MDedge Family Medicine

TOPLINE:

Patients with cutaneous lupus erythematosus (CLE) experienced improved symptoms with iberdomide, a cereblon modulator, added to standard lupus medications, particularly in subacute and chronic cases.

METHODOLOGY:

• Researchers conducted a randomized phase 2 trial to evaluate the efficacy and safety of iberdomide in 288 patients with CLE (mean age, 45 years; 97% women). Iberdomide is a cereblon modulator, which results in degradation of two transcription factors of immune cell development and homeostasis — Ikaros and Aiolos — that have been implicated in the genetic predisposition of systemic lupus.
• CLE Disease Area and Severity Index Activity (CLASI-A) endpoints included mean percent change from baseline and ≥ 50% reduction from baseline (CLASI-50), which were evaluated in all patients with baseline CLASI-A scores ≥ 8 and by CLE subtypes (acute, subacute, and chronic).
• At baseline, 56% of patients had acute CLE, 29% had chronic CLE, and 16% had subacute CLE; 28% of patients had a baseline CLASI-A score ≥ 8.
• Patients were randomly assigned to receive oral iberdomide (0.45 mg, 0.30 mg, 0.15 mg, or placebo daily) for 24 weeks while continuing standard lupus medications. At week 24, patients on placebo were rerandomized to iberdomide 0.45 mg or 0.30 mg once a day, while those on iberdomide continued their assigned dose through week 52.

TAKEAWAY:

• Among patients with baseline CLASI-A ≥ 8, the mean change in CLASI-A score from baseline at week 24 was −66.7% for those on iberdomide 0.45 mg vs −54.2% for placebo (P = .295).
• At week 24, patients with subacute CLE showed a significantly greater mean percent change from baseline in CLASI-A with iberdomide 0.45 mg vs placebo (−90.5% vs −51.2%; P = .007), while no significant differences were observed with the 0.45-mg dose vs placebo in patients with chronic or acute CLE.
• Overall, CLASI-50 responses were not significantly different among those on 0.45 mg vs placebo (55.6% vs 44.6%). The proportions of patients achieving CLASI-50 at week 24 were significantly greater for iberdomide 0.45 mg vs placebo for those with subacute CLE (91.7% vs 52.9%; P = .035) and chronic CLE (62.1% vs 27.8%; P = .029), but not for those with baseline CLASI-A ≥ 8 (66.7% vs 50%).
• More than 80% of patients had treatment-emergent adverse events (TEAEs), which were mostly mild to moderate. Over 2 years, the most common were urinary tract infections, upper respiratory tract infections, neutropenia, and nasopharyngitis. TEAEs leading to iberdomide discontinuation in one or more patients were neutropenia (n = 7), rash (n = 7), increased hepatic enzymes (n = 4), and deep vein thrombosis (n = 3).

IN PRACTICE:

“Data from this phase 2 trial of iberdomide in patients with SLE suggest that a greater proportion of patients with subacute or chronic CLE who received the higher dose of 0.45 mg iberdomide achieved CLASI-50 vs placebo. For the overall population, CLASI-50 response was not significantly different between treatment groups at week 24, partly due to a high placebo response that may have been driven by patients with acute CLE,” the authors wrote.

SOURCE:

The study was led by Victoria P. Werth, MD, of the University of Pennsylvania and the Veteran’s Administration Medical Center, both in Philadelphia, and was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The study included small patient subgroups for different CLE subtypes, which may affect the generalizability of the findings. CLE subtype was determined by the investigator without additional photographic adjudication. Additionally, the use of background lupus medications could have influenced the placebo group’s response, limiting the ability to observe the treatment effect of iberdomide monotherapy.

DISCLOSURES:

The study was funded by Bristol-Myers Squibb. Six authors reported being employed by Bristol-Myers Squibb, and several others reported consultancy and research support from various sources including Bristol-Myers Squibb.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with cutaneous lupus erythematosus (CLE) experienced improved symptoms with iberdomide, a cereblon modulator, added to standard lupus medications, particularly in subacute and chronic cases.

METHODOLOGY:

• Researchers conducted a randomized phase 2 trial to evaluate the efficacy and safety of iberdomide in 288 patients with CLE (mean age, 45 years; 97% women). Iberdomide is a cereblon modulator, which results in degradation of two transcription factors of immune cell development and homeostasis — Ikaros and Aiolos — that have been implicated in the genetic predisposition of systemic lupus.
• CLE Disease Area and Severity Index Activity (CLASI-A) endpoints included mean percent change from baseline and ≥ 50% reduction from baseline (CLASI-50), which were evaluated in all patients with baseline CLASI-A scores ≥ 8 and by CLE subtypes (acute, subacute, and chronic).
• At baseline, 56% of patients had acute CLE, 29% had chronic CLE, and 16% had subacute CLE; 28% of patients had a baseline CLASI-A score ≥ 8.
• Patients were randomly assigned to receive oral iberdomide (0.45 mg, 0.30 mg, 0.15 mg, or placebo daily) for 24 weeks while continuing standard lupus medications. At week 24, patients on placebo were rerandomized to iberdomide 0.45 mg or 0.30 mg once a day, while those on iberdomide continued their assigned dose through week 52.

TAKEAWAY:

• Among patients with baseline CLASI-A ≥ 8, the mean change in CLASI-A score from baseline at week 24 was −66.7% for those on iberdomide 0.45 mg vs −54.2% for placebo (P = .295).
• At week 24, patients with subacute CLE showed a significantly greater mean percent change from baseline in CLASI-A with iberdomide 0.45 mg vs placebo (−90.5% vs −51.2%; P = .007), while no significant differences were observed with the 0.45-mg dose vs placebo in patients with chronic or acute CLE.
• Overall, CLASI-50 responses were not significantly different among those on 0.45 mg vs placebo (55.6% vs 44.6%). The proportions of patients achieving CLASI-50 at week 24 were significantly greater for iberdomide 0.45 mg vs placebo for those with subacute CLE (91.7% vs 52.9%; P = .035) and chronic CLE (62.1% vs 27.8%; P = .029), but not for those with baseline CLASI-A ≥ 8 (66.7% vs 50%).
• More than 80% of patients had treatment-emergent adverse events (TEAEs), which were mostly mild to moderate. Over 2 years, the most common were urinary tract infections, upper respiratory tract infections, neutropenia, and nasopharyngitis. TEAEs leading to iberdomide discontinuation in one or more patients were neutropenia (n = 7), rash (n = 7), increased hepatic enzymes (n = 4), and deep vein thrombosis (n = 3).

IN PRACTICE:

“Data from this phase 2 trial of iberdomide in patients with SLE suggest that a greater proportion of patients with subacute or chronic CLE who received the higher dose of 0.45 mg iberdomide achieved CLASI-50 vs placebo. For the overall population, CLASI-50 response was not significantly different between treatment groups at week 24, partly due to a high placebo response that may have been driven by patients with acute CLE,” the authors wrote.

SOURCE:

The study was led by Victoria P. Werth, MD, of the University of Pennsylvania and the Veteran’s Administration Medical Center, both in Philadelphia, and was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The study included small patient subgroups for different CLE subtypes, which may affect the generalizability of the findings. CLE subtype was determined by the investigator without additional photographic adjudication. Additionally, the use of background lupus medications could have influenced the placebo group’s response, limiting the ability to observe the treatment effect of iberdomide monotherapy.

DISCLOSURES:

The study was funded by Bristol-Myers Squibb. Six authors reported being employed by Bristol-Myers Squibb, and several others reported consultancy and research support from various sources including Bristol-Myers Squibb.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with cutaneous lupus erythematosus (CLE) experienced improved symptoms with iberdomide, a cereblon modulator, added to standard lupus medications, particularly in subacute and chronic cases.

METHODOLOGY:

• Researchers conducted a randomized phase 2 trial to evaluate the efficacy and safety of iberdomide in 288 patients with CLE (mean age, 45 years; 97% women). Iberdomide is a cereblon modulator, which results in degradation of two transcription factors of immune cell development and homeostasis — Ikaros and Aiolos — that have been implicated in the genetic predisposition of systemic lupus.
• CLE Disease Area and Severity Index Activity (CLASI-A) endpoints included mean percent change from baseline and ≥ 50% reduction from baseline (CLASI-50), which were evaluated in all patients with baseline CLASI-A scores ≥ 8 and by CLE subtypes (acute, subacute, and chronic).
• At baseline, 56% of patients had acute CLE, 29% had chronic CLE, and 16% had subacute CLE; 28% of patients had a baseline CLASI-A score ≥ 8.
• Patients were randomly assigned to receive oral iberdomide (0.45 mg, 0.30 mg, 0.15 mg, or placebo daily) for 24 weeks while continuing standard lupus medications. At week 24, patients on placebo were rerandomized to iberdomide 0.45 mg or 0.30 mg once a day, while those on iberdomide continued their assigned dose through week 52.

TAKEAWAY:

• Among patients with baseline CLASI-A ≥ 8, the mean change in CLASI-A score from baseline at week 24 was −66.7% for those on iberdomide 0.45 mg vs −54.2% for placebo (P = .295).
• At week 24, patients with subacute CLE showed a significantly greater mean percent change from baseline in CLASI-A with iberdomide 0.45 mg vs placebo (−90.5% vs −51.2%; P = .007), while no significant differences were observed with the 0.45-mg dose vs placebo in patients with chronic or acute CLE.
• Overall, CLASI-50 responses were not significantly different among those on 0.45 mg vs placebo (55.6% vs 44.6%). The proportions of patients achieving CLASI-50 at week 24 were significantly greater for iberdomide 0.45 mg vs placebo for those with subacute CLE (91.7% vs 52.9%; P = .035) and chronic CLE (62.1% vs 27.8%; P = .029), but not for those with baseline CLASI-A ≥ 8 (66.7% vs 50%).
• More than 80% of patients had treatment-emergent adverse events (TEAEs), which were mostly mild to moderate. Over 2 years, the most common were urinary tract infections, upper respiratory tract infections, neutropenia, and nasopharyngitis. TEAEs leading to iberdomide discontinuation in one or more patients were neutropenia (n = 7), rash (n = 7), increased hepatic enzymes (n = 4), and deep vein thrombosis (n = 3).

IN PRACTICE:

“Data from this phase 2 trial of iberdomide in patients with SLE suggest that a greater proportion of patients with subacute or chronic CLE who received the higher dose of 0.45 mg iberdomide achieved CLASI-50 vs placebo. For the overall population, CLASI-50 response was not significantly different between treatment groups at week 24, partly due to a high placebo response that may have been driven by patients with acute CLE,” the authors wrote.

SOURCE:

The study was led by Victoria P. Werth, MD, of the University of Pennsylvania and the Veteran’s Administration Medical Center, both in Philadelphia, and was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The study included small patient subgroups for different CLE subtypes, which may affect the generalizability of the findings. CLE subtype was determined by the investigator without additional photographic adjudication. Additionally, the use of background lupus medications could have influenced the placebo group’s response, limiting the ability to observe the treatment effect of iberdomide monotherapy.

DISCLOSURES:

The study was funded by Bristol-Myers Squibb. Six authors reported being employed by Bristol-Myers Squibb, and several others reported consultancy and research support from various sources including Bristol-Myers Squibb.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

BOSTON — Social adversity is associated with worse survival among patients with pulmonary hypertension (PH), according to a new retrospective study of a New York City population. Among HIV+ patients with heart failure, PH was associated with about a threefold increase in all-cause mortality, but that risk increased to about sevenfold when social adversity, identified by a licensed social worker, was also present.

A sub-analysis of both HIV+ and HIV– patients showed worse mortality outcomes with social adversity in both groups.

“Almost the majority of patients that we treat have either some social adversity or no insurance or are undocumented, so as a group of residents, we decided to study the impact of these factors on their health and the care that can be provided. We started using the two cohorts and now we keep it going with every new resident,” said Luca Biavati, MD, who presented the study at the CHEST Annual Meeting.

“The presence of any form of socioeconomic disadvantage is negatively impacting care and for a large part of the population, there are some factors that could probably be addressed by either an institutional or hospital policy,” said Dr. Biavati, who is an internal medicine resident at Jacobi Medical Center, New York.

Other factors are more difficult to address, such as lack of education. “[Some patients] don’t understand the gravity of their issue and medical condition until it’s too late, and then they’re not fit enough for the treatment, or just because of the social situation, they cannot qualify for advanced therapies,” said Dr. Biavati.

The researchers established two cohorts: One consisting of patients with HIV and heart failure who may or may not have had PH and one comprising patients with PH with or without HIV and heart failure. In the HIV/heart failure group, PH without social adversity was associated with a nearly threefold increase in all-cause mortality (hazard ratio [HR], 2.83; P = .004), whereas PH with social adversity was linked to a more than sevenfold increase in all-cause mortality (HR, 7.14; P < .001). Social adversity without PA was associated with a more than fourfold increase (HR, 4.47; P < .001).

Within the PH cohort, social adversity was associated with lower survival (P < .001). When the researchers broke down the results by types of social adversity, they found statistically significant relationships between greater mortality risk and economic instability within the HIV+ population (HR, 2.59; P = .040), transportation issues within the HIV– population (HR, 12.8; P < .001), and lack of social or family support within both the HIV– (HR, 5.49; P < .001) and the HIV+ population (HR, 2.03; P = .028). 

The research has prompted interventions, which are now being studied at the institution, according to Dr. Biavati. “We have a policy of giving medications in bags when we discharge a patient with a social adversity. We literally go to the pharmacy, bring up the bag of medication, and we [put it] in their hands before they leave the hospital. They get a 1- or 3-month supply, depending on the medication, and then we usually discharge them with a clinical appointment already scheduled with either a pulmonary or primary care provider, and we usually call them before every appointment to confirm that they’re coming. That increases the chances of some success, but there’s still a very long way to go,” said Dr. Biavati.

Dr. Biavati was blinded to the results of the intervention, so he could not report on whether it was working. “But I can tell you that I’ve had busier clinics, so hopefully that means that they’re showing up more,” he said.

The problem is complex, according to Sandeep Jain, MD, who moderated the session. “Social adversity means lack of education. Lack of education means lack of compliance. Lack of compliance means what can you do if people are not taking medications? So it’s all matched together. It’s all lack of education and lack of money, lack of family support. And these drugs they have to take every single day. It’s not that easy. It’s very easy for us to say I had antiretroviral treatment for 6 months. It is almost impossible to continue regular treatment for that long [for a patient with social adversity]. You can’t blame them if they aren’t taking treatments. It’s very difficult for them,” said Dr. Jain.

That underscores the need for interventions that can address the needs of patients with social adversity. “We have to [practice] medicine considering the social situation of the patient and not just the medicine that we study in books. That’s kind of what we are faced with every day. We have therapies, and then life happens. It’s much harder to care for those patients,” said Dr. Biavati.

Dr. Biavati and Dr. Jain reported no relevant financial relationships.
 

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

BOSTON — Social adversity is associated with worse survival among patients with pulmonary hypertension (PH), according to a new retrospective study of a New York City population. Among HIV+ patients with heart failure, PH was associated with about a threefold increase in all-cause mortality, but that risk increased to about sevenfold when social adversity, identified by a licensed social worker, was also present.

A sub-analysis of both HIV+ and HIV– patients showed worse mortality outcomes with social adversity in both groups.

“Almost the majority of patients that we treat have either some social adversity or no insurance or are undocumented, so as a group of residents, we decided to study the impact of these factors on their health and the care that can be provided. We started using the two cohorts and now we keep it going with every new resident,” said Luca Biavati, MD, who presented the study at the CHEST Annual Meeting.

“The presence of any form of socioeconomic disadvantage is negatively impacting care and for a large part of the population, there are some factors that could probably be addressed by either an institutional or hospital policy,” said Dr. Biavati, who is an internal medicine resident at Jacobi Medical Center, New York.

Other factors are more difficult to address, such as lack of education. “[Some patients] don’t understand the gravity of their issue and medical condition until it’s too late, and then they’re not fit enough for the treatment, or just because of the social situation, they cannot qualify for advanced therapies,” said Dr. Biavati.

