. Drama continued to unfold. She reported that her baby was breach, that she had a second uterus with a second pregnancy simultaneously, and that the baby had COVID.

Hayley also claimed that her partner had come to the hospital, had raped her, and had brandished a gun. When the doula called the police, they did not find Hayley at the hospital or elsewhere.

In case 5, a “grandmother” contacted “Lisa” to find a doula for her daughter-in-law, “Anna.” Hours later, Anna was giving birth, and the baby had to be taken to the hospital because of cardiac and breathing problems. The doula heard nothing more after a few weeks.

However, at least three other doulas said they had supported the same “family.”
 

Online training program

In all cases, the doulas were not paid for their time. Reports to the police prompted no action because no money had changed hands. Some doulas said they felt bereaved, angry, or “silly” that they had been hoodwinked. All noted how difficult it was to disengage from clients who seemed to be in peril.

Ms. Barrow decided to create an online training program in which doulas are advised on how to stay safe while working online.

DoulaMatch, which matches birth support specialists with women in the United States and Canada, offers tips to help protect doulas from hoaxes.

Kim James, BDT(DONA), ICCE, LCCE, CLE, the owner and operator of DoulaMatch, said the organization is aware of “scammers who waste everyone’s time and have found doulas to be the latest easy targets.”

However, she noted, “I’ve only very occasionally and anecdotally heard about people fabricating a pregnancy for emotional gratification.”

In his 2000 article, Dr. Feldman offers clues to help detect hoaxers. He advises clinicians to be wary of the following:

• Cases in which the length, frequency, and duration of posts are incongruous with the severity of the illness the person is claiming to have; for example, someone who claims to be in  submitting detailed posts.
• Near-fatal exacerbations of illness alternating with miraculous recoveries.
• Personal claims that are fantastic, are contradicted by later posts, or are disproved.
• Continual dramatic events occurring in the person’s life, especially when others in a group become the focus of attention.
• Others ostensibly posting on behalf of the individual who have identical patterns of writing, such as making grammatical errors, misspellings, and using stylistic idiosyncrasies.

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

A new study documents a handful of cases of women with Munchausen syndrome by Internet who targeted doulas in the United Kingdom during the COVID-19 lockdown. The women pretended to have a variety of dramatic perinatal crises that garnered them significant attention from birth support professionals.

The five cases were investigated by Kathryn Newns, MSc, DClinPsy, a clinical psychologist in Cambridge, England, who said the cases were brought to her attention by a doula she herself had used for the birth of her own child a decade earlier.

Dr. Newns said she believes these are not isolated cases – either geographically or in terms of the specialty involved.

“I don’t think it is likely that this is only happening in the United Kingdom. And I’m sure it’s not just happening in the doula world,” Dr. Newns told this news organization.

Coinvestigator Marc Feldman, MD, a clinical professor of psychiatry at the University of Alabama, Tuscaloosa, coined the term “Munchausen by Internet” in a 2000 article. The expression refers to use of electronic media to perpetrate hoaxes that reward posers with sympathy, control, or emotional gratification. The hoaxers do not seek financial gain.

“The ease of carrying out Munchausen behaviors makes me think that it must be much more common than it ever was,” Dr. Feldman said in an interview.

He noted that the new DSM-5 will eliminate the terms “Munchausen” and “Munchausen by Internet” and will clarify that “factitious disorder” can be partly or wholly carried out online.

The study was published in the May issue of the Annals of Clinical Psychiatry.
 

A warning for others

In the past, those with factitious disorder had to go to medical libraries to study up on the ailment they wanted to feign. They would then present to an emergency department or a doctor’s office and act convincingly, Dr. Feldman said.

“Now all you have to do is go to Wikipedia and you can become an expert on a medical ailment within a few minutes,” he added.

In the five cases described in the study, the hoaxers created rich stories, especially in cases 1 and 2. In those cases, the perpetrator turned out to be the same person. Subterfuge “obviously made it much harder to know she wasn’t who she purported to be,” said Dr. Newns.

Dr. Feldman noted that in Munchausen by Internet, there may be some element of truth within the stories.

For health care professionals, “it takes a considerable leap to assume that somebody who’s talking about some dreaded ailment is in fact exaggerating or outright lying,” he said.

In the five cases described in the study, persons contacted doulas, then related traumatic stories and described dramatic, immediate needs. All of the doulas were working remotely because of the COVID-19 pandemic. This likely made it easier for the perpetrators to pull off the hoaxes. The health care professionals agreed to share their experiences in the hopes of warning others.
 

Elaborate scenarios

The first two cases were ultimately determined to involve one person who had created elaborate scenarios.

In case 1, the hoaxer, who called herself “Jessica,” texted the doula “Charlotte” when she was allegedly 39 weeks’ pregnant. She said she was unable to go to the hospital because of the COVID-19 risks to her husband, who had cystic fibrosis and had recently undergone a heart and lung transplant.

The husband “Jordan” took over communications, using the same WhatsApp number as Jessica, as Jessica went into labor.

Ostensibly, a midwife team had come to Jessica’s and Jordan’s house. When the doula was on the phone with Jordan, she heard Jessica crying, grunting, and screaming, and then, at 2:00 a.m., she heard the sound of a baby crying. A photo of the baby was texted to Charlotte.

