Rheumatology News

PHILADELPHIA – What works in the clinic can also work in community settings: Patients who are overweight or obese with knee osteoarthritis can find relief from pain through diet and exercise programs conducted in recreation centers, local gyms, fitness centers, and other places close to home, according to investigators in a pragmatic randomized trial.

The Weight Loss and Exercise for Communities With Arthritis in North Carolina (WE-CAN) study was modeled after the successful Intensive Diet and Exercise for Arthritis trial, which showed that adults randomized to 18 months of either a diet and exercise program or diet alone had more weight loss and larger reductions in levels of the inflammatory cytokine interleukin-6 than patients randomized to exercise alone, and that diet alone was associated with greater reductions in knee compressive force than exercise alone.

That study was conducted by Stephen P. Messier, PhD, and colleagues at Wake Forest University, Winston-Salem, N.C.. As previously reported, the investigators also saw continued benefits for participants years after the original trial.

With the WE-CAN trial, results of which were reported at the annual meeting of the American College of Rheumatology, Dr. Messier and colleagues took the intervention one step further, randomizing 823 community-dwelling adults who were overweight or obese (body mass index [BMI], ≥ 27 kg/m2) with knee OA to either an 18-month diet and exercise intervention or attention control group consisting of five 1-hour face-to-face meetings over 18 months, plus information packets and phone sessions during alternate months.

“Compared to the control group, diet plus exercise had a statistically significant but modest reduction in pain. Diet plus exercise was 20% more likely to attain a clinically important 2-point improvement in pain,” Dr. Messier said in an oral abstract session at ACR.
 

Real-world setting

The primary goal of WE-CAN was to “determine whether adaptation of a diet and exercise academic center–based efficacy trial to community settings results in a statistically significant reduction in pain relative to an attention control.”

Ariel Skelley/Getty Images

A total of 3,751 potential candidates were screened, and 823 were randomized and assigned to either a diet and exercise arm (414) or attention control arm (409). Of the patients randomized, 336 in the diet/exercise arm and 322 in the control arm attended the final 18-month follow-up visit.

The exercise component consisted of a 15-minute walking period, followed by a 20-minute weight-training period, and ending with a second 15-minute walking period. The diet goal was 10% or greater weight loss, aided by a distribution of low-calorie recipes to produce a reduced-calorie diet of the patient’s choice, with the option to include nutritional powder to make low-calories shakes as meal replacements, one or two per day for the first 6 months, with the option of one per day for the remaining months.

The pragmatic components included the use of established community facilities in both urban and rural counties in North Carolina, broad inclusion criteria, patient-centered outcomes, use of community-based staff to deliver the treatment, nonphysicians trained by study physicians to perform knee exams, and various means of communication, Dr. Messier said.

Participants in each arm were closely matched by demographic and clinical characteristics, with a mean age of 64.5 years in the diet/exercise group and 64.7 years in the attention control group, respective mean weight of 100.7 kg and 101.1 kg, and respective BMI of 36.7 and 36.9. Women comprised about 77% of participants in each group.
 

Endpoints met

The trial met its primary endpoint of a significantly greater reduction in pain at 18 months in the diet and exercise group as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and scored on a scale of 0 (no pain) to 20 (worst pain).

In an analysis adjusted for sex, BMI, and baseline values, there was a 32% reduction in pain scores from baseline in the active intervention arm versus 24% in the control arm (P = .02).

In all, 60.2% of participants assigned to diet and exercise had a minimum reduction in pain scores of at least 2 points at 18 months, compared with 49.7% of participants assigned to the attention control group. This translated into a relative risk for achieving at least a 2-point improvement with diet and exercise was 1.20 (P = .01).

Among participants who remained in the study for the entire 18 months, there were significant improvements in the diet and exercise group compared with controls in the prespecified secondary endpoints of weight change (–8 kg vs. –2 kg), waist circumference, WOMAC function, 6-minute walk distance, and mean Short Form–36 health-related quality of life subscale (P < .001 for all comparisons).

Dr. Messier acknowledged that the diagnosis of knee OA was based only on ACR clinical criteria and was not confirmed with imaging. In addition, offering patients the option of free meal replacement limited the pragmatic nature of the intervention.

He also noted that the 24% reduction in pain seen in the control group suggests that interacting with patients can improve clinical outcomes.
 

‘Tour de force’

In the question-and-answer session following Dr. Messier’s presentation, David T. Felson, MD, a rheumatologist at Boston Medical Center, called in and said the study was “a tour de force” and congratulated Dr. Messier and colleagues on “a lovely study.”

Richard Mark Kirkner/MDedge News

Dr. Felson asked whether the investigators had conducted a mediation analysis to determine what proportion of the improvement was attributable to weight loss, and whether patients assigned to exercise were sticking with it throughout the study.

Dr. Messier replied that they had not yet done a mediation analysis but were continuing to examine the data. Regarding the exercise question, he noted that “the adherence was over 80% for 6 months and over 70% for the whole 18 months, so they did a really nice job.”

In an interview, session moderator Anne Davidson, MBBS, director of the rheumatology program at Northwell Health in Manhasset, N.Y., commented that the investigators managed to accomplish a very challenging task.

“In terms of recruitment of patients with engagement of community facilities and quality of data, I would say that, as far as an osteoarthritis study goes, this was really a tremendous effort on the part of all people involved,” she said.

She noted that, while the WE-CAN program may work in North Carolina, there may be barriers to implementing it elsewhere, such as large suburban areas where some patients experience food insecurity and others have difficulty with transportation and access to treatment facilities.

“The question here that remains is, as Dr. Felson asked, what is the contribution of weight loss and what is the contribution of exercise? Because if it’s just weight loss, we have a whole lot of new things coming to help with that,” she said.

The WE-CAN study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Messier disclosed that GNC, a health food and nutrition chain, donated the meal replacements used by patients. Dr. Davidson reported no relevant conflicts of interest.

PHILADELPHIA – What works in the clinic can also work in community settings: Patients who are overweight or obese with knee osteoarthritis can find relief from pain through diet and exercise programs conducted in recreation centers, local gyms, fitness centers, and other places close to home, according to investigators in a pragmatic randomized trial.

The Weight Loss and Exercise for Communities With Arthritis in North Carolina (WE-CAN) study was modeled after the successful Intensive Diet and Exercise for Arthritis trial, which showed that adults randomized to 18 months of either a diet and exercise program or diet alone had more weight loss and larger reductions in levels of the inflammatory cytokine interleukin-6 than patients randomized to exercise alone, and that diet alone was associated with greater reductions in knee compressive force than exercise alone.

That study was conducted by Stephen P. Messier, PhD, and colleagues at Wake Forest University, Winston-Salem, N.C.. As previously reported, the investigators also saw continued benefits for participants years after the original trial.

With the WE-CAN trial, results of which were reported at the annual meeting of the American College of Rheumatology, Dr. Messier and colleagues took the intervention one step further, randomizing 823 community-dwelling adults who were overweight or obese (body mass index [BMI], ≥ 27 kg/m2) with knee OA to either an 18-month diet and exercise intervention or attention control group consisting of five 1-hour face-to-face meetings over 18 months, plus information packets and phone sessions during alternate months.

“Compared to the control group, diet plus exercise had a statistically significant but modest reduction in pain. Diet plus exercise was 20% more likely to attain a clinically important 2-point improvement in pain,” Dr. Messier said in an oral abstract session at ACR.
 

Real-world setting

The primary goal of WE-CAN was to “determine whether adaptation of a diet and exercise academic center–based efficacy trial to community settings results in a statistically significant reduction in pain relative to an attention control.”

Ariel Skelley/Getty Images

A total of 3,751 potential candidates were screened, and 823 were randomized and assigned to either a diet and exercise arm (414) or attention control arm (409). Of the patients randomized, 336 in the diet/exercise arm and 322 in the control arm attended the final 18-month follow-up visit.

The exercise component consisted of a 15-minute walking period, followed by a 20-minute weight-training period, and ending with a second 15-minute walking period. The diet goal was 10% or greater weight loss, aided by a distribution of low-calorie recipes to produce a reduced-calorie diet of the patient’s choice, with the option to include nutritional powder to make low-calories shakes as meal replacements, one or two per day for the first 6 months, with the option of one per day for the remaining months.

The pragmatic components included the use of established community facilities in both urban and rural counties in North Carolina, broad inclusion criteria, patient-centered outcomes, use of community-based staff to deliver the treatment, nonphysicians trained by study physicians to perform knee exams, and various means of communication, Dr. Messier said.

Participants in each arm were closely matched by demographic and clinical characteristics, with a mean age of 64.5 years in the diet/exercise group and 64.7 years in the attention control group, respective mean weight of 100.7 kg and 101.1 kg, and respective BMI of 36.7 and 36.9. Women comprised about 77% of participants in each group.
 

Endpoints met

The trial met its primary endpoint of a significantly greater reduction in pain at 18 months in the diet and exercise group as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and scored on a scale of 0 (no pain) to 20 (worst pain).

In an analysis adjusted for sex, BMI, and baseline values, there was a 32% reduction in pain scores from baseline in the active intervention arm versus 24% in the control arm (P = .02).

In all, 60.2% of participants assigned to diet and exercise had a minimum reduction in pain scores of at least 2 points at 18 months, compared with 49.7% of participants assigned to the attention control group. This translated into a relative risk for achieving at least a 2-point improvement with diet and exercise was 1.20 (P = .01).

Among participants who remained in the study for the entire 18 months, there were significant improvements in the diet and exercise group compared with controls in the prespecified secondary endpoints of weight change (–8 kg vs. –2 kg), waist circumference, WOMAC function, 6-minute walk distance, and mean Short Form–36 health-related quality of life subscale (P < .001 for all comparisons).

Dr. Messier acknowledged that the diagnosis of knee OA was based only on ACR clinical criteria and was not confirmed with imaging. In addition, offering patients the option of free meal replacement limited the pragmatic nature of the intervention.

He also noted that the 24% reduction in pain seen in the control group suggests that interacting with patients can improve clinical outcomes.
 

‘Tour de force’

In the question-and-answer session following Dr. Messier’s presentation, David T. Felson, MD, a rheumatologist at Boston Medical Center, called in and said the study was “a tour de force” and congratulated Dr. Messier and colleagues on “a lovely study.”

Richard Mark Kirkner/MDedge News

Dr. Felson asked whether the investigators had conducted a mediation analysis to determine what proportion of the improvement was attributable to weight loss, and whether patients assigned to exercise were sticking with it throughout the study.

Dr. Messier replied that they had not yet done a mediation analysis but were continuing to examine the data. Regarding the exercise question, he noted that “the adherence was over 80% for 6 months and over 70% for the whole 18 months, so they did a really nice job.”

In an interview, session moderator Anne Davidson, MBBS, director of the rheumatology program at Northwell Health in Manhasset, N.Y., commented that the investigators managed to accomplish a very challenging task.

“In terms of recruitment of patients with engagement of community facilities and quality of data, I would say that, as far as an osteoarthritis study goes, this was really a tremendous effort on the part of all people involved,” she said.

She noted that, while the WE-CAN program may work in North Carolina, there may be barriers to implementing it elsewhere, such as large suburban areas where some patients experience food insecurity and others have difficulty with transportation and access to treatment facilities.

“The question here that remains is, as Dr. Felson asked, what is the contribution of weight loss and what is the contribution of exercise? Because if it’s just weight loss, we have a whole lot of new things coming to help with that,” she said.

The WE-CAN study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Messier disclosed that GNC, a health food and nutrition chain, donated the meal replacements used by patients. Dr. Davidson reported no relevant conflicts of interest.

PHILADELPHIA – What works in the clinic can also work in community settings: Patients who are overweight or obese with knee osteoarthritis can find relief from pain through diet and exercise programs conducted in recreation centers, local gyms, fitness centers, and other places close to home, according to investigators in a pragmatic randomized trial.

The Weight Loss and Exercise for Communities With Arthritis in North Carolina (WE-CAN) study was modeled after the successful Intensive Diet and Exercise for Arthritis trial, which showed that adults randomized to 18 months of either a diet and exercise program or diet alone had more weight loss and larger reductions in levels of the inflammatory cytokine interleukin-6 than patients randomized to exercise alone, and that diet alone was associated with greater reductions in knee compressive force than exercise alone.

That study was conducted by Stephen P. Messier, PhD, and colleagues at Wake Forest University, Winston-Salem, N.C.. As previously reported, the investigators also saw continued benefits for participants years after the original trial.

With the WE-CAN trial, results of which were reported at the annual meeting of the American College of Rheumatology, Dr. Messier and colleagues took the intervention one step further, randomizing 823 community-dwelling adults who were overweight or obese (body mass index [BMI], ≥ 27 kg/m2) with knee OA to either an 18-month diet and exercise intervention or attention control group consisting of five 1-hour face-to-face meetings over 18 months, plus information packets and phone sessions during alternate months.

“Compared to the control group, diet plus exercise had a statistically significant but modest reduction in pain. Diet plus exercise was 20% more likely to attain a clinically important 2-point improvement in pain,” Dr. Messier said in an oral abstract session at ACR.
 

Real-world setting

The primary goal of WE-CAN was to “determine whether adaptation of a diet and exercise academic center–based efficacy trial to community settings results in a statistically significant reduction in pain relative to an attention control.”

Ariel Skelley/Getty Images

A total of 3,751 potential candidates were screened, and 823 were randomized and assigned to either a diet and exercise arm (414) or attention control arm (409). Of the patients randomized, 336 in the diet/exercise arm and 322 in the control arm attended the final 18-month follow-up visit.

The exercise component consisted of a 15-minute walking period, followed by a 20-minute weight-training period, and ending with a second 15-minute walking period. The diet goal was 10% or greater weight loss, aided by a distribution of low-calorie recipes to produce a reduced-calorie diet of the patient’s choice, with the option to include nutritional powder to make low-calories shakes as meal replacements, one or two per day for the first 6 months, with the option of one per day for the remaining months.

The pragmatic components included the use of established community facilities in both urban and rural counties in North Carolina, broad inclusion criteria, patient-centered outcomes, use of community-based staff to deliver the treatment, nonphysicians trained by study physicians to perform knee exams, and various means of communication, Dr. Messier said.

Participants in each arm were closely matched by demographic and clinical characteristics, with a mean age of 64.5 years in the diet/exercise group and 64.7 years in the attention control group, respective mean weight of 100.7 kg and 101.1 kg, and respective BMI of 36.7 and 36.9. Women comprised about 77% of participants in each group.
 