The researchers established two cohorts: One consisting of patients with HIV and heart failure who may or may not have had PH and one comprising patients with PH with or without HIV and heart failure. In the HIV/heart failure group, PH without social adversity was associated with a nearly threefold increase in all-cause mortality (hazard ratio [HR], 2.83; P = .004), whereas PH with social adversity was linked to a more than sevenfold increase in all-cause mortality (HR, 7.14; P < .001). Social adversity without PA was associated with a more than fourfold increase (HR, 4.47; P < .001).

Within the PH cohort, social adversity was associated with lower survival (P < .001). When the researchers broke down the results by types of social adversity, they found statistically significant relationships between greater mortality risk and economic instability within the HIV+ population (HR, 2.59; P = .040), transportation issues within the HIV– population (HR, 12.8; P < .001), and lack of social or family support within both the HIV– (HR, 5.49; P < .001) and the HIV+ population (HR, 2.03; P = .028). 

The research has prompted interventions, which are now being studied at the institution, according to Dr. Biavati. “We have a policy of giving medications in bags when we discharge a patient with a social adversity. We literally go to the pharmacy, bring up the bag of medication, and we [put it] in their hands before they leave the hospital. They get a 1- or 3-month supply, depending on the medication, and then we usually discharge them with a clinical appointment already scheduled with either a pulmonary or primary care provider, and we usually call them before every appointment to confirm that they’re coming. That increases the chances of some success, but there’s still a very long way to go,” said Dr. Biavati.

Dr. Biavati was blinded to the results of the intervention, so he could not report on whether it was working. “But I can tell you that I’ve had busier clinics, so hopefully that means that they’re showing up more,” he said.

The problem is complex, according to Sandeep Jain, MD, who moderated the session. “Social adversity means lack of education. Lack of education means lack of compliance. Lack of compliance means what can you do if people are not taking medications? So it’s all matched together. It’s all lack of education and lack of money, lack of family support. And these drugs they have to take every single day. It’s not that easy. It’s very easy for us to say I had antiretroviral treatment for 6 months. It is almost impossible to continue regular treatment for that long [for a patient with social adversity]. You can’t blame them if they aren’t taking treatments. It’s very difficult for them,” said Dr. Jain.

That underscores the need for interventions that can address the needs of patients with social adversity. “We have to [practice] medicine considering the social situation of the patient and not just the medicine that we study in books. That’s kind of what we are faced with every day. We have therapies, and then life happens. It’s much harder to care for those patients,” said Dr. Biavati.

Dr. Biavati and Dr. Jain reported no relevant financial relationships.
 

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

BOSTON — Social adversity is associated with worse survival among patients with pulmonary hypertension (PH), according to a new retrospective study of a New York City population. Among HIV+ patients with heart failure, PH was associated with about a threefold increase in all-cause mortality, but that risk increased to about sevenfold when social adversity, identified by a licensed social worker, was also present.

A sub-analysis of both HIV+ and HIV– patients showed worse mortality outcomes with social adversity in both groups.

“Almost the majority of patients that we treat have either some social adversity or no insurance or are undocumented, so as a group of residents, we decided to study the impact of these factors on their health and the care that can be provided. We started using the two cohorts and now we keep it going with every new resident,” said Luca Biavati, MD, who presented the study at the CHEST Annual Meeting.

“The presence of any form of socioeconomic disadvantage is negatively impacting care and for a large part of the population, there are some factors that could probably be addressed by either an institutional or hospital policy,” said Dr. Biavati, who is an internal medicine resident at Jacobi Medical Center, New York.

Other factors are more difficult to address, such as lack of education. “[Some patients] don’t understand the gravity of their issue and medical condition until it’s too late, and then they’re not fit enough for the treatment, or just because of the social situation, they cannot qualify for advanced therapies,” said Dr. Biavati.

The researchers established two cohorts: One consisting of patients with HIV and heart failure who may or may not have had PH and one comprising patients with PH with or without HIV and heart failure. In the HIV/heart failure group, PH without social adversity was associated with a nearly threefold increase in all-cause mortality (hazard ratio [HR], 2.83; P = .004), whereas PH with social adversity was linked to a more than sevenfold increase in all-cause mortality (HR, 7.14; P < .001). Social adversity without PA was associated with a more than fourfold increase (HR, 4.47; P < .001).

Within the PH cohort, social adversity was associated with lower survival (P < .001). When the researchers broke down the results by types of social adversity, they found statistically significant relationships between greater mortality risk and economic instability within the HIV+ population (HR, 2.59; P = .040), transportation issues within the HIV– population (HR, 12.8; P < .001), and lack of social or family support within both the HIV– (HR, 5.49; P < .001) and the HIV+ population (HR, 2.03; P = .028). 

The research has prompted interventions, which are now being studied at the institution, according to Dr. Biavati. “We have a policy of giving medications in bags when we discharge a patient with a social adversity. We literally go to the pharmacy, bring up the bag of medication, and we [put it] in their hands before they leave the hospital. They get a 1- or 3-month supply, depending on the medication, and then we usually discharge them with a clinical appointment already scheduled with either a pulmonary or primary care provider, and we usually call them before every appointment to confirm that they’re coming. That increases the chances of some success, but there’s still a very long way to go,” said Dr. Biavati.

Dr. Biavati was blinded to the results of the intervention, so he could not report on whether it was working. “But I can tell you that I’ve had busier clinics, so hopefully that means that they’re showing up more,” he said.

The problem is complex, according to Sandeep Jain, MD, who moderated the session. “Social adversity means lack of education. Lack of education means lack of compliance. Lack of compliance means what can you do if people are not taking medications? So it’s all matched together. It’s all lack of education and lack of money, lack of family support. And these drugs they have to take every single day. It’s not that easy. It’s very easy for us to say I had antiretroviral treatment for 6 months. It is almost impossible to continue regular treatment for that long [for a patient with social adversity]. You can’t blame them if they aren’t taking treatments. It’s very difficult for them,” said Dr. Jain.

That underscores the need for interventions that can address the needs of patients with social adversity. “We have to [practice] medicine considering the social situation of the patient and not just the medicine that we study in books. That’s kind of what we are faced with every day. We have therapies, and then life happens. It’s much harder to care for those patients,” said Dr. Biavati.

Dr. Biavati and Dr. Jain reported no relevant financial relationships.
 

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

TOPLINE: 

Virtual yoga classes significantly reduced chronic low back pain intensity and improved back-related function in health system employees. Improvements were sustained at 24 weeks, with reduced pain medication use and better sleep quality.

METHODOLOGY:

• A single-blinded, 24-week, 2-arm, randomized clinical trial was conducted from May 3, 2022, through May 23, 2023, comparing live-streamed yoga classes with a wait-list control among adults with chronic low back pain.
• A total of 140 participants aged 18-64 years with chronic low back pain were recruited from the Cleveland Clinic Employee Health Plan.
• Inclusion criteria included a mean low back pain intensity score of at least 4 on an 11-point numerical rating scale and daily back pain interference about half or more of the days.
• The intervention consisted of 12 consecutive weekly, 60-minute, virtual, live-streamed hatha yoga group classes.

Coprimary outcomes were mean pain intensity in the previous week on the 11-point numerical rating scale and back-related function as assessed using the 23-point modified Roland Morris Disability Questionnaire at 12 weeks.

TAKEAWAY:

• Participants in the virtual yoga group showed greater reductions in mean pain intensity at 12 weeks (mean change, –1.5 points; P < .001) and 24 weeks (mean change, –2.3 points; P < .001) compared to the wait-list control group.
• Back-related function improved significantly in the virtual yoga group at 12 weeks (mean change, –2.8 points; P < .001) and 24 weeks (mean change, –4.6 points; P < .001), compared with the control group.
• Virtual yoga participants reported 21.2 percentage points less use of any analgesic medication during the past week at 24 weeks, compared with the control group.
• Sleep quality improved more in the virtual yoga group at 12 weeks (mean change, 0.4 points; P = .008) and 24 weeks (mean change, 0.4 points; P = .005), compared with the control group.

IN PRACTICE:

“Given the demonstrated noninferiority of yoga to physical therapy, structured virtual yoga programs and physical therapy are reasonable choices for patients with [chronic low back pain] depending on accessibility, cost, and patient preference. These findings support the call by the National Academy of Medicine for increased evidenced-based pain treatments that can be disseminated via technology-based platforms,” wrote the authors of the study.

SOURCE:

The study was led by Hallie Tankha, PhD, Cleveland Clinic in Ohio. It was published online on November 1, 2024, in JAMA Network Open.

LIMITATIONS: 

The study had a low adherence rate, with only 36.6% of participants attending at least 50% of the yoga classes. There was also a higher rate of missing data in the yoga group compared to the control group. The study did not include a longer-term follow-up assessment beyond 24 weeks.

DISCLOSURES:

This study was supported by grants from Cleveland Clinic Healthcare Delivery and Implementation Science Center. One coauthor disclosed receiving personal fees from the Blue Cross Blue Shield Association. Eric Roseen, DC, PhD, reported receiving grants from the National Institutes of Health National Center for Complementary and Integrative Health. One coauthor disclosed receiving personal fees from UpToDate and grants from NCCIH related to yoga and tai chi for treatment of pain. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE: 

Virtual yoga classes significantly reduced chronic low back pain intensity and improved back-related function in health system employees. Improvements were sustained at 24 weeks, with reduced pain medication use and better sleep quality.

METHODOLOGY:

• A single-blinded, 24-week, 2-arm, randomized clinical trial was conducted from May 3, 2022, through May 23, 2023, comparing live-streamed yoga classes with a wait-list control among adults with chronic low back pain.
• A total of 140 participants aged 18-64 years with chronic low back pain were recruited from the Cleveland Clinic Employee Health Plan.
• Inclusion criteria included a mean low back pain intensity score of at least 4 on an 11-point numerical rating scale and daily back pain interference about half or more of the days.
• The intervention consisted of 12 consecutive weekly, 60-minute, virtual, live-streamed hatha yoga group classes.

Coprimary outcomes were mean pain intensity in the previous week on the 11-point numerical rating scale and back-related function as assessed using the 23-point modified Roland Morris Disability Questionnaire at 12 weeks.

TAKEAWAY:

• Participants in the virtual yoga group showed greater reductions in mean pain intensity at 12 weeks (mean change, –1.5 points; P < .001) and 24 weeks (mean change, –2.3 points; P < .001) compared to the wait-list control group.
• Back-related function improved significantly in the virtual yoga group at 12 weeks (mean change, –2.8 points; P < .001) and 24 weeks (mean change, –4.6 points; P < .001), compared with the control group.
• Virtual yoga participants reported 21.2 percentage points less use of any analgesic medication during the past week at 24 weeks, compared with the control group.
• Sleep quality improved more in the virtual yoga group at 12 weeks (mean change, 0.4 points; P = .008) and 24 weeks (mean change, 0.4 points; P = .005), compared with the control group.

IN PRACTICE:

“Given the demonstrated noninferiority of yoga to physical therapy, structured virtual yoga programs and physical therapy are reasonable choices for patients with [chronic low back pain] depending on accessibility, cost, and patient preference. These findings support the call by the National Academy of Medicine for increased evidenced-based pain treatments that can be disseminated via technology-based platforms,” wrote the authors of the study.

SOURCE:

The study was led by Hallie Tankha, PhD, Cleveland Clinic in Ohio. It was published online on November 1, 2024, in JAMA Network Open.

LIMITATIONS: 

The study had a low adherence rate, with only 36.6% of participants attending at least 50% of the yoga classes. There was also a higher rate of missing data in the yoga group compared to the control group. The study did not include a longer-term follow-up assessment beyond 24 weeks.

DISCLOSURES:

This study was supported by grants from Cleveland Clinic Healthcare Delivery and Implementation Science Center. One coauthor disclosed receiving personal fees from the Blue Cross Blue Shield Association. Eric Roseen, DC, PhD, reported receiving grants from the National Institutes of Health National Center for Complementary and Integrative Health. One coauthor disclosed receiving personal fees from UpToDate and grants from NCCIH related to yoga and tai chi for treatment of pain. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE: 

Virtual yoga classes significantly reduced chronic low back pain intensity and improved back-related function in health system employees. Improvements were sustained at 24 weeks, with reduced pain medication use and better sleep quality.

METHODOLOGY:

• A single-blinded, 24-week, 2-arm, randomized clinical trial was conducted from May 3, 2022, through May 23, 2023, comparing live-streamed yoga classes with a wait-list control among adults with chronic low back pain.
• A total of 140 participants aged 18-64 years with chronic low back pain were recruited from the Cleveland Clinic Employee Health Plan.
• Inclusion criteria included a mean low back pain intensity score of at least 4 on an 11-point numerical rating scale and daily back pain interference about half or more of the days.
• The intervention consisted of 12 consecutive weekly, 60-minute, virtual, live-streamed hatha yoga group classes.

Coprimary outcomes were mean pain intensity in the previous week on the 11-point numerical rating scale and back-related function as assessed using the 23-point modified Roland Morris Disability Questionnaire at 12 weeks.

TAKEAWAY:

• Participants in the virtual yoga group showed greater reductions in mean pain intensity at 12 weeks (mean change, –1.5 points; P < .001) and 24 weeks (mean change, –2.3 points; P < .001) compared to the wait-list control group.
• Back-related function improved significantly in the virtual yoga group at 12 weeks (mean change, –2.8 points; P < .001) and 24 weeks (mean change, –4.6 points; P < .001), compared with the control group.
• Virtual yoga participants reported 21.2 percentage points less use of any analgesic medication during the past week at 24 weeks, compared with the control group.
• Sleep quality improved more in the virtual yoga group at 12 weeks (mean change, 0.4 points; P = .008) and 24 weeks (mean change, 0.4 points; P = .005), compared with the control group.

IN PRACTICE:

“Given the demonstrated noninferiority of yoga to physical therapy, structured virtual yoga programs and physical therapy are reasonable choices for patients with [chronic low back pain] depending on accessibility, cost, and patient preference. These findings support the call by the National Academy of Medicine for increased evidenced-based pain treatments that can be disseminated via technology-based platforms,” wrote the authors of the study.

SOURCE:

The study was led by Hallie Tankha, PhD, Cleveland Clinic in Ohio. It was published online on November 1, 2024, in JAMA Network Open.

LIMITATIONS: 

The study had a low adherence rate, with only 36.6% of participants attending at least 50% of the yoga classes. There was also a higher rate of missing data in the yoga group compared to the control group. The study did not include a longer-term follow-up assessment beyond 24 weeks.

DISCLOSURES:

This study was supported by grants from Cleveland Clinic Healthcare Delivery and Implementation Science Center. One coauthor disclosed receiving personal fees from the Blue Cross Blue Shield Association. Eric Roseen, DC, PhD, reported receiving grants from the National Institutes of Health National Center for Complementary and Integrative Health. One coauthor disclosed receiving personal fees from UpToDate and grants from NCCIH related to yoga and tai chi for treatment of pain. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Approximately one third of parents of children with atopic dermatitis reported little or no improvement with elimination diets, and nearly 80% reintroduced the eliminated foods, based on survey data from nearly 300 parents.

Although atopic dermatitis can be associated with an increased risk for food allergies, major allergy organizations do not currently recommend elimination diets as a treatment for atopic dermatitis, said Nadia Makkoukdji, MD, a pediatrician at Jackson Memorial Hospital, Miami, in a presentation at the American College of Allergy, Asthma, and Immunology (ACAAI) Annual Scientific Meeting.

“A fear of drastic dietary changes often prevents families from seeking the care their children need,” Makkoukdji said in an interview. In the clinical setting, Makkoukdji noted that she has seen many patients who have started food elimination diets on their own or as recommended by other doctors, and that these diets can lead to dangers such as the development of immunoglobulin E–mediated food allergies on reintroduction of eliminated foods and malnutrition. They can also produce “emotional stress in children and anxiety or depression, while also adding stress to parents and the entire family.”

Makkoukdji conducted the study to explore parents’ perceptions of these diets in management of their children’s atopic dermatitis, she said.