Soon, there were many problems. Jessica allegedly had a postpartum hemorrhage, and mother and baby were taken to separate hospitals. The baby was then diagnosed with congenital heart disease.

Over the next week, “midwives” started texting back and forth with Charlotte. The doula began to have doubts and asked a midwife to share a visual communication.

After receiving no response, Charlotte used a video call, got Jessica on screen, and told her she thought there was no baby. Jessica said the baby was real and showed a “growth chart” as proof of the 5-day-old baby’s existence. The birth and baby noises were later determined to be recordings.
 

Child deaths

After sharing information among themselves on a private Facebook group, the doulas determined that the person in case 2, “Dakota,” was the same woman who was involved in case 1.

In case 2, a doula had spent 2 years supporting Dakota through the deaths of a parent and her baby, who had a congenital defect. A baby-loss charity had also worked with Dakota but could not confirm the baby’s existence.

Dakota had gone so far as to make a video for the doula that showed a hospital room. In a voice-over, Dakota thanks everyone for the support she received as the baby died.

In case 3, “Hannah” texted a doula seeking emotional but not birth support. The doula, Nikki Barrow, has recounted the case on her own blog.

Hannah became desperate when she went into labor. Ms. Barrow remained close via texts, phone, and video calls, even as the baby supposedly died after 3 days. The doula lit a candle for the baby and cried with Hannah.

Ms. Barrow was eventually able to break away from Hannah, saying she was not a bereavement specialist. However, days later, Hannah tracked her down and claimed she had an infection in her heart and did not have much time to live. At that point, Ms. Barrow stopped all contact.

She determined from other doulas that Hannah had been hoaxing doulas for 4 or 5 years. Some had offered to get her help, but she refused and ended all contact.
 

Multiple COVID crises?

In case 4, a woman sought support on a doula-centered Facebook page and said her partner “Jack” would be in touch. Jack sent the doula hundreds of emails, texts, and WhatsApp messages and then said he was hospitalized with COVID. The woman, “Hayley,” was also soon diagnosed with COVID.

Hayley refused video contact and did not share photos. Drama continued to unfold. She reported that her baby was breach, that she had a second uterus with a second pregnancy simultaneously, and that the baby had COVID.

Hayley also claimed that her partner had come to the hospital, had raped her, and had brandished a gun. When the doula called the police, they did not find Hayley at the hospital or elsewhere.

In case 5, a “grandmother” contacted “Lisa” to find a doula for her daughter-in-law, “Anna.” Hours later, Anna was giving birth, and the baby had to be taken to the hospital because of cardiac and breathing problems. The doula heard nothing more after a few weeks.

However, at least three other doulas said they had supported the same “family.”
 

Online training program

In all cases, the doulas were not paid for their time. Reports to the police prompted no action because no money had changed hands. Some doulas said they felt bereaved, angry, or “silly” that they had been hoodwinked. All noted how difficult it was to disengage from clients who seemed to be in peril.

Ms. Barrow decided to create an online training program in which doulas are advised on how to stay safe while working online.

DoulaMatch, which matches birth support specialists with women in the United States and Canada, offers tips to help protect doulas from hoaxes.

Kim James, BDT(DONA), ICCE, LCCE, CLE, the owner and operator of DoulaMatch, said the organization is aware of “scammers who waste everyone’s time and have found doulas to be the latest easy targets.”

However, she noted, “I’ve only very occasionally and anecdotally heard about people fabricating a pregnancy for emotional gratification.”

In his 2000 article, Dr. Feldman offers clues to help detect hoaxers. He advises clinicians to be wary of the following:

• Cases in which the length, frequency, and duration of posts are incongruous with the severity of the illness the person is claiming to have; for example, someone who claims to be in  submitting detailed posts.
• Near-fatal exacerbations of illness alternating with miraculous recoveries.
• Personal claims that are fantastic, are contradicted by later posts, or are disproved.
• Continual dramatic events occurring in the person’s life, especially when others in a group become the focus of attention.
• Others ostensibly posting on behalf of the individual who have identical patterns of writing, such as making grammatical errors, misspellings, and using stylistic idiosyncrasies.

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

A new study documents a handful of cases of women with Munchausen syndrome by Internet who targeted doulas in the United Kingdom during the COVID-19 lockdown. The women pretended to have a variety of dramatic perinatal crises that garnered them significant attention from birth support professionals.

The five cases were investigated by Kathryn Newns, MSc, DClinPsy, a clinical psychologist in Cambridge, England, who said the cases were brought to her attention by a doula she herself had used for the birth of her own child a decade earlier.

Dr. Newns said she believes these are not isolated cases – either geographically or in terms of the specialty involved.

“I don’t think it is likely that this is only happening in the United Kingdom. And I’m sure it’s not just happening in the doula world,” Dr. Newns told this news organization.

Coinvestigator Marc Feldman, MD, a clinical professor of psychiatry at the University of Alabama, Tuscaloosa, coined the term “Munchausen by Internet” in a 2000 article. The expression refers to use of electronic media to perpetrate hoaxes that reward posers with sympathy, control, or emotional gratification. The hoaxers do not seek financial gain.

