Federal Practitioner

Samples from patients in the United States and Kenya show an increasing emergence of previously undetected vancomycin-resistant strains of Clostridioides difficile, sparking concern as recurrences in the treatment of C. difficile infection (CDI) continue to rise.

“Our results may help explain a decreasing effectiveness of antibiotic-based therapy in C. difficile infection, since a significant proportion of patients harboring strains with reduced susceptibility to vancomycin may not respond to treatment,” reported the authors in research published recently in Clinical Infectious Diseases.

The spread of the resistant strains “has serious public health implications, underscoring an urgent need for a comprehensive analysis of the circulating strains to help inform clinical decisions,” they added.

Commenting on the findings, Cornelius J. Clancy, MD, professor of medicine at the University of Pittsburgh, and chief of infectious diseases at the Veterans Affairs Pittsburgh Healthcare System, echoed the concern.

“The casual belief has been that [C. difficile] strains at most centers can be assumed to be vancomycin susceptible,” he told this news organization. “This study shows that this assumption can no longer be taken as a given.”

Dr. Clancy, who was not involved with this research, noted that “based on this study, there might be need for the Infectious Diseases Society of America and other organizations to offer guidance on generating good, quality surveillance data for C. difficile resistance.”

With C. difficile showing the ability to resist multiple antibiotics, drugs in the armamentarium to treat the infection have declined in recent years, and recurrences with the infection are reported in up to 25% of cases.

Oral vancomycin is recommended as the antibiotic of choice by the IDSA and the Society for Healthcare Epidemiology of America for severe as well as nonsevere cases of CDI, and although there are reports of nine vancomycin-resistant gene clusters, most involve Enterococcus.

To take a closer look at the prevalence of vancomycin-resistant C. difficile strains, first author Charles Darkoh, PhD, with the Center for Infectious Diseases at the University of Texas Health Science Center, Houston, and colleagues analyzed stool samples from patients with CDI, including 438 patients in Houston, taken between 2012 and 2017, and 98 in Nairobi, Kenya, taken in 2017.

They found that, among samples from patients in Houston, over the time period, 26% showed vancomycin nonsusceptible C. difficile isolates and 29% had isolates that were metronidazole resistant.

And among samples from the Nairobi patients, 67% harbored vancomycin-resistant isolates and 85% had isolates resistant to metronidazole.

Of note, the proportion of samples containing vancomycin-resistant C. difficile in the Houston patients showed a marked increase over time, from «complete absence» in 2012 to approximately 35% in 2017, the authors reported.

“These nonsusceptibility rates significantly exceeded prior reports from other studies conducted in the United States and Europe from 2011 to 2014, suggesting a lower percentage of resistance to both metronidazole and vancomycin,” the authors wrote.

Further experiments on mouse models infected with one of the vancomycin-resistant isolates showed that treatment with vancomycin failed to eradicate the infection, and 5-day survival was significantly lower after vancomycin treatment in those mice (25%) versus those infected with strains known to be vancomycin sensitive (50%).
 

Unrecognized genetic strains

Whole-genome sequencing of 10 of the resistant isolates showed no matches with gene clusters that have been previously recognized as being vancomycin resistant, suggesting the emergence of new clusters.

“Together, these results suggest unknown genetic elements associated with vancomycin nonsusceptibility in isolates circulating in the patient population,” the authors wrote.

Dr. Darkoh told this news organization that the research team is currently working to further investigate the patterns and mechanisms.

“We are currently working on a follow-up study for the next 5 years to find out how widespread this is,” he said. “We want to make sure it’s not necessarily just occurring in the settings we studied, and we also need to establish the mechanism of resistance.”

Further commenting on the results, Dr. Clancy noted that “the extent of resistance caught many in the field a bit off guard, as they are higher than previously reported.”

“The data are also concerning because most centers do not routinely test C. difficile for drug susceptibility.”

Dr. Clancy noted that “another immediately pressing need is to understand mechanisms of resistance. It was quite striking that vancomycin-resistant strains in this study did not carry vanA genes, pointing to previously unrecognized mechanisms of resistance.”

“As is often the case, antibiotic overuse was likely a factor in the resistances, with overtesting often leading to overtreatment of C. difficile,” Dr. Clancy said. “The situation may have been compounded by failure to appreciate how entrenched C. difficile resistance may be at certain hospitals, since widespread susceptibility testing is generally not routinely performed.”

As alternative treatments, Dr. Clancy pointed to the recent IDSA update, which included a stronger endorsement of fidaxomicin.

“Of course, there is also the need to assure that data on resistance to agents like fidaxomicin are generated going forward,” he noted.

The study was supported by was supported by National Institutes of Health, the National Institute of Allergy and Infectious Diseases, the Texas Medical Center Digestive Diseases Center, and the University of Texas Health Science Center. Dr. Darkoh has disclosed no relevant financial relationships. One coauthor received grant support from Merck, Entasis Pharmaceuticals, and MeMed Diagnostics. Dr. Clancy disclosed advisory board, consulting and/or research relationships with Merck, Qpex Biopharma, Shionogi, Astellas, Cidara, Scynexis, and Needham & Associates.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

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

Samples from patients in the United States and Kenya show an increasing emergence of previously undetected vancomycin-resistant strains of Clostridioides difficile, sparking concern as recurrences in the treatment of C. difficile infection (CDI) continue to rise.

“Our results may help explain a decreasing effectiveness of antibiotic-based therapy in C. difficile infection, since a significant proportion of patients harboring strains with reduced susceptibility to vancomycin may not respond to treatment,” reported the authors in research published recently in Clinical Infectious Diseases.

The spread of the resistant strains “has serious public health implications, underscoring an urgent need for a comprehensive analysis of the circulating strains to help inform clinical decisions,” they added.

Commenting on the findings, Cornelius J. Clancy, MD, professor of medicine at the University of Pittsburgh, and chief of infectious diseases at the Veterans Affairs Pittsburgh Healthcare System, echoed the concern.

“The casual belief has been that [C. difficile] strains at most centers can be assumed to be vancomycin susceptible,” he told this news organization. “This study shows that this assumption can no longer be taken as a given.”

Dr. Clancy, who was not involved with this research, noted that “based on this study, there might be need for the Infectious Diseases Society of America and other organizations to offer guidance on generating good, quality surveillance data for C. difficile resistance.”

With C. difficile showing the ability to resist multiple antibiotics, drugs in the armamentarium to treat the infection have declined in recent years, and recurrences with the infection are reported in up to 25% of cases.

Oral vancomycin is recommended as the antibiotic of choice by the IDSA and the Society for Healthcare Epidemiology of America for severe as well as nonsevere cases of CDI, and although there are reports of nine vancomycin-resistant gene clusters, most involve Enterococcus.

To take a closer look at the prevalence of vancomycin-resistant C. difficile strains, first author Charles Darkoh, PhD, with the Center for Infectious Diseases at the University of Texas Health Science Center, Houston, and colleagues analyzed stool samples from patients with CDI, including 438 patients in Houston, taken between 2012 and 2017, and 98 in Nairobi, Kenya, taken in 2017.

They found that, among samples from patients in Houston, over the time period, 26% showed vancomycin nonsusceptible C. difficile isolates and 29% had isolates that were metronidazole resistant.

And among samples from the Nairobi patients, 67% harbored vancomycin-resistant isolates and 85% had isolates resistant to metronidazole.

Of note, the proportion of samples containing vancomycin-resistant C. difficile in the Houston patients showed a marked increase over time, from «complete absence» in 2012 to approximately 35% in 2017, the authors reported.

“These nonsusceptibility rates significantly exceeded prior reports from other studies conducted in the United States and Europe from 2011 to 2014, suggesting a lower percentage of resistance to both metronidazole and vancomycin,” the authors wrote.

Further experiments on mouse models infected with one of the vancomycin-resistant isolates showed that treatment with vancomycin failed to eradicate the infection, and 5-day survival was significantly lower after vancomycin treatment in those mice (25%) versus those infected with strains known to be vancomycin sensitive (50%).
 

Unrecognized genetic strains

Whole-genome sequencing of 10 of the resistant isolates showed no matches with gene clusters that have been previously recognized as being vancomycin resistant, suggesting the emergence of new clusters.

“Together, these results suggest unknown genetic elements associated with vancomycin nonsusceptibility in isolates circulating in the patient population,” the authors wrote.

Dr. Darkoh told this news organization that the research team is currently working to further investigate the patterns and mechanisms.

“We are currently working on a follow-up study for the next 5 years to find out how widespread this is,” he said. “We want to make sure it’s not necessarily just occurring in the settings we studied, and we also need to establish the mechanism of resistance.”

Further commenting on the results, Dr. Clancy noted that “the extent of resistance caught many in the field a bit off guard, as they are higher than previously reported.”

“The data are also concerning because most centers do not routinely test C. difficile for drug susceptibility.”

Dr. Clancy noted that “another immediately pressing need is to understand mechanisms of resistance. It was quite striking that vancomycin-resistant strains in this study did not carry vanA genes, pointing to previously unrecognized mechanisms of resistance.”

“As is often the case, antibiotic overuse was likely a factor in the resistances, with overtesting often leading to overtreatment of C. difficile,” Dr. Clancy said. “The situation may have been compounded by failure to appreciate how entrenched C. difficile resistance may be at certain hospitals, since widespread susceptibility testing is generally not routinely performed.”

As alternative treatments, Dr. Clancy pointed to the recent IDSA update, which included a stronger endorsement of fidaxomicin.

“Of course, there is also the need to assure that data on resistance to agents like fidaxomicin are generated going forward,” he noted.

The study was supported by was supported by National Institutes of Health, the National Institute of Allergy and Infectious Diseases, the Texas Medical Center Digestive Diseases Center, and the University of Texas Health Science Center. Dr. Darkoh has disclosed no relevant financial relationships. One coauthor received grant support from Merck, Entasis Pharmaceuticals, and MeMed Diagnostics. Dr. Clancy disclosed advisory board, consulting and/or research relationships with Merck, Qpex Biopharma, Shionogi, Astellas, Cidara, Scynexis, and Needham & Associates.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

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

Samples from patients in the United States and Kenya show an increasing emergence of previously undetected vancomycin-resistant strains of Clostridioides difficile, sparking concern as recurrences in the treatment of C. difficile infection (CDI) continue to rise.

“Our results may help explain a decreasing effectiveness of antibiotic-based therapy in C. difficile infection, since a significant proportion of patients harboring strains with reduced susceptibility to vancomycin may not respond to treatment,” reported the authors in research published recently in Clinical Infectious Diseases.

The spread of the resistant strains “has serious public health implications, underscoring an urgent need for a comprehensive analysis of the circulating strains to help inform clinical decisions,” they added.

Commenting on the findings, Cornelius J. Clancy, MD, professor of medicine at the University of Pittsburgh, and chief of infectious diseases at the Veterans Affairs Pittsburgh Healthcare System, echoed the concern.

“The casual belief has been that [C. difficile] strains at most centers can be assumed to be vancomycin susceptible,” he told this news organization. “This study shows that this assumption can no longer be taken as a given.”

Dr. Clancy, who was not involved with this research, noted that “based on this study, there might be need for the Infectious Diseases Society of America and other organizations to offer guidance on generating good, quality surveillance data for C. difficile resistance.”

With C. difficile showing the ability to resist multiple antibiotics, drugs in the armamentarium to treat the infection have declined in recent years, and recurrences with the infection are reported in up to 25% of cases.

Oral vancomycin is recommended as the antibiotic of choice by the IDSA and the Society for Healthcare Epidemiology of America for severe as well as nonsevere cases of CDI, and although there are reports of nine vancomycin-resistant gene clusters, most involve Enterococcus.

To take a closer look at the prevalence of vancomycin-resistant C. difficile strains, first author Charles Darkoh, PhD, with the Center for Infectious Diseases at the University of Texas Health Science Center, Houston, and colleagues analyzed stool samples from patients with CDI, including 438 patients in Houston, taken between 2012 and 2017, and 98 in Nairobi, Kenya, taken in 2017.

They found that, among samples from patients in Houston, over the time period, 26% showed vancomycin nonsusceptible C. difficile isolates and 29% had isolates that were metronidazole resistant.

And among samples from the Nairobi patients, 67% harbored vancomycin-resistant isolates and 85% had isolates resistant to metronidazole.

Of note, the proportion of samples containing vancomycin-resistant C. difficile in the Houston patients showed a marked increase over time, from «complete absence» in 2012 to approximately 35% in 2017, the authors reported.

“These nonsusceptibility rates significantly exceeded prior reports from other studies conducted in the United States and Europe from 2011 to 2014, suggesting a lower percentage of resistance to both metronidazole and vancomycin,” the authors wrote.

Further experiments on mouse models infected with one of the vancomycin-resistant isolates showed that treatment with vancomycin failed to eradicate the infection, and 5-day survival was significantly lower after vancomycin treatment in those mice (25%) versus those infected with strains known to be vancomycin sensitive (50%).
 

Unrecognized genetic strains

Whole-genome sequencing of 10 of the resistant isolates showed no matches with gene clusters that have been previously recognized as being vancomycin resistant, suggesting the emergence of new clusters.

“Together, these results suggest unknown genetic elements associated with vancomycin nonsusceptibility in isolates circulating in the patient population,” the authors wrote.

Dr. Darkoh told this news organization that the research team is currently working to further investigate the patterns and mechanisms.