Endpoints met

The trial met its primary endpoint of a significantly greater reduction in pain at 18 months in the diet and exercise group as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and scored on a scale of 0 (no pain) to 20 (worst pain).

In an analysis adjusted for sex, BMI, and baseline values, there was a 32% reduction in pain scores from baseline in the active intervention arm versus 24% in the control arm (P = .02).

In all, 60.2% of participants assigned to diet and exercise had a minimum reduction in pain scores of at least 2 points at 18 months, compared with 49.7% of participants assigned to the attention control group. This translated into a relative risk for achieving at least a 2-point improvement with diet and exercise was 1.20 (P = .01).

Among participants who remained in the study for the entire 18 months, there were significant improvements in the diet and exercise group compared with controls in the prespecified secondary endpoints of weight change (–8 kg vs. –2 kg), waist circumference, WOMAC function, 6-minute walk distance, and mean Short Form–36 health-related quality of life subscale (P < .001 for all comparisons).

Dr. Messier acknowledged that the diagnosis of knee OA was based only on ACR clinical criteria and was not confirmed with imaging. In addition, offering patients the option of free meal replacement limited the pragmatic nature of the intervention.

He also noted that the 24% reduction in pain seen in the control group suggests that interacting with patients can improve clinical outcomes.
 

‘Tour de force’

In the question-and-answer session following Dr. Messier’s presentation, David T. Felson, MD, a rheumatologist at Boston Medical Center, called in and said the study was “a tour de force” and congratulated Dr. Messier and colleagues on “a lovely study.”

Richard Mark Kirkner/MDedge News

Dr. Felson asked whether the investigators had conducted a mediation analysis to determine what proportion of the improvement was attributable to weight loss, and whether patients assigned to exercise were sticking with it throughout the study.

Dr. Messier replied that they had not yet done a mediation analysis but were continuing to examine the data. Regarding the exercise question, he noted that “the adherence was over 80% for 6 months and over 70% for the whole 18 months, so they did a really nice job.”

In an interview, session moderator Anne Davidson, MBBS, director of the rheumatology program at Northwell Health in Manhasset, N.Y., commented that the investigators managed to accomplish a very challenging task.

“In terms of recruitment of patients with engagement of community facilities and quality of data, I would say that, as far as an osteoarthritis study goes, this was really a tremendous effort on the part of all people involved,” she said.

She noted that, while the WE-CAN program may work in North Carolina, there may be barriers to implementing it elsewhere, such as large suburban areas where some patients experience food insecurity and others have difficulty with transportation and access to treatment facilities.

“The question here that remains is, as Dr. Felson asked, what is the contribution of weight loss and what is the contribution of exercise? Because if it’s just weight loss, we have a whole lot of new things coming to help with that,” she said.

The WE-CAN study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Messier disclosed that GNC, a health food and nutrition chain, donated the meal replacements used by patients. Dr. Davidson reported no relevant conflicts of interest.

Celiac disease is linked to juvenile idiopathic arthritis (JIA) in children and rheumatoid arthritis (RA) in adults, according to an analysis of nationwide data in Sweden.

Children with celiac disease are nearly three times as likely to develop JIA relative to the general population. Adults with celiac disease are nearly two times as likely to be diagnosed with RA.

“I hope that our study can ultimately change clinical practice by lowering the threshold to evaluate celiac disease patients for inflammatory joint diseases,” John B. Doyle, MD, a gastroenterology fellow at Columbia University Irving Medical Center in New York, told this news organization.

“Inflammatory joint diseases, such as JIA and RA, are notoriously difficult to diagnose given their variable presentations,” he said. “But if JIA or RA can be identified sooner by physicians, patients will ultimately benefit by starting disease-modifying therapy earlier in their disease course.”

The study was published online in The American Journal of Gastroenterology.
 

Analyzing associations

Celiac disease has been linked to numerous autoimmune diseases, including type 1 diabetes, autoimmune thyroid disease, lupus, and inflammatory bowel disease (IBD), Dr. Doyle noted. However, a definitive epidemiologic association between celiac disease and inflammatory joint diseases such as JIA or RA hasn›t been established.

Dr. Doyle and colleagues conducted a nationwide population-based, retrospective matched cohort study using the Epidemiology Strengthened by Histopathology Reports in Sweden. They identified 24,014 patients diagnosed with biopsy-proven celiac disease between 2004 and 2017.

With these data, each patient was matched to five reference individuals in the general population by age, sex, calendar year, and geographic region, for a total of 117,397 people without a previous diagnosis of celiac disease. The researchers calculated the incidence and estimated the relative risk for JIA in patients younger than 18 years and RA in patients aged 18 years or older.

For those younger than 18 years, the incidence rate of JIA was 5.9 per 10,000 person-years among the 9,415 patients with celiac disease versus 2.2 per 10,000 person-years in the general population, over a follow-up of 7 years. Those with celiac disease were 2.7 times as likely to develop JIA.

The association between celiac disease and JIA remained similar after adjustment for education, Nordic country of birth, type 1 diabetes, autoimmune thyroid disease, lupus, and IBD. The incidence rate of JIA among patients with celiac disease was higher in both females and males, and across all age groups studied.

When 6,703 children with celiac disease were compared with their 9,089 siblings without celiac disease, the higher risk for JIA in patients with celiac disease fell slightly short of statistical significance.

For those aged 18 years or older, the incidence rate of RA was 8.4 per 10,000 person-years among the 14,599 patients with celiac disease versus 5.1 per 10,000 person-years in the general population, over a follow-up of 8.8 years. Those with celiac disease were 1.7 times as likely to develop RA.

As with the younger cohort, the association between celiac disease and RA in the adult group remained similar after adjustment for education, Nordic country of birth, type 1 diabetes, autoimmune thyroid disease, lupus, and IBD. Although both men and women with celiac disease had higher rates of RA, the risk was higher among those in whom disease was diagnosed at age 18-59 years compared with those who received a diagnosis at age 60 years or older.

When 9,578 adults with celiac disease were compared with their 17,067 siblings without celiac disease, the risk for RA remained higher in patients with celiac disease.

This suggests “that the association between celiac disease and RA is unlikely to be explained by environmental factors alone,” Dr. Doyle said.
 

Additional findings

Notably, the primary analysis excluded patients diagnosed with JIA or RA before their celiac disease diagnosis. In additional analyses, however, significant associations emerged.

Among children with celiac disease, 0.5% had a previous diagnosis of JIA, compared with 0.1% of matched comparators. Those with celiac disease were 3.5 times more likely to have a JIA diagnosis.

Among adults with celiac disease, 0.9% had a previous diagnosis of RA, compared with 0.6% of matched comparators. Those with celiac disease were 1.4 times more likely to have a RA diagnosis.

“We found that diagnoses of these types of arthritis were more common before a diagnosis of celiac disease compared to the general population,” Benjamin Lebwohl, MD, director of clinical research at the Celiac Disease Center at Columbia University, New York, told this news organization.

“This suggests that undiagnosed and untreated celiac disease might be contributing to these others autoimmune conditions,” he said.

Dr. Doyle and Dr. Lebwohl emphasized the practical implications for clinicians caring for patients with celiac disease. Among patients with celiac disease and inflammatory joint symptoms, clinicians should have a low threshold to evaluate for JIA or RA, they said.

“Particularly in pediatrics, we are trained to screen patients with JIA for celiac disease, but this study points to the possible bidirectional association and the importance of maintaining a clinical suspicion for JIA and RA among established celiac disease patients,” Marisa Stahl, MD, assistant professor of pediatrics and associate program director of the pediatric gastroenterology, hepatology, and nutrition fellowship training program at the University of Colorado at Denver, Aurora, said in an interview.

Dr. Stahl, who wasn’t involved with this study, conducts research at the Colorado Center for Celiac Disease. She and colleagues are focused on understanding the genetic and environmental factors that lead to the development of celiac disease and other autoimmune diseases.

Given the clear association between celiac disease and other autoimmune diseases, Dr. Stahl agreed that clinicians should have a low threshold for screening, with “additional workup for other autoimmune diseases once an autoimmune diagnosis is established.”

The study was supported by Karolinska Institutet and the Swedish Research Council. Dr. Lebwohl coordinates a study on behalf of the Swedish IBD quality register, which has received funding from Janssen. The other authors declared no conflicts of interest. Dr. Stahl reported no relevant disclosures.

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

Celiac disease is linked to juvenile idiopathic arthritis (JIA) in children and rheumatoid arthritis (RA) in adults, according to an analysis of nationwide data in Sweden.

Children with celiac disease are nearly three times as likely to develop JIA relative to the general population. Adults with celiac disease are nearly two times as likely to be diagnosed with RA.

“I hope that our study can ultimately change clinical practice by lowering the threshold to evaluate celiac disease patients for inflammatory joint diseases,” John B. Doyle, MD, a gastroenterology fellow at Columbia University Irving Medical Center in New York, told this news organization.

“Inflammatory joint diseases, such as JIA and RA, are notoriously difficult to diagnose given their variable presentations,” he said. “But if JIA or RA can be identified sooner by physicians, patients will ultimately benefit by starting disease-modifying therapy earlier in their disease course.”

The study was published online in The American Journal of Gastroenterology.
 

Analyzing associations

Celiac disease has been linked to numerous autoimmune diseases, including type 1 diabetes, autoimmune thyroid disease, lupus, and inflammatory bowel disease (IBD), Dr. Doyle noted. However, a definitive epidemiologic association between celiac disease and inflammatory joint diseases such as JIA or RA hasn›t been established.

Dr. Doyle and colleagues conducted a nationwide population-based, retrospective matched cohort study using the Epidemiology Strengthened by Histopathology Reports in Sweden. They identified 24,014 patients diagnosed with biopsy-proven celiac disease between 2004 and 2017.

With these data, each patient was matched to five reference individuals in the general population by age, sex, calendar year, and geographic region, for a total of 117,397 people without a previous diagnosis of celiac disease. The researchers calculated the incidence and estimated the relative risk for JIA in patients younger than 18 years and RA in patients aged 18 years or older.

For those younger than 18 years, the incidence rate of JIA was 5.9 per 10,000 person-years among the 9,415 patients with celiac disease versus 2.2 per 10,000 person-years in the general population, over a follow-up of 7 years. Those with celiac disease were 2.7 times as likely to develop JIA.

The association between celiac disease and JIA remained similar after adjustment for education, Nordic country of birth, type 1 diabetes, autoimmune thyroid disease, lupus, and IBD. The incidence rate of JIA among patients with celiac disease was higher in both females and males, and across all age groups studied.

When 6,703 children with celiac disease were compared with their 9,089 siblings without celiac disease, the higher risk for JIA in patients with celiac disease fell slightly short of statistical significance.

For those aged 18 years or older, the incidence rate of RA was 8.4 per 10,000 person-years among the 14,599 patients with celiac disease versus 5.1 per 10,000 person-years in the general population, over a follow-up of 8.8 years. Those with celiac disease were 1.7 times as likely to develop RA.

As with the younger cohort, the association between celiac disease and RA in the adult group remained similar after adjustment for education, Nordic country of birth, type 1 diabetes, autoimmune thyroid disease, lupus, and IBD. Although both men and women with celiac disease had higher rates of RA, the risk was higher among those in whom disease was diagnosed at age 18-59 years compared with those who received a diagnosis at age 60 years or older.

When 9,578 adults with celiac disease were compared with their 17,067 siblings without celiac disease, the risk for RA remained higher in patients with celiac disease.

This suggests “that the association between celiac disease and RA is unlikely to be explained by environmental factors alone,” Dr. Doyle said.
 

Additional findings

Notably, the primary analysis excluded patients diagnosed with JIA or RA before their celiac disease diagnosis. In additional analyses, however, significant associations emerged.

Among children with celiac disease, 0.5% had a previous diagnosis of JIA, compared with 0.1% of matched comparators. Those with celiac disease were 3.5 times more likely to have a JIA diagnosis.

Among adults with celiac disease, 0.9% had a previous diagnosis of RA, compared with 0.6% of matched comparators. Those with celiac disease were 1.4 times more likely to have a RA diagnosis.

“We found that diagnoses of these types of arthritis were more common before a diagnosis of celiac disease compared to the general population,” Benjamin Lebwohl, MD, director of clinical research at the Celiac Disease Center at Columbia University, New York, told this news organization.

“This suggests that undiagnosed and untreated celiac disease might be contributing to these others autoimmune conditions,” he said.

Dr. Doyle and Dr. Lebwohl emphasized the practical implications for clinicians caring for patients with celiac disease. Among patients with celiac disease and inflammatory joint symptoms, clinicians should have a low threshold to evaluate for JIA or RA, they said.

“Particularly in pediatrics, we are trained to screen patients with JIA for celiac disease, but this study points to the possible bidirectional association and the importance of maintaining a clinical suspicion for JIA and RA among established celiac disease patients,” Marisa Stahl, MD, assistant professor of pediatrics and associate program director of the pediatric gastroenterology, hepatology, and nutrition fellowship training program at the University of Colorado at Denver, Aurora, said in an interview.

Dr. Stahl, who wasn’t involved with this study, conducts research at the Colorado Center for Celiac Disease. She and colleagues are focused on understanding the genetic and environmental factors that lead to the development of celiac disease and other autoimmune diseases.

Given the clear association between celiac disease and other autoimmune diseases, Dr. Stahl agreed that clinicians should have a low threshold for screening, with “additional workup for other autoimmune diseases once an autoimmune diagnosis is established.”

The study was supported by Karolinska Institutet and the Swedish Research Council. Dr. Lebwohl coordinates a study on behalf of the Swedish IBD quality register, which has received funding from Janssen. The other authors declared no conflicts of interest. Dr. Stahl reported no relevant disclosures.

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

Celiac disease is linked to juvenile idiopathic arthritis (JIA) in children and rheumatoid arthritis (RA) in adults, according to an analysis of nationwide data in Sweden.

Children with celiac disease are nearly three times as likely to develop JIA relative to the general population. Adults with celiac disease are nearly two times as likely to be diagnosed with RA.

“I hope that our study can ultimately change clinical practice by lowering the threshold to evaluate celiac disease patients for inflammatory joint diseases,” John B. Doyle, MD, a gastroenterology fellow at Columbia University Irving Medical Center in New York, told this news organization.

“Inflammatory joint diseases, such as JIA and RA, are notoriously difficult to diagnose given their variable presentations,” he said. “But if JIA or RA can be identified sooner by physicians, patients will ultimately benefit by starting disease-modifying therapy earlier in their disease course.”

The study was published online in The American Journal of Gastroenterology.
 