“The ease of carrying out Munchausen behaviors makes me think that it must be much more common than it ever was,” Dr. Feldman said in an interview.

He noted that the new DSM-5 will eliminate the terms “Munchausen” and “Munchausen by Internet” and will clarify that “factitious disorder” can be partly or wholly carried out online.

The study was published in the May issue of the Annals of Clinical Psychiatry.
 

A warning for others

In the past, those with factitious disorder had to go to medical libraries to study up on the ailment they wanted to feign. They would then present to an emergency department or a doctor’s office and act convincingly, Dr. Feldman said.

“Now all you have to do is go to Wikipedia and you can become an expert on a medical ailment within a few minutes,” he added.

In the five cases described in the study, the hoaxers created rich stories, especially in cases 1 and 2. In those cases, the perpetrator turned out to be the same person. Subterfuge “obviously made it much harder to know she wasn’t who she purported to be,” said Dr. Newns.

Dr. Feldman noted that in Munchausen by Internet, there may be some element of truth within the stories.

For health care professionals, “it takes a considerable leap to assume that somebody who’s talking about some dreaded ailment is in fact exaggerating or outright lying,” he said.

In the five cases described in the study, persons contacted doulas, then related traumatic stories and described dramatic, immediate needs. All of the doulas were working remotely because of the COVID-19 pandemic. This likely made it easier for the perpetrators to pull off the hoaxes. The health care professionals agreed to share their experiences in the hopes of warning others.
 

Elaborate scenarios

The first two cases were ultimately determined to involve one person who had created elaborate scenarios.

In case 1, the hoaxer, who called herself “Jessica,” texted the doula “Charlotte” when she was allegedly 39 weeks’ pregnant. She said she was unable to go to the hospital because of the COVID-19 risks to her husband, who had cystic fibrosis and had recently undergone a heart and lung transplant.

The husband “Jordan” took over communications, using the same WhatsApp number as Jessica, as Jessica went into labor.

Ostensibly, a midwife team had come to Jessica’s and Jordan’s house. When the doula was on the phone with Jordan, she heard Jessica crying, grunting, and screaming, and then, at 2:00 a.m., she heard the sound of a baby crying. A photo of the baby was texted to Charlotte.

Soon, there were many problems. Jessica allegedly had a postpartum hemorrhage, and mother and baby were taken to separate hospitals. The baby was then diagnosed with congenital heart disease.

Over the next week, “midwives” started texting back and forth with Charlotte. The doula began to have doubts and asked a midwife to share a visual communication.

After receiving no response, Charlotte used a video call, got Jessica on screen, and told her she thought there was no baby. Jessica said the baby was real and showed a “growth chart” as proof of the 5-day-old baby’s existence. The birth and baby noises were later determined to be recordings.
 

Child deaths

After sharing information among themselves on a private Facebook group, the doulas determined that the person in case 2, “Dakota,” was the same woman who was involved in case 1.

In case 2, a doula had spent 2 years supporting Dakota through the deaths of a parent and her baby, who had a congenital defect. A baby-loss charity had also worked with Dakota but could not confirm the baby’s existence.

Dakota had gone so far as to make a video for the doula that showed a hospital room. In a voice-over, Dakota thanks everyone for the support she received as the baby died.

In case 3, “Hannah” texted a doula seeking emotional but not birth support. The doula, Nikki Barrow, has recounted the case on her own blog.

Hannah became desperate when she went into labor. Ms. Barrow remained close via texts, phone, and video calls, even as the baby supposedly died after 3 days. The doula lit a candle for the baby and cried with Hannah.

Ms. Barrow was eventually able to break away from Hannah, saying she was not a bereavement specialist. However, days later, Hannah tracked her down and claimed she had an infection in her heart and did not have much time to live. At that point, Ms. Barrow stopped all contact.

She determined from other doulas that Hannah had been hoaxing doulas for 4 or 5 years. Some had offered to get her help, but she refused and ended all contact.
 

Multiple COVID crises?

In case 4, a woman sought support on a doula-centered Facebook page and said her partner “Jack” would be in touch. Jack sent the doula hundreds of emails, texts, and WhatsApp messages and then said he was hospitalized with COVID. The woman, “Hayley,” was also soon diagnosed with COVID.

Hayley refused video contact and did not share photos. Drama continued to unfold. She reported that her baby was breach, that she had a second uterus with a second pregnancy simultaneously, and that the baby had COVID.

Hayley also claimed that her partner had come to the hospital, had raped her, and had brandished a gun. When the doula called the police, they did not find Hayley at the hospital or elsewhere.

In case 5, a “grandmother” contacted “Lisa” to find a doula for her daughter-in-law, “Anna.” Hours later, Anna was giving birth, and the baby had to be taken to the hospital because of cardiac and breathing problems. The doula heard nothing more after a few weeks.

However, at least three other doulas said they had supported the same “family.”
 

Online training program

In all cases, the doulas were not paid for their time. Reports to the police prompted no action because no money had changed hands. Some doulas said they felt bereaved, angry, or “silly” that they had been hoodwinked. All noted how difficult it was to disengage from clients who seemed to be in peril.