In the study, Makkoukdji and colleagues sought to understand parents’ perceptions of the role of diet in atopic dermatitis in their children. The researchers reviewed surveys from 298 parents of children with atopic dermatitis who were seen at a single academic center. Parents completed the surveys in the emergency department or in an allergy, dermatology, and general pediatrics clinic.

Overall, 42% of parents identified food triggers for their child’s atopic dermatitis. The most commonly identified triggers were milk (32%), tree nuts/seeds/peanuts (16%), and eggs (11%).

Of the parents who reported food triggers, 23% removed the suspected trigger food from the child’s diet completely, 20% removed suspected trigger foods from their own diets while breastfeeding, and 19% changed their infant’s formula.

In the wake of the elimination diets, 38% of the parents reported no improvement in their child’s atopic dermatitis, 35% reported a 25% improvement, and 9% reported complete resolution. The majority (79%) reintroduced eliminated foods and reported no recurrence of atopic dermatitis symptoms.

The researchers were surprised by how many parents changed their child’s diet in the belief that certain foods exacerbated their child’s atopic dermatitis, “although this perception aligns with the common concern that food allergens can trigger or worsen atopic dermatitis flares,” Makkoukdji said.

The current study highlights the need for more awareness of the limited impact of dietary modifications on atopic dermatitis in the absence of confirmed food allergies, Makkoukdji said. “Our study shows that food elimination diets are still commonly being used by parents in the local Miami population.”

The findings were limited by several factors, including the use of data from a single center and the focus only on pediatric patients, but the primary goal was to assess parental perceptions of AD flares in relation to dietary choices, said Makkoukdji. “Future studies that include larger and more diverse populations would be valuable for the field.”
 

Dietary Modifications Don’t Live Up to Hype

“Food continues to be one of the most discussed aspects of atopic dermatitis,” Peter Lio, MD, clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine, Chicago, Illinois, said in an interview.

“Almost all of my patients and families ask about dietary modifications, even though almost all of them have experimented with it to some degree,” said Lio. In his experience, diet plays a small role, if any, in the day-to-day management of atopic dermatitis.

This lack of effect of dietary changes is often frustrating to patients because of the persistent “common wisdom” that points to diet as a root cause of atopic dermatitis, Lio said. “Many practitioners continue to recommend excluding foods such as gluten or dairy from the diet, but generally these are only of modest help,” and although patients wish that dietary changes would fix the problem, most are left wondering why these changes didn’t help them.

The current study findings “reflect my own experience after nearly 20 years of being deeply immersed in the world of atopic dermatitis,” Lio said. Although the takeaway message does not argue against eating healthy foods, some foods do seem to make AD worse in some patients and may have nonallergic pro-inflammatory effects.

“In those cases, it is reasonable to limit or avoid those foods. However, it is extremely difficult to tell what food or foods are driving flare-ups when things are out of control, so dietary modification is generally not the best place to start,” he said.

True food allergies are much more common in patients with atopic dermatitis compared with individuals without atopic dermatitis, but the current study is not addressing these types of allergies, Lio emphasized. “If someone has true allergy to peanuts, for example, they should not be eating them; we also know that they are not ‘cheating’ because these patients would not merely have an eczema flare; they would have urticaria, angioedema, or anaphylaxis. There is tremendous confusion around this point and lots of confusion around allergy testing and its limitations.”

In addition, patients with atopic dermatitis are more likely than those without atopic dermatitis to have abnormalities in the gut microbiome and gut barrier, Lio said.

Abnormalities in the gut microbiome are different from the concept of allergy and may fall into the more complex category of barrier and microbiome disruptors, he said. Therefore, “the food category may not be nearly as important as the specific preparation of the food along with the additives (such as preservatives and emulsifiers) that may actually be driving the problem.”

Although in the past many clinicians advised patients to try cutting out certain foods to see whether atopic dermatitis symptoms improved, this strategy is not without risk, said Lio. “There have been incredible advancements in understanding the role of the gut in tolerization to foods.” Recent research has shown that by eating foods regularly, particularly those such as peanuts that seem to have more allergic potential, the body becomes tolerant, and this prevents the development of true food allergies.

As for additional research, many questions remain about the effects of types of foods, processing methods, and timing of introduction of foods on atopic dermatitis, Lio noted.

“Atopic dermatitis is a systemic condition with the immune system, with the skin/gut/respiratory barriers and microbiome involved; I think we now have a broader view of how big and complex the landscape really is,” he said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Lio had no disclosures relevant to elimination diets but disclosed serving on the speakers bureau for AbbVie, Arcutis Biotherapeutics, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche–Posay/L’Oréal, Pfizer, Pierre Fabre Dermatologie, Regeneron/Sanofi Genzyme, and Verrica Pharmaceuticals; serving on consulting/advisory boards; or having stock options for many pharmaceutical companies. Lio also disclosed a patent pending for a Theraplex product with royalties paid and is a board member and Scientific Advisory Committee member emeritus of the National Eczema Association.

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

Approximately one third of parents of children with atopic dermatitis reported little or no improvement with elimination diets, and nearly 80% reintroduced the eliminated foods, based on survey data from nearly 300 parents.

Although atopic dermatitis can be associated with an increased risk for food allergies, major allergy organizations do not currently recommend elimination diets as a treatment for atopic dermatitis, said Nadia Makkoukdji, MD, a pediatrician at Jackson Memorial Hospital, Miami, in a presentation at the American College of Allergy, Asthma, and Immunology (ACAAI) Annual Scientific Meeting.

“A fear of drastic dietary changes often prevents families from seeking the care their children need,” Makkoukdji said in an interview. In the clinical setting, Makkoukdji noted that she has seen many patients who have started food elimination diets on their own or as recommended by other doctors, and that these diets can lead to dangers such as the development of immunoglobulin E–mediated food allergies on reintroduction of eliminated foods and malnutrition. They can also produce “emotional stress in children and anxiety or depression, while also adding stress to parents and the entire family.”

Makkoukdji conducted the study to explore parents’ perceptions of these diets in management of their children’s atopic dermatitis, she said.

In the study, Makkoukdji and colleagues sought to understand parents’ perceptions of the role of diet in atopic dermatitis in their children. The researchers reviewed surveys from 298 parents of children with atopic dermatitis who were seen at a single academic center. Parents completed the surveys in the emergency department or in an allergy, dermatology, and general pediatrics clinic.

Overall, 42% of parents identified food triggers for their child’s atopic dermatitis. The most commonly identified triggers were milk (32%), tree nuts/seeds/peanuts (16%), and eggs (11%).

Of the parents who reported food triggers, 23% removed the suspected trigger food from the child’s diet completely, 20% removed suspected trigger foods from their own diets while breastfeeding, and 19% changed their infant’s formula.

In the wake of the elimination diets, 38% of the parents reported no improvement in their child’s atopic dermatitis, 35% reported a 25% improvement, and 9% reported complete resolution. The majority (79%) reintroduced eliminated foods and reported no recurrence of atopic dermatitis symptoms.

The researchers were surprised by how many parents changed their child’s diet in the belief that certain foods exacerbated their child’s atopic dermatitis, “although this perception aligns with the common concern that food allergens can trigger or worsen atopic dermatitis flares,” Makkoukdji said.

The current study highlights the need for more awareness of the limited impact of dietary modifications on atopic dermatitis in the absence of confirmed food allergies, Makkoukdji said. “Our study shows that food elimination diets are still commonly being used by parents in the local Miami population.”

The findings were limited by several factors, including the use of data from a single center and the focus only on pediatric patients, but the primary goal was to assess parental perceptions of AD flares in relation to dietary choices, said Makkoukdji. “Future studies that include larger and more diverse populations would be valuable for the field.”
 

Dietary Modifications Don’t Live Up to Hype

“Food continues to be one of the most discussed aspects of atopic dermatitis,” Peter Lio, MD, clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine, Chicago, Illinois, said in an interview.

“Almost all of my patients and families ask about dietary modifications, even though almost all of them have experimented with it to some degree,” said Lio. In his experience, diet plays a small role, if any, in the day-to-day management of atopic dermatitis.

This lack of effect of dietary changes is often frustrating to patients because of the persistent “common wisdom” that points to diet as a root cause of atopic dermatitis, Lio said. “Many practitioners continue to recommend excluding foods such as gluten or dairy from the diet, but generally these are only of modest help,” and although patients wish that dietary changes would fix the problem, most are left wondering why these changes didn’t help them.

The current study findings “reflect my own experience after nearly 20 years of being deeply immersed in the world of atopic dermatitis,” Lio said. Although the takeaway message does not argue against eating healthy foods, some foods do seem to make AD worse in some patients and may have nonallergic pro-inflammatory effects.

“In those cases, it is reasonable to limit or avoid those foods. However, it is extremely difficult to tell what food or foods are driving flare-ups when things are out of control, so dietary modification is generally not the best place to start,” he said.

True food allergies are much more common in patients with atopic dermatitis compared with individuals without atopic dermatitis, but the current study is not addressing these types of allergies, Lio emphasized. “If someone has true allergy to peanuts, for example, they should not be eating them; we also know that they are not ‘cheating’ because these patients would not merely have an eczema flare; they would have urticaria, angioedema, or anaphylaxis. There is tremendous confusion around this point and lots of confusion around allergy testing and its limitations.”

In addition, patients with atopic dermatitis are more likely than those without atopic dermatitis to have abnormalities in the gut microbiome and gut barrier, Lio said.

Abnormalities in the gut microbiome are different from the concept of allergy and may fall into the more complex category of barrier and microbiome disruptors, he said. Therefore, “the food category may not be nearly as important as the specific preparation of the food along with the additives (such as preservatives and emulsifiers) that may actually be driving the problem.”

Although in the past many clinicians advised patients to try cutting out certain foods to see whether atopic dermatitis symptoms improved, this strategy is not without risk, said Lio. “There have been incredible advancements in understanding the role of the gut in tolerization to foods.” Recent research has shown that by eating foods regularly, particularly those such as peanuts that seem to have more allergic potential, the body becomes tolerant, and this prevents the development of true food allergies.

As for additional research, many questions remain about the effects of types of foods, processing methods, and timing of introduction of foods on atopic dermatitis, Lio noted.

“Atopic dermatitis is a systemic condition with the immune system, with the skin/gut/respiratory barriers and microbiome involved; I think we now have a broader view of how big and complex the landscape really is,” he said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Lio had no disclosures relevant to elimination diets but disclosed serving on the speakers bureau for AbbVie, Arcutis Biotherapeutics, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche–Posay/L’Oréal, Pfizer, Pierre Fabre Dermatologie, Regeneron/Sanofi Genzyme, and Verrica Pharmaceuticals; serving on consulting/advisory boards; or having stock options for many pharmaceutical companies. Lio also disclosed a patent pending for a Theraplex product with royalties paid and is a board member and Scientific Advisory Committee member emeritus of the National Eczema Association.

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

Approximately one third of parents of children with atopic dermatitis reported little or no improvement with elimination diets, and nearly 80% reintroduced the eliminated foods, based on survey data from nearly 300 parents.

Although atopic dermatitis can be associated with an increased risk for food allergies, major allergy organizations do not currently recommend elimination diets as a treatment for atopic dermatitis, said Nadia Makkoukdji, MD, a pediatrician at Jackson Memorial Hospital, Miami, in a presentation at the American College of Allergy, Asthma, and Immunology (ACAAI) Annual Scientific Meeting.

“A fear of drastic dietary changes often prevents families from seeking the care their children need,” Makkoukdji said in an interview. In the clinical setting, Makkoukdji noted that she has seen many patients who have started food elimination diets on their own or as recommended by other doctors, and that these diets can lead to dangers such as the development of immunoglobulin E–mediated food allergies on reintroduction of eliminated foods and malnutrition. They can also produce “emotional stress in children and anxiety or depression, while also adding stress to parents and the entire family.”

Makkoukdji conducted the study to explore parents’ perceptions of these diets in management of their children’s atopic dermatitis, she said.

In the study, Makkoukdji and colleagues sought to understand parents’ perceptions of the role of diet in atopic dermatitis in their children. The researchers reviewed surveys from 298 parents of children with atopic dermatitis who were seen at a single academic center. Parents completed the surveys in the emergency department or in an allergy, dermatology, and general pediatrics clinic.

Overall, 42% of parents identified food triggers for their child’s atopic dermatitis. The most commonly identified triggers were milk (32%), tree nuts/seeds/peanuts (16%), and eggs (11%).

Of the parents who reported food triggers, 23% removed the suspected trigger food from the child’s diet completely, 20% removed suspected trigger foods from their own diets while breastfeeding, and 19% changed their infant’s formula.

In the wake of the elimination diets, 38% of the parents reported no improvement in their child’s atopic dermatitis, 35% reported a 25% improvement, and 9% reported complete resolution. The majority (79%) reintroduced eliminated foods and reported no recurrence of atopic dermatitis symptoms.

The researchers were surprised by how many parents changed their child’s diet in the belief that certain foods exacerbated their child’s atopic dermatitis, “although this perception aligns with the common concern that food allergens can trigger or worsen atopic dermatitis flares,” Makkoukdji said.

The current study highlights the need for more awareness of the limited impact of dietary modifications on atopic dermatitis in the absence of confirmed food allergies, Makkoukdji said. “Our study shows that food elimination diets are still commonly being used by parents in the local Miami population.”

The findings were limited by several factors, including the use of data from a single center and the focus only on pediatric patients, but the primary goal was to assess parental perceptions of AD flares in relation to dietary choices, said Makkoukdji. “Future studies that include larger and more diverse populations would be valuable for the field.”
 

Dietary Modifications Don’t Live Up to Hype

“Food continues to be one of the most discussed aspects of atopic dermatitis,” Peter Lio, MD, clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine, Chicago, Illinois, said in an interview.

“Almost all of my patients and families ask about dietary modifications, even though almost all of them have experimented with it to some degree,” said Lio. In his experience, diet plays a small role, if any, in the day-to-day management of atopic dermatitis.

This lack of effect of dietary changes is often frustrating to patients because of the persistent “common wisdom” that points to diet as a root cause of atopic dermatitis, Lio said. “Many practitioners continue to recommend excluding foods such as gluten or dairy from the diet, but generally these are only of modest help,” and although patients wish that dietary changes would fix the problem, most are left wondering why these changes didn’t help them.

The current study findings “reflect my own experience after nearly 20 years of being deeply immersed in the world of atopic dermatitis,” Lio said. Although the takeaway message does not argue against eating healthy foods, some foods do seem to make AD worse in some patients and may have nonallergic pro-inflammatory effects.

“In those cases, it is reasonable to limit or avoid those foods. However, it is extremely difficult to tell what food or foods are driving flare-ups when things are out of control, so dietary modification is generally not the best place to start,” he said.

True food allergies are much more common in patients with atopic dermatitis compared with individuals without atopic dermatitis, but the current study is not addressing these types of allergies, Lio emphasized. “If someone has true allergy to peanuts, for example, they should not be eating them; we also know that they are not ‘cheating’ because these patients would not merely have an eczema flare; they would have urticaria, angioedema, or anaphylaxis. There is tremendous confusion around this point and lots of confusion around allergy testing and its limitations.”

In addition, patients with atopic dermatitis are more likely than those without atopic dermatitis to have abnormalities in the gut microbiome and gut barrier, Lio said.

Abnormalities in the gut microbiome are different from the concept of allergy and may fall into the more complex category of barrier and microbiome disruptors, he said. Therefore, “the food category may not be nearly as important as the specific preparation of the food along with the additives (such as preservatives and emulsifiers) that may actually be driving the problem.”

Although in the past many clinicians advised patients to try cutting out certain foods to see whether atopic dermatitis symptoms improved, this strategy is not without risk, said Lio. “There have been incredible advancements in understanding the role of the gut in tolerization to foods.” Recent research has shown that by eating foods regularly, particularly those such as peanuts that seem to have more allergic potential, the body becomes tolerant, and this prevents the development of true food allergies.

As for additional research, many questions remain about the effects of types of foods, processing methods, and timing of introduction of foods on atopic dermatitis, Lio noted.