Analyzing associations

Celiac disease has been linked to numerous autoimmune diseases, including type 1 diabetes, autoimmune thyroid disease, lupus, and inflammatory bowel disease (IBD), Dr. Doyle noted. However, a definitive epidemiologic association between celiac disease and inflammatory joint diseases such as JIA or RA hasn›t been established.

Dr. Doyle and colleagues conducted a nationwide population-based, retrospective matched cohort study using the Epidemiology Strengthened by Histopathology Reports in Sweden. They identified 24,014 patients diagnosed with biopsy-proven celiac disease between 2004 and 2017.

With these data, each patient was matched to five reference individuals in the general population by age, sex, calendar year, and geographic region, for a total of 117,397 people without a previous diagnosis of celiac disease. The researchers calculated the incidence and estimated the relative risk for JIA in patients younger than 18 years and RA in patients aged 18 years or older.

For those younger than 18 years, the incidence rate of JIA was 5.9 per 10,000 person-years among the 9,415 patients with celiac disease versus 2.2 per 10,000 person-years in the general population, over a follow-up of 7 years. Those with celiac disease were 2.7 times as likely to develop JIA.

The association between celiac disease and JIA remained similar after adjustment for education, Nordic country of birth, type 1 diabetes, autoimmune thyroid disease, lupus, and IBD. The incidence rate of JIA among patients with celiac disease was higher in both females and males, and across all age groups studied.

When 6,703 children with celiac disease were compared with their 9,089 siblings without celiac disease, the higher risk for JIA in patients with celiac disease fell slightly short of statistical significance.

For those aged 18 years or older, the incidence rate of RA was 8.4 per 10,000 person-years among the 14,599 patients with celiac disease versus 5.1 per 10,000 person-years in the general population, over a follow-up of 8.8 years. Those with celiac disease were 1.7 times as likely to develop RA.

As with the younger cohort, the association between celiac disease and RA in the adult group remained similar after adjustment for education, Nordic country of birth, type 1 diabetes, autoimmune thyroid disease, lupus, and IBD. Although both men and women with celiac disease had higher rates of RA, the risk was higher among those in whom disease was diagnosed at age 18-59 years compared with those who received a diagnosis at age 60 years or older.

When 9,578 adults with celiac disease were compared with their 17,067 siblings without celiac disease, the risk for RA remained higher in patients with celiac disease.

This suggests “that the association between celiac disease and RA is unlikely to be explained by environmental factors alone,” Dr. Doyle said.
 

Additional findings

Notably, the primary analysis excluded patients diagnosed with JIA or RA before their celiac disease diagnosis. In additional analyses, however, significant associations emerged.

Among children with celiac disease, 0.5% had a previous diagnosis of JIA, compared with 0.1% of matched comparators. Those with celiac disease were 3.5 times more likely to have a JIA diagnosis.

Among adults with celiac disease, 0.9% had a previous diagnosis of RA, compared with 0.6% of matched comparators. Those with celiac disease were 1.4 times more likely to have a RA diagnosis.

“We found that diagnoses of these types of arthritis were more common before a diagnosis of celiac disease compared to the general population,” Benjamin Lebwohl, MD, director of clinical research at the Celiac Disease Center at Columbia University, New York, told this news organization.

“This suggests that undiagnosed and untreated celiac disease might be contributing to these others autoimmune conditions,” he said.

Dr. Doyle and Dr. Lebwohl emphasized the practical implications for clinicians caring for patients with celiac disease. Among patients with celiac disease and inflammatory joint symptoms, clinicians should have a low threshold to evaluate for JIA or RA, they said.

“Particularly in pediatrics, we are trained to screen patients with JIA for celiac disease, but this study points to the possible bidirectional association and the importance of maintaining a clinical suspicion for JIA and RA among established celiac disease patients,” Marisa Stahl, MD, assistant professor of pediatrics and associate program director of the pediatric gastroenterology, hepatology, and nutrition fellowship training program at the University of Colorado at Denver, Aurora, said in an interview.

Dr. Stahl, who wasn’t involved with this study, conducts research at the Colorado Center for Celiac Disease. She and colleagues are focused on understanding the genetic and environmental factors that lead to the development of celiac disease and other autoimmune diseases.

Given the clear association between celiac disease and other autoimmune diseases, Dr. Stahl agreed that clinicians should have a low threshold for screening, with “additional workup for other autoimmune diseases once an autoimmune diagnosis is established.”

The study was supported by Karolinska Institutet and the Swedish Research Council. Dr. Lebwohl coordinates a study on behalf of the Swedish IBD quality register, which has received funding from Janssen. The other authors declared no conflicts of interest. Dr. Stahl reported no relevant disclosures.

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

They call me and I go.

– William Carlos Williams

I never get sick. I’ve never had the flu. When everyone’s got a cold, I’m somehow immune. The last time I threw up was June 29th, 1980. You see, I work out almost daily, eat vegan, and sleep plenty. I drink gallons of pressed juice and throw down a few high-quality supplements. Yes, I’m that guy: The one who never gets sick. Well, I was anyway.

I am no longer that guy since our little girl became a supersocial little toddler. My undefeated welterweight “never-sick” title has been obliterated by multiple knockouts. One was a wicked adenovirus that broke the no-vomit streak. At one point, I lay on the luxury gray tile bathroom floor hoping to go unconscious to make the nausea stop. I actually called out sick that day. Then with a nasty COVID-despite-vaccine infection. I called out again. Later with a hacking lower respiratory – RSV?! – bug. Called out. All of which our 2-year-old blonde, curly-haired vector transmitted to me with remarkable efficiency.

In fact, we reached the high water mark for physicians calling out sick from my department this year. That’s saying a lot. Our docs, like most, don’t call out sick.

We physicians have legendary stamina. Compared with other professionals, we are no less likely to become ill but a whopping 80% less likely to call out sick.

Presenteeism is our physician version of Omerta, a code of honor to never give in even at the expense of our, or our family’s, health and well-being. Every medical student is regaled with stories of physicians getting an IV before rounds or finishing clinic after their water broke. Why? In part it’s an indoctrination into this thing of ours we call Medicine: An elitist club that admits only those able to pass O-chem and hold diarrhea. But it is also because our medical system is so brittle that the slightest bend causes it to shatter. When I cancel a clinic, patients who have waited weeks for their spot have to be sent home. And for critical cases or those patients who don’t get the message, my already slammed colleagues have to cram the unlucky ones in between already-scheduled appointments. The guilt induced by inconveniencing our colleagues and our patients is more potent than dry heaves. And so we go. Suck it up. Sip ginger ale. Load up on acetaminophen. Carry on. This harms not only us, but also patients whom we put in the path of transmission. We become terrible 2-year-olds.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

They call me and I go.

– William Carlos Williams

I never get sick. I’ve never had the flu. When everyone’s got a cold, I’m somehow immune. The last time I threw up was June 29th, 1980. You see, I work out almost daily, eat vegan, and sleep plenty. I drink gallons of pressed juice and throw down a few high-quality supplements. Yes, I’m that guy: The one who never gets sick. Well, I was anyway.

I am no longer that guy since our little girl became a supersocial little toddler. My undefeated welterweight “never-sick” title has been obliterated by multiple knockouts. One was a wicked adenovirus that broke the no-vomit streak. At one point, I lay on the luxury gray tile bathroom floor hoping to go unconscious to make the nausea stop. I actually called out sick that day. Then with a nasty COVID-despite-vaccine infection. I called out again. Later with a hacking lower respiratory – RSV?! – bug. Called out. All of which our 2-year-old blonde, curly-haired vector transmitted to me with remarkable efficiency.

In fact, we reached the high water mark for physicians calling out sick from my department this year. That’s saying a lot. Our docs, like most, don’t call out sick.

We physicians have legendary stamina. Compared with other professionals, we are no less likely to become ill but a whopping 80% less likely to call out sick.

Presenteeism is our physician version of Omerta, a code of honor to never give in even at the expense of our, or our family’s, health and well-being. Every medical student is regaled with stories of physicians getting an IV before rounds or finishing clinic after their water broke. Why? In part it’s an indoctrination into this thing of ours we call Medicine: An elitist club that admits only those able to pass O-chem and hold diarrhea. But it is also because our medical system is so brittle that the slightest bend causes it to shatter. When I cancel a clinic, patients who have waited weeks for their spot have to be sent home. And for critical cases or those patients who don’t get the message, my already slammed colleagues have to cram the unlucky ones in between already-scheduled appointments. The guilt induced by inconveniencing our colleagues and our patients is more potent than dry heaves. And so we go. Suck it up. Sip ginger ale. Load up on acetaminophen. Carry on. This harms not only us, but also patients whom we put in the path of transmission. We become terrible 2-year-olds.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

They call me and I go.

– William Carlos Williams

I never get sick. I’ve never had the flu. When everyone’s got a cold, I’m somehow immune. The last time I threw up was June 29th, 1980. You see, I work out almost daily, eat vegan, and sleep plenty. I drink gallons of pressed juice and throw down a few high-quality supplements. Yes, I’m that guy: The one who never gets sick. Well, I was anyway.

I am no longer that guy since our little girl became a supersocial little toddler. My undefeated welterweight “never-sick” title has been obliterated by multiple knockouts. One was a wicked adenovirus that broke the no-vomit streak. At one point, I lay on the luxury gray tile bathroom floor hoping to go unconscious to make the nausea stop. I actually called out sick that day. Then with a nasty COVID-despite-vaccine infection. I called out again. Later with a hacking lower respiratory – RSV?! – bug. Called out. All of which our 2-year-old blonde, curly-haired vector transmitted to me with remarkable efficiency.

In fact, we reached the high water mark for physicians calling out sick from my department this year. That’s saying a lot. Our docs, like most, don’t call out sick.

We physicians have legendary stamina. Compared with other professionals, we are no less likely to become ill but a whopping 80% less likely to call out sick.

Presenteeism is our physician version of Omerta, a code of honor to never give in even at the expense of our, or our family’s, health and well-being. Every medical student is regaled with stories of physicians getting an IV before rounds or finishing clinic after their water broke. Why? In part it’s an indoctrination into this thing of ours we call Medicine: An elitist club that admits only those able to pass O-chem and hold diarrhea. But it is also because our medical system is so brittle that the slightest bend causes it to shatter. When I cancel a clinic, patients who have waited weeks for their spot have to be sent home. And for critical cases or those patients who don’t get the message, my already slammed colleagues have to cram the unlucky ones in between already-scheduled appointments. The guilt induced by inconveniencing our colleagues and our patients is more potent than dry heaves. And so we go. Suck it up. Sip ginger ale. Load up on acetaminophen. Carry on. This harms not only us, but also patients whom we put in the path of transmission. We become terrible 2-year-olds.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

What’s the opposite of an antibiotic?

Everyone knows that LOTME loves a good dichotomy: yin/yang, good/evil, heads/tails, particle/wave, peanut butter/jelly. They’re all great. We’re also big fans of microbiomes, particularly the gut microbiome. But what if we could combine the two? A healthy and nutritious story about the gut microbiome, with a dash of added dichotomy for flavor. Is such a thing even possible? Let’s find out.

Nastya Dulhiier/Unsplash

First, we need an antibiotic, a drug designed to fight bacterial infections. If you’ve got strep throat, otitis media, or bubonic plague, there’s a good chance you will receive an antibiotic. That antibiotic will kill the bad bacteria that are making you sick, but it will also kill a lot of the good bacteria that inhabit your gut microbiome, which results in side effects like bloating and diarrhea.

It comes down to diversity, explained Elisa Marroquin, PhD, of Texas Christian University (Go Horned Frogs!): “In a human community, we need people that have different professions because we don’t all know how to do every single job. And so the same happens with bacteria. We need lots of different gut bacteria that know how to do different things.”

She and her colleagues reviewed 29 studies published over the last 7 years and found a way to preserve the diversity of a human gut microbiome that’s dealing with an antibiotic. Their solution? Prescribe a probiotic.

The way to fight the effects of stopping a bacterial infection is to provide food for what are, basically, other bacterial infections. Antibiotic/probiotic is a prescription for dichotomy, and it means we managed to combine gut microbiomes with a dichotomy. And you didn’t think we could do it.
 

The earphone of hearing aids

It’s estimated that up to 75% of people who need hearing aids don’t wear them. Why? Well, there’s the social stigma about not wanting to appear too old, and then there’s the cost factor.

Antoni Shkraba/Pexels

Is there a cheaper, less stigmatizing option to amplify hearing? The answer, according to otolaryngologist Yen-fu Cheng, MD, of Taipei Veterans General Hospital and associates, is wireless earphones. AirPods, if you want to be brand specific.

Airpods can be on the more expensive side – running about $129 for AirPods 2 and $249 for AirPods Pro – but when compared with premium hearing aids ($10,000), or even basic aids (about $1,500), the Apple products come off inexpensive after all.

The team tested the premium and basic hearing aids against the AirPods 2 and the AirPod Pro using Apple’s Live Listen feature, which helps amplify sound through the company’s wireless earphones and iPhones and was initially designed to assist people with normal hearing in situations such as birdwatching.

The AirPods Pro worked just as well as the basic hearing aid but not quite as well as the premium hearing aid in a quiet setting, while the AirPods 2 performed the worst. When tested in a noisy setting, the AirPods Pro was pretty comparable to the premium hearing aid, as long as the noise came from a lateral direction. Neither of the AirPod models did as well as the hearing aids with head-on noises.

Wireless earbuds may not be the perfect solution from a clinical standpoint, but they’re a good start for people who don’t have access to hearing aids, Dr. Cheng noted.

So who says headphones damage your hearing? They might actually help.
 

Now I lay me down to sleep, I pray the computer my soul to keep

Radiation is the boring hazard of space travel. No one dies in a space horror movie because they’ve been slowly exposed to too much cosmic radiation. It’s always “thrown out the airlock” this and “eaten by a xenomorph” that.

Michael Chiara/Unsplash

Radiation, however, is not something that can be ignored, but it turns out that a potential solution is another science fiction staple: artificial hibernation. Generally in sci-fi, hibernation is a plot convenience to get people from point A to point B in a ship that doesn’t break the laws of physics. Here on Earth, though, it is well known that animals naturally entering a state of torpor during hibernation gain significant resistance to radiation.

The problem, of course, is that humans don’t hibernate, and no matter how hard people who work 100-hour weeks for Elon Musk try, sleeping for months on end is simply something we can’t do. However, a new study shows that it’s possible to induce this torpor state in animals that don’t naturally hibernate. By injecting rats with adenosine 5’-monophosphate monohydrate and keeping them in a room held at 16° C, an international team of scientists successfully induced a synthetic torpor state.