“We are currently working on a follow-up study for the next 5 years to find out how widespread this is,” he said. “We want to make sure it’s not necessarily just occurring in the settings we studied, and we also need to establish the mechanism of resistance.”

Further commenting on the results, Dr. Clancy noted that “the extent of resistance caught many in the field a bit off guard, as they are higher than previously reported.”

“The data are also concerning because most centers do not routinely test C. difficile for drug susceptibility.”

Dr. Clancy noted that “another immediately pressing need is to understand mechanisms of resistance. It was quite striking that vancomycin-resistant strains in this study did not carry vanA genes, pointing to previously unrecognized mechanisms of resistance.”

“As is often the case, antibiotic overuse was likely a factor in the resistances, with overtesting often leading to overtreatment of C. difficile,” Dr. Clancy said. “The situation may have been compounded by failure to appreciate how entrenched C. difficile resistance may be at certain hospitals, since widespread susceptibility testing is generally not routinely performed.”

As alternative treatments, Dr. Clancy pointed to the recent IDSA update, which included a stronger endorsement of fidaxomicin.

“Of course, there is also the need to assure that data on resistance to agents like fidaxomicin are generated going forward,” he noted.

The study was supported by was supported by National Institutes of Health, the National Institute of Allergy and Infectious Diseases, the Texas Medical Center Digestive Diseases Center, and the University of Texas Health Science Center. Dr. Darkoh has disclosed no relevant financial relationships. One coauthor received grant support from Merck, Entasis Pharmaceuticals, and MeMed Diagnostics. Dr. Clancy disclosed advisory board, consulting and/or research relationships with Merck, Qpex Biopharma, Shionogi, Astellas, Cidara, Scynexis, and Needham & Associates.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

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

Just a few changes to your diet could add years to your life, but the sooner you start the better.

Maintaining a healthy diet is important, but most people find this difficult to do daily. In a new study, researchers examined the effects of individual healthful and nonhealthful types of foods and estimated the impact by age and sex of swapping some for others.

“Sustained change from a typical to an optimized diet from early age could translate into an increase in life expectancy of more than 10 years,” say the Norwegian scientists who conducted the study, published in PLOS Medicine on Feb. 8.

Lisovskaya/iStock/Getty Images

They developed an online tool that anyone can use to get an idea of how individual food choices can affect life expectancy.

The biggest overall impact comes from eating more plant-based foods (legumes), whole grains and nuts, and less red and processed meat. Fruits and vegetables also have a positive health impact, but on average people who eat a typical Western diet are already consuming those in relatively high amounts. Fish is included on the healthful list, whereas sugar-sweetened beverages (sodas) and foods based on refined [white] grains, such as white bread, are among those to be avoided.

The study found that although it’s never too late to start, young adults can expect to see more years gained by adopting healthful eating than would older adults.

“Our results indicate that for individuals with a typical Western diet, sustained dietary changes at any age may give substantial health benefits, although the gains are the largest if changes start early in life,” said the researchers.

Depending on how many healthy dietary “switches” are made and maintained and the amounts consumed, a 20-year-old man in the United States could extend his life up to 13 years, and a 20-year old woman by 11 years.

That number drops with age but changing from a typical diet to the optimized diet at age 60 years could still increase life expectancy by 8 years for women and 9 years for men, and even an 80-year-old female could gain more than 3 years with healthier food choices.

Until now, research in this area has shown health benefits associated with separate food groups or specific diet patterns, while focusing less on the health impact of other dietary changes. The statistical ‘modeling’ approach used in this study bridges that gap, the researchers said.

“Understanding the relative health potential of different food groups could enable people to make feasible and significant health gains,” they concluded.

A version of this article was first published on WebMD.com.

Just a few changes to your diet could add years to your life, but the sooner you start the better.

Maintaining a healthy diet is important, but most people find this difficult to do daily. In a new study, researchers examined the effects of individual healthful and nonhealthful types of foods and estimated the impact by age and sex of swapping some for others.

“Sustained change from a typical to an optimized diet from early age could translate into an increase in life expectancy of more than 10 years,” say the Norwegian scientists who conducted the study, published in PLOS Medicine on Feb. 8.

Lisovskaya/iStock/Getty Images

They developed an online tool that anyone can use to get an idea of how individual food choices can affect life expectancy.

The biggest overall impact comes from eating more plant-based foods (legumes), whole grains and nuts, and less red and processed meat. Fruits and vegetables also have a positive health impact, but on average people who eat a typical Western diet are already consuming those in relatively high amounts. Fish is included on the healthful list, whereas sugar-sweetened beverages (sodas) and foods based on refined [white] grains, such as white bread, are among those to be avoided.

The study found that although it’s never too late to start, young adults can expect to see more years gained by adopting healthful eating than would older adults.

“Our results indicate that for individuals with a typical Western diet, sustained dietary changes at any age may give substantial health benefits, although the gains are the largest if changes start early in life,” said the researchers.

Depending on how many healthy dietary “switches” are made and maintained and the amounts consumed, a 20-year-old man in the United States could extend his life up to 13 years, and a 20-year old woman by 11 years.

That number drops with age but changing from a typical diet to the optimized diet at age 60 years could still increase life expectancy by 8 years for women and 9 years for men, and even an 80-year-old female could gain more than 3 years with healthier food choices.

Until now, research in this area has shown health benefits associated with separate food groups or specific diet patterns, while focusing less on the health impact of other dietary changes. The statistical ‘modeling’ approach used in this study bridges that gap, the researchers said.

“Understanding the relative health potential of different food groups could enable people to make feasible and significant health gains,” they concluded.

A version of this article was first published on WebMD.com.

Just a few changes to your diet could add years to your life, but the sooner you start the better.

Maintaining a healthy diet is important, but most people find this difficult to do daily. In a new study, researchers examined the effects of individual healthful and nonhealthful types of foods and estimated the impact by age and sex of swapping some for others.

“Sustained change from a typical to an optimized diet from early age could translate into an increase in life expectancy of more than 10 years,” say the Norwegian scientists who conducted the study, published in PLOS Medicine on Feb. 8.

Lisovskaya/iStock/Getty Images

They developed an online tool that anyone can use to get an idea of how individual food choices can affect life expectancy.

The biggest overall impact comes from eating more plant-based foods (legumes), whole grains and nuts, and less red and processed meat. Fruits and vegetables also have a positive health impact, but on average people who eat a typical Western diet are already consuming those in relatively high amounts. Fish is included on the healthful list, whereas sugar-sweetened beverages (sodas) and foods based on refined [white] grains, such as white bread, are among those to be avoided.

The study found that although it’s never too late to start, young adults can expect to see more years gained by adopting healthful eating than would older adults.

“Our results indicate that for individuals with a typical Western diet, sustained dietary changes at any age may give substantial health benefits, although the gains are the largest if changes start early in life,” said the researchers.

Depending on how many healthy dietary “switches” are made and maintained and the amounts consumed, a 20-year-old man in the United States could extend his life up to 13 years, and a 20-year old woman by 11 years.

That number drops with age but changing from a typical diet to the optimized diet at age 60 years could still increase life expectancy by 8 years for women and 9 years for men, and even an 80-year-old female could gain more than 3 years with healthier food choices.

Until now, research in this area has shown health benefits associated with separate food groups or specific diet patterns, while focusing less on the health impact of other dietary changes. The statistical ‘modeling’ approach used in this study bridges that gap, the researchers said.

“Understanding the relative health potential of different food groups could enable people to make feasible and significant health gains,” they concluded.

A version of this article was first published on WebMD.com.

Early, permanent discontinuation of venetoclax in the treatment of relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) is linked to shortened survival outcomes, but temporary interruption shows no impact on survival, underscoring the importance of preventing discontinuation.

“There’s not a lot of awareness about the fact that you’re probably better off not permanently discontinuing treatment,” Anthony R. Mato, first author of the research published in Haematologica, said in an interview.

Courtsey Memorial Sloan Kettering Cancer Center

“Instead, attempting dose reductions with later resumption to complete the planned schedule for treatment probably could improve outcomes,” said Dr. Mato, who is director of the CLL Program at Memorial Sloan Kettering Cancer Center in New York.

Venetoclax, a potent B-cell lymphoma-2 (BCL2) inhibitor, provides a novel, chemotherapy-free treatment option for first-line and r/r CLL. While its safety profile is manageable, treatment interruptions are very common, and premature discontinuations are reported in about a third of patients, often because of adverse events.

Lacking data on the effects of those interruptions on survival outcomes, Dr. Mato and colleagues conducted a post hoc analysis of the phase 3 MURANO trial. In this open-label study, treatment with six cycles of venetoclax in combination with rituximab followed by venetoclax once daily for a total of 2 years showed superior progression-free survival, compared with six cycles of bendamustine plus rituximab in patients with r/r CLL (P < .0001).

The current analysis involved 194 intention-to-treat patients from the trial’s venetoclax arm, among whom 140 (72%) completed 2 years of therapy, and 54 (28%) prematurely discontinued treatment. The most common reasons for discontinuation were adverse events (53.7%) and disease progression (22.2%).

Among those with early discontinuation for any reason except disease progression, the rate of progression-free survival was significantly inferior, compared with those who completed the treatment (hazard ratio, 5.98; P < .0001), as was the rate or discontinuation caused specifically by adverse events, which most commonly involved neutropenia or thrombocytopenia (HR, 5.82; P < .0001).

Those who discontinued had a mean duration of venetoclax therapy of 11.3 months, compared with 24.4 months for all patients. For each additional month of venetoclax therapy, there was a significantly lower risk of a progression-free survival event (P = .0263) and of an overall survival event (P < .0001).

The treatment interruption rate was much higher, at 69% (134), involving neutropenia in 43% (84) of instances and requiring dose reductions in 23% (45) of cases.

However, in contrast to permanent discontinuations, the temporary interruptions and dose reductions had no significant effect on progression-free or overall survival, regardless of the duration.

“Improved progression-free and overall survival were associated with greater cumulative venetoclax treatment exposure,” the authors wrote.

“The results of these analyses highlight the importance of appropriately managing treatment modifications to ensure optimal outcomes for patients receiving targeted treatment for CLL,” they said.

Key measures including “better supportive care, use of growth factors, and more aggressive strategies for dose reduction could potentially help to improve or decrease the number of patients discontinuing due to an adverse event,” Dr. Mato added.“We can’t say definitively because this is not a randomized study – it’s a retrospective analysis from a randomized study – but those measures likely could have a positive impact on patient outcomes.”

The study received support from Genentech and AbbVie. Dr. Mato reported consulting or other relationships with AbbVie, AstraZeneca, Celgene, DTRM, Genentech, Janssen, Loxo, PCYC, Sunesis, and TG Therapeutics.

Early, permanent discontinuation of venetoclax in the treatment of relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) is linked to shortened survival outcomes, but temporary interruption shows no impact on survival, underscoring the importance of preventing discontinuation.

“There’s not a lot of awareness about the fact that you’re probably better off not permanently discontinuing treatment,” Anthony R. Mato, first author of the research published in Haematologica, said in an interview.

Courtsey Memorial Sloan Kettering Cancer Center

“Instead, attempting dose reductions with later resumption to complete the planned schedule for treatment probably could improve outcomes,” said Dr. Mato, who is director of the CLL Program at Memorial Sloan Kettering Cancer Center in New York.

Venetoclax, a potent B-cell lymphoma-2 (BCL2) inhibitor, provides a novel, chemotherapy-free treatment option for first-line and r/r CLL. While its safety profile is manageable, treatment interruptions are very common, and premature discontinuations are reported in about a third of patients, often because of adverse events.

Lacking data on the effects of those interruptions on survival outcomes, Dr. Mato and colleagues conducted a post hoc analysis of the phase 3 MURANO trial. In this open-label study, treatment with six cycles of venetoclax in combination with rituximab followed by venetoclax once daily for a total of 2 years showed superior progression-free survival, compared with six cycles of bendamustine plus rituximab in patients with r/r CLL (P < .0001).

The current analysis involved 194 intention-to-treat patients from the trial’s venetoclax arm, among whom 140 (72%) completed 2 years of therapy, and 54 (28%) prematurely discontinued treatment. The most common reasons for discontinuation were adverse events (53.7%) and disease progression (22.2%).

Among those with early discontinuation for any reason except disease progression, the rate of progression-free survival was significantly inferior, compared with those who completed the treatment (hazard ratio, 5.98; P < .0001), as was the rate or discontinuation caused specifically by adverse events, which most commonly involved neutropenia or thrombocytopenia (HR, 5.82; P < .0001).

Those who discontinued had a mean duration of venetoclax therapy of 11.3 months, compared with 24.4 months for all patients. For each additional month of venetoclax therapy, there was a significantly lower risk of a progression-free survival event (P = .0263) and of an overall survival event (P < .0001).

The treatment interruption rate was much higher, at 69% (134), involving neutropenia in 43% (84) of instances and requiring dose reductions in 23% (45) of cases.

However, in contrast to permanent discontinuations, the temporary interruptions and dose reductions had no significant effect on progression-free or overall survival, regardless of the duration.

“Improved progression-free and overall survival were associated with greater cumulative venetoclax treatment exposure,” the authors wrote.

“The results of these analyses highlight the importance of appropriately managing treatment modifications to ensure optimal outcomes for patients receiving targeted treatment for CLL,” they said.