“Atopic dermatitis is a systemic condition with the immune system, with the skin/gut/respiratory barriers and microbiome involved; I think we now have a broader view of how big and complex the landscape really is,” he said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Lio had no disclosures relevant to elimination diets but disclosed serving on the speakers bureau for AbbVie, Arcutis Biotherapeutics, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche–Posay/L’Oréal, Pfizer, Pierre Fabre Dermatologie, Regeneron/Sanofi Genzyme, and Verrica Pharmaceuticals; serving on consulting/advisory boards; or having stock options for many pharmaceutical companies. Lio also disclosed a patent pending for a Theraplex product with royalties paid and is a board member and Scientific Advisory Committee member emeritus of the National Eczema Association.

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

Many people with rheumatologic diseases try supplements for symptom relief. Here’s what you need to know about some common picks.

Dietary supplements were a $159 billion business in the United States in 2023, and many people with rheumatologic diseases are buying in. Research suggests more than 6 in 10 people with fibromyalgia, nearly 8 in 10 people with Sjögren’s disease, and more than 8 in 10 people with rheumatoid arthritis (RA) take dietary supplements.

Whatever the symptom — pain, swelling, or fatigue — you can probably find a supplement purporting to relieve it. But do these supplements work, and are they safe? A study review in RMD Open comprising 24 systematic reviews and 150 original articles suggests more high-quality research is needed on the effects of dietary supplements on rheumatologic diseases. Most studies have focused on RA or osteoarthritis (OA), where the evidence level is moderate at best.

Dr. Janet Funk

“The studies in this space are usually not very high quality because there’s no money to support them, among other things, plus the products are disparate,” said Janet Funk, MD, MS, professor in the School of Nutritional Sciences and Wellness at the University of Arizona, Tucson. She recommended brushing up on supplements and finding out what patients are taking so you can offer advice and watch for drug-supplement interactions.

When asked for a medication list, many patients forget to report supplements, Funk said. “You have to prompt them specifically. I think some physicians have very negative views about supplements because so little data is known, and patients might pick up on that and decide not to report their use.” She recommended saying something like: “To give you the best possible care, I want to know everything you’re taking, including supplements. The things I’m prescribing could maybe interact with the things you’re taking, so I want to make sure I know about all of it so that together we can figure out if the combination of things is safe.”

The quality of dietary supplements varies, and they aren’t regulated like drugs by the Food and Drug Administration. Funk recommended selecting products verified by NSF or ConsumerLab. They test supplements to ensure the label reflects what’s inside.

This news organization scoured the literature and asked experts to weigh in on the evidence behind popular supplements in rheumatology today.
 

The Essential Nutrients

Vitamin supplements are a staple in many homes — but are they helpful? “Individual vitamin supplements will not provide any benefit unless the person is deficient in a specific vitamin or mineral,” according to Elena Philippou, PhD, RD, associate professor of nutrition-dietetics at the University of Nicosia in Cyprus, and Elena Nikiphorou, MBBS, a rheumatologist at King’s College London in England. For some patients, deficiency is a reality. A retrospective cohort study in The Journal of Clinical Medicine found that people with RA were 17% more likely than age-matched control individuals to have nutrient deficiencies, perhaps because symptoms like fatigue, pain, and nausea affect their eating habits. Here’s what the science says about common vitamin supplements.

Dr. Elena Philippou

Vitamin D. This hormone-like vitamin, which attaches to receptors on immune cells to tamp down inflammation, was the most popular dietary supplement among rheumatology patients in a recent study from the United Kingdom. Vitamin D deficiency is common in people with RA, lupus, Sjögren’s disease, ankylosing spondylitis, systemic sclerosis, and fibromyalgia. In some cases, vitamin D levels track with disease activity, research suggests. Corticosteroids can also make vitamin D deficiency more likely. Can supplements help?

In RA, evidence points to small improvements. A systematic review of 11 studies including 3049 patients published in Nutrition Reviews showed that vitamin D supplements significantly reduced patients’ pain and Disease Activity Score in 28 joints (DAS28) using both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

The research is mixed on the benefits of vitamin D supplementation for fibromyalgia symptoms, according to a study review in SN Comprehensive Clinical Medicine that included two studies and 80 patients on supplementation. However, researchers said it’s still worth discussing the potential benefits of taking vitamin D.

“Vitamin D supplementation is important in the context of various rheumatic diseases to prevent or treat bone disease,” said Philippou and Nikiphorou. “People with rheumatic disease should speak to their healthcare provider and ask to check their blood vitamin D concentration.” The results can help you recommend a dose.

Folate. Patients on methotrexate should take folic acid supplements under the guidance of a healthcare provider, said Philippou and Nikiphorou. The reason: Methotrexate can deplete folic acid levels, increasing the risk for side effects. An analysis of adverse event reports published showed that methotrexate users who took folic acid (or tumor necrosis factor–alpha inhibitors) had a reduced risk for hepatotoxicity or myelosuppression. A commonly recommended dose is 1 mg/d.

Vitamin B12. In a 2024 perspective paper in Rheumatology International, researchers said physicians should assess vitamin B12 levels early in the diagnostic process of rheumatologic diseases. One reason: Many symptoms of pernicious anemia, like fatigue, mimic symptoms of rheumatologic diseases. The gastrointestinal (GI) effects of systemic sclerosis could bring on vitamin B12 deficiency. In a small study in The Journal of Clinical Rheumatology, 44 of 62 patients with systemic sclerosis had low vitamin B12 levels.

Vitamin E. Vitamin E deficiency is rare in healthy adults. However, some medical conditions, like inflammatory bowel disease and malabsorption disorders, can make vitamin E deficiency more likely. In RA, a vitamin E supplement could help reduce joint swelling and sensitivity, according to a systematic review of nine studies including 39,845 patients in The European Journal of Clinical Nutrition. Researchers credit the nutrient’s role in aiding intestinal repair. Use with caution, as this supplement can increase bleeding risk in doses over 1000 mg/d.

Vitamin A. Like vitamin E, vitamin A deficiency is rare in the United States. The risk of oversupplementing is higher than undersupplementing. However, vitamin A deficiency can happen in people with chronic pancreatic, liver, or GI problems. In people with deficiency, a vitamin A supplement can help relieve dry eye symptoms common in Sjögren’s disease, suggests a narrative review published in Nutrients. Vitamin A might help reduce ocular surface changes by supporting the production of proteins that protect the outermost surfaces of the eyes. The recommended daily allowance for vitamin A is 900 μg. High-dose supplements can cause toxicity, resulting in GI symptoms and problems like lethargy, drowsiness, increased intracranial pressure, and skin changes.
 

The Replacements

These substances are similar to naturally occurring compounds in our bodies. The question is whether ingesting them yields benefits.

Glucosamine and chondroitin. Glucosamine and chondroitin occur naturally in our bodies and help us form and protect connective tissues. In pill form, this combo is the most popular dietary supplement for OA, according to research in the journal Maturitas. But studies of its effectiveness yield mixed results. A systematic review of 25 studies published in Inflammopharmacology showed that, in patients with knee OA, supplementation with about 1500 mg of glucosamine per day reduced tibiofemoral joint space narrowing, while supplementation with about 800 mg/d of chondroitin reduced pain intensity and improved physical function, compared with placebo. The duo of glucosamine and chondroitin did not bring significant benefits, perhaps because more studies are needed. Most side effects were mild, but some literature points to the potential for glucosamine to increase warfarin’s blood-thinning effects.

Omega-3 fatty acids. Fish oil is a top-selling supplement, and it might be helpful in inflammatory rheumatologic diseases. A systematic review of 30 studies including 710 patients published in Arthritis Research & Therapy showed that omega-3 fatty acid supplements can improve pain, swollen and tender joint count, DAS28 scores, and Health Assessment Questionnaire scores in patients with RA, psoriatic arthritis, or ankylosing spondylitis. In patients with lupus, a study review that included five studies and 284 patients in The International Journal of Environmental Research and Public Health suggested omega-3 fatty acid supplements could improve ESR, CRP, disease activity, inflammatory markers, oxidative stress, lipid levels, and endothelial function.

Omega-3 fatty acids have anti-inflammatory effects that might explain their benefits. In patients with RA, for example, fish oil supplementation was associated with elevated blood levels of resolvins and protectins, which help quell inflammation, according to a study in Prostaglandins, Leukotrienes and Essential Fatty Acids.

Philippou and Nikiphorou recommended combining food and supplements: Eat oily fish at least twice a week, regularly consume plant-based sources of omega-3s — like chia seeds, flaxseeds, or walnuts — and consider a daily supplement that contains 2 g of omega-3s from docosahexaenoic acid and eicosapentaenoic acid. Most fish oil side effects are mild, like heartburn and bad breath. Fish oil can have blood-thinning effects at high doses, so special attention is needed for patients on anticoagulants.

Probiotics. Building up the good bacteria in your gut might help you fight the effects of rheumatologic diseases. A systematic review of 80 randomized controlled trials in BMC Medicine suggested that therapies targeting the gut microbiota might improve the symptoms or inflammatory factors in celiac disease, lupus, juvenile idiopathic arthritis, psoriasis, Sjögren’s disease, multiple sclerosis, systemic sclerosis, Crohn’s disease, and ulcerative colitis. Probiotics were also shown to relieve pain in fibromyalgia, but they didn’t affect scores on the Fibromyalgia Impact Questionnaire. Probiotics were not helpful in spondyloarthritis or RA. There were no adverse events. By improving the balance of bacteria in the gut, probiotics might inhibit pro-inflammatory factors and signaling pathways and regulate CD4+ T-cell differentiation, the researchers wrote.

Not all probiotic supplements are created equal. Effects can vary by microorganism and dose. Until more high-quality studies are published, Philippou and Nikiphorou recommend daily consumption of probiotic food sources such as yogurt, kefir, sauerkraut, kimchi, tempeh, miso, and kombucha, along with prebiotic food sources such as bananas, onion, artichokes, asparagus, oats, leeks, and garlic.

Collagen. An increasingly popular supplement for hair, skin, and nails, some collagen peptide or hydrolyzed collagen supplements come with claims about joint health, too. Inside our bodies, collagen helps build joints. As a supplement, the jury is still out. A systematic review of 19 studies in The International Journal of Rheumatic Diseases suggested more research is needed to determine whether collagen supplements are harmful or helpful in OA or RA. Studies haven’t shown adverse events, and doses typically range from 2.5 to 15 g/d.

Coenzyme Q10 (CoQ10). This antioxidant occurs naturally in our cells and is produced through microbial fermentation for use in dietary supplements. A study review of 20 articles including 483 patients in Clinical Nutrition ESPEN concluded that CoQ10 supplementation up to 300 mg/d was beneficial in RA, fibromyalgia, or antiphospholipid syndrome (APS).

In RA, CoQ10 supplementation improved disease activity index, ESR, and cytokine levels and decreased malondialdehyde. CoQ10 might protect against the overproduction of reactive oxygen species that can promote inflammation and joint damage, the researchers said. In fibromyalgia, CoQ10 was linked with improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire in most of the included studies. CoQ10 might help in fibromyalgia by improving mitochondrial dysfunction. In APS, CoQ10 improved endothelial function and decreased prothrombotic and pro-inflammatory mediators. CoQ10 might change the expression of genes that promote atherosclerosis. A few patients had GI side effects like nausea and diarrhea, but the supplements were generally well tolerated.

Melatonin. Commonly touted as a sleep aid, this hormone has immune and anti-inflammatory activities that could benefit people with rheumatologic diseases. A study review of 13 articles including 533 patients in Clinical Nutrition ESPEN concluded that melatonin can help improve sleep, pain, and mood in fibromyalgia, OA, and osteoporosis but not in RA. Side effects were minimal, but a few people experienced nausea, drowsiness, nightmares, or headaches. Doses of 5-6 mg/d are likely safe for most adults.
 

The Plant-Derived Antioxidants

Many supplements used in rheumatology are antioxidants derived from herbs, spices, or other plants. When plants encounter stressors, like temperature changes or hungry insects, their secondary metabolism revs up and creates compounds with biological properties. Some of these substances influence inflammatory pathways in the human body, said Luís Silva, PhD, a medicinal chemistry researcher at the Polytechnic Institute of Guarda in Portugal. “If it is possible to reduce these kinds of anti-inflammatory processes, it is also possible that we could help people with inflammatory diseases to a good life, or a better life.”

Dr. Luís Silva

Turmeric and curcumin. You might see this supplement labeled as turmeric, a golden spice in curry powder, or curcumin, an antioxidant compound known as a curcuminoid in turmeric. Curcuminoids might reduce inflammation by scavenging free radicals and inhibiting enzymes that make prostaglandins, Silva said.

Turmeric is the most popular herbal supplement for people with RA, according to Funk’s research. A study review of six publications including 539 patients in Frontiers in Immunology showed that curcumin supplements improved RA patients’ ESR, DAS, swollen joint count, and tender joint count. Turmeric could help patients with OA, too. Patients with OA who took 1000 mg/d of curcumin improved their pain and function, according to a systematic review including 12 studies and 1438 participants in the journal Nutrients. In lupus, small studies are promising but inconclusive, suggested a study review in Frontiers in Immunology.

Watch patients taking turmeric and methotrexate closely, Funk said. Both have been associated with liver problems. Some users also experience GI symptoms like diarrhea because turmeric doesn’t absorb well in the GI tract.

Milk thistle (silymarin). This flowering plant is often marketed as a liver-supporting supplement, but research also suggests promise in RA and OA. A systematic review of 12 studies in Current Rheumatology Reviews suggested that silymarin supplements might help relieve pain, reduce inflammation, and protect the cartilage matrix, synovial membrane, and cartilage cells in joints. This supplement might help via immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic properties, the researchers said. Doses of 250-750 mg appear to be safe. Side effects such as gastroenteritis, diarrhea, bloating, and headache can occur.

Boswellia serrata. Sourced from the resin of a tree that grows in dry, mountainous regions of Asia and Africa, Boswellia serrata can help relieve joint pain and stiffness and improve joint function in OA, suggested a systematic review of seven trials involving 545 patients in BMC Complementary Medicine and Therapies. Users saw benefits when taking 100-250 mg/d for 4 weeks or more. Compounds in Boswellia serrata may inhibit 5-lipoxygenase, an enzyme involved in producing inflammatory leukotrienes. No adverse events were reported. In some studies, users have reported GI side effects.

Ginger. Ginger is a popular herbal supplement among people with RA, Funk’s research suggested. One small clinical trial involving 70 patients with RA in the journal Gene showed that taking 1500 mg/d of ginger for 12 weeks improved their DAS and boosted their expression of FoxP3 genes, which are linked with the function of regulatory T cells. A meta-analysis including three studies with 330 patients taking ginger published in the journal Nutrients suggested ginger can reduce pain and systemic inflammation in people with OA. Preclinical studies suggested phenolic compounds in this spicy root, such as gingerols, reduce inflammation through multiple mechanisms.

Funk’s research revealed wide variation in the quality of ginger supplements, reinforcing the importance of selecting an independently verified product. Research suggested a safe dose is up to 2-2.5 g/kg body weight.

Resveratrol. Found in red grapes and red wine, this compound is particularly good at blocking COX-2 enzymes, an important step in the inflammatory cascade, Silva said. “Because of their chemical structure, they have great affinity to these enzymes to lead to their inhibition,” he said. A study review of five articles including 481 patients in The European Journal of Rheumatology showed that people with OA, RA, or Takayasu arteritis who took 250-1000 mg/d of resveratrol saw improvements in pain, function, disease activity, joint swelling, and inflammation, with no side effects.

Cinnamon. This warming spice is gaining popularity as a supplement, reported the American Botanical Council. Cinnamon is often marketed as lowering blood sugar and supporting bone health. In a small study of 36 women with RA published in The Journal of the American College of Nutrition, participants who consumed 2 g/d of cinnamon powder had reduced DASs along with reduced pain and tender and swollen joint counts. Cinnamon may reduce pain by inhibiting prostaglandin and blunt inflammation by reducing the release of arachidonic acid from cell membranes, according to a study review in Frontiers in Pharmacology. GI problems and allergic reactions are among the most common side effects.

Funk, Nikiphorou, Philippou, and Silva all had no relevant disclosures.

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

Many people with rheumatologic diseases try supplements for symptom relief. Here’s what you need to know about some common picks.