That’s not all they did: The scientists also exposed the hibernating rats to a large dose of radiation approximating that found in deep space. Which isn’t something we’d like to explain to our significant other when we got home from work. “So how was your day?” “Oh, I irradiated a bunch of sleeping rats. … Don’t worry they’re fine!” Which they were. Thanks to the hypoxic and hypothermic state, the tissue was spared damage from the high-energy ion radiation.

Obviously, there’s a big difference between a rat and a human and a lot of work to be done, but the study does show that artificial hibernation is possible. Perhaps one day we’ll be able to fall asleep and wake up light-years away under an alien sky, and we won’t be horrifically mutated or riddled with cancer. If, however, you find yourself in hibernation on your way to Jupiter (or Saturn) to investigate a mysterious black monolith, we suggest sleeping with one eye open and gripping your pillow tight.

What’s the opposite of an antibiotic?

Everyone knows that LOTME loves a good dichotomy: yin/yang, good/evil, heads/tails, particle/wave, peanut butter/jelly. They’re all great. We’re also big fans of microbiomes, particularly the gut microbiome. But what if we could combine the two? A healthy and nutritious story about the gut microbiome, with a dash of added dichotomy for flavor. Is such a thing even possible? Let’s find out.

Nastya Dulhiier/Unsplash

First, we need an antibiotic, a drug designed to fight bacterial infections. If you’ve got strep throat, otitis media, or bubonic plague, there’s a good chance you will receive an antibiotic. That antibiotic will kill the bad bacteria that are making you sick, but it will also kill a lot of the good bacteria that inhabit your gut microbiome, which results in side effects like bloating and diarrhea.

It comes down to diversity, explained Elisa Marroquin, PhD, of Texas Christian University (Go Horned Frogs!): “In a human community, we need people that have different professions because we don’t all know how to do every single job. And so the same happens with bacteria. We need lots of different gut bacteria that know how to do different things.”

She and her colleagues reviewed 29 studies published over the last 7 years and found a way to preserve the diversity of a human gut microbiome that’s dealing with an antibiotic. Their solution? Prescribe a probiotic.

The way to fight the effects of stopping a bacterial infection is to provide food for what are, basically, other bacterial infections. Antibiotic/probiotic is a prescription for dichotomy, and it means we managed to combine gut microbiomes with a dichotomy. And you didn’t think we could do it.
 

The earphone of hearing aids

It’s estimated that up to 75% of people who need hearing aids don’t wear them. Why? Well, there’s the social stigma about not wanting to appear too old, and then there’s the cost factor.

Antoni Shkraba/Pexels

Is there a cheaper, less stigmatizing option to amplify hearing? The answer, according to otolaryngologist Yen-fu Cheng, MD, of Taipei Veterans General Hospital and associates, is wireless earphones. AirPods, if you want to be brand specific.

Airpods can be on the more expensive side – running about $129 for AirPods 2 and $249 for AirPods Pro – but when compared with premium hearing aids ($10,000), or even basic aids (about $1,500), the Apple products come off inexpensive after all.

The team tested the premium and basic hearing aids against the AirPods 2 and the AirPod Pro using Apple’s Live Listen feature, which helps amplify sound through the company’s wireless earphones and iPhones and was initially designed to assist people with normal hearing in situations such as birdwatching.

The AirPods Pro worked just as well as the basic hearing aid but not quite as well as the premium hearing aid in a quiet setting, while the AirPods 2 performed the worst. When tested in a noisy setting, the AirPods Pro was pretty comparable to the premium hearing aid, as long as the noise came from a lateral direction. Neither of the AirPod models did as well as the hearing aids with head-on noises.

Wireless earbuds may not be the perfect solution from a clinical standpoint, but they’re a good start for people who don’t have access to hearing aids, Dr. Cheng noted.

So who says headphones damage your hearing? They might actually help.
 

Now I lay me down to sleep, I pray the computer my soul to keep

Radiation is the boring hazard of space travel. No one dies in a space horror movie because they’ve been slowly exposed to too much cosmic radiation. It’s always “thrown out the airlock” this and “eaten by a xenomorph” that.

Michael Chiara/Unsplash

Radiation, however, is not something that can be ignored, but it turns out that a potential solution is another science fiction staple: artificial hibernation. Generally in sci-fi, hibernation is a plot convenience to get people from point A to point B in a ship that doesn’t break the laws of physics. Here on Earth, though, it is well known that animals naturally entering a state of torpor during hibernation gain significant resistance to radiation.

The problem, of course, is that humans don’t hibernate, and no matter how hard people who work 100-hour weeks for Elon Musk try, sleeping for months on end is simply something we can’t do. However, a new study shows that it’s possible to induce this torpor state in animals that don’t naturally hibernate. By injecting rats with adenosine 5’-monophosphate monohydrate and keeping them in a room held at 16° C, an international team of scientists successfully induced a synthetic torpor state.

That’s not all they did: The scientists also exposed the hibernating rats to a large dose of radiation approximating that found in deep space. Which isn’t something we’d like to explain to our significant other when we got home from work. “So how was your day?” “Oh, I irradiated a bunch of sleeping rats. … Don’t worry they’re fine!” Which they were. Thanks to the hypoxic and hypothermic state, the tissue was spared damage from the high-energy ion radiation.

Obviously, there’s a big difference between a rat and a human and a lot of work to be done, but the study does show that artificial hibernation is possible. Perhaps one day we’ll be able to fall asleep and wake up light-years away under an alien sky, and we won’t be horrifically mutated or riddled with cancer. If, however, you find yourself in hibernation on your way to Jupiter (or Saturn) to investigate a mysterious black monolith, we suggest sleeping with one eye open and gripping your pillow tight.

What’s the opposite of an antibiotic?

Everyone knows that LOTME loves a good dichotomy: yin/yang, good/evil, heads/tails, particle/wave, peanut butter/jelly. They’re all great. We’re also big fans of microbiomes, particularly the gut microbiome. But what if we could combine the two? A healthy and nutritious story about the gut microbiome, with a dash of added dichotomy for flavor. Is such a thing even possible? Let’s find out.

Nastya Dulhiier/Unsplash

First, we need an antibiotic, a drug designed to fight bacterial infections. If you’ve got strep throat, otitis media, or bubonic plague, there’s a good chance you will receive an antibiotic. That antibiotic will kill the bad bacteria that are making you sick, but it will also kill a lot of the good bacteria that inhabit your gut microbiome, which results in side effects like bloating and diarrhea.

It comes down to diversity, explained Elisa Marroquin, PhD, of Texas Christian University (Go Horned Frogs!): “In a human community, we need people that have different professions because we don’t all know how to do every single job. And so the same happens with bacteria. We need lots of different gut bacteria that know how to do different things.”

She and her colleagues reviewed 29 studies published over the last 7 years and found a way to preserve the diversity of a human gut microbiome that’s dealing with an antibiotic. Their solution? Prescribe a probiotic.

The way to fight the effects of stopping a bacterial infection is to provide food for what are, basically, other bacterial infections. Antibiotic/probiotic is a prescription for dichotomy, and it means we managed to combine gut microbiomes with a dichotomy. And you didn’t think we could do it.
 

The earphone of hearing aids

It’s estimated that up to 75% of people who need hearing aids don’t wear them. Why? Well, there’s the social stigma about not wanting to appear too old, and then there’s the cost factor.

Antoni Shkraba/Pexels

Is there a cheaper, less stigmatizing option to amplify hearing? The answer, according to otolaryngologist Yen-fu Cheng, MD, of Taipei Veterans General Hospital and associates, is wireless earphones. AirPods, if you want to be brand specific.

Airpods can be on the more expensive side – running about $129 for AirPods 2 and $249 for AirPods Pro – but when compared with premium hearing aids ($10,000), or even basic aids (about $1,500), the Apple products come off inexpensive after all.

The team tested the premium and basic hearing aids against the AirPods 2 and the AirPod Pro using Apple’s Live Listen feature, which helps amplify sound through the company’s wireless earphones and iPhones and was initially designed to assist people with normal hearing in situations such as birdwatching.

The AirPods Pro worked just as well as the basic hearing aid but not quite as well as the premium hearing aid in a quiet setting, while the AirPods 2 performed the worst. When tested in a noisy setting, the AirPods Pro was pretty comparable to the premium hearing aid, as long as the noise came from a lateral direction. Neither of the AirPod models did as well as the hearing aids with head-on noises.

Wireless earbuds may not be the perfect solution from a clinical standpoint, but they’re a good start for people who don’t have access to hearing aids, Dr. Cheng noted.

So who says headphones damage your hearing? They might actually help.
 

Now I lay me down to sleep, I pray the computer my soul to keep

Radiation is the boring hazard of space travel. No one dies in a space horror movie because they’ve been slowly exposed to too much cosmic radiation. It’s always “thrown out the airlock” this and “eaten by a xenomorph” that.

Michael Chiara/Unsplash

Radiation, however, is not something that can be ignored, but it turns out that a potential solution is another science fiction staple: artificial hibernation. Generally in sci-fi, hibernation is a plot convenience to get people from point A to point B in a ship that doesn’t break the laws of physics. Here on Earth, though, it is well known that animals naturally entering a state of torpor during hibernation gain significant resistance to radiation.

The problem, of course, is that humans don’t hibernate, and no matter how hard people who work 100-hour weeks for Elon Musk try, sleeping for months on end is simply something we can’t do. However, a new study shows that it’s possible to induce this torpor state in animals that don’t naturally hibernate. By injecting rats with adenosine 5’-monophosphate monohydrate and keeping them in a room held at 16° C, an international team of scientists successfully induced a synthetic torpor state.

That’s not all they did: The scientists also exposed the hibernating rats to a large dose of radiation approximating that found in deep space. Which isn’t something we’d like to explain to our significant other when we got home from work. “So how was your day?” “Oh, I irradiated a bunch of sleeping rats. … Don’t worry they’re fine!” Which they were. Thanks to the hypoxic and hypothermic state, the tissue was spared damage from the high-energy ion radiation.

Obviously, there’s a big difference between a rat and a human and a lot of work to be done, but the study does show that artificial hibernation is possible. Perhaps one day we’ll be able to fall asleep and wake up light-years away under an alien sky, and we won’t be horrifically mutated or riddled with cancer. If, however, you find yourself in hibernation on your way to Jupiter (or Saturn) to investigate a mysterious black monolith, we suggest sleeping with one eye open and gripping your pillow tight.

PHILADELPHIA – Hydroxychloroquine (HCQ) isn’t any more effective at preventing or delaying the onset of rheumatoid arthritis than placebo, based on interim results of a randomized clinical trial reported at the annual meeting of the American College of Rheumatology. Despite that futility, the percentage of patients who actually went on to develop clinical RA was lower than investigators expected, and the trial supports the use of a key biomarker for identifying RA.

While the StopRA trial was halted early because of futility of the treatment, investigators are continuing to mine the gathered data to deepen their understanding of disease progression and the potential of HCQ to improve symptoms in RA patients, said lead study author Kevin D. Deane, MD, PhD, of the University of Colorado at Denver, Aurora.

Richard Mark Kirkner/MDedge News

Overall, around 35% of the study participants on average developed RA, Dr. Deane said. “We were expecting somewhat more,” he said. “Teasing out who’s really going to progress to RA during a study and who’s not is going to be incredibly important.”

StopRA enrolled 144 adults who had elevated anti–cyclic citrullinated peptide antibodies (CCP3) levels of at least 40 units (about twice the normal level) but no history if inflammatory arthritis, randomizing them on a 1:1 basis to either HCQ (200-400 mg a day based on weight) or placebo for a 1-year treatment regimen.

The study identified participants through rheumatology clinics, testing of first-degree relatives with established RA, health fairs, blood donors, and biobanks. The interim findings are based on 2 years of follow-up after the last dose.

The study focused on HCQ because it has a relatively low risk profile with good safety and tolerability, is easy to administer, and is relatively low cost, Dr. Deane said.

StopRA study failed to meet its primary endpoint: to determine if 1 year of treatment with HCQ reduced the risk of developing inflammatory arthritis and classifiable RA at the end of 3 years in the study population. At the time of the interim analysis, 34% of patients in the HCQ arm and 36% in the placebo arm had developed RA (P = .844), Dr. Deane said. Baseline characteristics were balanced in both treatment arms.

The findings also support the use of CCP3 as a biomarker for RA, Dr. Deane said.

Now that the trial has been terminated, Dr. Deane said investigators are going to review the final data and perform secondary analyses for further clarity on the impact HCQ may have on RA.

“The future analysis should hopefully say if this treatment actually changes symptoms,” he said in an interview. “Because, if somebody felt better on the drug or had a milder form of rheumatoid arthritis once they developed it, that could potentially be a benefit.”

Dr. Deane noted the TREAT EARLIER trial similarly found that a 1-year course of methotrexate didn’t prevent the onset of clinical arthritis, but it did alter the disease course as measured in MRI-detected inflammation, related symptoms, and impairment.

“We’re hoping to look at those things and hopefully look at biologic changes over time,” Dr. Deane said of the extended analysis. “We’re not sure if the drug was associated with changes in biomarkers yet still didn’t halt progression to RA. That might be interesting, because those biomarkers might not be fundamentally related to the disease, but other mechanisms may be. That could give us some insights.”

Richard Mark Kirkner/MDedge News

Session moderator Ted Mikuls, MD, a professor of rheumatology at the University of Nebraska Medical Center, Omaha, said further mining of the study data is warranted.

“It’s common in a study like that, which took a lot of time and investment, to really take a deep dive into the data to make sure there aren’t signals that we’re missing,” he said in an interview.

One of the challenges with the study may have been patient enrollment, Dr. Mikuls noted. “I wonder about the study population in terms of where they recruit patients from. Who’s more likely to get RA? Is it patients who already have symptoms? Is it asymptomatic patients from biobanks? If it’s arthralgia joint pain patients, maybe by the time you have joint and autoantibody positivity it’s too late to have an intervention.”

The National Institute of Allergy and Infectious Diseases sponsored the study. Dr. Deane disclosed a relationship with Werfen. Dr. Mikuls has no relevant disclosures.
 

PHILADELPHIA – Hydroxychloroquine (HCQ) isn’t any more effective at preventing or delaying the onset of rheumatoid arthritis than placebo, based on interim results of a randomized clinical trial reported at the annual meeting of the American College of Rheumatology. Despite that futility, the percentage of patients who actually went on to develop clinical RA was lower than investigators expected, and the trial supports the use of a key biomarker for identifying RA.