Key measures including “better supportive care, use of growth factors, and more aggressive strategies for dose reduction could potentially help to improve or decrease the number of patients discontinuing due to an adverse event,” Dr. Mato added.“We can’t say definitively because this is not a randomized study – it’s a retrospective analysis from a randomized study – but those measures likely could have a positive impact on patient outcomes.”

The study received support from Genentech and AbbVie. Dr. Mato reported consulting or other relationships with AbbVie, AstraZeneca, Celgene, DTRM, Genentech, Janssen, Loxo, PCYC, Sunesis, and TG Therapeutics.

Early, permanent discontinuation of venetoclax in the treatment of relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) is linked to shortened survival outcomes, but temporary interruption shows no impact on survival, underscoring the importance of preventing discontinuation.

“There’s not a lot of awareness about the fact that you’re probably better off not permanently discontinuing treatment,” Anthony R. Mato, first author of the research published in Haematologica, said in an interview.

Courtsey Memorial Sloan Kettering Cancer Center

“Instead, attempting dose reductions with later resumption to complete the planned schedule for treatment probably could improve outcomes,” said Dr. Mato, who is director of the CLL Program at Memorial Sloan Kettering Cancer Center in New York.

Venetoclax, a potent B-cell lymphoma-2 (BCL2) inhibitor, provides a novel, chemotherapy-free treatment option for first-line and r/r CLL. While its safety profile is manageable, treatment interruptions are very common, and premature discontinuations are reported in about a third of patients, often because of adverse events.

Lacking data on the effects of those interruptions on survival outcomes, Dr. Mato and colleagues conducted a post hoc analysis of the phase 3 MURANO trial. In this open-label study, treatment with six cycles of venetoclax in combination with rituximab followed by venetoclax once daily for a total of 2 years showed superior progression-free survival, compared with six cycles of bendamustine plus rituximab in patients with r/r CLL (P < .0001).

The current analysis involved 194 intention-to-treat patients from the trial’s venetoclax arm, among whom 140 (72%) completed 2 years of therapy, and 54 (28%) prematurely discontinued treatment. The most common reasons for discontinuation were adverse events (53.7%) and disease progression (22.2%).

Among those with early discontinuation for any reason except disease progression, the rate of progression-free survival was significantly inferior, compared with those who completed the treatment (hazard ratio, 5.98; P < .0001), as was the rate or discontinuation caused specifically by adverse events, which most commonly involved neutropenia or thrombocytopenia (HR, 5.82; P < .0001).

Those who discontinued had a mean duration of venetoclax therapy of 11.3 months, compared with 24.4 months for all patients. For each additional month of venetoclax therapy, there was a significantly lower risk of a progression-free survival event (P = .0263) and of an overall survival event (P < .0001).

The treatment interruption rate was much higher, at 69% (134), involving neutropenia in 43% (84) of instances and requiring dose reductions in 23% (45) of cases.

However, in contrast to permanent discontinuations, the temporary interruptions and dose reductions had no significant effect on progression-free or overall survival, regardless of the duration.

“Improved progression-free and overall survival were associated with greater cumulative venetoclax treatment exposure,” the authors wrote.

“The results of these analyses highlight the importance of appropriately managing treatment modifications to ensure optimal outcomes for patients receiving targeted treatment for CLL,” they said.

Key measures including “better supportive care, use of growth factors, and more aggressive strategies for dose reduction could potentially help to improve or decrease the number of patients discontinuing due to an adverse event,” Dr. Mato added.“We can’t say definitively because this is not a randomized study – it’s a retrospective analysis from a randomized study – but those measures likely could have a positive impact on patient outcomes.”

The study received support from Genentech and AbbVie. Dr. Mato reported consulting or other relationships with AbbVie, AstraZeneca, Celgene, DTRM, Genentech, Janssen, Loxo, PCYC, Sunesis, and TG Therapeutics.

It’s a story of promise at a time of urgent need.

Scientists are optimistic about new evidence into what is causing long COVID, a panel of research experts brought together by the New York State Department of Health said.

They proposed many theories on what might be driving long COVID. A role for a virus “cryptic reservoir” that could reactivate at any time, “viral remnants” that trigger chronic inflammation, and action by “autoimmune antibodies” that cause ongoing symptoms are possibilities.

In fact, it’s likely that research will show long COVID is a condition with more than one cause, the experts said during a recent webinar.

People might experience post-infection problems, including organ damage that takes time to heal after initial COVID-19 illness. Or they may be living with post-immune factors, including ongoing immune system responses triggered by autoantibodies.

Determining the cause or causes of long COVID is essential for treatment. For example, if one person’s symptoms persist because of an overactive immune system, “we need to provide immunosuppressant therapies,” Akiko Iwasaki, PhD, said. “But we don’t want to give that to someone who has a persistent virus reservoir,” meaning remnants of the virus remain in their bodies.

Interestingly, a study preprint, which has not been peer reviewed, found dogs were accurate more than half the time in sniffing out long COVID, said Dr. Iwasaki, professor of immunobiology and developmental biology at Yale University, New Haven, Conn.

The dogs were tasked with identifying 45 people with long COVID versus 188 people without it. The findings suggest the presence of a unique chemical in the sweat of people with long COVID that could someday lead to a diagnostic test.
 

Viral persistence possible

If one of the main theories holds, it could be that the coronavirus somehow remains in the body in some form for some people after COVID-19.

Mady Hornig, MD, agreed this is a possibility that needs to be investigated further.

“A weakened immune response to an infection may mean that you have cryptic reservoirs of virus that are continuing to cause symptoms,” she said during the briefing. Dr. Hornig is a doctor-scientist specializing in epidemiology at Columbia University, New York.

“That may explain why some patients with long COVID feel better after vaccination,” because the vaccine creates a strong antibody response to fight COVID-19, Dr. Iwasaki said.

Researchers are unearthing additional potential factors contributing to long COVID.

Viral persistence could also reactivate other dormant viruses in the body, such as Epstein-Barr virus (EBV), said Lawrence Purpura, MD, MPH, an infectious disease specialist at New York Presbyterian/Columbia University. Reactivation of Epstein-Barr is one of four identifying signs of long COVID revealed in a Jan. 25 study published in the journal Cell.
 

Immune overactivation also possible?

For other people with long COVID, it’s not the virus sticking around but the body’s reaction that’s the issue.

Investigators suggest autoimmunity plays a role, and they point to the presence of autoantibodies, for example.

When these autoantibodies persist, they can cause tissue and organ damage over time.

Other investigators are proposing “immune exhaustion” in long COVID because of similarities to chronic fatigue syndrome, Dr. Hornig said.

“It should be ‘all hands on deck’ for research into long COVID,” she said. “The number of disabled individuals who will likely qualify for a diagnosis of [chronic fatigue syndrome] is growing by the second.”
 

Forging ahead on future research

It’s clear there is more work to do. There are investigators working on banking tissue samples from people with long COVID to learn more, for example.

Also, finding a biomarker unique to long COVID could vastly improve the precision of diagnosing long COVID, especially if the dog sniffing option does not pan out.

Of the thousands of biomarker possibilities, Dr. Hornig said, “maybe that’s one or two that ultimately make a real impact on patient care. So it’s going to be critical to find those quickly, translate them, and make them available.”

In the meantime, some answers might come from a large study sponsored by the National Institutes of Health. The NIH is funding the “Researching COVID to Enhance Recovery” project using $470 million from the American Rescue Plan. Investigators at NYU Langone Health are leading the effort and plan to share the wealth by funding more than 100 researchers at more than 30 institutions to create a “metacohort” to study long COVID. More information is available at recovercovid.org.

“Fortunately, through the global research effort, we are now really starting to expand our understanding of how long COVID manifests, how common it is, and what the underlying mechanisms may be,” Dr. Purpura said.

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

It’s a story of promise at a time of urgent need.

Scientists are optimistic about new evidence into what is causing long COVID, a panel of research experts brought together by the New York State Department of Health said.

They proposed many theories on what might be driving long COVID. A role for a virus “cryptic reservoir” that could reactivate at any time, “viral remnants” that trigger chronic inflammation, and action by “autoimmune antibodies” that cause ongoing symptoms are possibilities.

In fact, it’s likely that research will show long COVID is a condition with more than one cause, the experts said during a recent webinar.

People might experience post-infection problems, including organ damage that takes time to heal after initial COVID-19 illness. Or they may be living with post-immune factors, including ongoing immune system responses triggered by autoantibodies.

Determining the cause or causes of long COVID is essential for treatment. For example, if one person’s symptoms persist because of an overactive immune system, “we need to provide immunosuppressant therapies,” Akiko Iwasaki, PhD, said. “But we don’t want to give that to someone who has a persistent virus reservoir,” meaning remnants of the virus remain in their bodies.

Interestingly, a study preprint, which has not been peer reviewed, found dogs were accurate more than half the time in sniffing out long COVID, said Dr. Iwasaki, professor of immunobiology and developmental biology at Yale University, New Haven, Conn.

The dogs were tasked with identifying 45 people with long COVID versus 188 people without it. The findings suggest the presence of a unique chemical in the sweat of people with long COVID that could someday lead to a diagnostic test.
 

Viral persistence possible

If one of the main theories holds, it could be that the coronavirus somehow remains in the body in some form for some people after COVID-19.

Mady Hornig, MD, agreed this is a possibility that needs to be investigated further.

“A weakened immune response to an infection may mean that you have cryptic reservoirs of virus that are continuing to cause symptoms,” she said during the briefing. Dr. Hornig is a doctor-scientist specializing in epidemiology at Columbia University, New York.

“That may explain why some patients with long COVID feel better after vaccination,” because the vaccine creates a strong antibody response to fight COVID-19, Dr. Iwasaki said.

Researchers are unearthing additional potential factors contributing to long COVID.

Viral persistence could also reactivate other dormant viruses in the body, such as Epstein-Barr virus (EBV), said Lawrence Purpura, MD, MPH, an infectious disease specialist at New York Presbyterian/Columbia University. Reactivation of Epstein-Barr is one of four identifying signs of long COVID revealed in a Jan. 25 study published in the journal Cell.
 

Immune overactivation also possible?

For other people with long COVID, it’s not the virus sticking around but the body’s reaction that’s the issue.

Investigators suggest autoimmunity plays a role, and they point to the presence of autoantibodies, for example.

When these autoantibodies persist, they can cause tissue and organ damage over time.

Other investigators are proposing “immune exhaustion” in long COVID because of similarities to chronic fatigue syndrome, Dr. Hornig said.

“It should be ‘all hands on deck’ for research into long COVID,” she said. “The number of disabled individuals who will likely qualify for a diagnosis of [chronic fatigue syndrome] is growing by the second.”
 

Forging ahead on future research

It’s clear there is more work to do. There are investigators working on banking tissue samples from people with long COVID to learn more, for example.

Also, finding a biomarker unique to long COVID could vastly improve the precision of diagnosing long COVID, especially if the dog sniffing option does not pan out.

Of the thousands of biomarker possibilities, Dr. Hornig said, “maybe that’s one or two that ultimately make a real impact on patient care. So it’s going to be critical to find those quickly, translate them, and make them available.”

In the meantime, some answers might come from a large study sponsored by the National Institutes of Health. The NIH is funding the “Researching COVID to Enhance Recovery” project using $470 million from the American Rescue Plan. Investigators at NYU Langone Health are leading the effort and plan to share the wealth by funding more than 100 researchers at more than 30 institutions to create a “metacohort” to study long COVID. More information is available at recovercovid.org.

“Fortunately, through the global research effort, we are now really starting to expand our understanding of how long COVID manifests, how common it is, and what the underlying mechanisms may be,” Dr. Purpura said.

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

It’s a story of promise at a time of urgent need.

Scientists are optimistic about new evidence into what is causing long COVID, a panel of research experts brought together by the New York State Department of Health said.

They proposed many theories on what might be driving long COVID. A role for a virus “cryptic reservoir” that could reactivate at any time, “viral remnants” that trigger chronic inflammation, and action by “autoimmune antibodies” that cause ongoing symptoms are possibilities.

In fact, it’s likely that research will show long COVID is a condition with more than one cause, the experts said during a recent webinar.

People might experience post-infection problems, including organ damage that takes time to heal after initial COVID-19 illness. Or they may be living with post-immune factors, including ongoing immune system responses triggered by autoantibodies.

Determining the cause or causes of long COVID is essential for treatment. For example, if one person’s symptoms persist because of an overactive immune system, “we need to provide immunosuppressant therapies,” Akiko Iwasaki, PhD, said. “But we don’t want to give that to someone who has a persistent virus reservoir,” meaning remnants of the virus remain in their bodies.

Interestingly, a study preprint, which has not been peer reviewed, found dogs were accurate more than half the time in sniffing out long COVID, said Dr. Iwasaki, professor of immunobiology and developmental biology at Yale University, New Haven, Conn.

The dogs were tasked with identifying 45 people with long COVID versus 188 people without it. The findings suggest the presence of a unique chemical in the sweat of people with long COVID that could someday lead to a diagnostic test.
 

Viral persistence possible

If one of the main theories holds, it could be that the coronavirus somehow remains in the body in some form for some people after COVID-19.

Mady Hornig, MD, agreed this is a possibility that needs to be investigated further.

“A weakened immune response to an infection may mean that you have cryptic reservoirs of virus that are continuing to cause symptoms,” she said during the briefing. Dr. Hornig is a doctor-scientist specializing in epidemiology at Columbia University, New York.