Dietary supplements were a $159 billion business in the United States in 2023, and many people with rheumatologic diseases are buying in. Research suggests more than 6 in 10 people with fibromyalgia, nearly 8 in 10 people with Sjögren’s disease, and more than 8 in 10 people with rheumatoid arthritis (RA) take dietary supplements.

Whatever the symptom — pain, swelling, or fatigue — you can probably find a supplement purporting to relieve it. But do these supplements work, and are they safe? A study review in RMD Open comprising 24 systematic reviews and 150 original articles suggests more high-quality research is needed on the effects of dietary supplements on rheumatologic diseases. Most studies have focused on RA or osteoarthritis (OA), where the evidence level is moderate at best.

Dr. Janet Funk

“The studies in this space are usually not very high quality because there’s no money to support them, among other things, plus the products are disparate,” said Janet Funk, MD, MS, professor in the School of Nutritional Sciences and Wellness at the University of Arizona, Tucson. She recommended brushing up on supplements and finding out what patients are taking so you can offer advice and watch for drug-supplement interactions.

When asked for a medication list, many patients forget to report supplements, Funk said. “You have to prompt them specifically. I think some physicians have very negative views about supplements because so little data is known, and patients might pick up on that and decide not to report their use.” She recommended saying something like: “To give you the best possible care, I want to know everything you’re taking, including supplements. The things I’m prescribing could maybe interact with the things you’re taking, so I want to make sure I know about all of it so that together we can figure out if the combination of things is safe.”

The quality of dietary supplements varies, and they aren’t regulated like drugs by the Food and Drug Administration. Funk recommended selecting products verified by NSF or ConsumerLab. They test supplements to ensure the label reflects what’s inside.

This news organization scoured the literature and asked experts to weigh in on the evidence behind popular supplements in rheumatology today.
 

The Essential Nutrients

Vitamin supplements are a staple in many homes — but are they helpful? “Individual vitamin supplements will not provide any benefit unless the person is deficient in a specific vitamin or mineral,” according to Elena Philippou, PhD, RD, associate professor of nutrition-dietetics at the University of Nicosia in Cyprus, and Elena Nikiphorou, MBBS, a rheumatologist at King’s College London in England. For some patients, deficiency is a reality. A retrospective cohort study in The Journal of Clinical Medicine found that people with RA were 17% more likely than age-matched control individuals to have nutrient deficiencies, perhaps because symptoms like fatigue, pain, and nausea affect their eating habits. Here’s what the science says about common vitamin supplements.

Dr. Elena Philippou

Vitamin D. This hormone-like vitamin, which attaches to receptors on immune cells to tamp down inflammation, was the most popular dietary supplement among rheumatology patients in a recent study from the United Kingdom. Vitamin D deficiency is common in people with RA, lupus, Sjögren’s disease, ankylosing spondylitis, systemic sclerosis, and fibromyalgia. In some cases, vitamin D levels track with disease activity, research suggests. Corticosteroids can also make vitamin D deficiency more likely. Can supplements help?

In RA, evidence points to small improvements. A systematic review of 11 studies including 3049 patients published in Nutrition Reviews showed that vitamin D supplements significantly reduced patients’ pain and Disease Activity Score in 28 joints (DAS28) using both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

The research is mixed on the benefits of vitamin D supplementation for fibromyalgia symptoms, according to a study review in SN Comprehensive Clinical Medicine that included two studies and 80 patients on supplementation. However, researchers said it’s still worth discussing the potential benefits of taking vitamin D.

“Vitamin D supplementation is important in the context of various rheumatic diseases to prevent or treat bone disease,” said Philippou and Nikiphorou. “People with rheumatic disease should speak to their healthcare provider and ask to check their blood vitamin D concentration.” The results can help you recommend a dose.

Folate. Patients on methotrexate should take folic acid supplements under the guidance of a healthcare provider, said Philippou and Nikiphorou. The reason: Methotrexate can deplete folic acid levels, increasing the risk for side effects. An analysis of adverse event reports published showed that methotrexate users who took folic acid (or tumor necrosis factor–alpha inhibitors) had a reduced risk for hepatotoxicity or myelosuppression. A commonly recommended dose is 1 mg/d.

Vitamin B12. In a 2024 perspective paper in Rheumatology International, researchers said physicians should assess vitamin B12 levels early in the diagnostic process of rheumatologic diseases. One reason: Many symptoms of pernicious anemia, like fatigue, mimic symptoms of rheumatologic diseases. The gastrointestinal (GI) effects of systemic sclerosis could bring on vitamin B12 deficiency. In a small study in The Journal of Clinical Rheumatology, 44 of 62 patients with systemic sclerosis had low vitamin B12 levels.

Vitamin E. Vitamin E deficiency is rare in healthy adults. However, some medical conditions, like inflammatory bowel disease and malabsorption disorders, can make vitamin E deficiency more likely. In RA, a vitamin E supplement could help reduce joint swelling and sensitivity, according to a systematic review of nine studies including 39,845 patients in The European Journal of Clinical Nutrition. Researchers credit the nutrient’s role in aiding intestinal repair. Use with caution, as this supplement can increase bleeding risk in doses over 1000 mg/d.

Vitamin A. Like vitamin E, vitamin A deficiency is rare in the United States. The risk of oversupplementing is higher than undersupplementing. However, vitamin A deficiency can happen in people with chronic pancreatic, liver, or GI problems. In people with deficiency, a vitamin A supplement can help relieve dry eye symptoms common in Sjögren’s disease, suggests a narrative review published in Nutrients. Vitamin A might help reduce ocular surface changes by supporting the production of proteins that protect the outermost surfaces of the eyes. The recommended daily allowance for vitamin A is 900 μg. High-dose supplements can cause toxicity, resulting in GI symptoms and problems like lethargy, drowsiness, increased intracranial pressure, and skin changes.
 

The Replacements

These substances are similar to naturally occurring compounds in our bodies. The question is whether ingesting them yields benefits.

Glucosamine and chondroitin. Glucosamine and chondroitin occur naturally in our bodies and help us form and protect connective tissues. In pill form, this combo is the most popular dietary supplement for OA, according to research in the journal Maturitas. But studies of its effectiveness yield mixed results. A systematic review of 25 studies published in Inflammopharmacology showed that, in patients with knee OA, supplementation with about 1500 mg of glucosamine per day reduced tibiofemoral joint space narrowing, while supplementation with about 800 mg/d of chondroitin reduced pain intensity and improved physical function, compared with placebo. The duo of glucosamine and chondroitin did not bring significant benefits, perhaps because more studies are needed. Most side effects were mild, but some literature points to the potential for glucosamine to increase warfarin’s blood-thinning effects.

Omega-3 fatty acids. Fish oil is a top-selling supplement, and it might be helpful in inflammatory rheumatologic diseases. A systematic review of 30 studies including 710 patients published in Arthritis Research & Therapy showed that omega-3 fatty acid supplements can improve pain, swollen and tender joint count, DAS28 scores, and Health Assessment Questionnaire scores in patients with RA, psoriatic arthritis, or ankylosing spondylitis. In patients with lupus, a study review that included five studies and 284 patients in The International Journal of Environmental Research and Public Health suggested omega-3 fatty acid supplements could improve ESR, CRP, disease activity, inflammatory markers, oxidative stress, lipid levels, and endothelial function.

Omega-3 fatty acids have anti-inflammatory effects that might explain their benefits. In patients with RA, for example, fish oil supplementation was associated with elevated blood levels of resolvins and protectins, which help quell inflammation, according to a study in Prostaglandins, Leukotrienes and Essential Fatty Acids.

Philippou and Nikiphorou recommended combining food and supplements: Eat oily fish at least twice a week, regularly consume plant-based sources of omega-3s — like chia seeds, flaxseeds, or walnuts — and consider a daily supplement that contains 2 g of omega-3s from docosahexaenoic acid and eicosapentaenoic acid. Most fish oil side effects are mild, like heartburn and bad breath. Fish oil can have blood-thinning effects at high doses, so special attention is needed for patients on anticoagulants.

Probiotics. Building up the good bacteria in your gut might help you fight the effects of rheumatologic diseases. A systematic review of 80 randomized controlled trials in BMC Medicine suggested that therapies targeting the gut microbiota might improve the symptoms or inflammatory factors in celiac disease, lupus, juvenile idiopathic arthritis, psoriasis, Sjögren’s disease, multiple sclerosis, systemic sclerosis, Crohn’s disease, and ulcerative colitis. Probiotics were also shown to relieve pain in fibromyalgia, but they didn’t affect scores on the Fibromyalgia Impact Questionnaire. Probiotics were not helpful in spondyloarthritis or RA. There were no adverse events. By improving the balance of bacteria in the gut, probiotics might inhibit pro-inflammatory factors and signaling pathways and regulate CD4+ T-cell differentiation, the researchers wrote.

Not all probiotic supplements are created equal. Effects can vary by microorganism and dose. Until more high-quality studies are published, Philippou and Nikiphorou recommend daily consumption of probiotic food sources such as yogurt, kefir, sauerkraut, kimchi, tempeh, miso, and kombucha, along with prebiotic food sources such as bananas, onion, artichokes, asparagus, oats, leeks, and garlic.

Collagen. An increasingly popular supplement for hair, skin, and nails, some collagen peptide or hydrolyzed collagen supplements come with claims about joint health, too. Inside our bodies, collagen helps build joints. As a supplement, the jury is still out. A systematic review of 19 studies in The International Journal of Rheumatic Diseases suggested more research is needed to determine whether collagen supplements are harmful or helpful in OA or RA. Studies haven’t shown adverse events, and doses typically range from 2.5 to 15 g/d.

Coenzyme Q10 (CoQ10). This antioxidant occurs naturally in our cells and is produced through microbial fermentation for use in dietary supplements. A study review of 20 articles including 483 patients in Clinical Nutrition ESPEN concluded that CoQ10 supplementation up to 300 mg/d was beneficial in RA, fibromyalgia, or antiphospholipid syndrome (APS).

In RA, CoQ10 supplementation improved disease activity index, ESR, and cytokine levels and decreased malondialdehyde. CoQ10 might protect against the overproduction of reactive oxygen species that can promote inflammation and joint damage, the researchers said. In fibromyalgia, CoQ10 was linked with improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire in most of the included studies. CoQ10 might help in fibromyalgia by improving mitochondrial dysfunction. In APS, CoQ10 improved endothelial function and decreased prothrombotic and pro-inflammatory mediators. CoQ10 might change the expression of genes that promote atherosclerosis. A few patients had GI side effects like nausea and diarrhea, but the supplements were generally well tolerated.

Melatonin. Commonly touted as a sleep aid, this hormone has immune and anti-inflammatory activities that could benefit people with rheumatologic diseases. A study review of 13 articles including 533 patients in Clinical Nutrition ESPEN concluded that melatonin can help improve sleep, pain, and mood in fibromyalgia, OA, and osteoporosis but not in RA. Side effects were minimal, but a few people experienced nausea, drowsiness, nightmares, or headaches. Doses of 5-6 mg/d are likely safe for most adults.
 

The Plant-Derived Antioxidants

Many supplements used in rheumatology are antioxidants derived from herbs, spices, or other plants. When plants encounter stressors, like temperature changes or hungry insects, their secondary metabolism revs up and creates compounds with biological properties. Some of these substances influence inflammatory pathways in the human body, said Luís Silva, PhD, a medicinal chemistry researcher at the Polytechnic Institute of Guarda in Portugal. “If it is possible to reduce these kinds of anti-inflammatory processes, it is also possible that we could help people with inflammatory diseases to a good life, or a better life.”

Dr. Luís Silva

Turmeric and curcumin. You might see this supplement labeled as turmeric, a golden spice in curry powder, or curcumin, an antioxidant compound known as a curcuminoid in turmeric. Curcuminoids might reduce inflammation by scavenging free radicals and inhibiting enzymes that make prostaglandins, Silva said.

Turmeric is the most popular herbal supplement for people with RA, according to Funk’s research. A study review of six publications including 539 patients in Frontiers in Immunology showed that curcumin supplements improved RA patients’ ESR, DAS, swollen joint count, and tender joint count. Turmeric could help patients with OA, too. Patients with OA who took 1000 mg/d of curcumin improved their pain and function, according to a systematic review including 12 studies and 1438 participants in the journal Nutrients. In lupus, small studies are promising but inconclusive, suggested a study review in Frontiers in Immunology.

Watch patients taking turmeric and methotrexate closely, Funk said. Both have been associated with liver problems. Some users also experience GI symptoms like diarrhea because turmeric doesn’t absorb well in the GI tract.

Milk thistle (silymarin). This flowering plant is often marketed as a liver-supporting supplement, but research also suggests promise in RA and OA. A systematic review of 12 studies in Current Rheumatology Reviews suggested that silymarin supplements might help relieve pain, reduce inflammation, and protect the cartilage matrix, synovial membrane, and cartilage cells in joints. This supplement might help via immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic properties, the researchers said. Doses of 250-750 mg appear to be safe. Side effects such as gastroenteritis, diarrhea, bloating, and headache can occur.

Boswellia serrata. Sourced from the resin of a tree that grows in dry, mountainous regions of Asia and Africa, Boswellia serrata can help relieve joint pain and stiffness and improve joint function in OA, suggested a systematic review of seven trials involving 545 patients in BMC Complementary Medicine and Therapies. Users saw benefits when taking 100-250 mg/d for 4 weeks or more. Compounds in Boswellia serrata may inhibit 5-lipoxygenase, an enzyme involved in producing inflammatory leukotrienes. No adverse events were reported. In some studies, users have reported GI side effects.

Ginger. Ginger is a popular herbal supplement among people with RA, Funk’s research suggested. One small clinical trial involving 70 patients with RA in the journal Gene showed that taking 1500 mg/d of ginger for 12 weeks improved their DAS and boosted their expression of FoxP3 genes, which are linked with the function of regulatory T cells. A meta-analysis including three studies with 330 patients taking ginger published in the journal Nutrients suggested ginger can reduce pain and systemic inflammation in people with OA. Preclinical studies suggested phenolic compounds in this spicy root, such as gingerols, reduce inflammation through multiple mechanisms.

Funk’s research revealed wide variation in the quality of ginger supplements, reinforcing the importance of selecting an independently verified product. Research suggested a safe dose is up to 2-2.5 g/kg body weight.

Resveratrol. Found in red grapes and red wine, this compound is particularly good at blocking COX-2 enzymes, an important step in the inflammatory cascade, Silva said. “Because of their chemical structure, they have great affinity to these enzymes to lead to their inhibition,” he said. A study review of five articles including 481 patients in The European Journal of Rheumatology showed that people with OA, RA, or Takayasu arteritis who took 250-1000 mg/d of resveratrol saw improvements in pain, function, disease activity, joint swelling, and inflammation, with no side effects.

Cinnamon. This warming spice is gaining popularity as a supplement, reported the American Botanical Council. Cinnamon is often marketed as lowering blood sugar and supporting bone health. In a small study of 36 women with RA published in The Journal of the American College of Nutrition, participants who consumed 2 g/d of cinnamon powder had reduced DASs along with reduced pain and tender and swollen joint counts. Cinnamon may reduce pain by inhibiting prostaglandin and blunt inflammation by reducing the release of arachidonic acid from cell membranes, according to a study review in Frontiers in Pharmacology. GI problems and allergic reactions are among the most common side effects.

Funk, Nikiphorou, Philippou, and Silva all had no relevant disclosures.

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

Many people with rheumatologic diseases try supplements for symptom relief. Here’s what you need to know about some common picks.

Dietary supplements were a $159 billion business in the United States in 2023, and many people with rheumatologic diseases are buying in. Research suggests more than 6 in 10 people with fibromyalgia, nearly 8 in 10 people with Sjögren’s disease, and more than 8 in 10 people with rheumatoid arthritis (RA) take dietary supplements.

Whatever the symptom — pain, swelling, or fatigue — you can probably find a supplement purporting to relieve it. But do these supplements work, and are they safe? A study review in RMD Open comprising 24 systematic reviews and 150 original articles suggests more high-quality research is needed on the effects of dietary supplements on rheumatologic diseases. Most studies have focused on RA or osteoarthritis (OA), where the evidence level is moderate at best.