Ms. Barrow decided to create an online training program in which doulas are advised on how to stay safe while working online.

DoulaMatch, which matches birth support specialists with women in the United States and Canada, offers tips to help protect doulas from hoaxes.

Kim James, BDT(DONA), ICCE, LCCE, CLE, the owner and operator of DoulaMatch, said the organization is aware of “scammers who waste everyone’s time and have found doulas to be the latest easy targets.”

However, she noted, “I’ve only very occasionally and anecdotally heard about people fabricating a pregnancy for emotional gratification.”

In his 2000 article, Dr. Feldman offers clues to help detect hoaxers. He advises clinicians to be wary of the following:

• Cases in which the length, frequency, and duration of posts are incongruous with the severity of the illness the person is claiming to have; for example, someone who claims to be in  submitting detailed posts.
• Near-fatal exacerbations of illness alternating with miraculous recoveries.
• Personal claims that are fantastic, are contradicted by later posts, or are disproved.
• Continual dramatic events occurring in the person’s life, especially when others in a group become the focus of attention.
• Others ostensibly posting on behalf of the individual who have identical patterns of writing, such as making grammatical errors, misspellings, and using stylistic idiosyncrasies.

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

In recent years, a new genre of medical intervention has started to emerge – digital therapeutics. In the wake of promising results in a number of conditions, one high-profile approval by the Food and Drug Administration, and several ongoing clinical studies, neurologists (and other doctors) may soon be prescribing video games alongside conventional therapies for several conditions.

“Digital therapeutics refers to a software-based intervention. It’s not just digital information or digital monitoring, it’s an alternative treatment option based on software,” said John Krakauer, MD, professor of neurology, neuroscience, and physical medicine and rehabilitation at The Johns Hopkins University, Baltimore.

Dr. Krakauer explained that the nervous system is especially amenable to gamified therapies because of its unique ability to learn. “It’s an experience-dependent plastic system. You really want to have a high-intensity, high-dose behavioral intervention to try and rewire and train the nervous system.

“In other words, digital therapeutics complements what happens in physical and occupational therapy sessions with scientifically-informed behavioral interventions based on technology and software,” he said.
 

The digital dolphin treating stroke

Dr. Krakauer, chief scientific adviser to the company MindMaze, studies immersive digital therapies to enhance neurorehabilitation following stroke. He works on MindPod Dolphin, a virtual reality game that trains motor control of the upper extremities by having the patient simulate swimming in the ocean like a dolphin.

“Your movement is tracked, there are artificial intelligence algorithms controlling the difficulty, and the whole purpose is to take your nervous system for a ride, outside the context of activities of daily living. Patients are so engaged and immersed that they don’t even realize they’re making high-quality, high-intensity, high-dose movements of their arm.”

In a pilot trial called SMARTS2, his group found that MindPod Dolphin was about twice as effective as regular rehabilitation for upper extremity motor recovery in patients who had had a stroke. A larger trial is currently underway in New Zealand.

Another preliminary study found that MindPod Dolphin had positive effects on the physical and cognitive health of elderly patients in an assisted-living facility. Now, MindPod Dolphin is being studied around the world in patients with multiple sclerosis, Parkinson’s disease, concussion, and traumatic brain injury (TBI). There is even a Department of Defense–funded trial underway for veterans with TBI.
 

Reaching young patients through virtual play

Isabela Granic, PhD, director of the Games for Emotional and Mental Health Lab, and professor and chair of the developmental psychopathology department in the Behavioural Science Institute at Radboud University in the Netherlands, studies gamified therapy for depression and anxiety.

“We take evidence-based techniques in the mental health clinical world or developmental research, such as cognitive-behavioral therapy (CBT) or exposure therapy, and then embed them in games to use a different engine for delivering something we otherwise know works,” she said.

Data for a game she developed called MindLight are promising so far. “We have randomized controlled trials showing that we can cut young people’s anxiety in half after they have as little as five 1-hour sessions per week. We’ve shown that we can get the same benefits as CBT for these young people, which is huge.” MindLight also has proved effective for treating anxiety in children with autism.
 

A first for therapeutic video games

In the summer of 2020, EndeavorRx, made by Akili Interactive, became the first prescription video game to be approved by the FDA. The game, which is designed to improve attention function, is currently authorized for children aged 8-12 with attention-deficit/hyperactivity disorder.

Players complete “missions” by steering an aircraft through complex obstacle courses and collecting targets. The prescription directs the child to complete five missions each day for 5 days per week. It is recommended that patients use EndeavorRx for at least 4 weeks. Researchers are hopeful that, moving forward, the game will also prove effective for other cognitive disorders, including dementias and mild cognitive impairment.

EndeavorRx is even being studied for its efficacy in combating brain fog in COVID-19 long-haulers. A team of researchers led by Faith Gunning, PhD, psychologist and vice chair of research in the department of psychiatry at Weill Cornell Medicine, New York, is performing a trial of EndeavorRx for post–COVID-19 cognitive dysfunction.