While the StopRA trial was halted early because of futility of the treatment, investigators are continuing to mine the gathered data to deepen their understanding of disease progression and the potential of HCQ to improve symptoms in RA patients, said lead study author Kevin D. Deane, MD, PhD, of the University of Colorado at Denver, Aurora.

Richard Mark Kirkner/MDedge News

Overall, around 35% of the study participants on average developed RA, Dr. Deane said. “We were expecting somewhat more,” he said. “Teasing out who’s really going to progress to RA during a study and who’s not is going to be incredibly important.”

StopRA enrolled 144 adults who had elevated anti–cyclic citrullinated peptide antibodies (CCP3) levels of at least 40 units (about twice the normal level) but no history if inflammatory arthritis, randomizing them on a 1:1 basis to either HCQ (200-400 mg a day based on weight) or placebo for a 1-year treatment regimen.

The study identified participants through rheumatology clinics, testing of first-degree relatives with established RA, health fairs, blood donors, and biobanks. The interim findings are based on 2 years of follow-up after the last dose.

The study focused on HCQ because it has a relatively low risk profile with good safety and tolerability, is easy to administer, and is relatively low cost, Dr. Deane said.

StopRA study failed to meet its primary endpoint: to determine if 1 year of treatment with HCQ reduced the risk of developing inflammatory arthritis and classifiable RA at the end of 3 years in the study population. At the time of the interim analysis, 34% of patients in the HCQ arm and 36% in the placebo arm had developed RA (P = .844), Dr. Deane said. Baseline characteristics were balanced in both treatment arms.

The findings also support the use of CCP3 as a biomarker for RA, Dr. Deane said.

Now that the trial has been terminated, Dr. Deane said investigators are going to review the final data and perform secondary analyses for further clarity on the impact HCQ may have on RA.

“The future analysis should hopefully say if this treatment actually changes symptoms,” he said in an interview. “Because, if somebody felt better on the drug or had a milder form of rheumatoid arthritis once they developed it, that could potentially be a benefit.”

Dr. Deane noted the TREAT EARLIER trial similarly found that a 1-year course of methotrexate didn’t prevent the onset of clinical arthritis, but it did alter the disease course as measured in MRI-detected inflammation, related symptoms, and impairment.

“We’re hoping to look at those things and hopefully look at biologic changes over time,” Dr. Deane said of the extended analysis. “We’re not sure if the drug was associated with changes in biomarkers yet still didn’t halt progression to RA. That might be interesting, because those biomarkers might not be fundamentally related to the disease, but other mechanisms may be. That could give us some insights.”

Richard Mark Kirkner/MDedge News

Session moderator Ted Mikuls, MD, a professor of rheumatology at the University of Nebraska Medical Center, Omaha, said further mining of the study data is warranted.

“It’s common in a study like that, which took a lot of time and investment, to really take a deep dive into the data to make sure there aren’t signals that we’re missing,” he said in an interview.

One of the challenges with the study may have been patient enrollment, Dr. Mikuls noted. “I wonder about the study population in terms of where they recruit patients from. Who’s more likely to get RA? Is it patients who already have symptoms? Is it asymptomatic patients from biobanks? If it’s arthralgia joint pain patients, maybe by the time you have joint and autoantibody positivity it’s too late to have an intervention.”

The National Institute of Allergy and Infectious Diseases sponsored the study. Dr. Deane disclosed a relationship with Werfen. Dr. Mikuls has no relevant disclosures.
 

PHILADELPHIA – Hydroxychloroquine (HCQ) isn’t any more effective at preventing or delaying the onset of rheumatoid arthritis than placebo, based on interim results of a randomized clinical trial reported at the annual meeting of the American College of Rheumatology. Despite that futility, the percentage of patients who actually went on to develop clinical RA was lower than investigators expected, and the trial supports the use of a key biomarker for identifying RA.

While the StopRA trial was halted early because of futility of the treatment, investigators are continuing to mine the gathered data to deepen their understanding of disease progression and the potential of HCQ to improve symptoms in RA patients, said lead study author Kevin D. Deane, MD, PhD, of the University of Colorado at Denver, Aurora.

Richard Mark Kirkner/MDedge News

Overall, around 35% of the study participants on average developed RA, Dr. Deane said. “We were expecting somewhat more,” he said. “Teasing out who’s really going to progress to RA during a study and who’s not is going to be incredibly important.”

StopRA enrolled 144 adults who had elevated anti–cyclic citrullinated peptide antibodies (CCP3) levels of at least 40 units (about twice the normal level) but no history if inflammatory arthritis, randomizing them on a 1:1 basis to either HCQ (200-400 mg a day based on weight) or placebo for a 1-year treatment regimen.

The study identified participants through rheumatology clinics, testing of first-degree relatives with established RA, health fairs, blood donors, and biobanks. The interim findings are based on 2 years of follow-up after the last dose.

The study focused on HCQ because it has a relatively low risk profile with good safety and tolerability, is easy to administer, and is relatively low cost, Dr. Deane said.

StopRA study failed to meet its primary endpoint: to determine if 1 year of treatment with HCQ reduced the risk of developing inflammatory arthritis and classifiable RA at the end of 3 years in the study population. At the time of the interim analysis, 34% of patients in the HCQ arm and 36% in the placebo arm had developed RA (P = .844), Dr. Deane said. Baseline characteristics were balanced in both treatment arms.

The findings also support the use of CCP3 as a biomarker for RA, Dr. Deane said.

Now that the trial has been terminated, Dr. Deane said investigators are going to review the final data and perform secondary analyses for further clarity on the impact HCQ may have on RA.

“The future analysis should hopefully say if this treatment actually changes symptoms,” he said in an interview. “Because, if somebody felt better on the drug or had a milder form of rheumatoid arthritis once they developed it, that could potentially be a benefit.”

Dr. Deane noted the TREAT EARLIER trial similarly found that a 1-year course of methotrexate didn’t prevent the onset of clinical arthritis, but it did alter the disease course as measured in MRI-detected inflammation, related symptoms, and impairment.

“We’re hoping to look at those things and hopefully look at biologic changes over time,” Dr. Deane said of the extended analysis. “We’re not sure if the drug was associated with changes in biomarkers yet still didn’t halt progression to RA. That might be interesting, because those biomarkers might not be fundamentally related to the disease, but other mechanisms may be. That could give us some insights.”

Richard Mark Kirkner/MDedge News

Session moderator Ted Mikuls, MD, a professor of rheumatology at the University of Nebraska Medical Center, Omaha, said further mining of the study data is warranted.

“It’s common in a study like that, which took a lot of time and investment, to really take a deep dive into the data to make sure there aren’t signals that we’re missing,” he said in an interview.

One of the challenges with the study may have been patient enrollment, Dr. Mikuls noted. “I wonder about the study population in terms of where they recruit patients from. Who’s more likely to get RA? Is it patients who already have symptoms? Is it asymptomatic patients from biobanks? If it’s arthralgia joint pain patients, maybe by the time you have joint and autoantibody positivity it’s too late to have an intervention.”

The National Institute of Allergy and Infectious Diseases sponsored the study. Dr. Deane disclosed a relationship with Werfen. Dr. Mikuls has no relevant disclosures.
 

Roughly 7% of all adult Americans may currently have had long COVID, with symptoms that have lasted 3 months or longer, according to the latest U.S. government survey done in October. More than a quarter say their condition is severe enough to significantly limit their day-to-day activities – yet the problem is only barely starting to get the attention of employers, the health care system, and policymakers.

With no cure or treatment in sight, long COVID is already burdening not only the health care system, but also the economy – and that burden is set to grow. Many experts worry about the possible long-term ripple effects, from increased spending on medical care costs to lost wages due to not being able to work, as well as the policy implications that come with addressing these issues.

“At this point, anyone who’s looking at this seriously would say this is a huge deal,” says senior Brookings Institution fellow Katie Bach, the author of a study that analyzed long COVID’s impact on the labor market.

“We need a real concerted focus on treating these people, which means both research and the clinical side, and figuring out how to build a labor market that is more inclusive of people with disabilities,” she said.

It’s not only that many people are affected. It’s that they are often affected for months and possibly even years.

The U.S. government figures suggest more than 18 million people could have symptoms of long COVID right now. The latest Household Pulse Survey by the Census Bureau and the National Center for Health Statistics takes data from 41,415 people.

A preprint of a study by researchers from City University of New York, posted on medRxiv in September and based on a similar population survey done between June 30 and July 2, drew comparable results. The study has not been peer reviewed.

More than 7% of all those who answered said they had long COVID at the time of the survey, which the researchers said corresponded to approximately 18.5 million U.S. adults. The same study found that a quarter of those, or an estimated 4.7 million adults, said their daily activities were impacted “a lot.”

This can translate into pain not only for the patients, but for governments and employers, too.

In high-income countries around the world, government surveys and other studies are shedding light on the extent to which post-COVID-19 symptoms – commonly known as long COVID – are affecting populations. While results vary, they generally fall within similar ranges.

The World Health Organization estimates that between 10% and 20% of those with COVID-19 go on to have an array of medium- to long-term post-COVID-19 symptoms that range from mild to debilitating. The U.S. Government Accountability Office puts that estimate at 10% to 30%; one of the latest studies published at the end of October in The Journal of the American Medical Association found that 15% of U.S. adults who had tested positive for COVID-19 reported current long COVID symptoms. Elsewhere, a study from the Netherlands published in The Lancet in August found that one in eight COVID-19 cases, or 12.7%, were likely to become long COVID.

“It’s very clear that the condition is devastating people’s lives and livelihoods,” WHO Director-General Tedros Adhanom Ghebreyesus wrote in an article for The Guardian newspaper in October.

“The world has already lost a significant number of the workforce to illness, death, fatigue, unplanned retirement due to an increase in long-term disability, which not only impacts the health system, but is a hit to the overarching economy … the impact of long COVID for all countries is very serious and needs immediate and sustained action equivalent to its scale.”
 

Global snapshot: Lasting symptoms, impact on activities

Patients describe a spectrum of persistent issues, with extreme fatigue, brain fog or cognitive problems, and shortness of breath among the most common complaints. Many also have manageable symptoms that worsen significantly after even mild physical or mental exertion.

Women appear almost twice as likely as men to get long COVID. Many patients have other medical conditions and disabilities that make them more vulnerable to the condition. Those who face greater obstacles accessing health care due to discrimination or socioeconomic inequity are at higher risk as well. 

While many are older, a large number are also in their prime working age. The Census Bureau data show that people ages 40-49 are more likely than any other group to get long COVID, which has broader implications for labor markets and the global economy. Already, experts have estimated that long COVID is likely to cost the U.S. trillions of dollars and affect multiple industries.

“Whether they’re in the financial world, the medical system, lawyers, they’re telling me they’re sitting at the computer screen and they’re unable to process the data,” said Zachary Schwartz, MD, medical director for Vancouver General Hospital’s Post-COVID-19 Recovery Clinic.

“That is what’s most distressing for people, in that they’re not working, they’re not making money, and they don’t know when, or if, they’re going to get better.”

Nearly a third of respondents in the Census Bureau’s Household Pulse Survey who said they have had COVID-19 reported symptoms that lasted 3 months or longer. People between the ages of 30 and 59 were the most affected, with about 32% reporting symptoms. Across the entire adult U.S. population, the survey found that 1 in 7 adults have had long COVID at some point during the pandemic, with about 1 in 18 saying it limited their activity to some degree, and 1 in 50 saying they have faced “a lot” of limits on their activities. Any way these numbers are dissected, long COVID has impacted a large swath of the population.

Yet research into the causes and possible treatments of long COVID is just getting underway.

“The amount of energy and time devoted to it is way, way less than it should, given how many people are likely affected,” said David Cutler, PhD, professor of economics at Harvard University, Cambridge, Mass., who has written about the economic cost of long COVID. “We’re way, way underdoing it here. And I think that’s really a terrible thing.”

Population surveys and studies from around the world show that long COVID lives up to its name, with people reporting serious symptoms for months on end.

In October, Statistics Canada and the Public Health Agency of Canada published early results from a questionnaire done between spring and summer 2022 that found just under 15% of adults who had a confirmed or suspected case of COVID-19 went on to have new or continuing symptoms 3 or more months later. Nearly half, or 47.3%, dealt with symptoms that lasted a year or more. More than one in five said their symptoms “often or always” limited their day-to-day activities, which included routine tasks such as preparing meals, doing errands and chores, and basic functions such as personal care and moving around in their homes.

Nearly three-quarters of workers or students said they missed an average of 20 days of work or school. 

“We haven’t yet been able to determine exactly when symptoms resolve,” said Rainu Kaushal, MD, the senior associate dean for clinical research at Weill Cornell Medicine in New York. She is co-leading a national study on long COVID in adults and children, funded by the National Institutes of Health RECOVER Initiative.

“But there does seem to be, for many of the milder symptoms, resolution at about 4-6 weeks. There seems to be a second point of resolution around 6 months for certain symptoms, and then some symptoms do seem to be permanent, and those tend to be patients who have underlying conditions,” she said.
 

Reducing the risk

Given all the data so far, experts recommend urgent policy changes to help people with long COVID.

“The population needs to be prepared, that understanding long COVID is going to be a very long and difficult process,” said Alexander Charney, MD, PhD, associate professor and the lead principal investigator of the RECOVER adult cohort at Icahn School of Medicine at Mount Sinai in New York. He said the government can do a great deal to help, including setting up a network of connected clinics treating long COVID, standardizing best practices, and sharing information.

“That would go a long way towards making sure that every person feels like they’re not too far away from a clinic where they can get treated for this particular condition,” he said.

But the only known way to prevent long COVID is to prevent COVID-19 infections in the first place, experts say. That means equitable access to tests, therapeutics, and vaccines.

“I will say that avoiding COVID remains the best treatment in the arsenal right now,” said Dr. Kaushal. This means masking, avoiding crowded places with poor ventilation and high exposure risk, and being up to date on vaccinations, she said.

A number of papers – including a large U.K. study published in May 2022, another one from July, and the JAMA study from October – all suggest that vaccinations can help reduce the risk of long COVID.

“I am absolutely of the belief that vaccination has reduced the incidence and overall amount of long COVID … [and is] still by far the best thing the public can do,” said Dr. Schwartz.

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

Roughly 7% of all adult Americans may currently have had long COVID, with symptoms that have lasted 3 months or longer, according to the latest U.S. government survey done in October. More than a quarter say their condition is severe enough to significantly limit their day-to-day activities – yet the problem is only barely starting to get the attention of employers, the health care system, and policymakers.