Dr. Janet Funk

“The studies in this space are usually not very high quality because there’s no money to support them, among other things, plus the products are disparate,” said Janet Funk, MD, MS, professor in the School of Nutritional Sciences and Wellness at the University of Arizona, Tucson. She recommended brushing up on supplements and finding out what patients are taking so you can offer advice and watch for drug-supplement interactions.

When asked for a medication list, many patients forget to report supplements, Funk said. “You have to prompt them specifically. I think some physicians have very negative views about supplements because so little data is known, and patients might pick up on that and decide not to report their use.” She recommended saying something like: “To give you the best possible care, I want to know everything you’re taking, including supplements. The things I’m prescribing could maybe interact with the things you’re taking, so I want to make sure I know about all of it so that together we can figure out if the combination of things is safe.”

The quality of dietary supplements varies, and they aren’t regulated like drugs by the Food and Drug Administration. Funk recommended selecting products verified by NSF or ConsumerLab. They test supplements to ensure the label reflects what’s inside.

This news organization scoured the literature and asked experts to weigh in on the evidence behind popular supplements in rheumatology today.
 

The Essential Nutrients

Vitamin supplements are a staple in many homes — but are they helpful? “Individual vitamin supplements will not provide any benefit unless the person is deficient in a specific vitamin or mineral,” according to Elena Philippou, PhD, RD, associate professor of nutrition-dietetics at the University of Nicosia in Cyprus, and Elena Nikiphorou, MBBS, a rheumatologist at King’s College London in England. For some patients, deficiency is a reality. A retrospective cohort study in The Journal of Clinical Medicine found that people with RA were 17% more likely than age-matched control individuals to have nutrient deficiencies, perhaps because symptoms like fatigue, pain, and nausea affect their eating habits. Here’s what the science says about common vitamin supplements.

Dr. Elena Philippou

Vitamin D. This hormone-like vitamin, which attaches to receptors on immune cells to tamp down inflammation, was the most popular dietary supplement among rheumatology patients in a recent study from the United Kingdom. Vitamin D deficiency is common in people with RA, lupus, Sjögren’s disease, ankylosing spondylitis, systemic sclerosis, and fibromyalgia. In some cases, vitamin D levels track with disease activity, research suggests. Corticosteroids can also make vitamin D deficiency more likely. Can supplements help?

In RA, evidence points to small improvements. A systematic review of 11 studies including 3049 patients published in Nutrition Reviews showed that vitamin D supplements significantly reduced patients’ pain and Disease Activity Score in 28 joints (DAS28) using both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

The research is mixed on the benefits of vitamin D supplementation for fibromyalgia symptoms, according to a study review in SN Comprehensive Clinical Medicine that included two studies and 80 patients on supplementation. However, researchers said it’s still worth discussing the potential benefits of taking vitamin D.

“Vitamin D supplementation is important in the context of various rheumatic diseases to prevent or treat bone disease,” said Philippou and Nikiphorou. “People with rheumatic disease should speak to their healthcare provider and ask to check their blood vitamin D concentration.” The results can help you recommend a dose.

Folate. Patients on methotrexate should take folic acid supplements under the guidance of a healthcare provider, said Philippou and Nikiphorou. The reason: Methotrexate can deplete folic acid levels, increasing the risk for side effects. An analysis of adverse event reports published showed that methotrexate users who took folic acid (or tumor necrosis factor–alpha inhibitors) had a reduced risk for hepatotoxicity or myelosuppression. A commonly recommended dose is 1 mg/d.

Vitamin B12. In a 2024 perspective paper in Rheumatology International, researchers said physicians should assess vitamin B12 levels early in the diagnostic process of rheumatologic diseases. One reason: Many symptoms of pernicious anemia, like fatigue, mimic symptoms of rheumatologic diseases. The gastrointestinal (GI) effects of systemic sclerosis could bring on vitamin B12 deficiency. In a small study in The Journal of Clinical Rheumatology, 44 of 62 patients with systemic sclerosis had low vitamin B12 levels.

Vitamin E. Vitamin E deficiency is rare in healthy adults. However, some medical conditions, like inflammatory bowel disease and malabsorption disorders, can make vitamin E deficiency more likely. In RA, a vitamin E supplement could help reduce joint swelling and sensitivity, according to a systematic review of nine studies including 39,845 patients in The European Journal of Clinical Nutrition. Researchers credit the nutrient’s role in aiding intestinal repair. Use with caution, as this supplement can increase bleeding risk in doses over 1000 mg/d.

Vitamin A. Like vitamin E, vitamin A deficiency is rare in the United States. The risk of oversupplementing is higher than undersupplementing. However, vitamin A deficiency can happen in people with chronic pancreatic, liver, or GI problems. In people with deficiency, a vitamin A supplement can help relieve dry eye symptoms common in Sjögren’s disease, suggests a narrative review published in Nutrients. Vitamin A might help reduce ocular surface changes by supporting the production of proteins that protect the outermost surfaces of the eyes. The recommended daily allowance for vitamin A is 900 μg. High-dose supplements can cause toxicity, resulting in GI symptoms and problems like lethargy, drowsiness, increased intracranial pressure, and skin changes.
 

The Replacements

These substances are similar to naturally occurring compounds in our bodies. The question is whether ingesting them yields benefits.

Glucosamine and chondroitin. Glucosamine and chondroitin occur naturally in our bodies and help us form and protect connective tissues. In pill form, this combo is the most popular dietary supplement for OA, according to research in the journal Maturitas. But studies of its effectiveness yield mixed results. A systematic review of 25 studies published in Inflammopharmacology showed that, in patients with knee OA, supplementation with about 1500 mg of glucosamine per day reduced tibiofemoral joint space narrowing, while supplementation with about 800 mg/d of chondroitin reduced pain intensity and improved physical function, compared with placebo. The duo of glucosamine and chondroitin did not bring significant benefits, perhaps because more studies are needed. Most side effects were mild, but some literature points to the potential for glucosamine to increase warfarin’s blood-thinning effects.

Omega-3 fatty acids. Fish oil is a top-selling supplement, and it might be helpful in inflammatory rheumatologic diseases. A systematic review of 30 studies including 710 patients published in Arthritis Research & Therapy showed that omega-3 fatty acid supplements can improve pain, swollen and tender joint count, DAS28 scores, and Health Assessment Questionnaire scores in patients with RA, psoriatic arthritis, or ankylosing spondylitis. In patients with lupus, a study review that included five studies and 284 patients in The International Journal of Environmental Research and Public Health suggested omega-3 fatty acid supplements could improve ESR, CRP, disease activity, inflammatory markers, oxidative stress, lipid levels, and endothelial function.

Omega-3 fatty acids have anti-inflammatory effects that might explain their benefits. In patients with RA, for example, fish oil supplementation was associated with elevated blood levels of resolvins and protectins, which help quell inflammation, according to a study in Prostaglandins, Leukotrienes and Essential Fatty Acids.

Philippou and Nikiphorou recommended combining food and supplements: Eat oily fish at least twice a week, regularly consume plant-based sources of omega-3s — like chia seeds, flaxseeds, or walnuts — and consider a daily supplement that contains 2 g of omega-3s from docosahexaenoic acid and eicosapentaenoic acid. Most fish oil side effects are mild, like heartburn and bad breath. Fish oil can have blood-thinning effects at high doses, so special attention is needed for patients on anticoagulants.

Probiotics. Building up the good bacteria in your gut might help you fight the effects of rheumatologic diseases. A systematic review of 80 randomized controlled trials in BMC Medicine suggested that therapies targeting the gut microbiota might improve the symptoms or inflammatory factors in celiac disease, lupus, juvenile idiopathic arthritis, psoriasis, Sjögren’s disease, multiple sclerosis, systemic sclerosis, Crohn’s disease, and ulcerative colitis. Probiotics were also shown to relieve pain in fibromyalgia, but they didn’t affect scores on the Fibromyalgia Impact Questionnaire. Probiotics were not helpful in spondyloarthritis or RA. There were no adverse events. By improving the balance of bacteria in the gut, probiotics might inhibit pro-inflammatory factors and signaling pathways and regulate CD4+ T-cell differentiation, the researchers wrote.

Not all probiotic supplements are created equal. Effects can vary by microorganism and dose. Until more high-quality studies are published, Philippou and Nikiphorou recommend daily consumption of probiotic food sources such as yogurt, kefir, sauerkraut, kimchi, tempeh, miso, and kombucha, along with prebiotic food sources such as bananas, onion, artichokes, asparagus, oats, leeks, and garlic.

Collagen. An increasingly popular supplement for hair, skin, and nails, some collagen peptide or hydrolyzed collagen supplements come with claims about joint health, too. Inside our bodies, collagen helps build joints. As a supplement, the jury is still out. A systematic review of 19 studies in The International Journal of Rheumatic Diseases suggested more research is needed to determine whether collagen supplements are harmful or helpful in OA or RA. Studies haven’t shown adverse events, and doses typically range from 2.5 to 15 g/d.

Coenzyme Q10 (CoQ10). This antioxidant occurs naturally in our cells and is produced through microbial fermentation for use in dietary supplements. A study review of 20 articles including 483 patients in Clinical Nutrition ESPEN concluded that CoQ10 supplementation up to 300 mg/d was beneficial in RA, fibromyalgia, or antiphospholipid syndrome (APS).

In RA, CoQ10 supplementation improved disease activity index, ESR, and cytokine levels and decreased malondialdehyde. CoQ10 might protect against the overproduction of reactive oxygen species that can promote inflammation and joint damage, the researchers said. In fibromyalgia, CoQ10 was linked with improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire in most of the included studies. CoQ10 might help in fibromyalgia by improving mitochondrial dysfunction. In APS, CoQ10 improved endothelial function and decreased prothrombotic and pro-inflammatory mediators. CoQ10 might change the expression of genes that promote atherosclerosis. A few patients had GI side effects like nausea and diarrhea, but the supplements were generally well tolerated.

Melatonin. Commonly touted as a sleep aid, this hormone has immune and anti-inflammatory activities that could benefit people with rheumatologic diseases. A study review of 13 articles including 533 patients in Clinical Nutrition ESPEN concluded that melatonin can help improve sleep, pain, and mood in fibromyalgia, OA, and osteoporosis but not in RA. Side effects were minimal, but a few people experienced nausea, drowsiness, nightmares, or headaches. Doses of 5-6 mg/d are likely safe for most adults.
 

The Plant-Derived Antioxidants

Many supplements used in rheumatology are antioxidants derived from herbs, spices, or other plants. When plants encounter stressors, like temperature changes or hungry insects, their secondary metabolism revs up and creates compounds with biological properties. Some of these substances influence inflammatory pathways in the human body, said Luís Silva, PhD, a medicinal chemistry researcher at the Polytechnic Institute of Guarda in Portugal. “If it is possible to reduce these kinds of anti-inflammatory processes, it is also possible that we could help people with inflammatory diseases to a good life, or a better life.”

Dr. Luís Silva

Turmeric and curcumin. You might see this supplement labeled as turmeric, a golden spice in curry powder, or curcumin, an antioxidant compound known as a curcuminoid in turmeric. Curcuminoids might reduce inflammation by scavenging free radicals and inhibiting enzymes that make prostaglandins, Silva said.

Turmeric is the most popular herbal supplement for people with RA, according to Funk’s research. A study review of six publications including 539 patients in Frontiers in Immunology showed that curcumin supplements improved RA patients’ ESR, DAS, swollen joint count, and tender joint count. Turmeric could help patients with OA, too. Patients with OA who took 1000 mg/d of curcumin improved their pain and function, according to a systematic review including 12 studies and 1438 participants in the journal Nutrients. In lupus, small studies are promising but inconclusive, suggested a study review in Frontiers in Immunology.

Watch patients taking turmeric and methotrexate closely, Funk said. Both have been associated with liver problems. Some users also experience GI symptoms like diarrhea because turmeric doesn’t absorb well in the GI tract.

Milk thistle (silymarin). This flowering plant is often marketed as a liver-supporting supplement, but research also suggests promise in RA and OA. A systematic review of 12 studies in Current Rheumatology Reviews suggested that silymarin supplements might help relieve pain, reduce inflammation, and protect the cartilage matrix, synovial membrane, and cartilage cells in joints. This supplement might help via immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic properties, the researchers said. Doses of 250-750 mg appear to be safe. Side effects such as gastroenteritis, diarrhea, bloating, and headache can occur.

Boswellia serrata. Sourced from the resin of a tree that grows in dry, mountainous regions of Asia and Africa, Boswellia serrata can help relieve joint pain and stiffness and improve joint function in OA, suggested a systematic review of seven trials involving 545 patients in BMC Complementary Medicine and Therapies. Users saw benefits when taking 100-250 mg/d for 4 weeks or more. Compounds in Boswellia serrata may inhibit 5-lipoxygenase, an enzyme involved in producing inflammatory leukotrienes. No adverse events were reported. In some studies, users have reported GI side effects.

Ginger. Ginger is a popular herbal supplement among people with RA, Funk’s research suggested. One small clinical trial involving 70 patients with RA in the journal Gene showed that taking 1500 mg/d of ginger for 12 weeks improved their DAS and boosted their expression of FoxP3 genes, which are linked with the function of regulatory T cells. A meta-analysis including three studies with 330 patients taking ginger published in the journal Nutrients suggested ginger can reduce pain and systemic inflammation in people with OA. Preclinical studies suggested phenolic compounds in this spicy root, such as gingerols, reduce inflammation through multiple mechanisms.

Funk’s research revealed wide variation in the quality of ginger supplements, reinforcing the importance of selecting an independently verified product. Research suggested a safe dose is up to 2-2.5 g/kg body weight.

Resveratrol. Found in red grapes and red wine, this compound is particularly good at blocking COX-2 enzymes, an important step in the inflammatory cascade, Silva said. “Because of their chemical structure, they have great affinity to these enzymes to lead to their inhibition,” he said. A study review of five articles including 481 patients in The European Journal of Rheumatology showed that people with OA, RA, or Takayasu arteritis who took 250-1000 mg/d of resveratrol saw improvements in pain, function, disease activity, joint swelling, and inflammation, with no side effects.

Cinnamon. This warming spice is gaining popularity as a supplement, reported the American Botanical Council. Cinnamon is often marketed as lowering blood sugar and supporting bone health. In a small study of 36 women with RA published in The Journal of the American College of Nutrition, participants who consumed 2 g/d of cinnamon powder had reduced DASs along with reduced pain and tender and swollen joint counts. Cinnamon may reduce pain by inhibiting prostaglandin and blunt inflammation by reducing the release of arachidonic acid from cell membranes, according to a study review in Frontiers in Pharmacology. GI problems and allergic reactions are among the most common side effects.

Funk, Nikiphorou, Philippou, and Silva all had no relevant disclosures.

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

LOS ANGELES — Metformin prescribed within a week of SARS-CoV-2 infection was associated with a 53% reduction in long COVID or death over 6 months in people without diabetes or prediabetes, according to data presented at the Infectious Disease Week (IDWeek) 2024 Annual Meeting.

Long COVID was determined by using the diagnostic code U09.9 or a computable phenotype based on symptoms and conditions. Most participants in this study were infected with the Omicron variant.

Researchers, led by Carolyn Bramante, MD, MPH, an internist, pediatrician, and obesity medicine specialist at the University of Minnesota Medical School in Minneapolis, simulated a randomized controlled trial of metformin vs control using the National COVID Cohort Collaborative (N3C) Electronic Health Record Database.

The intervention was a prescription for metformin within 6 days of SARS-CoV-2 infection. Those in the control group, which was designed to mimic placebo, had a prescription for fluvoxamine, fluticasone, ivermectin, or montelukast (all drugs that have been used off-label for COVID but have shown no effect on acute COVID outcomes in clinical trials). Exclusions included anyone with a previous metformin prescription or a comparator prescription; any indication for chronic metformin use; or a contraindication for metformin.
 

Why Study Metformin for Long COVID?