“That may explain why some patients with long COVID feel better after vaccination,” because the vaccine creates a strong antibody response to fight COVID-19, Dr. Iwasaki said.

Researchers are unearthing additional potential factors contributing to long COVID.

Viral persistence could also reactivate other dormant viruses in the body, such as Epstein-Barr virus (EBV), said Lawrence Purpura, MD, MPH, an infectious disease specialist at New York Presbyterian/Columbia University. Reactivation of Epstein-Barr is one of four identifying signs of long COVID revealed in a Jan. 25 study published in the journal Cell.
 

Immune overactivation also possible?

For other people with long COVID, it’s not the virus sticking around but the body’s reaction that’s the issue.

Investigators suggest autoimmunity plays a role, and they point to the presence of autoantibodies, for example.

When these autoantibodies persist, they can cause tissue and organ damage over time.

Other investigators are proposing “immune exhaustion” in long COVID because of similarities to chronic fatigue syndrome, Dr. Hornig said.

“It should be ‘all hands on deck’ for research into long COVID,” she said. “The number of disabled individuals who will likely qualify for a diagnosis of [chronic fatigue syndrome] is growing by the second.”
 

Forging ahead on future research

It’s clear there is more work to do. There are investigators working on banking tissue samples from people with long COVID to learn more, for example.

Also, finding a biomarker unique to long COVID could vastly improve the precision of diagnosing long COVID, especially if the dog sniffing option does not pan out.

Of the thousands of biomarker possibilities, Dr. Hornig said, “maybe that’s one or two that ultimately make a real impact on patient care. So it’s going to be critical to find those quickly, translate them, and make them available.”

In the meantime, some answers might come from a large study sponsored by the National Institutes of Health. The NIH is funding the “Researching COVID to Enhance Recovery” project using $470 million from the American Rescue Plan. Investigators at NYU Langone Health are leading the effort and plan to share the wealth by funding more than 100 researchers at more than 30 institutions to create a “metacohort” to study long COVID. More information is available at recovercovid.org.

“Fortunately, through the global research effort, we are now really starting to expand our understanding of how long COVID manifests, how common it is, and what the underlying mechanisms may be,” Dr. Purpura said.

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

Several relatively large real-world analyses of Janus kinase inhibitors (JAKi) in patients with rheumatoid arthritis appear to show that the oral small-molecule drugs are discontinued and retained at rates similar to or better than biologic disease-modifying antirheumatic drugs (bDMARDs), including tumor necrosis factor inhibitors (TNFi), according to studies presented at the annual meeting of the Canadian Rheumatology Association.

The findings of these studies, although conducted prior to the Food and Drug Administration’s September 2021 announcement of a boxed warning for JAKi, do not lend support to the warning’s message of higher risks of major adverse cardiovascular events (MACE), blood clots, cancer, and death associated with JAKi.

In one study, discontinuation of JAKi-class drugs was less common than discontinuation of bDMARD-class drugs, including tumor necrosis factor inhibitors (TNFi), according to a multicenter team of investigators led by Janet Pope, MD, a professor in the division of rheumatology at the University of Western Ontario, London.

The greater durability of the JAKi relative to TNFi “seem to be driven by a greater loss of efficacy in bDMARDs over time,” reported Samir Magdy Iskander, a medical student at the university, who presented the data.
 

JAKi rival bDMARDs for long-term retention

In a separate but larger analysis, the retention rates with the JAKi tofacitinib (Xeljanz) and TNFi in two RA registries in Canada were about the same after a mean follow-up of 23.2 months (36.9% vs. 37.5%), but the tofacitinib group was at a relative disadvantage. Relative to the bDMARD group, patients taking JAKi were more likely to have had prior treatment with a bDMARD (66.9% vs. 33.9%), to have a higher median baseline Clinical Disease Activity Index (CDAI) score (22.1 vs. 20.0; P < .05), and to be older (59.5 vs. 57.6 years).

In this study, 1,318 patients with RA enrolled in the Ontario Best Practices Research Initiative (OBRI) or a Quebec cohort called RHUMADATA were evaluated, reported Mohammad Movahedi, MD, PhD, of the Institute of Health Policy, Management, and Evaluation at the University of Toronto.

“We have not yet analyzed the reasons for discontinuation, but the data show that retention is about the same, meaning that selection of one agent over the other should be tailored according to patient characteristics,” Dr. Movahedi said.

Reasons for discontinuation were presented in the other observational study, which included 333 adult patients with RA from two centers in Ontario. The discontinuation rate for adverse events was approximately 20% in both groups (HR, 1.0005; P = .98). However, the discontinuation rate for lack of efficacy favored the JAKi, reaching statistical significance.
 

TNFi failure for lack of efficacy is higher

“For lack of efficacy, the discontinuation rate was about 35% lower on the JAKi [HR, 0.6543; P = .029],” Mr. Iskander reported. Relative to those taking a TNFi, those on a JAKi demonstrated “greater durability regardless of gender, age, disease duration, and prior lines of therapy.”

In a population of patients who have not achieved an adequate response to conventional synthetic DMARDs (csDMARDs), which describes the study population from the two Ontario centers, JAKi “may be considered as a preferable method of treatment,” Mr. Iskander said.

Pointing out that many clinicians have interpreted the boxed warning as a relative contraindication for use of JAKi as first-line therapy in patients with an inadequate response to csDMARDs, Marinka Twilt, MD, PhD, the moderator of the scientific session where these data were presented, questioned the conclusion. In the boxed warning, clinicians and patients are advised to consider an increased risk of serious infections, malignancy, and cardiovascular-related mortality in individuals older than 50 years.

In response, Mr. Iskander said that the data were collected and analyzed prior to the change in labeling. He acknowledged that this study was not designed to capture long-term risks, such as cardiovascular disease or malignancy. In this analysis, the safety and tolerability of JAKi and bDMARDs appeared comparable.
 

NEJM published study leading to boxed warning

Just a week prior to the CRA annual meeting, the New England Journal of Medicine published an FDA-mandated postmarketing trial of tofacitinib that was used by the agency to justify the boxed warning for JAKi with indications for artitis and other inflammatory diseases. In that open-label trial, more than 4,000 patients aged 50 years or older with at least one additional cardiovascular risk factor were randomized to 5 mg tofacitinib twice daily, 10 mg tofacitinib twice daily, or a TNFi (adalimumab or etanercept).

The efficacy of the therapies was similar, but tofacitinib failed to meet predefined noninferiority criteria for the co–primary endpoints of MACE or cancer (excluding nonmelanoma skin cancer). For tofacitinib relative to TNFi, the hazard ratio was 1.33 for MACE and 1.48 for cancers. The JAKi was also associated with higher incidences of opportunistic infections.

Mr. Iskander noted that Canadian clinical practice guidelines currently identify JAKi as a reasonable first-line alternative to bDMARDs after inadequate response to csDMARDs. While his data support that position, Dr. Twilt indicated that the benefit-to-risk ratio of JAKi might need recalculation based on the data that led the FDA to issue its boxed warning. She questioned whether the language regarding the relative role of JAKi and bDMARDs will change in coming RA guideline revisions.

Dr. Iskander reported no potential conflicts of interest. Dr. Movahedi did not list any personal conflicts of interest but acknowledged that OBRI received unrestricted grants from a variety of pharmaceutical companies, including those that manufacture bDMARDs and JAKi. Dr. Twilt reported no potential conflicts of interest.

Several relatively large real-world analyses of Janus kinase inhibitors (JAKi) in patients with rheumatoid arthritis appear to show that the oral small-molecule drugs are discontinued and retained at rates similar to or better than biologic disease-modifying antirheumatic drugs (bDMARDs), including tumor necrosis factor inhibitors (TNFi), according to studies presented at the annual meeting of the Canadian Rheumatology Association.

The findings of these studies, although conducted prior to the Food and Drug Administration’s September 2021 announcement of a boxed warning for JAKi, do not lend support to the warning’s message of higher risks of major adverse cardiovascular events (MACE), blood clots, cancer, and death associated with JAKi.

In one study, discontinuation of JAKi-class drugs was less common than discontinuation of bDMARD-class drugs, including tumor necrosis factor inhibitors (TNFi), according to a multicenter team of investigators led by Janet Pope, MD, a professor in the division of rheumatology at the University of Western Ontario, London.

The greater durability of the JAKi relative to TNFi “seem to be driven by a greater loss of efficacy in bDMARDs over time,” reported Samir Magdy Iskander, a medical student at the university, who presented the data.
 

JAKi rival bDMARDs for long-term retention

In a separate but larger analysis, the retention rates with the JAKi tofacitinib (Xeljanz) and TNFi in two RA registries in Canada were about the same after a mean follow-up of 23.2 months (36.9% vs. 37.5%), but the tofacitinib group was at a relative disadvantage. Relative to the bDMARD group, patients taking JAKi were more likely to have had prior treatment with a bDMARD (66.9% vs. 33.9%), to have a higher median baseline Clinical Disease Activity Index (CDAI) score (22.1 vs. 20.0; P < .05), and to be older (59.5 vs. 57.6 years).

In this study, 1,318 patients with RA enrolled in the Ontario Best Practices Research Initiative (OBRI) or a Quebec cohort called RHUMADATA were evaluated, reported Mohammad Movahedi, MD, PhD, of the Institute of Health Policy, Management, and Evaluation at the University of Toronto.

“We have not yet analyzed the reasons for discontinuation, but the data show that retention is about the same, meaning that selection of one agent over the other should be tailored according to patient characteristics,” Dr. Movahedi said.

Reasons for discontinuation were presented in the other observational study, which included 333 adult patients with RA from two centers in Ontario. The discontinuation rate for adverse events was approximately 20% in both groups (HR, 1.0005; P = .98). However, the discontinuation rate for lack of efficacy favored the JAKi, reaching statistical significance.
 

TNFi failure for lack of efficacy is higher

“For lack of efficacy, the discontinuation rate was about 35% lower on the JAKi [HR, 0.6543; P = .029],” Mr. Iskander reported. Relative to those taking a TNFi, those on a JAKi demonstrated “greater durability regardless of gender, age, disease duration, and prior lines of therapy.”

In a population of patients who have not achieved an adequate response to conventional synthetic DMARDs (csDMARDs), which describes the study population from the two Ontario centers, JAKi “may be considered as a preferable method of treatment,” Mr. Iskander said.

Pointing out that many clinicians have interpreted the boxed warning as a relative contraindication for use of JAKi as first-line therapy in patients with an inadequate response to csDMARDs, Marinka Twilt, MD, PhD, the moderator of the scientific session where these data were presented, questioned the conclusion. In the boxed warning, clinicians and patients are advised to consider an increased risk of serious infections, malignancy, and cardiovascular-related mortality in individuals older than 50 years.

In response, Mr. Iskander said that the data were collected and analyzed prior to the change in labeling. He acknowledged that this study was not designed to capture long-term risks, such as cardiovascular disease or malignancy. In this analysis, the safety and tolerability of JAKi and bDMARDs appeared comparable.
 

NEJM published study leading to boxed warning

Just a week prior to the CRA annual meeting, the New England Journal of Medicine published an FDA-mandated postmarketing trial of tofacitinib that was used by the agency to justify the boxed warning for JAKi with indications for artitis and other inflammatory diseases. In that open-label trial, more than 4,000 patients aged 50 years or older with at least one additional cardiovascular risk factor were randomized to 5 mg tofacitinib twice daily, 10 mg tofacitinib twice daily, or a TNFi (adalimumab or etanercept).

The efficacy of the therapies was similar, but tofacitinib failed to meet predefined noninferiority criteria for the co–primary endpoints of MACE or cancer (excluding nonmelanoma skin cancer). For tofacitinib relative to TNFi, the hazard ratio was 1.33 for MACE and 1.48 for cancers. The JAKi was also associated with higher incidences of opportunistic infections.

Mr. Iskander noted that Canadian clinical practice guidelines currently identify JAKi as a reasonable first-line alternative to bDMARDs after inadequate response to csDMARDs. While his data support that position, Dr. Twilt indicated that the benefit-to-risk ratio of JAKi might need recalculation based on the data that led the FDA to issue its boxed warning. She questioned whether the language regarding the relative role of JAKi and bDMARDs will change in coming RA guideline revisions.

Dr. Iskander reported no potential conflicts of interest. Dr. Movahedi did not list any personal conflicts of interest but acknowledged that OBRI received unrestricted grants from a variety of pharmaceutical companies, including those that manufacture bDMARDs and JAKi. Dr. Twilt reported no potential conflicts of interest.

Several relatively large real-world analyses of Janus kinase inhibitors (JAKi) in patients with rheumatoid arthritis appear to show that the oral small-molecule drugs are discontinued and retained at rates similar to or better than biologic disease-modifying antirheumatic drugs (bDMARDs), including tumor necrosis factor inhibitors (TNFi), according to studies presented at the annual meeting of the Canadian Rheumatology Association.

The findings of these studies, although conducted prior to the Food and Drug Administration’s September 2021 announcement of a boxed warning for JAKi, do not lend support to the warning’s message of higher risks of major adverse cardiovascular events (MACE), blood clots, cancer, and death associated with JAKi.

In one study, discontinuation of JAKi-class drugs was less common than discontinuation of bDMARD-class drugs, including tumor necrosis factor inhibitors (TNFi), according to a multicenter team of investigators led by Janet Pope, MD, a professor in the division of rheumatology at the University of Western Ontario, London.