With no cure or treatment in sight, long COVID is already burdening not only the health care system, but also the economy – and that burden is set to grow. Many experts worry about the possible long-term ripple effects, from increased spending on medical care costs to lost wages due to not being able to work, as well as the policy implications that come with addressing these issues.

“At this point, anyone who’s looking at this seriously would say this is a huge deal,” says senior Brookings Institution fellow Katie Bach, the author of a study that analyzed long COVID’s impact on the labor market.

“We need a real concerted focus on treating these people, which means both research and the clinical side, and figuring out how to build a labor market that is more inclusive of people with disabilities,” she said.

It’s not only that many people are affected. It’s that they are often affected for months and possibly even years.

The U.S. government figures suggest more than 18 million people could have symptoms of long COVID right now. The latest Household Pulse Survey by the Census Bureau and the National Center for Health Statistics takes data from 41,415 people.

A preprint of a study by researchers from City University of New York, posted on medRxiv in September and based on a similar population survey done between June 30 and July 2, drew comparable results. The study has not been peer reviewed.

More than 7% of all those who answered said they had long COVID at the time of the survey, which the researchers said corresponded to approximately 18.5 million U.S. adults. The same study found that a quarter of those, or an estimated 4.7 million adults, said their daily activities were impacted “a lot.”

This can translate into pain not only for the patients, but for governments and employers, too.

In high-income countries around the world, government surveys and other studies are shedding light on the extent to which post-COVID-19 symptoms – commonly known as long COVID – are affecting populations. While results vary, they generally fall within similar ranges.

The World Health Organization estimates that between 10% and 20% of those with COVID-19 go on to have an array of medium- to long-term post-COVID-19 symptoms that range from mild to debilitating. The U.S. Government Accountability Office puts that estimate at 10% to 30%; one of the latest studies published at the end of October in The Journal of the American Medical Association found that 15% of U.S. adults who had tested positive for COVID-19 reported current long COVID symptoms. Elsewhere, a study from the Netherlands published in The Lancet in August found that one in eight COVID-19 cases, or 12.7%, were likely to become long COVID.

“It’s very clear that the condition is devastating people’s lives and livelihoods,” WHO Director-General Tedros Adhanom Ghebreyesus wrote in an article for The Guardian newspaper in October.

“The world has already lost a significant number of the workforce to illness, death, fatigue, unplanned retirement due to an increase in long-term disability, which not only impacts the health system, but is a hit to the overarching economy … the impact of long COVID for all countries is very serious and needs immediate and sustained action equivalent to its scale.”
 

Global snapshot: Lasting symptoms, impact on activities

Patients describe a spectrum of persistent issues, with extreme fatigue, brain fog or cognitive problems, and shortness of breath among the most common complaints. Many also have manageable symptoms that worsen significantly after even mild physical or mental exertion.

Women appear almost twice as likely as men to get long COVID. Many patients have other medical conditions and disabilities that make them more vulnerable to the condition. Those who face greater obstacles accessing health care due to discrimination or socioeconomic inequity are at higher risk as well. 

While many are older, a large number are also in their prime working age. The Census Bureau data show that people ages 40-49 are more likely than any other group to get long COVID, which has broader implications for labor markets and the global economy. Already, experts have estimated that long COVID is likely to cost the U.S. trillions of dollars and affect multiple industries.

“Whether they’re in the financial world, the medical system, lawyers, they’re telling me they’re sitting at the computer screen and they’re unable to process the data,” said Zachary Schwartz, MD, medical director for Vancouver General Hospital’s Post-COVID-19 Recovery Clinic.

“That is what’s most distressing for people, in that they’re not working, they’re not making money, and they don’t know when, or if, they’re going to get better.”

Nearly a third of respondents in the Census Bureau’s Household Pulse Survey who said they have had COVID-19 reported symptoms that lasted 3 months or longer. People between the ages of 30 and 59 were the most affected, with about 32% reporting symptoms. Across the entire adult U.S. population, the survey found that 1 in 7 adults have had long COVID at some point during the pandemic, with about 1 in 18 saying it limited their activity to some degree, and 1 in 50 saying they have faced “a lot” of limits on their activities. Any way these numbers are dissected, long COVID has impacted a large swath of the population.

Yet research into the causes and possible treatments of long COVID is just getting underway.

“The amount of energy and time devoted to it is way, way less than it should, given how many people are likely affected,” said David Cutler, PhD, professor of economics at Harvard University, Cambridge, Mass., who has written about the economic cost of long COVID. “We’re way, way underdoing it here. And I think that’s really a terrible thing.”

Population surveys and studies from around the world show that long COVID lives up to its name, with people reporting serious symptoms for months on end.

In October, Statistics Canada and the Public Health Agency of Canada published early results from a questionnaire done between spring and summer 2022 that found just under 15% of adults who had a confirmed or suspected case of COVID-19 went on to have new or continuing symptoms 3 or more months later. Nearly half, or 47.3%, dealt with symptoms that lasted a year or more. More than one in five said their symptoms “often or always” limited their day-to-day activities, which included routine tasks such as preparing meals, doing errands and chores, and basic functions such as personal care and moving around in their homes.

Nearly three-quarters of workers or students said they missed an average of 20 days of work or school. 

“We haven’t yet been able to determine exactly when symptoms resolve,” said Rainu Kaushal, MD, the senior associate dean for clinical research at Weill Cornell Medicine in New York. She is co-leading a national study on long COVID in adults and children, funded by the National Institutes of Health RECOVER Initiative.

“But there does seem to be, for many of the milder symptoms, resolution at about 4-6 weeks. There seems to be a second point of resolution around 6 months for certain symptoms, and then some symptoms do seem to be permanent, and those tend to be patients who have underlying conditions,” she said.
 

Reducing the risk

Given all the data so far, experts recommend urgent policy changes to help people with long COVID.

“The population needs to be prepared, that understanding long COVID is going to be a very long and difficult process,” said Alexander Charney, MD, PhD, associate professor and the lead principal investigator of the RECOVER adult cohort at Icahn School of Medicine at Mount Sinai in New York. He said the government can do a great deal to help, including setting up a network of connected clinics treating long COVID, standardizing best practices, and sharing information.

“That would go a long way towards making sure that every person feels like they’re not too far away from a clinic where they can get treated for this particular condition,” he said.

But the only known way to prevent long COVID is to prevent COVID-19 infections in the first place, experts say. That means equitable access to tests, therapeutics, and vaccines.

“I will say that avoiding COVID remains the best treatment in the arsenal right now,” said Dr. Kaushal. This means masking, avoiding crowded places with poor ventilation and high exposure risk, and being up to date on vaccinations, she said.

A number of papers – including a large U.K. study published in May 2022, another one from July, and the JAMA study from October – all suggest that vaccinations can help reduce the risk of long COVID.

“I am absolutely of the belief that vaccination has reduced the incidence and overall amount of long COVID … [and is] still by far the best thing the public can do,” said Dr. Schwartz.

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

Roughly 7% of all adult Americans may currently have had long COVID, with symptoms that have lasted 3 months or longer, according to the latest U.S. government survey done in October. More than a quarter say their condition is severe enough to significantly limit their day-to-day activities – yet the problem is only barely starting to get the attention of employers, the health care system, and policymakers.

With no cure or treatment in sight, long COVID is already burdening not only the health care system, but also the economy – and that burden is set to grow. Many experts worry about the possible long-term ripple effects, from increased spending on medical care costs to lost wages due to not being able to work, as well as the policy implications that come with addressing these issues.

“At this point, anyone who’s looking at this seriously would say this is a huge deal,” says senior Brookings Institution fellow Katie Bach, the author of a study that analyzed long COVID’s impact on the labor market.

“We need a real concerted focus on treating these people, which means both research and the clinical side, and figuring out how to build a labor market that is more inclusive of people with disabilities,” she said.

It’s not only that many people are affected. It’s that they are often affected for months and possibly even years.

The U.S. government figures suggest more than 18 million people could have symptoms of long COVID right now. The latest Household Pulse Survey by the Census Bureau and the National Center for Health Statistics takes data from 41,415 people.

A preprint of a study by researchers from City University of New York, posted on medRxiv in September and based on a similar population survey done between June 30 and July 2, drew comparable results. The study has not been peer reviewed.

More than 7% of all those who answered said they had long COVID at the time of the survey, which the researchers said corresponded to approximately 18.5 million U.S. adults. The same study found that a quarter of those, or an estimated 4.7 million adults, said their daily activities were impacted “a lot.”

This can translate into pain not only for the patients, but for governments and employers, too.

In high-income countries around the world, government surveys and other studies are shedding light on the extent to which post-COVID-19 symptoms – commonly known as long COVID – are affecting populations. While results vary, they generally fall within similar ranges.

The World Health Organization estimates that between 10% and 20% of those with COVID-19 go on to have an array of medium- to long-term post-COVID-19 symptoms that range from mild to debilitating. The U.S. Government Accountability Office puts that estimate at 10% to 30%; one of the latest studies published at the end of October in The Journal of the American Medical Association found that 15% of U.S. adults who had tested positive for COVID-19 reported current long COVID symptoms. Elsewhere, a study from the Netherlands published in The Lancet in August found that one in eight COVID-19 cases, or 12.7%, were likely to become long COVID.

“It’s very clear that the condition is devastating people’s lives and livelihoods,” WHO Director-General Tedros Adhanom Ghebreyesus wrote in an article for The Guardian newspaper in October.

“The world has already lost a significant number of the workforce to illness, death, fatigue, unplanned retirement due to an increase in long-term disability, which not only impacts the health system, but is a hit to the overarching economy … the impact of long COVID for all countries is very serious and needs immediate and sustained action equivalent to its scale.”
 

Global snapshot: Lasting symptoms, impact on activities

Patients describe a spectrum of persistent issues, with extreme fatigue, brain fog or cognitive problems, and shortness of breath among the most common complaints. Many also have manageable symptoms that worsen significantly after even mild physical or mental exertion.

Women appear almost twice as likely as men to get long COVID. Many patients have other medical conditions and disabilities that make them more vulnerable to the condition. Those who face greater obstacles accessing health care due to discrimination or socioeconomic inequity are at higher risk as well. 

While many are older, a large number are also in their prime working age. The Census Bureau data show that people ages 40-49 are more likely than any other group to get long COVID, which has broader implications for labor markets and the global economy. Already, experts have estimated that long COVID is likely to cost the U.S. trillions of dollars and affect multiple industries.

“Whether they’re in the financial world, the medical system, lawyers, they’re telling me they’re sitting at the computer screen and they’re unable to process the data,” said Zachary Schwartz, MD, medical director for Vancouver General Hospital’s Post-COVID-19 Recovery Clinic.

“That is what’s most distressing for people, in that they’re not working, they’re not making money, and they don’t know when, or if, they’re going to get better.”

Nearly a third of respondents in the Census Bureau’s Household Pulse Survey who said they have had COVID-19 reported symptoms that lasted 3 months or longer. People between the ages of 30 and 59 were the most affected, with about 32% reporting symptoms. Across the entire adult U.S. population, the survey found that 1 in 7 adults have had long COVID at some point during the pandemic, with about 1 in 18 saying it limited their activity to some degree, and 1 in 50 saying they have faced “a lot” of limits on their activities. Any way these numbers are dissected, long COVID has impacted a large swath of the population.

Yet research into the causes and possible treatments of long COVID is just getting underway.

“The amount of energy and time devoted to it is way, way less than it should, given how many people are likely affected,” said David Cutler, PhD, professor of economics at Harvard University, Cambridge, Mass., who has written about the economic cost of long COVID. “We’re way, way underdoing it here. And I think that’s really a terrible thing.”

Population surveys and studies from around the world show that long COVID lives up to its name, with people reporting serious symptoms for months on end.

In October, Statistics Canada and the Public Health Agency of Canada published early results from a questionnaire done between spring and summer 2022 that found just under 15% of adults who had a confirmed or suspected case of COVID-19 went on to have new or continuing symptoms 3 or more months later. Nearly half, or 47.3%, dealt with symptoms that lasted a year or more. More than one in five said their symptoms “often or always” limited their day-to-day activities, which included routine tasks such as preparing meals, doing errands and chores, and basic functions such as personal care and moving around in their homes.

Nearly three-quarters of workers or students said they missed an average of 20 days of work or school. 

“We haven’t yet been able to determine exactly when symptoms resolve,” said Rainu Kaushal, MD, the senior associate dean for clinical research at Weill Cornell Medicine in New York. She is co-leading a national study on long COVID in adults and children, funded by the National Institutes of Health RECOVER Initiative.

“But there does seem to be, for many of the milder symptoms, resolution at about 4-6 weeks. There seems to be a second point of resolution around 6 months for certain symptoms, and then some symptoms do seem to be permanent, and those tend to be patients who have underlying conditions,” she said.
 

Reducing the risk

Given all the data so far, experts recommend urgent policy changes to help people with long COVID.

“The population needs to be prepared, that understanding long COVID is going to be a very long and difficult process,” said Alexander Charney, MD, PhD, associate professor and the lead principal investigator of the RECOVER adult cohort at Icahn School of Medicine at Mount Sinai in New York. He said the government can do a great deal to help, including setting up a network of connected clinics treating long COVID, standardizing best practices, and sharing information.

“That would go a long way towards making sure that every person feels like they’re not too far away from a clinic where they can get treated for this particular condition,” he said.

But the only known way to prevent long COVID is to prevent COVID-19 infections in the first place, experts say. That means equitable access to tests, therapeutics, and vaccines.

“I will say that avoiding COVID remains the best treatment in the arsenal right now,” said Dr. Kaushal. This means masking, avoiding crowded places with poor ventilation and high exposure risk, and being up to date on vaccinations, she said.

A number of papers – including a large U.K. study published in May 2022, another one from July, and the JAMA study from October – all suggest that vaccinations can help reduce the risk of long COVID.

“I am absolutely of the belief that vaccination has reduced the incidence and overall amount of long COVID … [and is] still by far the best thing the public can do,” said Dr. Schwartz.

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

PHILADELPHIA – For patients with rheumatoid arthritis who are already at increased risk for major adverse cardiovascular events (MACE), NSAIDs may be safer than opioids, results of a new-user active comparator study suggest.

Among 6,866 patients with RA who started on opioids and 13,698 patients who started on NSAIDs for pain, the use of both weak and strong opioids was associated with a 33% increase in risk for all-cause mortality and a trend toward higher rates of venous thromboembolism (VTE), compared with NSAID use, reported Gulsen Ozen, MD, of the University of Nebraska Medical Center, Omaha.