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

In recent years, a new genre of medical intervention has started to emerge – digital therapeutics. In the wake of promising results in a number of conditions, one high-profile approval by the Food and Drug Administration, and several ongoing clinical studies, neurologists (and other doctors) may soon be prescribing video games alongside conventional therapies for several conditions.

“Digital therapeutics refers to a software-based intervention. It’s not just digital information or digital monitoring, it’s an alternative treatment option based on software,” said John Krakauer, MD, professor of neurology, neuroscience, and physical medicine and rehabilitation at The Johns Hopkins University, Baltimore.

Dr. Krakauer explained that the nervous system is especially amenable to gamified therapies because of its unique ability to learn. “It’s an experience-dependent plastic system. You really want to have a high-intensity, high-dose behavioral intervention to try and rewire and train the nervous system.

“In other words, digital therapeutics complements what happens in physical and occupational therapy sessions with scientifically-informed behavioral interventions based on technology and software,” he said.
 

The digital dolphin treating stroke

Dr. Krakauer, chief scientific adviser to the company MindMaze, studies immersive digital therapies to enhance neurorehabilitation following stroke. He works on MindPod Dolphin, a virtual reality game that trains motor control of the upper extremities by having the patient simulate swimming in the ocean like a dolphin.

“Your movement is tracked, there are artificial intelligence algorithms controlling the difficulty, and the whole purpose is to take your nervous system for a ride, outside the context of activities of daily living. Patients are so engaged and immersed that they don’t even realize they’re making high-quality, high-intensity, high-dose movements of their arm.”

In a pilot trial called SMARTS2, his group found that MindPod Dolphin was about twice as effective as regular rehabilitation for upper extremity motor recovery in patients who had had a stroke. A larger trial is currently underway in New Zealand.

Another preliminary study found that MindPod Dolphin had positive effects on the physical and cognitive health of elderly patients in an assisted-living facility. Now, MindPod Dolphin is being studied around the world in patients with multiple sclerosis, Parkinson’s disease, concussion, and traumatic brain injury (TBI). There is even a Department of Defense–funded trial underway for veterans with TBI.
 

Reaching young patients through virtual play

Isabela Granic, PhD, director of the Games for Emotional and Mental Health Lab, and professor and chair of the developmental psychopathology department in the Behavioural Science Institute at Radboud University in the Netherlands, studies gamified therapy for depression and anxiety.

“We take evidence-based techniques in the mental health clinical world or developmental research, such as cognitive-behavioral therapy (CBT) or exposure therapy, and then embed them in games to use a different engine for delivering something we otherwise know works,” she said.

Data for a game she developed called MindLight are promising so far. “We have randomized controlled trials showing that we can cut young people’s anxiety in half after they have as little as five 1-hour sessions per week. We’ve shown that we can get the same benefits as CBT for these young people, which is huge.” MindLight also has proved effective for treating anxiety in children with autism.
 

A first for therapeutic video games

In the summer of 2020, EndeavorRx, made by Akili Interactive, became the first prescription video game to be approved by the FDA. The game, which is designed to improve attention function, is currently authorized for children aged 8-12 with attention-deficit/hyperactivity disorder.

Players complete “missions” by steering an aircraft through complex obstacle courses and collecting targets. The prescription directs the child to complete five missions each day for 5 days per week. It is recommended that patients use EndeavorRx for at least 4 weeks. Researchers are hopeful that, moving forward, the game will also prove effective for other cognitive disorders, including dementias and mild cognitive impairment.

EndeavorRx is even being studied for its efficacy in combating brain fog in COVID-19 long-haulers. A team of researchers led by Faith Gunning, PhD, psychologist and vice chair of research in the department of psychiatry at Weill Cornell Medicine, New York, is performing a trial of EndeavorRx for post–COVID-19 cognitive dysfunction.

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

In recent years, a new genre of medical intervention has started to emerge – digital therapeutics. In the wake of promising results in a number of conditions, one high-profile approval by the Food and Drug Administration, and several ongoing clinical studies, neurologists (and other doctors) may soon be prescribing video games alongside conventional therapies for several conditions.

“Digital therapeutics refers to a software-based intervention. It’s not just digital information or digital monitoring, it’s an alternative treatment option based on software,” said John Krakauer, MD, professor of neurology, neuroscience, and physical medicine and rehabilitation at The Johns Hopkins University, Baltimore.

Dr. Krakauer explained that the nervous system is especially amenable to gamified therapies because of its unique ability to learn. “It’s an experience-dependent plastic system. You really want to have a high-intensity, high-dose behavioral intervention to try and rewire and train the nervous system.

“In other words, digital therapeutics complements what happens in physical and occupational therapy sessions with scientifically-informed behavioral interventions based on technology and software,” he said.
 

The digital dolphin treating stroke

Dr. Krakauer, chief scientific adviser to the company MindMaze, studies immersive digital therapies to enhance neurorehabilitation following stroke. He works on MindPod Dolphin, a virtual reality game that trains motor control of the upper extremities by having the patient simulate swimming in the ocean like a dolphin.

“Your movement is tracked, there are artificial intelligence algorithms controlling the difficulty, and the whole purpose is to take your nervous system for a ride, outside the context of activities of daily living. Patients are so engaged and immersed that they don’t even realize they’re making high-quality, high-intensity, high-dose movements of their arm.”