The greater durability of the JAKi relative to TNFi “seem to be driven by a greater loss of efficacy in bDMARDs over time,” reported Samir Magdy Iskander, a medical student at the university, who presented the data.
 

JAKi rival bDMARDs for long-term retention

In a separate but larger analysis, the retention rates with the JAKi tofacitinib (Xeljanz) and TNFi in two RA registries in Canada were about the same after a mean follow-up of 23.2 months (36.9% vs. 37.5%), but the tofacitinib group was at a relative disadvantage. Relative to the bDMARD group, patients taking JAKi were more likely to have had prior treatment with a bDMARD (66.9% vs. 33.9%), to have a higher median baseline Clinical Disease Activity Index (CDAI) score (22.1 vs. 20.0; P < .05), and to be older (59.5 vs. 57.6 years).

In this study, 1,318 patients with RA enrolled in the Ontario Best Practices Research Initiative (OBRI) or a Quebec cohort called RHUMADATA were evaluated, reported Mohammad Movahedi, MD, PhD, of the Institute of Health Policy, Management, and Evaluation at the University of Toronto.

“We have not yet analyzed the reasons for discontinuation, but the data show that retention is about the same, meaning that selection of one agent over the other should be tailored according to patient characteristics,” Dr. Movahedi said.

Reasons for discontinuation were presented in the other observational study, which included 333 adult patients with RA from two centers in Ontario. The discontinuation rate for adverse events was approximately 20% in both groups (HR, 1.0005; P = .98). However, the discontinuation rate for lack of efficacy favored the JAKi, reaching statistical significance.
 

TNFi failure for lack of efficacy is higher

“For lack of efficacy, the discontinuation rate was about 35% lower on the JAKi [HR, 0.6543; P = .029],” Mr. Iskander reported. Relative to those taking a TNFi, those on a JAKi demonstrated “greater durability regardless of gender, age, disease duration, and prior lines of therapy.”

In a population of patients who have not achieved an adequate response to conventional synthetic DMARDs (csDMARDs), which describes the study population from the two Ontario centers, JAKi “may be considered as a preferable method of treatment,” Mr. Iskander said.

Pointing out that many clinicians have interpreted the boxed warning as a relative contraindication for use of JAKi as first-line therapy in patients with an inadequate response to csDMARDs, Marinka Twilt, MD, PhD, the moderator of the scientific session where these data were presented, questioned the conclusion. In the boxed warning, clinicians and patients are advised to consider an increased risk of serious infections, malignancy, and cardiovascular-related mortality in individuals older than 50 years.

In response, Mr. Iskander said that the data were collected and analyzed prior to the change in labeling. He acknowledged that this study was not designed to capture long-term risks, such as cardiovascular disease or malignancy. In this analysis, the safety and tolerability of JAKi and bDMARDs appeared comparable.
 

NEJM published study leading to boxed warning

Just a week prior to the CRA annual meeting, the New England Journal of Medicine published an FDA-mandated postmarketing trial of tofacitinib that was used by the agency to justify the boxed warning for JAKi with indications for artitis and other inflammatory diseases. In that open-label trial, more than 4,000 patients aged 50 years or older with at least one additional cardiovascular risk factor were randomized to 5 mg tofacitinib twice daily, 10 mg tofacitinib twice daily, or a TNFi (adalimumab or etanercept).

The efficacy of the therapies was similar, but tofacitinib failed to meet predefined noninferiority criteria for the co–primary endpoints of MACE or cancer (excluding nonmelanoma skin cancer). For tofacitinib relative to TNFi, the hazard ratio was 1.33 for MACE and 1.48 for cancers. The JAKi was also associated with higher incidences of opportunistic infections.

Mr. Iskander noted that Canadian clinical practice guidelines currently identify JAKi as a reasonable first-line alternative to bDMARDs after inadequate response to csDMARDs. While his data support that position, Dr. Twilt indicated that the benefit-to-risk ratio of JAKi might need recalculation based on the data that led the FDA to issue its boxed warning. She questioned whether the language regarding the relative role of JAKi and bDMARDs will change in coming RA guideline revisions.

Dr. Iskander reported no potential conflicts of interest. Dr. Movahedi did not list any personal conflicts of interest but acknowledged that OBRI received unrestricted grants from a variety of pharmaceutical companies, including those that manufacture bDMARDs and JAKi. Dr. Twilt reported no potential conflicts of interest.

The Endocrine Society is among several organizations and individuals petitioning the Food and Drug Administration to remove its approvals of bisphenol A (BPA), citing recent evidence that exposure to it is unsafe.

The chemical is used to make plastics in items such as food containers, pitchers, and inner linings of metal products. Small amounts of BPA can leak into food and beverages.

tezzstock/Thinkstock

The petition points to a December 2021 report by the European Food Safety Authority titled: “Re-evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs,” which summarizes evidence gathered since 2013.

It concludes that “there is a health concern from BPA exposure for all age groups.” Specific concerns include harm to the immune system and male and female reproductive systems.
 

Average American exposed to 5,000 times the safe level of BPA

The EFSA established a new “tolerable daily intake” of BPA of 0.04 ng/kg of body weight per day. By contrast, in 2014 the FDA estimated that the mean BPA intake for the U.S. population older than 2 years was 200 ng/kg bw/day and that the 90th percentile for BPA intake was 500 ng/kg of body weight per day.

“Using FDA’s own exposure estimates, the average American is exposed to more than 5000 times the safe level of 0.04 ng BPA/kg [body weight per day] set by the EFSA expert panel. Without a doubt, these values constitute a high health risk and support the conclusion that uses of BPA are not safe ... Given the magnitude of the overexposure, we request an expedited review by FDA,” the petition reads.

In addition to the Endocrine Society, which has long warned about the dangers of endocrine-disrupting chemicals, other signatories to the petition include the Environmental Defense Fund, Breast Cancer Prevention Partners, Clean Water Action/Clean Water Fund, Consumer Reports, Environmental Working Group, Healthy Babies Bright Futures, and the former director of the National Institute of Environmental Health Sciences and National Toxicology Program.

In a statement, Endocrine Society BPA expert Heather Patisaul, PhD, of North Carolina University, Raleigh, said the report’s findings “are extremely concerning and prove the point that even very low levels of BPA exposure can be harmful and lead to issues with reproductive health, breast cancer risk, behavior, and metabolism.”

“The FDA needs to acknowledge the science behind endocrine-disrupting chemicals and act accordingly to protect public health,” she urged.

The FDA is expected to decide within the next few days whether to open a docket to accept comments.

A final decision could take 6 months or longer, an Endocrine Society spokesperson told this news organization.

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

The Endocrine Society is among several organizations and individuals petitioning the Food and Drug Administration to remove its approvals of bisphenol A (BPA), citing recent evidence that exposure to it is unsafe.

The chemical is used to make plastics in items such as food containers, pitchers, and inner linings of metal products. Small amounts of BPA can leak into food and beverages.

tezzstock/Thinkstock

The petition points to a December 2021 report by the European Food Safety Authority titled: “Re-evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs,” which summarizes evidence gathered since 2013.

It concludes that “there is a health concern from BPA exposure for all age groups.” Specific concerns include harm to the immune system and male and female reproductive systems.
 

Average American exposed to 5,000 times the safe level of BPA

The EFSA established a new “tolerable daily intake” of BPA of 0.04 ng/kg of body weight per day. By contrast, in 2014 the FDA estimated that the mean BPA intake for the U.S. population older than 2 years was 200 ng/kg bw/day and that the 90th percentile for BPA intake was 500 ng/kg of body weight per day.

“Using FDA’s own exposure estimates, the average American is exposed to more than 5000 times the safe level of 0.04 ng BPA/kg [body weight per day] set by the EFSA expert panel. Without a doubt, these values constitute a high health risk and support the conclusion that uses of BPA are not safe ... Given the magnitude of the overexposure, we request an expedited review by FDA,” the petition reads.

In addition to the Endocrine Society, which has long warned about the dangers of endocrine-disrupting chemicals, other signatories to the petition include the Environmental Defense Fund, Breast Cancer Prevention Partners, Clean Water Action/Clean Water Fund, Consumer Reports, Environmental Working Group, Healthy Babies Bright Futures, and the former director of the National Institute of Environmental Health Sciences and National Toxicology Program.

In a statement, Endocrine Society BPA expert Heather Patisaul, PhD, of North Carolina University, Raleigh, said the report’s findings “are extremely concerning and prove the point that even very low levels of BPA exposure can be harmful and lead to issues with reproductive health, breast cancer risk, behavior, and metabolism.”

“The FDA needs to acknowledge the science behind endocrine-disrupting chemicals and act accordingly to protect public health,” she urged.

The FDA is expected to decide within the next few days whether to open a docket to accept comments.

A final decision could take 6 months or longer, an Endocrine Society spokesperson told this news organization.

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

The Endocrine Society is among several organizations and individuals petitioning the Food and Drug Administration to remove its approvals of bisphenol A (BPA), citing recent evidence that exposure to it is unsafe.

The chemical is used to make plastics in items such as food containers, pitchers, and inner linings of metal products. Small amounts of BPA can leak into food and beverages.

tezzstock/Thinkstock

The petition points to a December 2021 report by the European Food Safety Authority titled: “Re-evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs,” which summarizes evidence gathered since 2013.

It concludes that “there is a health concern from BPA exposure for all age groups.” Specific concerns include harm to the immune system and male and female reproductive systems.
 

Average American exposed to 5,000 times the safe level of BPA

The EFSA established a new “tolerable daily intake” of BPA of 0.04 ng/kg of body weight per day. By contrast, in 2014 the FDA estimated that the mean BPA intake for the U.S. population older than 2 years was 200 ng/kg bw/day and that the 90th percentile for BPA intake was 500 ng/kg of body weight per day.

“Using FDA’s own exposure estimates, the average American is exposed to more than 5000 times the safe level of 0.04 ng BPA/kg [body weight per day] set by the EFSA expert panel. Without a doubt, these values constitute a high health risk and support the conclusion that uses of BPA are not safe ... Given the magnitude of the overexposure, we request an expedited review by FDA,” the petition reads.

In addition to the Endocrine Society, which has long warned about the dangers of endocrine-disrupting chemicals, other signatories to the petition include the Environmental Defense Fund, Breast Cancer Prevention Partners, Clean Water Action/Clean Water Fund, Consumer Reports, Environmental Working Group, Healthy Babies Bright Futures, and the former director of the National Institute of Environmental Health Sciences and National Toxicology Program.

In a statement, Endocrine Society BPA expert Heather Patisaul, PhD, of North Carolina University, Raleigh, said the report’s findings “are extremely concerning and prove the point that even very low levels of BPA exposure can be harmful and lead to issues with reproductive health, breast cancer risk, behavior, and metabolism.”

“The FDA needs to acknowledge the science behind endocrine-disrupting chemicals and act accordingly to protect public health,” she urged.

The FDA is expected to decide within the next few days whether to open a docket to accept comments.

A final decision could take 6 months or longer, an Endocrine Society spokesperson told this news organization.

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

Researchers have found a simple, low-cost way to get more adults to complete a fecal immunochemical test (FIT) to screen for colorectal cancer (CRC).

In a randomized controlled trial, patients who received an electronic “primer” message through their patient portal before the test kit arrived in their mailbox were more apt to complete and return the test than peers who didn’t get the electronic message.

ChrisChrisW/iStock/Getty Images

Heads-up message boosts compliance

CRC screening rates in the United States remain well below the national benchmark of 80%, and COVID-19 hasn’t helped. As a result, multiple medical and professional societies have emphasized the use of a mailed FIT outreach program.

As part of the outreach program, researchers at UCLA Health developed an electronic primer message within the electronic patient portal to alert patients due for CRC screening that they would be receiving a FIT kit in the mail.

They tested the impact of the primer messages in a randomized controlled trial involving 2,339 adults (mean age, 59 years, 57.5% women). Out of these, 1,157 received the standard mailed FIT kit (control group) and 1,182 received the standard mailed FIT kit plus a primer message sent through their personal patient portal.

Adding the primer message significantly increased the FIT completion rate at 6 months by 5.5%, with rates of 37.6% in the intervention group versus 32.1% in the control group.

After adjusting for patient demographics, the primer (versus no primer) led to significantly increased odds of completing CRC screening (adjusted odds ratio: 1.29; 95% confidence interval, 1.08-1.53; P = .004).

The primer message also shortened the time to FIT screening by 3 days (35 days with the primer vs. 38 days without).

Dr. Goshgarian and Dr. Croymans believe the priming messages worked well in their patient population because at the beginning of the intervention they identified a potential lack of awareness of the incoming FIT kit mailer as a barrier to uptake.

“We believe patients were receiving the kits with minimal advanced warning and discarding it as a mistake or hesitant to complete it because they did not understand the value to them,” they told this news organization.

“Therefore, a priming message helped to bridge that gap and allowed patients to be aware of the incoming FIT kits, know why it was important to do the FIT kit, and ultimately led to increasing our FIT kit return rates and thus CRC screening,” they said.

The researchers caution that their findings may be more relevant to patient populations who are more engaged in their health or who are more technologically savvy. In the UCLA Health system, roughly 84% of patients have an activated patient portal.
 