Neil Osterweil/MDedge News

“Pain in RA is a very complex process, and we know that it’s not solely dependent on the disease activity, but there is no evidence that opioids have any benefit in long-term pain management, and it can even cause hyperalgesia. And as we show, it’s not safer than NSAIDs,” she said in an oral abstract session at the annual meeting of the American College of Rheumatology.

She stressed that patients should be assessed for non-RA causes of pain and should use nonpharmacologic methods when possible.

“If a pharmacological treatment is needed and NSAIDs are contraindicated, the lowest possible dose of weak opioids can be used for a very limited time for acute pain only,” she said.
 

Pain despite disease control

Even when their disease is well controlled, approximately 60% of patients with RA still report pain. NSAIDs are commonly used to treat pain in patients with RA, but they are associated with modest increases in risk for cardiovascular disease (CVD), gastrointestinal bleeding, renal injury, and hypertension.

Some providers are leery of NSAIDs and will instead prescribe either regular or intermittent opioids for pain control in their patients.

Disease-modifying antirheumatic drugs have only minimal pain-relieving benefits, “and even worse, opioids can delay initiation of DMARDs in RA,” Dr. Ozen said.

Opioids have been shown to increase oxidative stress, platelet aggregation, and myocardial fibrosis, as well as hypogonadism, weight gain, and CVD risk factors.

There is little evidence, however, on whether opioids are associated with cardiovascular events in patients with RA. This dearth of data prompted Dr. Ozen and colleagues to study the relative risks for MACE in patients with RA starting on opioids or NSAIDs for pain.

Matched cohorts

They used data from FORWARD, a joint Canadian and U.S. databank for rheumatic diseases, to conduct a new-user active comparator cohort study. The cohort included adults with RA without cancer who participated in FORWARD for a minimum of 1 year between 1998 and 2021.

The patients were followed either from drug initiation until 3 months after the end of treatment, defined as either discontinuation or a switch to a different analgesic, end of study follow-up, or the development of a MACE outcome.

The investigators used propensity score matching to compare each opioid initiator with two NSAID initiators. The participants were matched by age, sex, body mass index, smoking, alcohol, RA duration, disease activity, Health Assessment Questionnaire, visual analog scale for pain, joint surgeries, prior CVD and VTE, hypertension, diabetes, rheumatic diseases comorbidity index, osteoporosis/fractures, thyroid, chronic liver, kidney, lung and mental health diseases, hospitalizations, 36-Item Short Form Health Survey scores, and sleep scores.

The two groups were well matched, except for a slightly higher incidence of VTE in opioid initiators, although incidence rates were low in both groups (0.9% vs. 0.6% of NSAID initiators).
 

Higher death rate in opioid users

The incidence rate of MACE among opioid initiators was 20.6% versus18.9% among NSAID initiators, a difference that was not statistically significant. There were also no significant differences in incidence rates of the individual components of the MACE composite outcome: myocardial infarction, stroke, heart failure, CVD death, or VTE.

There were, however, significantly more deaths from any cause among patients in the opioid group, with an incidence rate of 13.5% versus 10.8% in the NSAID group.

An analysis of the associaion of drug type with outcomes, adjusted for propensity score weight and prior VTE showed that patients on opioids had a statistically significant hazard ratio for death from any cause of 1.33 (95% confidence interval, 1.06-1.67).

The increased risk for all-cause mortality occurred both in patients starting on weak opioids (hydrocodone, tramadol, codeine, pentazocine, and propoxyphene) and on strong opioids (hydromorphone, dihydromorphinone, oxymorphone, butorphanol, methadone, morphine, oxycodone, meperidine, and fentanyl).

As noted before, there was a trend toward an increased risk for VTE among opioid initiators, but this was not statistically significant.

The increase in risk was higher among patients on strong versus weak opioids, suggesting a dose-dependent relationship, Dr. Ozen said.

A comparison of opioid-associated risk for all-cause mortality vs. NSAIDs according to type (nonselective or selective) showed that most of the increase in risk was relative to selective cycloxygenase-2 inhibitors.

‘Beautiful’ analysis

“This is a beautiful piece of analysis on a really difficult question to address because the confounding is really hard to unpick,” commented James Galloway, MBBS, deputy head of the center for rheumatic diseases at King’s College London and consulting rheumatologist at King’s College Hospital, also in London.

“The headline message is that there didn’t appear to be a clear signal that NSAIDs were worse, which is what I thought the preexisting view might have been. And so, people may have paradoxically prescribed opioids in favor of NSAIDs in a person with cardiovascular risk,” he said in an interview. Dr. Galloway attended the oral abstract session but was not involved in the study.

The study was supported by a grant to Dr. Ozen from the Rheumatology Research Foundation. Dr. Galloway reported having no relevant disclosures.

PHILADELPHIA – For patients with rheumatoid arthritis who are already at increased risk for major adverse cardiovascular events (MACE), NSAIDs may be safer than opioids, results of a new-user active comparator study suggest.

Among 6,866 patients with RA who started on opioids and 13,698 patients who started on NSAIDs for pain, the use of both weak and strong opioids was associated with a 33% increase in risk for all-cause mortality and a trend toward higher rates of venous thromboembolism (VTE), compared with NSAID use, reported Gulsen Ozen, MD, of the University of Nebraska Medical Center, Omaha.

Neil Osterweil/MDedge News

“Pain in RA is a very complex process, and we know that it’s not solely dependent on the disease activity, but there is no evidence that opioids have any benefit in long-term pain management, and it can even cause hyperalgesia. And as we show, it’s not safer than NSAIDs,” she said in an oral abstract session at the annual meeting of the American College of Rheumatology.

She stressed that patients should be assessed for non-RA causes of pain and should use nonpharmacologic methods when possible.

“If a pharmacological treatment is needed and NSAIDs are contraindicated, the lowest possible dose of weak opioids can be used for a very limited time for acute pain only,” she said.
 

Pain despite disease control

Even when their disease is well controlled, approximately 60% of patients with RA still report pain. NSAIDs are commonly used to treat pain in patients with RA, but they are associated with modest increases in risk for cardiovascular disease (CVD), gastrointestinal bleeding, renal injury, and hypertension.

Some providers are leery of NSAIDs and will instead prescribe either regular or intermittent opioids for pain control in their patients.

Disease-modifying antirheumatic drugs have only minimal pain-relieving benefits, “and even worse, opioids can delay initiation of DMARDs in RA,” Dr. Ozen said.

Opioids have been shown to increase oxidative stress, platelet aggregation, and myocardial fibrosis, as well as hypogonadism, weight gain, and CVD risk factors.

There is little evidence, however, on whether opioids are associated with cardiovascular events in patients with RA. This dearth of data prompted Dr. Ozen and colleagues to study the relative risks for MACE in patients with RA starting on opioids or NSAIDs for pain.

Matched cohorts

They used data from FORWARD, a joint Canadian and U.S. databank for rheumatic diseases, to conduct a new-user active comparator cohort study. The cohort included adults with RA without cancer who participated in FORWARD for a minimum of 1 year between 1998 and 2021.

The patients were followed either from drug initiation until 3 months after the end of treatment, defined as either discontinuation or a switch to a different analgesic, end of study follow-up, or the development of a MACE outcome.

The investigators used propensity score matching to compare each opioid initiator with two NSAID initiators. The participants were matched by age, sex, body mass index, smoking, alcohol, RA duration, disease activity, Health Assessment Questionnaire, visual analog scale for pain, joint surgeries, prior CVD and VTE, hypertension, diabetes, rheumatic diseases comorbidity index, osteoporosis/fractures, thyroid, chronic liver, kidney, lung and mental health diseases, hospitalizations, 36-Item Short Form Health Survey scores, and sleep scores.

The two groups were well matched, except for a slightly higher incidence of VTE in opioid initiators, although incidence rates were low in both groups (0.9% vs. 0.6% of NSAID initiators).
 

Higher death rate in opioid users

The incidence rate of MACE among opioid initiators was 20.6% versus18.9% among NSAID initiators, a difference that was not statistically significant. There were also no significant differences in incidence rates of the individual components of the MACE composite outcome: myocardial infarction, stroke, heart failure, CVD death, or VTE.

There were, however, significantly more deaths from any cause among patients in the opioid group, with an incidence rate of 13.5% versus 10.8% in the NSAID group.

An analysis of the associaion of drug type with outcomes, adjusted for propensity score weight and prior VTE showed that patients on opioids had a statistically significant hazard ratio for death from any cause of 1.33 (95% confidence interval, 1.06-1.67).

The increased risk for all-cause mortality occurred both in patients starting on weak opioids (hydrocodone, tramadol, codeine, pentazocine, and propoxyphene) and on strong opioids (hydromorphone, dihydromorphinone, oxymorphone, butorphanol, methadone, morphine, oxycodone, meperidine, and fentanyl).

As noted before, there was a trend toward an increased risk for VTE among opioid initiators, but this was not statistically significant.

The increase in risk was higher among patients on strong versus weak opioids, suggesting a dose-dependent relationship, Dr. Ozen said.

A comparison of opioid-associated risk for all-cause mortality vs. NSAIDs according to type (nonselective or selective) showed that most of the increase in risk was relative to selective cycloxygenase-2 inhibitors.

‘Beautiful’ analysis

“This is a beautiful piece of analysis on a really difficult question to address because the confounding is really hard to unpick,” commented James Galloway, MBBS, deputy head of the center for rheumatic diseases at King’s College London and consulting rheumatologist at King’s College Hospital, also in London.

“The headline message is that there didn’t appear to be a clear signal that NSAIDs were worse, which is what I thought the preexisting view might have been. And so, people may have paradoxically prescribed opioids in favor of NSAIDs in a person with cardiovascular risk,” he said in an interview. Dr. Galloway attended the oral abstract session but was not involved in the study.

The study was supported by a grant to Dr. Ozen from the Rheumatology Research Foundation. Dr. Galloway reported having no relevant disclosures.

PHILADELPHIA – For patients with rheumatoid arthritis who are already at increased risk for major adverse cardiovascular events (MACE), NSAIDs may be safer than opioids, results of a new-user active comparator study suggest.

Among 6,866 patients with RA who started on opioids and 13,698 patients who started on NSAIDs for pain, the use of both weak and strong opioids was associated with a 33% increase in risk for all-cause mortality and a trend toward higher rates of venous thromboembolism (VTE), compared with NSAID use, reported Gulsen Ozen, MD, of the University of Nebraska Medical Center, Omaha.

Neil Osterweil/MDedge News

“Pain in RA is a very complex process, and we know that it’s not solely dependent on the disease activity, but there is no evidence that opioids have any benefit in long-term pain management, and it can even cause hyperalgesia. And as we show, it’s not safer than NSAIDs,” she said in an oral abstract session at the annual meeting of the American College of Rheumatology.

She stressed that patients should be assessed for non-RA causes of pain and should use nonpharmacologic methods when possible.

“If a pharmacological treatment is needed and NSAIDs are contraindicated, the lowest possible dose of weak opioids can be used for a very limited time for acute pain only,” she said.
 

Pain despite disease control

Even when their disease is well controlled, approximately 60% of patients with RA still report pain. NSAIDs are commonly used to treat pain in patients with RA, but they are associated with modest increases in risk for cardiovascular disease (CVD), gastrointestinal bleeding, renal injury, and hypertension.

Some providers are leery of NSAIDs and will instead prescribe either regular or intermittent opioids for pain control in their patients.

Disease-modifying antirheumatic drugs have only minimal pain-relieving benefits, “and even worse, opioids can delay initiation of DMARDs in RA,” Dr. Ozen said.

Opioids have been shown to increase oxidative stress, platelet aggregation, and myocardial fibrosis, as well as hypogonadism, weight gain, and CVD risk factors.

There is little evidence, however, on whether opioids are associated with cardiovascular events in patients with RA. This dearth of data prompted Dr. Ozen and colleagues to study the relative risks for MACE in patients with RA starting on opioids or NSAIDs for pain.

Matched cohorts

They used data from FORWARD, a joint Canadian and U.S. databank for rheumatic diseases, to conduct a new-user active comparator cohort study. The cohort included adults with RA without cancer who participated in FORWARD for a minimum of 1 year between 1998 and 2021.

The patients were followed either from drug initiation until 3 months after the end of treatment, defined as either discontinuation or a switch to a different analgesic, end of study follow-up, or the development of a MACE outcome.

The investigators used propensity score matching to compare each opioid initiator with two NSAID initiators. The participants were matched by age, sex, body mass index, smoking, alcohol, RA duration, disease activity, Health Assessment Questionnaire, visual analog scale for pain, joint surgeries, prior CVD and VTE, hypertension, diabetes, rheumatic diseases comorbidity index, osteoporosis/fractures, thyroid, chronic liver, kidney, lung and mental health diseases, hospitalizations, 36-Item Short Form Health Survey scores, and sleep scores.

The two groups were well matched, except for a slightly higher incidence of VTE in opioid initiators, although incidence rates were low in both groups (0.9% vs. 0.6% of NSAID initiators).
 

Higher death rate in opioid users

The incidence rate of MACE among opioid initiators was 20.6% versus18.9% among NSAID initiators, a difference that was not statistically significant. There were also no significant differences in incidence rates of the individual components of the MACE composite outcome: myocardial infarction, stroke, heart failure, CVD death, or VTE.

There were, however, significantly more deaths from any cause among patients in the opioid group, with an incidence rate of 13.5% versus 10.8% in the NSAID group.

An analysis of the associaion of drug type with outcomes, adjusted for propensity score weight and prior VTE showed that patients on opioids had a statistically significant hazard ratio for death from any cause of 1.33 (95% confidence interval, 1.06-1.67).

The increased risk for all-cause mortality occurred both in patients starting on weak opioids (hydrocodone, tramadol, codeine, pentazocine, and propoxyphene) and on strong opioids (hydromorphone, dihydromorphinone, oxymorphone, butorphanol, methadone, morphine, oxycodone, meperidine, and fentanyl).

As noted before, there was a trend toward an increased risk for VTE among opioid initiators, but this was not statistically significant.

The increase in risk was higher among patients on strong versus weak opioids, suggesting a dose-dependent relationship, Dr. Ozen said.

A comparison of opioid-associated risk for all-cause mortality vs. NSAIDs according to type (nonselective or selective) showed that most of the increase in risk was relative to selective cycloxygenase-2 inhibitors.