In a pilot trial called SMARTS2, his group found that MindPod Dolphin was about twice as effective as regular rehabilitation for upper extremity motor recovery in patients who had had a stroke. A larger trial is currently underway in New Zealand.

Another preliminary study found that MindPod Dolphin had positive effects on the physical and cognitive health of elderly patients in an assisted-living facility. Now, MindPod Dolphin is being studied around the world in patients with multiple sclerosis, Parkinson’s disease, concussion, and traumatic brain injury (TBI). There is even a Department of Defense–funded trial underway for veterans with TBI.
 

Reaching young patients through virtual play

Isabela Granic, PhD, director of the Games for Emotional and Mental Health Lab, and professor and chair of the developmental psychopathology department in the Behavioural Science Institute at Radboud University in the Netherlands, studies gamified therapy for depression and anxiety.

“We take evidence-based techniques in the mental health clinical world or developmental research, such as cognitive-behavioral therapy (CBT) or exposure therapy, and then embed them in games to use a different engine for delivering something we otherwise know works,” she said.

Data for a game she developed called MindLight are promising so far. “We have randomized controlled trials showing that we can cut young people’s anxiety in half after they have as little as five 1-hour sessions per week. We’ve shown that we can get the same benefits as CBT for these young people, which is huge.” MindLight also has proved effective for treating anxiety in children with autism.
 

A first for therapeutic video games

In the summer of 2020, EndeavorRx, made by Akili Interactive, became the first prescription video game to be approved by the FDA. The game, which is designed to improve attention function, is currently authorized for children aged 8-12 with attention-deficit/hyperactivity disorder.

Players complete “missions” by steering an aircraft through complex obstacle courses and collecting targets. The prescription directs the child to complete five missions each day for 5 days per week. It is recommended that patients use EndeavorRx for at least 4 weeks. Researchers are hopeful that, moving forward, the game will also prove effective for other cognitive disorders, including dementias and mild cognitive impairment.

EndeavorRx is even being studied for its efficacy in combating brain fog in COVID-19 long-haulers. A team of researchers led by Faith Gunning, PhD, psychologist and vice chair of research in the department of psychiatry at Weill Cornell Medicine, New York, is performing a trial of EndeavorRx for post–COVID-19 cognitive dysfunction.

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

“One of the most important considerations before switching HIV patients to injectable long-acting cabotegravir/rilpivirine [CAB/RPV LA; Cabenuva, ViiV Healthcare] is for the patient and the clinician to arrive at this decision together,” Elliot DeHaan, MD, told this news organization. “This therapy is not necessarily for everyone.”

Dr. DeHaan is lead author of the newly released clinical guideline from the New York State Department of Health AIDS Institute for use of CAB/RPV LA as replacement antiretroviral therapy (ART) in virally suppressed adults with HIV. He explained that the guidance expands upon Health & Human Services’ Feb. 24 CAB/RPV LA recommendations, highlighting some of the most important clinical and patient considerations necessary to implement injectable ART. “There are a lot of things that need to be laid out beforehand,” he said.
 

Gaining consensus

Approved by the FDA in late January 2021, CAB/RPV LA is considered an optimization strategy for individuals with HIV whose virus is suppressed by oral ART and who might prefer monthly injections to daily oral therapy. While there are various reasons why patients might wish to switch to a long-acting injectable, one of the primary concerns is adherence. Of note, the guidance points to phase 3 clinical study findings that suggest high levels (86%-91%) of patient satisfaction with CAB/RPV LA, which portends a promising future for this therapeutic approach.

With regard to patient preference, recommendations focus on the need to thoroughly discuss several critical requisites with potential candidates, including a 4-week lead-in daily oral ART course (CAB [Vocabria] 30 mg, RPV [Edurant] 25 mg) before initiating a loading dose. Patients should be advised of the potential for development of resistance should dosing be interrupted for any reason (CAB and RPV have extended half-lives ranging from mean 5.6 to 11.5 weeks for CAB and 13 to 28 weeks for RPV), as well as the need to return to oral bridging therapy if subsequent injections are not administered within the 7-day window period. If the maintenance dose is delayed beyond 2 months, a loading dose and restart is necessary.

CAB/RPV LA therapy is administered into opposing gluteal muscles (CAB into one gluteus medius and RPV into the contralateral gluteus medius), and injection-site pain beginning 1 day post-injection and lasting 3-4 days is common. In phase 3 clinical trials, as many as 83% of patients experienced adverse effects (AEs), which also include nodules, induration, and swelling at the injection sites. Fortunately, 99% of AEs were of mild to moderate severity. While pain tends to decline over several injections, Dr. DeHaan said that it’s an important part of the initial discussion about switching therapies.
 

Other considerations

Prior resistance testing, ART treatment history, and/or baseline genotypic resistance testing that includes both reverse transcriptase and integrase genes should be reviewed or conducted before initiating treatment. K103 mutations alone are not considered exclusionary. Virologic failures (defined as two consecutive plasma HIV-1 RNA measurements greater than 200 copies/mL), while rare, were reported in 13 clinical trial participants. Recent data suggest that patients who developed resistance despite adherence had at least two of three factors: a body mass index greater than 30 kg/m², the HIV-1 subtype A6/A1, and the presence of proviral RPV RAMS.