‘Good enhancement’ for health care systems

Reached for comment, Aasma Shaukat, MD, MPH, professor of medicine, NYU Langone Health, and first author of the American College of Gastroenterology (ACG) 2021 CRC screening guidelines, said the results are “interesting but not entirely surprising.”

“There’s literature supporting that a letter or notification prior to the FIT being mailed improves its uptake. Here, the authors applied it to their health care system in a quality improvement study and demonstrated it works,” Dr. Shaukat said.

“This is a good enhancement for health care systems where most of their patients are using or accessing their health chart portal,” added Dr. Shaukat.

“Caveats are that the generalizability is not known. It requires EHR [electronic health record] support tools and patients with access to a computer and enrolled and able to access their electronic chart, likely those with high literacy and English speaking.”

Funding for the study was provided by the UCLA Health Department of Medicine. Dr. Goshgarian, Dr. Croymans, and Dr. Shaukat have disclosed no relevant financial relationships.

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

Researchers have found a simple, low-cost way to get more adults to complete a fecal immunochemical test (FIT) to screen for colorectal cancer (CRC).

In a randomized controlled trial, patients who received an electronic “primer” message through their patient portal before the test kit arrived in their mailbox were more apt to complete and return the test than peers who didn’t get the electronic message.

ChrisChrisW/iStock/Getty Images

Heads-up message boosts compliance

CRC screening rates in the United States remain well below the national benchmark of 80%, and COVID-19 hasn’t helped. As a result, multiple medical and professional societies have emphasized the use of a mailed FIT outreach program.

As part of the outreach program, researchers at UCLA Health developed an electronic primer message within the electronic patient portal to alert patients due for CRC screening that they would be receiving a FIT kit in the mail.

They tested the impact of the primer messages in a randomized controlled trial involving 2,339 adults (mean age, 59 years, 57.5% women). Out of these, 1,157 received the standard mailed FIT kit (control group) and 1,182 received the standard mailed FIT kit plus a primer message sent through their personal patient portal.

Adding the primer message significantly increased the FIT completion rate at 6 months by 5.5%, with rates of 37.6% in the intervention group versus 32.1% in the control group.

After adjusting for patient demographics, the primer (versus no primer) led to significantly increased odds of completing CRC screening (adjusted odds ratio: 1.29; 95% confidence interval, 1.08-1.53; P = .004).

The primer message also shortened the time to FIT screening by 3 days (35 days with the primer vs. 38 days without).

Dr. Goshgarian and Dr. Croymans believe the priming messages worked well in their patient population because at the beginning of the intervention they identified a potential lack of awareness of the incoming FIT kit mailer as a barrier to uptake.

“We believe patients were receiving the kits with minimal advanced warning and discarding it as a mistake or hesitant to complete it because they did not understand the value to them,” they told this news organization.

“Therefore, a priming message helped to bridge that gap and allowed patients to be aware of the incoming FIT kits, know why it was important to do the FIT kit, and ultimately led to increasing our FIT kit return rates and thus CRC screening,” they said.

The researchers caution that their findings may be more relevant to patient populations who are more engaged in their health or who are more technologically savvy. In the UCLA Health system, roughly 84% of patients have an activated patient portal.
 

‘Good enhancement’ for health care systems

Reached for comment, Aasma Shaukat, MD, MPH, professor of medicine, NYU Langone Health, and first author of the American College of Gastroenterology (ACG) 2021 CRC screening guidelines, said the results are “interesting but not entirely surprising.”

“There’s literature supporting that a letter or notification prior to the FIT being mailed improves its uptake. Here, the authors applied it to their health care system in a quality improvement study and demonstrated it works,” Dr. Shaukat said.

“This is a good enhancement for health care systems where most of their patients are using or accessing their health chart portal,” added Dr. Shaukat.

“Caveats are that the generalizability is not known. It requires EHR [electronic health record] support tools and patients with access to a computer and enrolled and able to access their electronic chart, likely those with high literacy and English speaking.”

Funding for the study was provided by the UCLA Health Department of Medicine. Dr. Goshgarian, Dr. Croymans, and Dr. Shaukat have disclosed no relevant financial relationships.

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

Researchers have found a simple, low-cost way to get more adults to complete a fecal immunochemical test (FIT) to screen for colorectal cancer (CRC).

In a randomized controlled trial, patients who received an electronic “primer” message through their patient portal before the test kit arrived in their mailbox were more apt to complete and return the test than peers who didn’t get the electronic message.

ChrisChrisW/iStock/Getty Images

Heads-up message boosts compliance

CRC screening rates in the United States remain well below the national benchmark of 80%, and COVID-19 hasn’t helped. As a result, multiple medical and professional societies have emphasized the use of a mailed FIT outreach program.

As part of the outreach program, researchers at UCLA Health developed an electronic primer message within the electronic patient portal to alert patients due for CRC screening that they would be receiving a FIT kit in the mail.

They tested the impact of the primer messages in a randomized controlled trial involving 2,339 adults (mean age, 59 years, 57.5% women). Out of these, 1,157 received the standard mailed FIT kit (control group) and 1,182 received the standard mailed FIT kit plus a primer message sent through their personal patient portal.

Adding the primer message significantly increased the FIT completion rate at 6 months by 5.5%, with rates of 37.6% in the intervention group versus 32.1% in the control group.

After adjusting for patient demographics, the primer (versus no primer) led to significantly increased odds of completing CRC screening (adjusted odds ratio: 1.29; 95% confidence interval, 1.08-1.53; P = .004).

The primer message also shortened the time to FIT screening by 3 days (35 days with the primer vs. 38 days without).

Dr. Goshgarian and Dr. Croymans believe the priming messages worked well in their patient population because at the beginning of the intervention they identified a potential lack of awareness of the incoming FIT kit mailer as a barrier to uptake.

“We believe patients were receiving the kits with minimal advanced warning and discarding it as a mistake or hesitant to complete it because they did not understand the value to them,” they told this news organization.

“Therefore, a priming message helped to bridge that gap and allowed patients to be aware of the incoming FIT kits, know why it was important to do the FIT kit, and ultimately led to increasing our FIT kit return rates and thus CRC screening,” they said.

The researchers caution that their findings may be more relevant to patient populations who are more engaged in their health or who are more technologically savvy. In the UCLA Health system, roughly 84% of patients have an activated patient portal.
 

‘Good enhancement’ for health care systems

Reached for comment, Aasma Shaukat, MD, MPH, professor of medicine, NYU Langone Health, and first author of the American College of Gastroenterology (ACG) 2021 CRC screening guidelines, said the results are “interesting but not entirely surprising.”

“There’s literature supporting that a letter or notification prior to the FIT being mailed improves its uptake. Here, the authors applied it to their health care system in a quality improvement study and demonstrated it works,” Dr. Shaukat said.

“This is a good enhancement for health care systems where most of their patients are using or accessing their health chart portal,” added Dr. Shaukat.

“Caveats are that the generalizability is not known. It requires EHR [electronic health record] support tools and patients with access to a computer and enrolled and able to access their electronic chart, likely those with high literacy and English speaking.”

Funding for the study was provided by the UCLA Health Department of Medicine. Dr. Goshgarian, Dr. Croymans, and Dr. Shaukat have disclosed no relevant financial relationships.

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

Hundreds of Native American tribes have tentatively settled in what one of the lead attorneys describes as “an epic deal”: The top 3 pharmaceutical distributors in the US and Johnson & Johnson have agreed to pay $665 million for deceptive marketing practices and overdistribution of opioids. Native Americans were among those hardest hit by the opioid epidemic. Between 2006 and 2014, Native Americans were nearly 50% more likely than non-Natives to die of an opioid overdose. In 2014, they ranked number 1 for death by opioid overdose.

Overprescribing was rampant. In some areas, such as southwestern Virginia, eastern Kentucky, and Alabama, prescriptions were 5 to 6 times higher than the national average. The overprescribing was largely due to massive and aggressive billion-dollar marketing campaigns, which misrepresented the safety of opioid medications. Purdue Pharma, for instance, trained sales representatives to claim that the risk of addiction was “less than 1 percent.” In an interview with Smithsonian Magazine, Caleb Alexander, MD, codirector of Johns Hopkins’ Center for Drug Safety and Effectiveness, said, “When I was in residency training, we were taught that one needn’t worry about the addictive potential of opioids if a patient had true pain.” He said it was no accident that physicians were cultivated to overestimate the effectiveness for chronic, noncancer pain while underestimating the risks.

Native Americans were not only in the target group for prescriptions, but also apparently singularly targeted. “We were preyed upon,” said Chickasaw Nation Governor Bill Anoatubby in the Washington Post. “It was unconscionable.” A Washington Post analysis found that, between 2006 and 2014, opioid distributors shipped an average of 36 pills per person in the US. States in the so-called opioid belt (mostly Southern states), received an average of 60 to 66 pills per person. The distributors shipped 57 pills per person to Oklahoma, home to nearly 322,000 Native Americans. (The opioid death rate for Native Americans in Oklahoma from 2006 to 2014 was more than triple the nationwide rate for non-Natives.) In South Dakota as recently as 2015, enough opioids were prescribed to medicate every adult around-the-clock for 19 consecutive days. Native Americans comprise 9% of South Dakota’s population; however, almost 30% of the patients are being treated for opioid use disorder.

In the settlement, which is a first for tribes, McKesson, Cardinal Health, and AmerisourceBergen would pay $515 million over 7 years. Johnson & Johnson would contribute $150 million in 2 years to the federally recognized tribes. “This settlement is a real turning point in history,” said Lloyd Miller, one of the attorneys representing one-third of the litigating tribes.

But the money is still small compensation for ravaging millions of lives. “Flooding the Native community with Western medicine—sedating a population rather than seeking to understand its needs and challenges—is not an acceptable means of handling its trauma,” the Lakota People’s Law Project says in an article on its website. Thus, the money dispersal will be overseen by a panel of tribal health experts, to go toward programs that aid drug users and their communities.

The funds will be managed in a way that will consider the long-term damage, Native American leaders vow. Children, for instance, have not been exempt from the sequelae of the overprescribing. Foster care systems are “overrun” with children of addicted parents, the Law Project says, and the children are placed in homes outside the tribe. “In the long run, this has the potential to curtail tribal membership, break down familial lines, and degrade cultural values.”

Dealing with the problem has drained tribal resources—doubly strained by the COVID-19 epidemic. Chairman Douglas Yankton, of the Spirit Lake Nation in North Dakota, said in a statement, “The dollars that will flow to Tribes under this initial settlement will help fund crucial, on-reservation, culturally appropriate opioid treatment services.”

However, Chairman Kristopher Peters, of the Squaxin Island Tribe in Washington State, told the Washington Post, “There is no amount of money that’s going to solve the generational issues that have been created from this. Our hope is that we can use these funds to help revitalize our culture and help heal our people.”

Johnson & Johnson says it no longer sells prescription opioids in the US

Hundreds of Native American tribes have tentatively settled in what one of the lead attorneys describes as “an epic deal”: The top 3 pharmaceutical distributors in the US and Johnson & Johnson have agreed to pay $665 million for deceptive marketing practices and overdistribution of opioids. Native Americans were among those hardest hit by the opioid epidemic. Between 2006 and 2014, Native Americans were nearly 50% more likely than non-Natives to die of an opioid overdose. In 2014, they ranked number 1 for death by opioid overdose.

Overprescribing was rampant. In some areas, such as southwestern Virginia, eastern Kentucky, and Alabama, prescriptions were 5 to 6 times higher than the national average. The overprescribing was largely due to massive and aggressive billion-dollar marketing campaigns, which misrepresented the safety of opioid medications. Purdue Pharma, for instance, trained sales representatives to claim that the risk of addiction was “less than 1 percent.” In an interview with Smithsonian Magazine, Caleb Alexander, MD, codirector of Johns Hopkins’ Center for Drug Safety and Effectiveness, said, “When I was in residency training, we were taught that one needn’t worry about the addictive potential of opioids if a patient had true pain.” He said it was no accident that physicians were cultivated to overestimate the effectiveness for chronic, noncancer pain while underestimating the risks.

Native Americans were not only in the target group for prescriptions, but also apparently singularly targeted. “We were preyed upon,” said Chickasaw Nation Governor Bill Anoatubby in the Washington Post. “It was unconscionable.” A Washington Post analysis found that, between 2006 and 2014, opioid distributors shipped an average of 36 pills per person in the US. States in the so-called opioid belt (mostly Southern states), received an average of 60 to 66 pills per person. The distributors shipped 57 pills per person to Oklahoma, home to nearly 322,000 Native Americans. (The opioid death rate for Native Americans in Oklahoma from 2006 to 2014 was more than triple the nationwide rate for non-Natives.) In South Dakota as recently as 2015, enough opioids were prescribed to medicate every adult around-the-clock for 19 consecutive days. Native Americans comprise 9% of South Dakota’s population; however, almost 30% of the patients are being treated for opioid use disorder.

In the settlement, which is a first for tribes, McKesson, Cardinal Health, and AmerisourceBergen would pay $515 million over 7 years. Johnson & Johnson would contribute $150 million in 2 years to the federally recognized tribes. “This settlement is a real turning point in history,” said Lloyd Miller, one of the attorneys representing one-third of the litigating tribes.