‘Beautiful’ analysis

“This is a beautiful piece of analysis on a really difficult question to address because the confounding is really hard to unpick,” commented James Galloway, MBBS, deputy head of the center for rheumatic diseases at King’s College London and consulting rheumatologist at King’s College Hospital, also in London.

“The headline message is that there didn’t appear to be a clear signal that NSAIDs were worse, which is what I thought the preexisting view might have been. And so, people may have paradoxically prescribed opioids in favor of NSAIDs in a person with cardiovascular risk,” he said in an interview. Dr. Galloway attended the oral abstract session but was not involved in the study.

The study was supported by a grant to Dr. Ozen from the Rheumatology Research Foundation. Dr. Galloway reported having no relevant disclosures.

Boston dietitian Katarina Mollo, MEd, RDN, LDN, has virtually no memory of life without celiac disease (CD). Diagnosed at age 4, Dr. Mollo has been on a gluten-free diet for 41 years, which she says has kept her healthy and may also be why she hasn’t developed other autoimmune diseases. It’s also played a part in her thinking about screening patients with CD.

“I think [physicians] should definitely be screening people with celiac disease for autoimmune disorders, especially if they see things like anemia or if a child has dropped on the growth chart and has nutrient deficiencies,” said Dr. Mollo, whose daughter also has the disease. “I would recommend that they see someone who specializes in celiac disease so they can get monitored and have regular follow-up checks for nutrient deficiencies and other autoimmune disorders.”

Dr. Mollo’s views on screening are echoed by many CD specialists and physicians, who cite multiple studies that have found that people with the disease face higher risks for diabetes, thyroid conditions, arthritis, and other autoimmune disorders.

Gastroenterologist Alessio Fasano, MD, with Massachusetts General Hospital, Boston, said there has been a “shift in the paradigm in thinking” about cross-screening for CD and autoimmune disorders. As result, he believes the answer to the question of whether to routinely do so is a no-brainer.

“The bottom line is, if you have CD, it [should be] routine that during your annual follow-ups you check for the possibility of the onset of other autoimmune disease. And people with other autoimmune diseases, like type 1 diabetes, should also be screened for CD because of the comorbidity,” said Dr. Fasano, professor of pediatrics and gastroenterology at Harvard Medical School and professor of nutrition at the Harvard School of Public Health, both in Boston. “This is what we call good clinical practice.”
 

Screening, despite lack of consensus guidelines

Other CD specialists differ on the need for universal cross-screening but agree that, at least in some cases, people with one autoimmune disorder should be tested for others.

Jolanda Denham, MD, a pediatric gastroenterologist affiliated with Nemours Children’s Hospital in Orlando, routinely recommends that her patients with CD be screened for certain autoimmune disorders – such as type 1 diabetes and autoimmune thyroid and liver diseases – even though medical organizations have not developed clear consensus or standard guidelines on cross-screening.

“There currently is no evidence to support the screening of celiac patients for all autoimmune and rheumatologic disorders,” she said. “It is true that celiac disease is an autoimmune disorder, and as such, there is a definite increased risk of these disorders in patients with celiac disease and vice versa.”

Echoing Dr. Denham, New York–based gastroenterologist Benjamin Lebwohl, MD, president of the Society for the Study of Celiac Disease, urges physicians to look beyond consensus guidelines and to err on the side of caution and make the best decisions for their patients on a case-by-case basis.

“Given the increased risk of certain autoimmune conditions in people with celiac disease, it behooves physicians to have a low threshold to evaluate for these conditions if any suggestive symptoms are present,” said Dr. Lebwohl, director of clinical research at the Celiac Disease Center at Columbia University, New York.

“Whether to screen for these conditions among people who are entirely without symptoms is less certain, and there is no consensus on that. But it is reasonable and common to include some basic tests with annual blood work, such as thyroid function and a liver profile, since both autoimmune thyroid disease and autoimmune liver disease can be silent early on and the patient would potentially benefit from identification and treatment of these conditions,” he said.

The American Diabetes Association and the International Society of Pediatric and Adolescent Diabetes do recommend that people with diabetes be screened for CD years after diagnosis, noted Robert Rapaport, MD, a pediatric endocrinologist, with Kravis Children’s Hospital, New York. But in a study published in 2021, he and colleagues found that this wasn’t occurring, which prompted them to recommend yearly screening.

“There is a consensus that in children with type 1 diabetes, we screen them for other autoimmune disorders, specifically for thyroid disease and celiac disease,” said Dr. Rapaport, who is also Emma Elizabeth Sullivan Professor of Pediatric Endocrinology and Diabetes at Icahn School of Medicine at Mount Sinai, New York. “But there is no consensus going the other way – for patients with celiac disease, what other autoimmune conditions they should be screened for.”

This hasn’t kept some doctors from extending cross-screening efforts to their patients.

“At our center, we screen ... for thyroid disease and autoimmune liver disease as part of routine healthcare maintenance for our celiac disease patients. We discuss symptoms of diabetes and send screening with [hemoglobin] A1c for anyone who has symptoms,” said Lui Edwin, MD, a pediatric gastroenterologist with Children’s Hospital Colorado, Aurora, and director of the Colorado Center for Celiac Disease, who delivered a lecture on CD-autoimmune screening at the International Celiac Disease Symposium in October.

“It is definitely worth screening for celiac disease in [those with] other autoimmune disorders,” Dr. Edwin added.

“The symptoms can be very heterogeneous. Diagnosing and treating celiac disease can make a huge impact with respect to symptoms, quality of life, and preventing disease-related complications,” he said.
 

Mounting evidence linking CD to autoimmune disorders

Many studies have linked CD to a variety of other autoimmune disorders. The association could be due to common genetic factors or because CD might lead to such conditions. Researchers have found that people diagnosed with CD later in life are more likely to develop other autoimmune disorders.

Going gluten free has preventive advantages

In a landmark 2012 study, researchers with the Celiac Disease Center at Columbia University stopped short of recommending routine screening for the general public or asymptomatic individuals in high-prevalence groups. But they concluded that more screening of symptomatic individuals – and close relatives – would speed treatment for those with more than one autoimmune disorder.

They also noted that some studies have found that a gluten-free diet might help prevent the development of other autoimmune disorders.

Marisa Gallant Stahl, MD, a gastroenterologist with Children’s Hospital Colorado, agreed that it is important that physicians keep gluten-free diets in mind when determining which patients to cross-screen.

“The literature is mixed, but some studies suggest that treating celiac disease with a gluten-free diet actually augments the treatment and control of other autoimmune disorders [and] adherence to a gluten-free diet does reduce the risk of cancer associated with celiac disease,” she said.

Dr. Denham agreed. “Strict adherence to a gluten-free diet definitely protects against the development of enteropathy-associated T-cell lymphoma but may be protective against non-Hodgkin’s lymphoma and adenocarcinoma of the small intestine as well. All three are associated with long-term nonadherence to a gluten-free diet.”

She also noted that a gluten-free diet may help people with CD manage other autoimmune disorders, which can be complicated by CD.

“Good control of celiac disease will help prevent complications that can worsen symptoms and outcomes of concomitant autoimmune and rheumatologic disorders,” she said.
 

Other factors to consider

Dr. Fasano added that autoimmune disorders can be complicated by CD in cases in which oral medications or healthful foods are not properly absorbed in the intestines.

“For example, with Hashimoto’s disease, if you have hormone replacement with oral treatments and your intestines are not 100% functional because you have inflammation, then you may have a problem [with] the absorption of medications like levothyroxine,” he said.

“It’s the same story with diabetes. You don’t take insulin by mouth, but glucose [control] strongly depends on several factors, mostly what comes from the diet, and if it’s erratic, that can be a problem. ... So, the treatment of autoimmune diseases can be influenced by celiac disease,” he said.

In addition, Dr. Fasano and others believe that people with CD and other autoimmune disorders should be managed by a team of experts who can personalize the care on the basis of specific needs of the individual patient. These should include specialists, dietitians, mental health counselors, and family social workers.

“It has to be a multidisciplinary approach to maintain the good health of an individual,” Dr. Fasano said. “Celiac disease is the quintessential example in which the primary care physician needs to be the quarterback of the team, the patient is active in his or her health, and [specialists] not only deliver personalized care but also preventive intervention, particularly the prevention of comorbidities.”

Financial disclosures for those quoted in this article were not available at the time of publication.

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

Boston dietitian Katarina Mollo, MEd, RDN, LDN, has virtually no memory of life without celiac disease (CD). Diagnosed at age 4, Dr. Mollo has been on a gluten-free diet for 41 years, which she says has kept her healthy and may also be why she hasn’t developed other autoimmune diseases. It’s also played a part in her thinking about screening patients with CD.

“I think [physicians] should definitely be screening people with celiac disease for autoimmune disorders, especially if they see things like anemia or if a child has dropped on the growth chart and has nutrient deficiencies,” said Dr. Mollo, whose daughter also has the disease. “I would recommend that they see someone who specializes in celiac disease so they can get monitored and have regular follow-up checks for nutrient deficiencies and other autoimmune disorders.”

Dr. Mollo’s views on screening are echoed by many CD specialists and physicians, who cite multiple studies that have found that people with the disease face higher risks for diabetes, thyroid conditions, arthritis, and other autoimmune disorders.

Gastroenterologist Alessio Fasano, MD, with Massachusetts General Hospital, Boston, said there has been a “shift in the paradigm in thinking” about cross-screening for CD and autoimmune disorders. As result, he believes the answer to the question of whether to routinely do so is a no-brainer.

“The bottom line is, if you have CD, it [should be] routine that during your annual follow-ups you check for the possibility of the onset of other autoimmune disease. And people with other autoimmune diseases, like type 1 diabetes, should also be screened for CD because of the comorbidity,” said Dr. Fasano, professor of pediatrics and gastroenterology at Harvard Medical School and professor of nutrition at the Harvard School of Public Health, both in Boston. “This is what we call good clinical practice.”
 

Screening, despite lack of consensus guidelines

Other CD specialists differ on the need for universal cross-screening but agree that, at least in some cases, people with one autoimmune disorder should be tested for others.

Jolanda Denham, MD, a pediatric gastroenterologist affiliated with Nemours Children’s Hospital in Orlando, routinely recommends that her patients with CD be screened for certain autoimmune disorders – such as type 1 diabetes and autoimmune thyroid and liver diseases – even though medical organizations have not developed clear consensus or standard guidelines on cross-screening.

“There currently is no evidence to support the screening of celiac patients for all autoimmune and rheumatologic disorders,” she said. “It is true that celiac disease is an autoimmune disorder, and as such, there is a definite increased risk of these disorders in patients with celiac disease and vice versa.”

Echoing Dr. Denham, New York–based gastroenterologist Benjamin Lebwohl, MD, president of the Society for the Study of Celiac Disease, urges physicians to look beyond consensus guidelines and to err on the side of caution and make the best decisions for their patients on a case-by-case basis.

“Given the increased risk of certain autoimmune conditions in people with celiac disease, it behooves physicians to have a low threshold to evaluate for these conditions if any suggestive symptoms are present,” said Dr. Lebwohl, director of clinical research at the Celiac Disease Center at Columbia University, New York.

“Whether to screen for these conditions among people who are entirely without symptoms is less certain, and there is no consensus on that. But it is reasonable and common to include some basic tests with annual blood work, such as thyroid function and a liver profile, since both autoimmune thyroid disease and autoimmune liver disease can be silent early on and the patient would potentially benefit from identification and treatment of these conditions,” he said.

The American Diabetes Association and the International Society of Pediatric and Adolescent Diabetes do recommend that people with diabetes be screened for CD years after diagnosis, noted Robert Rapaport, MD, a pediatric endocrinologist, with Kravis Children’s Hospital, New York. But in a study published in 2021, he and colleagues found that this wasn’t occurring, which prompted them to recommend yearly screening.

“There is a consensus that in children with type 1 diabetes, we screen them for other autoimmune disorders, specifically for thyroid disease and celiac disease,” said Dr. Rapaport, who is also Emma Elizabeth Sullivan Professor of Pediatric Endocrinology and Diabetes at Icahn School of Medicine at Mount Sinai, New York. “But there is no consensus going the other way – for patients with celiac disease, what other autoimmune conditions they should be screened for.”

This hasn’t kept some doctors from extending cross-screening efforts to their patients.

“At our center, we screen ... for thyroid disease and autoimmune liver disease as part of routine healthcare maintenance for our celiac disease patients. We discuss symptoms of diabetes and send screening with [hemoglobin] A1c for anyone who has symptoms,” said Lui Edwin, MD, a pediatric gastroenterologist with Children’s Hospital Colorado, Aurora, and director of the Colorado Center for Celiac Disease, who delivered a lecture on CD-autoimmune screening at the International Celiac Disease Symposium in October.

“It is definitely worth screening for celiac disease in [those with] other autoimmune disorders,” Dr. Edwin added.

“The symptoms can be very heterogeneous. Diagnosing and treating celiac disease can make a huge impact with respect to symptoms, quality of life, and preventing disease-related complications,” he said.
 

Mounting evidence linking CD to autoimmune disorders

Many studies have linked CD to a variety of other autoimmune disorders. The association could be due to common genetic factors or because CD might lead to such conditions. Researchers have found that people diagnosed with CD later in life are more likely to develop other autoimmune disorders.

Going gluten free has preventive advantages

In a landmark 2012 study, researchers with the Celiac Disease Center at Columbia University stopped short of recommending routine screening for the general public or asymptomatic individuals in high-prevalence groups. But they concluded that more screening of symptomatic individuals – and close relatives – would speed treatment for those with more than one autoimmune disorder.

They also noted that some studies have found that a gluten-free diet might help prevent the development of other autoimmune disorders.

Marisa Gallant Stahl, MD, a gastroenterologist with Children’s Hospital Colorado, agreed that it is important that physicians keep gluten-free diets in mind when determining which patients to cross-screen.

“The literature is mixed, but some studies suggest that treating celiac disease with a gluten-free diet actually augments the treatment and control of other autoimmune disorders [and] adherence to a gluten-free diet does reduce the risk of cancer associated with celiac disease,” she said.

Dr. Denham agreed. “Strict adherence to a gluten-free diet definitely protects against the development of enteropathy-associated T-cell lymphoma but may be protective against non-Hodgkin’s lymphoma and adenocarcinoma of the small intestine as well. All three are associated with long-term nonadherence to a gluten-free diet.”

She also noted that a gluten-free diet may help people with CD manage other autoimmune disorders, which can be complicated by CD.

“Good control of celiac disease will help prevent complications that can worsen symptoms and outcomes of concomitant autoimmune and rheumatologic disorders,” she said.