CAB/RPV LA does not treat hepatitis B (HBV) coinfections, reinforcing the need for concurrent oral HBV therapy.

And there’s a paucity of data on the safety and efficacy of CAB/RPV in children and adolescents, or during pregnancy/lactation, precluding its use in those patient populations.
 

Clinical, institutional considerations

Adaptation of CAB/RPV LA as ART requires specific clinical institutional planning, especially in light of current pandemic-related resource and staffing limitations. Monthly dosing must be done within a 7-day window and requires preparations akin to initial loading doses. In addition to pharmacy resources and onsite storage requirements, the guidance points to patient scheduling and reminder systems, access (patient transportation, work constraints, parking), and most importantly, contingency plans for care (including oral bridging therapy) should a clinic be forced to shut down for any reason. Additional factors include billing protocols, insurance or third party authorizations, and provision of counseling and education training.

“Given that this is a completely new way of thinking among providers, we’re all learning together,” said David Koren, PharmD, MPH, a clinical pharmacy specialist in infectious diseases at Temple University, Philadelphia. “The guidelines provide a nice framework for taking the next step to operationalize these processes into practice, taking into account that barriers to implementation are still unknown.” Dr. Koren was not involved in the development of the guidelines.

Dr. DeHaan has disclosed no relevant financial relationships. Dr. Koren disclosed serving on a prior Advisory Panel for ViiV Healthcare US.

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

“One of the most important considerations before switching HIV patients to injectable long-acting cabotegravir/rilpivirine [CAB/RPV LA; Cabenuva, ViiV Healthcare] is for the patient and the clinician to arrive at this decision together,” Elliot DeHaan, MD, told this news organization. “This therapy is not necessarily for everyone.”

Dr. DeHaan is lead author of the newly released clinical guideline from the New York State Department of Health AIDS Institute for use of CAB/RPV LA as replacement antiretroviral therapy (ART) in virally suppressed adults with HIV. He explained that the guidance expands upon Health & Human Services’ Feb. 24 CAB/RPV LA recommendations, highlighting some of the most important clinical and patient considerations necessary to implement injectable ART. “There are a lot of things that need to be laid out beforehand,” he said.
 

Gaining consensus

Approved by the FDA in late January 2021, CAB/RPV LA is considered an optimization strategy for individuals with HIV whose virus is suppressed by oral ART and who might prefer monthly injections to daily oral therapy. While there are various reasons why patients might wish to switch to a long-acting injectable, one of the primary concerns is adherence. Of note, the guidance points to phase 3 clinical study findings that suggest high levels (86%-91%) of patient satisfaction with CAB/RPV LA, which portends a promising future for this therapeutic approach.

With regard to patient preference, recommendations focus on the need to thoroughly discuss several critical requisites with potential candidates, including a 4-week lead-in daily oral ART course (CAB [Vocabria] 30 mg, RPV [Edurant] 25 mg) before initiating a loading dose. Patients should be advised of the potential for development of resistance should dosing be interrupted for any reason (CAB and RPV have extended half-lives ranging from mean 5.6 to 11.5 weeks for CAB and 13 to 28 weeks for RPV), as well as the need to return to oral bridging therapy if subsequent injections are not administered within the 7-day window period. If the maintenance dose is delayed beyond 2 months, a loading dose and restart is necessary.

CAB/RPV LA therapy is administered into opposing gluteal muscles (CAB into one gluteus medius and RPV into the contralateral gluteus medius), and injection-site pain beginning 1 day post-injection and lasting 3-4 days is common. In phase 3 clinical trials, as many as 83% of patients experienced adverse effects (AEs), which also include nodules, induration, and swelling at the injection sites. Fortunately, 99% of AEs were of mild to moderate severity. While pain tends to decline over several injections, Dr. DeHaan said that it’s an important part of the initial discussion about switching therapies.
 

Other considerations

Prior resistance testing, ART treatment history, and/or baseline genotypic resistance testing that includes both reverse transcriptase and integrase genes should be reviewed or conducted before initiating treatment. K103 mutations alone are not considered exclusionary. Virologic failures (defined as two consecutive plasma HIV-1 RNA measurements greater than 200 copies/mL), while rare, were reported in 13 clinical trial participants. Recent data suggest that patients who developed resistance despite adherence had at least two of three factors: a body mass index greater than 30 kg/m², the HIV-1 subtype A6/A1, and the presence of proviral RPV RAMS.

CAB/RPV LA does not treat hepatitis B (HBV) coinfections, reinforcing the need for concurrent oral HBV therapy.

And there’s a paucity of data on the safety and efficacy of CAB/RPV in children and adolescents, or during pregnancy/lactation, precluding its use in those patient populations.
 

Clinical, institutional considerations

Adaptation of CAB/RPV LA as ART requires specific clinical institutional planning, especially in light of current pandemic-related resource and staffing limitations. Monthly dosing must be done within a 7-day window and requires preparations akin to initial loading doses. In addition to pharmacy resources and onsite storage requirements, the guidance points to patient scheduling and reminder systems, access (patient transportation, work constraints, parking), and most importantly, contingency plans for care (including oral bridging therapy) should a clinic be forced to shut down for any reason. Additional factors include billing protocols, insurance or third party authorizations, and provision of counseling and education training.