But the money is still small compensation for ravaging millions of lives. “Flooding the Native community with Western medicine—sedating a population rather than seeking to understand its needs and challenges—is not an acceptable means of handling its trauma,” the Lakota People’s Law Project says in an article on its website. Thus, the money dispersal will be overseen by a panel of tribal health experts, to go toward programs that aid drug users and their communities.

The funds will be managed in a way that will consider the long-term damage, Native American leaders vow. Children, for instance, have not been exempt from the sequelae of the overprescribing. Foster care systems are “overrun” with children of addicted parents, the Law Project says, and the children are placed in homes outside the tribe. “In the long run, this has the potential to curtail tribal membership, break down familial lines, and degrade cultural values.”

Dealing with the problem has drained tribal resources—doubly strained by the COVID-19 epidemic. Chairman Douglas Yankton, of the Spirit Lake Nation in North Dakota, said in a statement, “The dollars that will flow to Tribes under this initial settlement will help fund crucial, on-reservation, culturally appropriate opioid treatment services.”

However, Chairman Kristopher Peters, of the Squaxin Island Tribe in Washington State, told the Washington Post, “There is no amount of money that’s going to solve the generational issues that have been created from this. Our hope is that we can use these funds to help revitalize our culture and help heal our people.”

Johnson & Johnson says it no longer sells prescription opioids in the US

Hundreds of Native American tribes have tentatively settled in what one of the lead attorneys describes as “an epic deal”: The top 3 pharmaceutical distributors in the US and Johnson & Johnson have agreed to pay $665 million for deceptive marketing practices and overdistribution of opioids. Native Americans were among those hardest hit by the opioid epidemic. Between 2006 and 2014, Native Americans were nearly 50% more likely than non-Natives to die of an opioid overdose. In 2014, they ranked number 1 for death by opioid overdose.

Overprescribing was rampant. In some areas, such as southwestern Virginia, eastern Kentucky, and Alabama, prescriptions were 5 to 6 times higher than the national average. The overprescribing was largely due to massive and aggressive billion-dollar marketing campaigns, which misrepresented the safety of opioid medications. Purdue Pharma, for instance, trained sales representatives to claim that the risk of addiction was “less than 1 percent.” In an interview with Smithsonian Magazine, Caleb Alexander, MD, codirector of Johns Hopkins’ Center for Drug Safety and Effectiveness, said, “When I was in residency training, we were taught that one needn’t worry about the addictive potential of opioids if a patient had true pain.” He said it was no accident that physicians were cultivated to overestimate the effectiveness for chronic, noncancer pain while underestimating the risks.

Native Americans were not only in the target group for prescriptions, but also apparently singularly targeted. “We were preyed upon,” said Chickasaw Nation Governor Bill Anoatubby in the Washington Post. “It was unconscionable.” A Washington Post analysis found that, between 2006 and 2014, opioid distributors shipped an average of 36 pills per person in the US. States in the so-called opioid belt (mostly Southern states), received an average of 60 to 66 pills per person. The distributors shipped 57 pills per person to Oklahoma, home to nearly 322,000 Native Americans. (The opioid death rate for Native Americans in Oklahoma from 2006 to 2014 was more than triple the nationwide rate for non-Natives.) In South Dakota as recently as 2015, enough opioids were prescribed to medicate every adult around-the-clock for 19 consecutive days. Native Americans comprise 9% of South Dakota’s population; however, almost 30% of the patients are being treated for opioid use disorder.

In the settlement, which is a first for tribes, McKesson, Cardinal Health, and AmerisourceBergen would pay $515 million over 7 years. Johnson & Johnson would contribute $150 million in 2 years to the federally recognized tribes. “This settlement is a real turning point in history,” said Lloyd Miller, one of the attorneys representing one-third of the litigating tribes.

But the money is still small compensation for ravaging millions of lives. “Flooding the Native community with Western medicine—sedating a population rather than seeking to understand its needs and challenges—is not an acceptable means of handling its trauma,” the Lakota People’s Law Project says in an article on its website. Thus, the money dispersal will be overseen by a panel of tribal health experts, to go toward programs that aid drug users and their communities.

The funds will be managed in a way that will consider the long-term damage, Native American leaders vow. Children, for instance, have not been exempt from the sequelae of the overprescribing. Foster care systems are “overrun” with children of addicted parents, the Law Project says, and the children are placed in homes outside the tribe. “In the long run, this has the potential to curtail tribal membership, break down familial lines, and degrade cultural values.”

Dealing with the problem has drained tribal resources—doubly strained by the COVID-19 epidemic. Chairman Douglas Yankton, of the Spirit Lake Nation in North Dakota, said in a statement, “The dollars that will flow to Tribes under this initial settlement will help fund crucial, on-reservation, culturally appropriate opioid treatment services.”

However, Chairman Kristopher Peters, of the Squaxin Island Tribe in Washington State, told the Washington Post, “There is no amount of money that’s going to solve the generational issues that have been created from this. Our hope is that we can use these funds to help revitalize our culture and help heal our people.”

Johnson & Johnson says it no longer sells prescription opioids in the US

Long COVID continues to be a moving target – continuously evolving and still surprising doctors and patients who have sometimes incapacitating long-term symptoms.

Little about the disorder seems predictable at this point. People can have long COVID after asymptomatic, mild, or severe COVID-19, for example. And when a person gets long COVID – also known as long-haul COVID – symptoms can vary widely.

To address all the uncertainty, the New York State Department of Health gathered experts in primary care, pediatrics, physical medicine, rehabilitation, and pulmonology to answer some pressing questions.

New York in 2020 was the first epicenter of the pandemic in the United States, making it also the center of the long COVID epidemic, says Emily Lutterloh, MD, director of the Division of Epidemiology at the New York State Department of Health.
 

What do you do when you’re seeing a patient with long COVID for the first time?

The first exam varies because there are so many different ways long COVID presents itself, says Benjamin Abramoff, MD, a physical medicine and rehabilitation specialist at Penn Medicine in Philadelphia.

I’ve now been seriously ill with #LongCovid for 11 months. I was never hospitalized. I didn’t even have a “mild” covid case. Instead, I developed Long Covid from an asymptomatic infection.

I’m far from unique. Up to 1/5 of asymptomatic patients go on to have long-term symptoms.

— Ravi Veriah Jacques (@RaviHVJ) February 3, 2022

Assessing their previous and current care also helps to direct their ongoing management, says Zijian Chen, MD, medical director of the Center for Post-COVID Care at Mount Sinai Health System in New York.
 

Can vaccination help people with long COVID?

Anything that we can do to help prevent people from being critically ill or being hospitalized with COVID-19 is helpful to prevent long COVID, says Dr. Abramoff, who is also director of the long COVID clinic at the University of Pennsylvania, Philadelphia.

“So that’s something I always discuss with patients. In some research, sometimes patients do feel better after the vaccine,” he says.
 

What kind of therapies do you find helpful for your patients?

Rehabilitation is a key part of recovery from long COVID, Dr. Abramoff says. “It is very important to make this very patient-specific.”

“We have patients that are working. They’re already going to the gym in some cases but don’t feel like they have the same endurance,” he says. “And then we have patients who are so crippled by their fatigue that they can’t get out of bed.”
 

1/ What is #LongCOVID?!

A disabling malady from ongoing inflammation, autoimmunity, & potential viral reservoirs (GI, brain?)

NEW DATA: The Lungs “light up” on special MRI Scans 3 to 9 months later in patients never hospitalized for COVID.https://t.co/I2kyZ4cK5F pic.twitter.com/dL1P67L2DK

— WesElyMD (@WesElyMD) February 2, 2022

An exercise program can help people who have long COVID.

“There’s a big role for therapy services in the recovery of these patients,” says John Baratta, MD, of the department of physical medicine and rehabilitation at the University of North Carolina at Chapel Hill.

But the limited number of long COVID clinics can mean some people are unable to get to therapists trained on the needs of patients with lingering COVID symptoms. Educating community physical and occupational therapists is one solution.
 

How long does it take for people with long COVID to recover and get back to 100% if they can?

Specific numbers aren’t really available, Dr. Baratta says.

“But I can tell you the general trend that I see is that a lot of patients have a gradual improvement of symptoms. The slow but steady improvement with time may be the body’s natural healing process, a result of medical interventions, or both.”

It can help to reassure people with long COVID that they will not be discharged from care until they feel they’ve maximized their health, says Sharagim Kemp, DO, medical director of the COVID Recovery Program for Nuvance Health, a health system in New York and Connecticut.

It’s essential to set realistic recovery expectations and tell patients that not everyone will return to 100% of their pre-COVID functioning, she says.

“Once we are able to help them reset their expectations, there’s almost an accelerated recovery because they are not putting that pressure on themselves anymore,” Dr. Kemp says.
 

What are the most common symptoms you’re seeing in long COVID?

It’s helpful to think of long COVID as a very broad umbrella term, Dr. Abramoff says.

Echoing what many others have observed, fatigue, cognitive dysfunction or “brain fog,“ and shortness of breath or troubled breathing appear to be the most common symptoms, he says.

Some reported vague symptoms, Dr. Kemp says.

People may go to the doctor “not even realizing that they had COVID. That’s one of the important points here – to have a high index of suspicion for patients who come in with multiple symptoms,” she says.

For this reason, patients can report symptoms that don’t necessarily fit into any specialty, says Sarah J. Ryan, MD, an internal medicine doctor at Columbia University Irving Medical Center in New York. People say they are “just not themselves” or they are tired after their COVID-19 recovery.
 

Is there a connection between severe COVID cases and severe long COVID?

“It’s not like that at all. I would say that more than 80% of the patients that we see had mild to moderate illness and they were not hospitalized,” Dr. Baratta says.

Long COVID is a bit different in children and teenagers, says Ixsy Ramirez, MD, a pediatric pulmonologist at University of Michigan Health, Ann Arbor. Most patients in the long COVID clinic at the University of Michigan were previously healthy, and not children with asthma or other lung conditions as one might expect. In fact, many are student athletes, or were before they had long COVID.

In this population, shortness of breath is most common, followed by chest pain and fatigue. Unfortunately, the symptoms are so serious for many kids that their performance is limited, even if they can return to competitive play.
 

Are there defined criteria you use to diagnose long COVID? How do you give someone a diagnosis?

That’s an ever-evolving question, Dr. Kemp says. The generally accepted definition centers on persistent or new symptoms 4 weeks or more after the original COVID-19 illness, but there are exceptions.

Researchers are working on lab tests to help confirm the diagnosis. But without a definitive blood biomarker, getting to the diagnosis requires “some thorough detective work,” Dr. Ryan says.
 

Do you bring in mental health providers to help with treatment?

“We focus on mental health quite a bit actually,” says, Dr. Chen, cofounder of his institution’s COVID recovery clinic. Mount Sinai offers one-on-one and group mental health services, for example.

“Personally, I’ve seen patients that I did not expect to have such severe mental health changes” with long COVID.
 

One of the most powerful accounts and testimonies I have seen on what most #LongCovid patients experience when interacting with their doctors.

“I did not fit in a box, so they chose not to see me, even worse they made me feel like it was my fault for not fitting in their box” pic.twitter.com/7GQLBucuO5

— charlos (@loscharlos) February 3, 2022

Examples include severe depression, cases of acute psychosis, hallucinations, and other problems “that are really unexpected after a viral illness.”

Stony Brook University Hospital in New York has a long COVID clinic staffed by multiple primary care doctors who do exams and refer patients to services. A bonus of offering psychological services to all post-COVID patients is doctors get a more complete picture of each person and a better understanding of what they are going through, says Abigail Chua, MD, a pulmonologist at Stony Brook.

Some empathy is essential, Dr. Baratta says. “It’s important to recognize that a lot of these patients present with a sense of grief or loss for their prior life.”
 

What does the future hold?

A simple test to diagnose long COVID, combined with an effective treatment that helps people feel better within a week, would be ideal, Dr. Abramoff says.

“That would be lovely. But you know, we’re just not at that point.”

And it would be helpful to start identifying subtypes of long COVID so diagnosis and treatment can be more targeted, Dr. Abramoff says. Otherwise, “It’s going to be a very challenging approach to try to treat all of our patients with long COVID symptoms the same way.”

Good clinical trials likewise are needed to address all the subtleties of long COVID.

A number of long COVID centers are collaborating on research to find out more, Dr. Chen says. Actions include setting up a bank of tissue samples from people with long COVID so researchers can continue to figure out the condition.

One goal, Dr. Chen says, would be the ability to treat long COVID rather than just its symptoms.

Long COVID emphasizes the need to prevent people from getting COVID in the first place, Dr. Ramirez says. This will continue to be important, particularly when some people dismiss the seriousness of COVID, comparing it to a cold if they get it. That attitude discounts the large number of people who unfortunately go on to develop long-term, often debilitating, symptoms.

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

Long COVID continues to be a moving target – continuously evolving and still surprising doctors and patients who have sometimes incapacitating long-term symptoms.

Little about the disorder seems predictable at this point. People can have long COVID after asymptomatic, mild, or severe COVID-19, for example. And when a person gets long COVID – also known as long-haul COVID – symptoms can vary widely.

To address all the uncertainty, the New York State Department of Health gathered experts in primary care, pediatrics, physical medicine, rehabilitation, and pulmonology to answer some pressing questions.

New York in 2020 was the first epicenter of the pandemic in the United States, making it also the center of the long COVID epidemic, says Emily Lutterloh, MD, director of the Division of Epidemiology at the New York State Department of Health.
 