Dr. Bramante led a previous randomized controlled trial, COVID-OUT, with 1323 people that indicated metformin showed possible benefit for preventing the more severe components of COVID-19. She also led a 2020 review, in which she examined electronic health records from adults with type 2 diabetes or obesity. The researchers found that women taking metformin before they developed COVID-19 were significantly less likely to die after being hospitalized — although men didn’t see the same protective effect. Another randomized trial of 20 people found that 60% of those taking metformin vs 100% of those given a placebo had detectable SARS-CoV-2 viral load by day 4.

Other trials have highlighted the anti-inflammatory and antiviral properties of metformin. The existing evidence coupled with metformin’s well-established safety profile, led Dr. Bramante’s team to conduct the current simulated trial in people without diabetes or prediabetes. Dr. Bramante noted that metformin’s only US Food and Drug Administration–approved indication is for diabetes.

The current study featured a similar racial/ethnic makeup in the metformin and control groups: 16% and 17% were Black and 16% and 13% were Hispanic, respectively. Within 6 months, 4.0% in the metformin group developed long COVID or died compared with 8.5% in the control group (Relative Risk [RR], 0.47; 95% CI, 0.25-0.89). For prescriptions made on days 0-1 relative to infection, the RR was 0.39 (95% CI, 0.12-1.24). When metformin was prescribed on days 0-14, the RR was 0.75 (95% CI, 0.52-1.08).

The reason it’s important to have an active comparator is to control for things that can’t be measured, such as engagement in healthcare and the placebo effect, Dr. Bramante said.

Emily Erbelding, MD, MPH, director of the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, who was not part of the study, noted the potential implications of the findings.
 

Proven Safety and Low Cost of Metformin 

“We don’t have therapies for long COVID, and we don’t know how to prevent it in people who have SARS-CoV-2 infections,” Dr. Erbelding noted. “This analysis points to metformin, a drug that millions of people have taken safely for their diabetes or their borderline diabetes. It’s licensed, it’s out there, and it’s inexpensive. The fact that we have data that point to this potentially being a therapy is important. I think that’s the power of this.”

Dr. Erbelding said a strength of the study is the size of the N3C Electronic Health Record Database (with data on nearly 9 million COVID cases) the researchers used to simulate the randomized controlled trial.

“(These results) gives us a reason to think about doing a large randomized controlled study with metformin,” she said. However, there are some limitations, she noted.

“The definition of long COVID may not have been applied exactly the same way across all the patients and you don’t know what led the prescribers to prescribe metformin. There might have been confounders that couldn’t be controlled for or weren’t evident in the way they approached the data.”

This study has “relatively rigorous methodology for an observational study,” Dr. Erbelding said. “It’s novel to try to simulate a randomized controlled trial through a large, observational, electronic record–based cohort. Maybe we should be doing more of this because these bioinformatic systems exist now. And we need to get all the public health use out of them that we can.” 

“The fact that they may be unlocking something new here that needs follow-up in a truly randomized controlled trial is important as well because there are a lot of people out there suffering from long COVID.”

Bramante and Erbelding disclosed no relevant financial relationships. This research was supported in part by the intramural/extramural research program of the National Center for Advancing Translational Science, National Institutes of Health.
 

A version of this article appeared on Medscape.com.

LOS ANGELES — Metformin prescribed within a week of SARS-CoV-2 infection was associated with a 53% reduction in long COVID or death over 6 months in people without diabetes or prediabetes, according to data presented at the Infectious Disease Week (IDWeek) 2024 Annual Meeting.

Long COVID was determined by using the diagnostic code U09.9 or a computable phenotype based on symptoms and conditions. Most participants in this study were infected with the Omicron variant.

Researchers, led by Carolyn Bramante, MD, MPH, an internist, pediatrician, and obesity medicine specialist at the University of Minnesota Medical School in Minneapolis, simulated a randomized controlled trial of metformin vs control using the National COVID Cohort Collaborative (N3C) Electronic Health Record Database.

The intervention was a prescription for metformin within 6 days of SARS-CoV-2 infection. Those in the control group, which was designed to mimic placebo, had a prescription for fluvoxamine, fluticasone, ivermectin, or montelukast (all drugs that have been used off-label for COVID but have shown no effect on acute COVID outcomes in clinical trials). Exclusions included anyone with a previous metformin prescription or a comparator prescription; any indication for chronic metformin use; or a contraindication for metformin.
 

Why Study Metformin for Long COVID?

Dr. Bramante led a previous randomized controlled trial, COVID-OUT, with 1323 people that indicated metformin showed possible benefit for preventing the more severe components of COVID-19. She also led a 2020 review, in which she examined electronic health records from adults with type 2 diabetes or obesity. The researchers found that women taking metformin before they developed COVID-19 were significantly less likely to die after being hospitalized — although men didn’t see the same protective effect. Another randomized trial of 20 people found that 60% of those taking metformin vs 100% of those given a placebo had detectable SARS-CoV-2 viral load by day 4.

Other trials have highlighted the anti-inflammatory and antiviral properties of metformin. The existing evidence coupled with metformin’s well-established safety profile, led Dr. Bramante’s team to conduct the current simulated trial in people without diabetes or prediabetes. Dr. Bramante noted that metformin’s only US Food and Drug Administration–approved indication is for diabetes.

The current study featured a similar racial/ethnic makeup in the metformin and control groups: 16% and 17% were Black and 16% and 13% were Hispanic, respectively. Within 6 months, 4.0% in the metformin group developed long COVID or died compared with 8.5% in the control group (Relative Risk [RR], 0.47; 95% CI, 0.25-0.89). For prescriptions made on days 0-1 relative to infection, the RR was 0.39 (95% CI, 0.12-1.24). When metformin was prescribed on days 0-14, the RR was 0.75 (95% CI, 0.52-1.08).

The reason it’s important to have an active comparator is to control for things that can’t be measured, such as engagement in healthcare and the placebo effect, Dr. Bramante said.

Emily Erbelding, MD, MPH, director of the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, who was not part of the study, noted the potential implications of the findings.
 

Proven Safety and Low Cost of Metformin 

“We don’t have therapies for long COVID, and we don’t know how to prevent it in people who have SARS-CoV-2 infections,” Dr. Erbelding noted. “This analysis points to metformin, a drug that millions of people have taken safely for their diabetes or their borderline diabetes. It’s licensed, it’s out there, and it’s inexpensive. The fact that we have data that point to this potentially being a therapy is important. I think that’s the power of this.”

Dr. Erbelding said a strength of the study is the size of the N3C Electronic Health Record Database (with data on nearly 9 million COVID cases) the researchers used to simulate the randomized controlled trial.

“(These results) gives us a reason to think about doing a large randomized controlled study with metformin,” she said. However, there are some limitations, she noted.

“The definition of long COVID may not have been applied exactly the same way across all the patients and you don’t know what led the prescribers to prescribe metformin. There might have been confounders that couldn’t be controlled for or weren’t evident in the way they approached the data.”

This study has “relatively rigorous methodology for an observational study,” Dr. Erbelding said. “It’s novel to try to simulate a randomized controlled trial through a large, observational, electronic record–based cohort. Maybe we should be doing more of this because these bioinformatic systems exist now. And we need to get all the public health use out of them that we can.” 

“The fact that they may be unlocking something new here that needs follow-up in a truly randomized controlled trial is important as well because there are a lot of people out there suffering from long COVID.”

Bramante and Erbelding disclosed no relevant financial relationships. This research was supported in part by the intramural/extramural research program of the National Center for Advancing Translational Science, National Institutes of Health.
 

A version of this article appeared on Medscape.com.

LOS ANGELES — Metformin prescribed within a week of SARS-CoV-2 infection was associated with a 53% reduction in long COVID or death over 6 months in people without diabetes or prediabetes, according to data presented at the Infectious Disease Week (IDWeek) 2024 Annual Meeting.

Long COVID was determined by using the diagnostic code U09.9 or a computable phenotype based on symptoms and conditions. Most participants in this study were infected with the Omicron variant.

Researchers, led by Carolyn Bramante, MD, MPH, an internist, pediatrician, and obesity medicine specialist at the University of Minnesota Medical School in Minneapolis, simulated a randomized controlled trial of metformin vs control using the National COVID Cohort Collaborative (N3C) Electronic Health Record Database.

The intervention was a prescription for metformin within 6 days of SARS-CoV-2 infection. Those in the control group, which was designed to mimic placebo, had a prescription for fluvoxamine, fluticasone, ivermectin, or montelukast (all drugs that have been used off-label for COVID but have shown no effect on acute COVID outcomes in clinical trials). Exclusions included anyone with a previous metformin prescription or a comparator prescription; any indication for chronic metformin use; or a contraindication for metformin.
 

Why Study Metformin for Long COVID?

Dr. Bramante led a previous randomized controlled trial, COVID-OUT, with 1323 people that indicated metformin showed possible benefit for preventing the more severe components of COVID-19. She also led a 2020 review, in which she examined electronic health records from adults with type 2 diabetes or obesity. The researchers found that women taking metformin before they developed COVID-19 were significantly less likely to die after being hospitalized — although men didn’t see the same protective effect. Another randomized trial of 20 people found that 60% of those taking metformin vs 100% of those given a placebo had detectable SARS-CoV-2 viral load by day 4.

Other trials have highlighted the anti-inflammatory and antiviral properties of metformin. The existing evidence coupled with metformin’s well-established safety profile, led Dr. Bramante’s team to conduct the current simulated trial in people without diabetes or prediabetes. Dr. Bramante noted that metformin’s only US Food and Drug Administration–approved indication is for diabetes.

The current study featured a similar racial/ethnic makeup in the metformin and control groups: 16% and 17% were Black and 16% and 13% were Hispanic, respectively. Within 6 months, 4.0% in the metformin group developed long COVID or died compared with 8.5% in the control group (Relative Risk [RR], 0.47; 95% CI, 0.25-0.89). For prescriptions made on days 0-1 relative to infection, the RR was 0.39 (95% CI, 0.12-1.24). When metformin was prescribed on days 0-14, the RR was 0.75 (95% CI, 0.52-1.08).

The reason it’s important to have an active comparator is to control for things that can’t be measured, such as engagement in healthcare and the placebo effect, Dr. Bramante said.

Emily Erbelding, MD, MPH, director of the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, who was not part of the study, noted the potential implications of the findings.
 

Proven Safety and Low Cost of Metformin 

“We don’t have therapies for long COVID, and we don’t know how to prevent it in people who have SARS-CoV-2 infections,” Dr. Erbelding noted. “This analysis points to metformin, a drug that millions of people have taken safely for their diabetes or their borderline diabetes. It’s licensed, it’s out there, and it’s inexpensive. The fact that we have data that point to this potentially being a therapy is important. I think that’s the power of this.”

Dr. Erbelding said a strength of the study is the size of the N3C Electronic Health Record Database (with data on nearly 9 million COVID cases) the researchers used to simulate the randomized controlled trial.

“(These results) gives us a reason to think about doing a large randomized controlled study with metformin,” she said. However, there are some limitations, she noted.

“The definition of long COVID may not have been applied exactly the same way across all the patients and you don’t know what led the prescribers to prescribe metformin. There might have been confounders that couldn’t be controlled for or weren’t evident in the way they approached the data.”

This study has “relatively rigorous methodology for an observational study,” Dr. Erbelding said. “It’s novel to try to simulate a randomized controlled trial through a large, observational, electronic record–based cohort. Maybe we should be doing more of this because these bioinformatic systems exist now. And we need to get all the public health use out of them that we can.” 

“The fact that they may be unlocking something new here that needs follow-up in a truly randomized controlled trial is important as well because there are a lot of people out there suffering from long COVID.”

Bramante and Erbelding disclosed no relevant financial relationships. This research was supported in part by the intramural/extramural research program of the National Center for Advancing Translational Science, National Institutes of Health.
 

A version of this article appeared on Medscape.com.

A “digital twin” model successfully predicted adverse outcomes in intensive care unit (ICU) patients treated for sepsis. The research used an adaptive approach, updating time-sensitive values such as blood pressure and vitals every 15 minutes. The approach also took into account treatment decisions and has potential as a decision-making and educational tool.

The digital twin could reduce the risk for some interventions, according to Amos Lal, MD, who presented the study at the CHEST Annual Meeting. That’s because the model can predict the outcome. “You don’t actually have to make an intervention to the patient, which might be risky. By doing that, you can actually prevent a lot of harm,” said Dr. Lal, assistant professor of medicine at Mayo Clinic in Rochester, Minnesota.

The researchers used a one-dimensional convolutional neural network (CNN), similar to two-dimensional CNNs that are used to classify images, substituting the color channels used in imaging with 38 time-dependent variables. They applied it to predicting outcomes in the ICU, focusing on data generated within the first 24 hours of admission. The team made the model dynamic by adding time-sensitive data like vitals, laboratory values, and interventions every 15 minutes. That contrasts with existing models that are usually static, relying on values at admission or at 24 hours, for example. It also takes into account time-insensitive data like age, gender, and comorbidities. “Combining these two and coming up with the prediction model in real time can give you a more informed decision about how these patients are going to perform over a period of 2 weeks or 4 weeks of their stay within the ICU. And of course, as we get more and more data within the first 24 hours, the performance of the model improves as well,” said Dr. Lal.

The researchers tested the model by creating a virtual model of the patient and then performing an intervention on the patient and a simulated intervention on the virtual patient. “Then we advance the clock and the patient either improved or deteriorated, and we compared how the digital twin performed, whether the changes were concordant or discordant [between the virtual and real-world patients],” said Dr. Lal.

The model was designed to predict which patients with sepsis would be at greater risk for death or ICU stays longer than 14 days. It was created using data from 28,617 patients with critical care sepsis at a single hospital who were treated between 2011 and 2018, with 70% used as a training set, 20% as a test set, and 10% as a validation set. The researchers conducted an external validation using MIMIC-IV data on 30,903 patients from the Beth Israel Deaconess Medical Center in Boston. The model included 31 time-independent variables and 38 time-dependent variables that were collected every 15 minutes at the Mayo Clinic and every 60 minutes at Beth Israel Deaconess. Surgical patients represented 24% of the Mayo dataset and 58% of the MIMIC-IV dataset, but otherwise the two groups were demographically similar.

At 24 hours, the area under the receiver operating characteristic curve for predicting 14-day mortality was −0.82 in the Mayo validation cohort and −0.78 in the MIMIC validation cohort. The model improved in accuracy over time as more data were accumulated.

The session’s co-moderators, Sandeep Jain, MD, and Casey Cable, MD, praised the work. Dr. Cable, associate professor of pulmonary care medicine at VCU Health, Richmond, Virginia, noted that the model used both surgical patients and medical patients with sepsis, and the two groups can present quite differently. Another variable was the COVID pandemic, where some patients presented at the hospital when they were quite sick. “I’m curious how different starting points would play into it,” she said.

She called for institutions to develop such models on their own rather than relying on companies that might develop software solutions. “I think that this needs to be clinician-led, from the ground up,” said Dr. Cable.

Dr. Jain, an associate professor of pulmonary care medicine at Broward Health, suggested that such models might need to be individualized for each institution, but “my fear is it could become too expensive, so I think a group like CHEST could come together and [create] an open source system to have their researchers jumpstart the research on this,” he said.

Dr. Lal, Dr. Jain, and Dr. Cable reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A “digital twin” model successfully predicted adverse outcomes in intensive care unit (ICU) patients treated for sepsis. The research used an adaptive approach, updating time-sensitive values such as blood pressure and vitals every 15 minutes. The approach also took into account treatment decisions and has potential as a decision-making and educational tool.

The digital twin could reduce the risk for some interventions, according to Amos Lal, MD, who presented the study at the CHEST Annual Meeting. That’s because the model can predict the outcome. “You don’t actually have to make an intervention to the patient, which might be risky. By doing that, you can actually prevent a lot of harm,” said Dr. Lal, assistant professor of medicine at Mayo Clinic in Rochester, Minnesota.