“Given that this is a completely new way of thinking among providers, we’re all learning together,” said David Koren, PharmD, MPH, a clinical pharmacy specialist in infectious diseases at Temple University, Philadelphia. “The guidelines provide a nice framework for taking the next step to operationalize these processes into practice, taking into account that barriers to implementation are still unknown.” Dr. Koren was not involved in the development of the guidelines.

Dr. DeHaan has disclosed no relevant financial relationships. Dr. Koren disclosed serving on a prior Advisory Panel for ViiV Healthcare US.

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

“One of the most important considerations before switching HIV patients to injectable long-acting cabotegravir/rilpivirine [CAB/RPV LA; Cabenuva, ViiV Healthcare] is for the patient and the clinician to arrive at this decision together,” Elliot DeHaan, MD, told this news organization. “This therapy is not necessarily for everyone.”

Dr. DeHaan is lead author of the newly released clinical guideline from the New York State Department of Health AIDS Institute for use of CAB/RPV LA as replacement antiretroviral therapy (ART) in virally suppressed adults with HIV. He explained that the guidance expands upon Health & Human Services’ Feb. 24 CAB/RPV LA recommendations, highlighting some of the most important clinical and patient considerations necessary to implement injectable ART. “There are a lot of things that need to be laid out beforehand,” he said.
 

Gaining consensus

Approved by the FDA in late January 2021, CAB/RPV LA is considered an optimization strategy for individuals with HIV whose virus is suppressed by oral ART and who might prefer monthly injections to daily oral therapy. While there are various reasons why patients might wish to switch to a long-acting injectable, one of the primary concerns is adherence. Of note, the guidance points to phase 3 clinical study findings that suggest high levels (86%-91%) of patient satisfaction with CAB/RPV LA, which portends a promising future for this therapeutic approach.

With regard to patient preference, recommendations focus on the need to thoroughly discuss several critical requisites with potential candidates, including a 4-week lead-in daily oral ART course (CAB [Vocabria] 30 mg, RPV [Edurant] 25 mg) before initiating a loading dose. Patients should be advised of the potential for development of resistance should dosing be interrupted for any reason (CAB and RPV have extended half-lives ranging from mean 5.6 to 11.5 weeks for CAB and 13 to 28 weeks for RPV), as well as the need to return to oral bridging therapy if subsequent injections are not administered within the 7-day window period. If the maintenance dose is delayed beyond 2 months, a loading dose and restart is necessary.

CAB/RPV LA therapy is administered into opposing gluteal muscles (CAB into one gluteus medius and RPV into the contralateral gluteus medius), and injection-site pain beginning 1 day post-injection and lasting 3-4 days is common. In phase 3 clinical trials, as many as 83% of patients experienced adverse effects (AEs), which also include nodules, induration, and swelling at the injection sites. Fortunately, 99% of AEs were of mild to moderate severity. While pain tends to decline over several injections, Dr. DeHaan said that it’s an important part of the initial discussion about switching therapies.
 

Other considerations

Prior resistance testing, ART treatment history, and/or baseline genotypic resistance testing that includes both reverse transcriptase and integrase genes should be reviewed or conducted before initiating treatment. K103 mutations alone are not considered exclusionary. Virologic failures (defined as two consecutive plasma HIV-1 RNA measurements greater than 200 copies/mL), while rare, were reported in 13 clinical trial participants. Recent data suggest that patients who developed resistance despite adherence had at least two of three factors: a body mass index greater than 30 kg/m², the HIV-1 subtype A6/A1, and the presence of proviral RPV RAMS.

CAB/RPV LA does not treat hepatitis B (HBV) coinfections, reinforcing the need for concurrent oral HBV therapy.

And there’s a paucity of data on the safety and efficacy of CAB/RPV in children and adolescents, or during pregnancy/lactation, precluding its use in those patient populations.
 

Clinical, institutional considerations

Adaptation of CAB/RPV LA as ART requires specific clinical institutional planning, especially in light of current pandemic-related resource and staffing limitations. Monthly dosing must be done within a 7-day window and requires preparations akin to initial loading doses. In addition to pharmacy resources and onsite storage requirements, the guidance points to patient scheduling and reminder systems, access (patient transportation, work constraints, parking), and most importantly, contingency plans for care (including oral bridging therapy) should a clinic be forced to shut down for any reason. Additional factors include billing protocols, insurance or third party authorizations, and provision of counseling and education training.

“Given that this is a completely new way of thinking among providers, we’re all learning together,” said David Koren, PharmD, MPH, a clinical pharmacy specialist in infectious diseases at Temple University, Philadelphia. “The guidelines provide a nice framework for taking the next step to operationalize these processes into practice, taking into account that barriers to implementation are still unknown.” Dr. Koren was not involved in the development of the guidelines.

Dr. DeHaan has disclosed no relevant financial relationships. Dr. Koren disclosed serving on a prior Advisory Panel for ViiV Healthcare US.

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