What do you do when you’re seeing a patient with long COVID for the first time?

The first exam varies because there are so many different ways long COVID presents itself, says Benjamin Abramoff, MD, a physical medicine and rehabilitation specialist at Penn Medicine in Philadelphia.

I’ve now been seriously ill with #LongCovid for 11 months. I was never hospitalized. I didn’t even have a “mild” covid case. Instead, I developed Long Covid from an asymptomatic infection.

I’m far from unique. Up to 1/5 of asymptomatic patients go on to have long-term symptoms.

— Ravi Veriah Jacques (@RaviHVJ) February 3, 2022

Assessing their previous and current care also helps to direct their ongoing management, says Zijian Chen, MD, medical director of the Center for Post-COVID Care at Mount Sinai Health System in New York.
 

Can vaccination help people with long COVID?

Anything that we can do to help prevent people from being critically ill or being hospitalized with COVID-19 is helpful to prevent long COVID, says Dr. Abramoff, who is also director of the long COVID clinic at the University of Pennsylvania, Philadelphia.

“So that’s something I always discuss with patients. In some research, sometimes patients do feel better after the vaccine,” he says.
 

What kind of therapies do you find helpful for your patients?

Rehabilitation is a key part of recovery from long COVID, Dr. Abramoff says. “It is very important to make this very patient-specific.”

“We have patients that are working. They’re already going to the gym in some cases but don’t feel like they have the same endurance,” he says. “And then we have patients who are so crippled by their fatigue that they can’t get out of bed.”
 

1/ What is #LongCOVID?!

A disabling malady from ongoing inflammation, autoimmunity, & potential viral reservoirs (GI, brain?)

NEW DATA: The Lungs “light up” on special MRI Scans 3 to 9 months later in patients never hospitalized for COVID.https://t.co/I2kyZ4cK5F pic.twitter.com/dL1P67L2DK

— WesElyMD (@WesElyMD) February 2, 2022

An exercise program can help people who have long COVID.

“There’s a big role for therapy services in the recovery of these patients,” says John Baratta, MD, of the department of physical medicine and rehabilitation at the University of North Carolina at Chapel Hill.

But the limited number of long COVID clinics can mean some people are unable to get to therapists trained on the needs of patients with lingering COVID symptoms. Educating community physical and occupational therapists is one solution.
 

How long does it take for people with long COVID to recover and get back to 100% if they can?

Specific numbers aren’t really available, Dr. Baratta says.

“But I can tell you the general trend that I see is that a lot of patients have a gradual improvement of symptoms. The slow but steady improvement with time may be the body’s natural healing process, a result of medical interventions, or both.”

It can help to reassure people with long COVID that they will not be discharged from care until they feel they’ve maximized their health, says Sharagim Kemp, DO, medical director of the COVID Recovery Program for Nuvance Health, a health system in New York and Connecticut.

It’s essential to set realistic recovery expectations and tell patients that not everyone will return to 100% of their pre-COVID functioning, she says.

“Once we are able to help them reset their expectations, there’s almost an accelerated recovery because they are not putting that pressure on themselves anymore,” Dr. Kemp says.
 

What are the most common symptoms you’re seeing in long COVID?

It’s helpful to think of long COVID as a very broad umbrella term, Dr. Abramoff says.

Echoing what many others have observed, fatigue, cognitive dysfunction or “brain fog,“ and shortness of breath or troubled breathing appear to be the most common symptoms, he says.

Some reported vague symptoms, Dr. Kemp says.

People may go to the doctor “not even realizing that they had COVID. That’s one of the important points here – to have a high index of suspicion for patients who come in with multiple symptoms,” she says.

For this reason, patients can report symptoms that don’t necessarily fit into any specialty, says Sarah J. Ryan, MD, an internal medicine doctor at Columbia University Irving Medical Center in New York. People say they are “just not themselves” or they are tired after their COVID-19 recovery.
 

Is there a connection between severe COVID cases and severe long COVID?

“It’s not like that at all. I would say that more than 80% of the patients that we see had mild to moderate illness and they were not hospitalized,” Dr. Baratta says.

Long COVID is a bit different in children and teenagers, says Ixsy Ramirez, MD, a pediatric pulmonologist at University of Michigan Health, Ann Arbor. Most patients in the long COVID clinic at the University of Michigan were previously healthy, and not children with asthma or other lung conditions as one might expect. In fact, many are student athletes, or were before they had long COVID.

In this population, shortness of breath is most common, followed by chest pain and fatigue. Unfortunately, the symptoms are so serious for many kids that their performance is limited, even if they can return to competitive play.
 

Are there defined criteria you use to diagnose long COVID? How do you give someone a diagnosis?

That’s an ever-evolving question, Dr. Kemp says. The generally accepted definition centers on persistent or new symptoms 4 weeks or more after the original COVID-19 illness, but there are exceptions.

Researchers are working on lab tests to help confirm the diagnosis. But without a definitive blood biomarker, getting to the diagnosis requires “some thorough detective work,” Dr. Ryan says.
 

Do you bring in mental health providers to help with treatment?

“We focus on mental health quite a bit actually,” says, Dr. Chen, cofounder of his institution’s COVID recovery clinic. Mount Sinai offers one-on-one and group mental health services, for example.

“Personally, I’ve seen patients that I did not expect to have such severe mental health changes” with long COVID.
 

One of the most powerful accounts and testimonies I have seen on what most #LongCovid patients experience when interacting with their doctors.

“I did not fit in a box, so they chose not to see me, even worse they made me feel like it was my fault for not fitting in their box” pic.twitter.com/7GQLBucuO5

— charlos (@loscharlos) February 3, 2022

Examples include severe depression, cases of acute psychosis, hallucinations, and other problems “that are really unexpected after a viral illness.”

Stony Brook University Hospital in New York has a long COVID clinic staffed by multiple primary care doctors who do exams and refer patients to services. A bonus of offering psychological services to all post-COVID patients is doctors get a more complete picture of each person and a better understanding of what they are going through, says Abigail Chua, MD, a pulmonologist at Stony Brook.

Some empathy is essential, Dr. Baratta says. “It’s important to recognize that a lot of these patients present with a sense of grief or loss for their prior life.”
 

What does the future hold?

A simple test to diagnose long COVID, combined with an effective treatment that helps people feel better within a week, would be ideal, Dr. Abramoff says.

“That would be lovely. But you know, we’re just not at that point.”

And it would be helpful to start identifying subtypes of long COVID so diagnosis and treatment can be more targeted, Dr. Abramoff says. Otherwise, “It’s going to be a very challenging approach to try to treat all of our patients with long COVID symptoms the same way.”

Good clinical trials likewise are needed to address all the subtleties of long COVID.

A number of long COVID centers are collaborating on research to find out more, Dr. Chen says. Actions include setting up a bank of tissue samples from people with long COVID so researchers can continue to figure out the condition.

One goal, Dr. Chen says, would be the ability to treat long COVID rather than just its symptoms.

Long COVID emphasizes the need to prevent people from getting COVID in the first place, Dr. Ramirez says. This will continue to be important, particularly when some people dismiss the seriousness of COVID, comparing it to a cold if they get it. That attitude discounts the large number of people who unfortunately go on to develop long-term, often debilitating, symptoms.

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

Long COVID continues to be a moving target – continuously evolving and still surprising doctors and patients who have sometimes incapacitating long-term symptoms.

Little about the disorder seems predictable at this point. People can have long COVID after asymptomatic, mild, or severe COVID-19, for example. And when a person gets long COVID – also known as long-haul COVID – symptoms can vary widely.

To address all the uncertainty, the New York State Department of Health gathered experts in primary care, pediatrics, physical medicine, rehabilitation, and pulmonology to answer some pressing questions.

New York in 2020 was the first epicenter of the pandemic in the United States, making it also the center of the long COVID epidemic, says Emily Lutterloh, MD, director of the Division of Epidemiology at the New York State Department of Health.
 

What do you do when you’re seeing a patient with long COVID for the first time?

The first exam varies because there are so many different ways long COVID presents itself, says Benjamin Abramoff, MD, a physical medicine and rehabilitation specialist at Penn Medicine in Philadelphia.

I’ve now been seriously ill with #LongCovid for 11 months. I was never hospitalized. I didn’t even have a “mild” covid case. Instead, I developed Long Covid from an asymptomatic infection.

I’m far from unique. Up to 1/5 of asymptomatic patients go on to have long-term symptoms.

— Ravi Veriah Jacques (@RaviHVJ) February 3, 2022

Assessing their previous and current care also helps to direct their ongoing management, says Zijian Chen, MD, medical director of the Center for Post-COVID Care at Mount Sinai Health System in New York.
 

Can vaccination help people with long COVID?

Anything that we can do to help prevent people from being critically ill or being hospitalized with COVID-19 is helpful to prevent long COVID, says Dr. Abramoff, who is also director of the long COVID clinic at the University of Pennsylvania, Philadelphia.

“So that’s something I always discuss with patients. In some research, sometimes patients do feel better after the vaccine,” he says.
 

What kind of therapies do you find helpful for your patients?

Rehabilitation is a key part of recovery from long COVID, Dr. Abramoff says. “It is very important to make this very patient-specific.”

“We have patients that are working. They’re already going to the gym in some cases but don’t feel like they have the same endurance,” he says. “And then we have patients who are so crippled by their fatigue that they can’t get out of bed.”
 

1/ What is #LongCOVID?!

A disabling malady from ongoing inflammation, autoimmunity, & potential viral reservoirs (GI, brain?)

NEW DATA: The Lungs “light up” on special MRI Scans 3 to 9 months later in patients never hospitalized for COVID.https://t.co/I2kyZ4cK5F pic.twitter.com/dL1P67L2DK

— WesElyMD (@WesElyMD) February 2, 2022

An exercise program can help people who have long COVID.

“There’s a big role for therapy services in the recovery of these patients,” says John Baratta, MD, of the department of physical medicine and rehabilitation at the University of North Carolina at Chapel Hill.

But the limited number of long COVID clinics can mean some people are unable to get to therapists trained on the needs of patients with lingering COVID symptoms. Educating community physical and occupational therapists is one solution.
 

How long does it take for people with long COVID to recover and get back to 100% if they can?

Specific numbers aren’t really available, Dr. Baratta says.

“But I can tell you the general trend that I see is that a lot of patients have a gradual improvement of symptoms. The slow but steady improvement with time may be the body’s natural healing process, a result of medical interventions, or both.”

It can help to reassure people with long COVID that they will not be discharged from care until they feel they’ve maximized their health, says Sharagim Kemp, DO, medical director of the COVID Recovery Program for Nuvance Health, a health system in New York and Connecticut.

It’s essential to set realistic recovery expectations and tell patients that not everyone will return to 100% of their pre-COVID functioning, she says.

“Once we are able to help them reset their expectations, there’s almost an accelerated recovery because they are not putting that pressure on themselves anymore,” Dr. Kemp says.
 

What are the most common symptoms you’re seeing in long COVID?

It’s helpful to think of long COVID as a very broad umbrella term, Dr. Abramoff says.

Echoing what many others have observed, fatigue, cognitive dysfunction or “brain fog,“ and shortness of breath or troubled breathing appear to be the most common symptoms, he says.

Some reported vague symptoms, Dr. Kemp says.

People may go to the doctor “not even realizing that they had COVID. That’s one of the important points here – to have a high index of suspicion for patients who come in with multiple symptoms,” she says.

For this reason, patients can report symptoms that don’t necessarily fit into any specialty, says Sarah J. Ryan, MD, an internal medicine doctor at Columbia University Irving Medical Center in New York. People say they are “just not themselves” or they are tired after their COVID-19 recovery.
 

Is there a connection between severe COVID cases and severe long COVID?

“It’s not like that at all. I would say that more than 80% of the patients that we see had mild to moderate illness and they were not hospitalized,” Dr. Baratta says.

Long COVID is a bit different in children and teenagers, says Ixsy Ramirez, MD, a pediatric pulmonologist at University of Michigan Health, Ann Arbor. Most patients in the long COVID clinic at the University of Michigan were previously healthy, and not children with asthma or other lung conditions as one might expect. In fact, many are student athletes, or were before they had long COVID.

In this population, shortness of breath is most common, followed by chest pain and fatigue. Unfortunately, the symptoms are so serious for many kids that their performance is limited, even if they can return to competitive play.
 

Are there defined criteria you use to diagnose long COVID? How do you give someone a diagnosis?

That’s an ever-evolving question, Dr. Kemp says. The generally accepted definition centers on persistent or new symptoms 4 weeks or more after the original COVID-19 illness, but there are exceptions.

Researchers are working on lab tests to help confirm the diagnosis. But without a definitive blood biomarker, getting to the diagnosis requires “some thorough detective work,” Dr. Ryan says.
 

Do you bring in mental health providers to help with treatment?

“We focus on mental health quite a bit actually,” says, Dr. Chen, cofounder of his institution’s COVID recovery clinic. Mount Sinai offers one-on-one and group mental health services, for example.

“Personally, I’ve seen patients that I did not expect to have such severe mental health changes” with long COVID.
 

One of the most powerful accounts and testimonies I have seen on what most #LongCovid patients experience when interacting with their doctors.

“I did not fit in a box, so they chose not to see me, even worse they made me feel like it was my fault for not fitting in their box” pic.twitter.com/7GQLBucuO5

— charlos (@loscharlos) February 3, 2022