The researchers used a one-dimensional convolutional neural network (CNN), similar to two-dimensional CNNs that are used to classify images, substituting the color channels used in imaging with 38 time-dependent variables. They applied it to predicting outcomes in the ICU, focusing on data generated within the first 24 hours of admission. The team made the model dynamic by adding time-sensitive data like vitals, laboratory values, and interventions every 15 minutes. That contrasts with existing models that are usually static, relying on values at admission or at 24 hours, for example. It also takes into account time-insensitive data like age, gender, and comorbidities. “Combining these two and coming up with the prediction model in real time can give you a more informed decision about how these patients are going to perform over a period of 2 weeks or 4 weeks of their stay within the ICU. And of course, as we get more and more data within the first 24 hours, the performance of the model improves as well,” said Dr. Lal.

The researchers tested the model by creating a virtual model of the patient and then performing an intervention on the patient and a simulated intervention on the virtual patient. “Then we advance the clock and the patient either improved or deteriorated, and we compared how the digital twin performed, whether the changes were concordant or discordant [between the virtual and real-world patients],” said Dr. Lal.

The model was designed to predict which patients with sepsis would be at greater risk for death or ICU stays longer than 14 days. It was created using data from 28,617 patients with critical care sepsis at a single hospital who were treated between 2011 and 2018, with 70% used as a training set, 20% as a test set, and 10% as a validation set. The researchers conducted an external validation using MIMIC-IV data on 30,903 patients from the Beth Israel Deaconess Medical Center in Boston. The model included 31 time-independent variables and 38 time-dependent variables that were collected every 15 minutes at the Mayo Clinic and every 60 minutes at Beth Israel Deaconess. Surgical patients represented 24% of the Mayo dataset and 58% of the MIMIC-IV dataset, but otherwise the two groups were demographically similar.

At 24 hours, the area under the receiver operating characteristic curve for predicting 14-day mortality was −0.82 in the Mayo validation cohort and −0.78 in the MIMIC validation cohort. The model improved in accuracy over time as more data were accumulated.

The session’s co-moderators, Sandeep Jain, MD, and Casey Cable, MD, praised the work. Dr. Cable, associate professor of pulmonary care medicine at VCU Health, Richmond, Virginia, noted that the model used both surgical patients and medical patients with sepsis, and the two groups can present quite differently. Another variable was the COVID pandemic, where some patients presented at the hospital when they were quite sick. “I’m curious how different starting points would play into it,” she said.

She called for institutions to develop such models on their own rather than relying on companies that might develop software solutions. “I think that this needs to be clinician-led, from the ground up,” said Dr. Cable.

Dr. Jain, an associate professor of pulmonary care medicine at Broward Health, suggested that such models might need to be individualized for each institution, but “my fear is it could become too expensive, so I think a group like CHEST could come together and [create] an open source system to have their researchers jumpstart the research on this,” he said.

Dr. Lal, Dr. Jain, and Dr. Cable reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A “digital twin” model successfully predicted adverse outcomes in intensive care unit (ICU) patients treated for sepsis. The research used an adaptive approach, updating time-sensitive values such as blood pressure and vitals every 15 minutes. The approach also took into account treatment decisions and has potential as a decision-making and educational tool.

The digital twin could reduce the risk for some interventions, according to Amos Lal, MD, who presented the study at the CHEST Annual Meeting. That’s because the model can predict the outcome. “You don’t actually have to make an intervention to the patient, which might be risky. By doing that, you can actually prevent a lot of harm,” said Dr. Lal, assistant professor of medicine at Mayo Clinic in Rochester, Minnesota.

The researchers used a one-dimensional convolutional neural network (CNN), similar to two-dimensional CNNs that are used to classify images, substituting the color channels used in imaging with 38 time-dependent variables. They applied it to predicting outcomes in the ICU, focusing on data generated within the first 24 hours of admission. The team made the model dynamic by adding time-sensitive data like vitals, laboratory values, and interventions every 15 minutes. That contrasts with existing models that are usually static, relying on values at admission or at 24 hours, for example. It also takes into account time-insensitive data like age, gender, and comorbidities. “Combining these two and coming up with the prediction model in real time can give you a more informed decision about how these patients are going to perform over a period of 2 weeks or 4 weeks of their stay within the ICU. And of course, as we get more and more data within the first 24 hours, the performance of the model improves as well,” said Dr. Lal.

The researchers tested the model by creating a virtual model of the patient and then performing an intervention on the patient and a simulated intervention on the virtual patient. “Then we advance the clock and the patient either improved or deteriorated, and we compared how the digital twin performed, whether the changes were concordant or discordant [between the virtual and real-world patients],” said Dr. Lal.

The model was designed to predict which patients with sepsis would be at greater risk for death or ICU stays longer than 14 days. It was created using data from 28,617 patients with critical care sepsis at a single hospital who were treated between 2011 and 2018, with 70% used as a training set, 20% as a test set, and 10% as a validation set. The researchers conducted an external validation using MIMIC-IV data on 30,903 patients from the Beth Israel Deaconess Medical Center in Boston. The model included 31 time-independent variables and 38 time-dependent variables that were collected every 15 minutes at the Mayo Clinic and every 60 minutes at Beth Israel Deaconess. Surgical patients represented 24% of the Mayo dataset and 58% of the MIMIC-IV dataset, but otherwise the two groups were demographically similar.

At 24 hours, the area under the receiver operating characteristic curve for predicting 14-day mortality was −0.82 in the Mayo validation cohort and −0.78 in the MIMIC validation cohort. The model improved in accuracy over time as more data were accumulated.

The session’s co-moderators, Sandeep Jain, MD, and Casey Cable, MD, praised the work. Dr. Cable, associate professor of pulmonary care medicine at VCU Health, Richmond, Virginia, noted that the model used both surgical patients and medical patients with sepsis, and the two groups can present quite differently. Another variable was the COVID pandemic, where some patients presented at the hospital when they were quite sick. “I’m curious how different starting points would play into it,” she said.

She called for institutions to develop such models on their own rather than relying on companies that might develop software solutions. “I think that this needs to be clinician-led, from the ground up,” said Dr. Cable.

Dr. Jain, an associate professor of pulmonary care medicine at Broward Health, suggested that such models might need to be individualized for each institution, but “my fear is it could become too expensive, so I think a group like CHEST could come together and [create] an open source system to have their researchers jumpstart the research on this,” he said.

Dr. Lal, Dr. Jain, and Dr. Cable reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

BOSTON — Patients with COPD are at an increased risk for fatal pulmonary embolism (PE) and may require personalized, targeted thromboprophylaxis. Those are the conclusions of investigators who analyzed public health data and found that patients with COPD have a markedly increased risk for PE-related death, particularly among those aged 65-85 years.

The data suggest that “maybe we should start thinking about if we are admitting a patient with COPD in that specific age group, higher thromboprophylaxis for PE,” said Marwa Oudah, MD, a pulmonary hypertension fellow at the University of Pennsylvania, Philadelphia. She presented her group’s findings in a rapid-fire oral abstract session at the CHEST Annual Meeting.
 

Known Risk Factor

COPD is a known risk factor for PE. To estimate how the obstructive lung disease may contribute to PE-related deaths among patients of varying ages, Oudah and colleagues drew data on deaths due to an underlying cause of PE from 1999 to 2020 from the Centers for Disease Control and Prevention’s WONDER database.

They stratified the patients into two groups — those with or without COPD — whose data were included in the Multiple Causes of Death dataset, according to age groups ranging from 35 years to over 100 years. The investigators calculated proportional mortality ratios in the non-COPD group and applied these to the COPD-positive group among different age ranges to estimate the observed vs expected number of deaths.

A total of 10,434 persons who died from PE and had COPD listed among causes of death were identified. The sample was evenly divided by sex. The peak range of deaths was among those aged 75-84 years.

The authors saw an increase in PE-related mortality among patients with COPD aged 65-85 years (P < .001).

The ratios of observed-to-expected deaths among patients in this age range were “substantially greater than 1” said Oudah, with patients aged 75-79 years at highest risk for PE-related death, with an observed-to-expected ratio of 1.443.

In contrast, the rate of observed deaths among patients aged 85-89 years was similar to the expected rate, suggesting that the COPD-PE interaction may wane among older patients, she said.

Among patients aged 35-64 years, the risk for death from PE was not significantly higher for any of the 5-year age categories.

The investigators emphasized that “given the observed trend, individualized patient assessments are imperative to optimize preventable measures against PE in the aging COPD population.”
 

Confounding Comorbidities

In an interview, a pulmonary specialist who was not involved in the study commented that older persons with COPD tend to have multiple comorbidities that may contribute to the risk for PE.

“Older patients have so many comorbidities, and their risk for pulmonary embolism and thromboembolic disease is pretty high, so I’m not surprised that 75 to 79 years olds are having a higher mortality from PE, but it’s a little difficult to say whether that’s due to COPD,” said Krishna Sundar, MBBS, MD, FCCP, a pulmonary, sleep medicine, and critical care medicine specialist at St. John’s Medical Center in Jackson, Wyoming, who moderated the session.

The authors did not report a study funding source. Oudah and Sundar reported no relevant financial relationships.

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

BOSTON — Patients with COPD are at an increased risk for fatal pulmonary embolism (PE) and may require personalized, targeted thromboprophylaxis. Those are the conclusions of investigators who analyzed public health data and found that patients with COPD have a markedly increased risk for PE-related death, particularly among those aged 65-85 years.

The data suggest that “maybe we should start thinking about if we are admitting a patient with COPD in that specific age group, higher thromboprophylaxis for PE,” said Marwa Oudah, MD, a pulmonary hypertension fellow at the University of Pennsylvania, Philadelphia. She presented her group’s findings in a rapid-fire oral abstract session at the CHEST Annual Meeting.
 

Known Risk Factor

COPD is a known risk factor for PE. To estimate how the obstructive lung disease may contribute to PE-related deaths among patients of varying ages, Oudah and colleagues drew data on deaths due to an underlying cause of PE from 1999 to 2020 from the Centers for Disease Control and Prevention’s WONDER database.

They stratified the patients into two groups — those with or without COPD — whose data were included in the Multiple Causes of Death dataset, according to age groups ranging from 35 years to over 100 years. The investigators calculated proportional mortality ratios in the non-COPD group and applied these to the COPD-positive group among different age ranges to estimate the observed vs expected number of deaths.

A total of 10,434 persons who died from PE and had COPD listed among causes of death were identified. The sample was evenly divided by sex. The peak range of deaths was among those aged 75-84 years.

The authors saw an increase in PE-related mortality among patients with COPD aged 65-85 years (P < .001).

The ratios of observed-to-expected deaths among patients in this age range were “substantially greater than 1” said Oudah, with patients aged 75-79 years at highest risk for PE-related death, with an observed-to-expected ratio of 1.443.

In contrast, the rate of observed deaths among patients aged 85-89 years was similar to the expected rate, suggesting that the COPD-PE interaction may wane among older patients, she said.

Among patients aged 35-64 years, the risk for death from PE was not significantly higher for any of the 5-year age categories.

The investigators emphasized that “given the observed trend, individualized patient assessments are imperative to optimize preventable measures against PE in the aging COPD population.”
 

Confounding Comorbidities

In an interview, a pulmonary specialist who was not involved in the study commented that older persons with COPD tend to have multiple comorbidities that may contribute to the risk for PE.

“Older patients have so many comorbidities, and their risk for pulmonary embolism and thromboembolic disease is pretty high, so I’m not surprised that 75 to 79 years olds are having a higher mortality from PE, but it’s a little difficult to say whether that’s due to COPD,” said Krishna Sundar, MBBS, MD, FCCP, a pulmonary, sleep medicine, and critical care medicine specialist at St. John’s Medical Center in Jackson, Wyoming, who moderated the session.

The authors did not report a study funding source. Oudah and Sundar reported no relevant financial relationships.

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

BOSTON — Patients with COPD are at an increased risk for fatal pulmonary embolism (PE) and may require personalized, targeted thromboprophylaxis. Those are the conclusions of investigators who analyzed public health data and found that patients with COPD have a markedly increased risk for PE-related death, particularly among those aged 65-85 years.

The data suggest that “maybe we should start thinking about if we are admitting a patient with COPD in that specific age group, higher thromboprophylaxis for PE,” said Marwa Oudah, MD, a pulmonary hypertension fellow at the University of Pennsylvania, Philadelphia. She presented her group’s findings in a rapid-fire oral abstract session at the CHEST Annual Meeting.
 

Known Risk Factor

COPD is a known risk factor for PE. To estimate how the obstructive lung disease may contribute to PE-related deaths among patients of varying ages, Oudah and colleagues drew data on deaths due to an underlying cause of PE from 1999 to 2020 from the Centers for Disease Control and Prevention’s WONDER database.

They stratified the patients into two groups — those with or without COPD — whose data were included in the Multiple Causes of Death dataset, according to age groups ranging from 35 years to over 100 years. The investigators calculated proportional mortality ratios in the non-COPD group and applied these to the COPD-positive group among different age ranges to estimate the observed vs expected number of deaths.

A total of 10,434 persons who died from PE and had COPD listed among causes of death were identified. The sample was evenly divided by sex. The peak range of deaths was among those aged 75-84 years.

The authors saw an increase in PE-related mortality among patients with COPD aged 65-85 years (P < .001).

The ratios of observed-to-expected deaths among patients in this age range were “substantially greater than 1” said Oudah, with patients aged 75-79 years at highest risk for PE-related death, with an observed-to-expected ratio of 1.443.

In contrast, the rate of observed deaths among patients aged 85-89 years was similar to the expected rate, suggesting that the COPD-PE interaction may wane among older patients, she said.

Among patients aged 35-64 years, the risk for death from PE was not significantly higher for any of the 5-year age categories.

The investigators emphasized that “given the observed trend, individualized patient assessments are imperative to optimize preventable measures against PE in the aging COPD population.”
 

Confounding Comorbidities

In an interview, a pulmonary specialist who was not involved in the study commented that older persons with COPD tend to have multiple comorbidities that may contribute to the risk for PE.

“Older patients have so many comorbidities, and their risk for pulmonary embolism and thromboembolic disease is pretty high, so I’m not surprised that 75 to 79 years olds are having a higher mortality from PE, but it’s a little difficult to say whether that’s due to COPD,” said Krishna Sundar, MBBS, MD, FCCP, a pulmonary, sleep medicine, and critical care medicine specialist at St. John’s Medical Center in Jackson, Wyoming, who moderated the session.

The authors did not report a study funding source. Oudah and Sundar reported no relevant financial relationships.

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

BOSTON — Patients with COPD who have exacerbations requiring hospitalization should be monitored for cardiac arrhythmias, investigators said.

This recommendation is based on results of a study of medical records showing that among more than 20,000 hospitalizations for patients with COPD without concurrent heart failure (HF), 40% patients had at least 6 minutes of daily atrial fibrillation (AF) burden, and nearly half of these patients had at least an hour of daily AF burden; patients with COPD and concurrent HF had similar daily AF burdens, reported Trent Fischer, MD, MS, senior principal scientist at Medtronic in Minneapolis.

“We can conclude that AF burden increases in the weeks after a hospitalization for COPD if they don’t have a concurrent diagnosis of heart failure. Also, having concurrent heart failure increases the risk of atrial fibrillation and increases the atrial fibrillation burden around the time of COPD hospitalization,” he said in a rapid-fire oral abstract session at the CHEST Annual Meeting.

The findings indicated a need for increased vigilance for AF around the time of a serious COPD exacerbation and may explain at least some of the increased risks for stroke observed in patients who are hospitalized for COPD exacerbations, he said.
 

Retrospective Study

Dr. Fischer and colleagues conducted the study to characterize the AF burden among patients both with and without HF who were hospitalized for acute COPD exacerbation and to determine the temporal relationship between AF and hospitalization.

They drew data from 2007 through 2021 on patients with implantable cardioverter defibrillators, cardiac resynchronization therapy devices, pacemakers, and implantable cardiac monitors, using the Optum de-identified electronic health record dataset linked with Medtronic’s CareLink database to conduct a retrospective analysis.

They looked at admissions for COPD linked to available device diagnostic parameters between 30 days prior to and 60 days after admission for COPD.

They identified a total of 20,056 COPD hospitalizations for patients with concurrent HF and 3877 for those without HF.

Among patients with HF, 43% had a daily AF burden of at least 6 minutes, and 22% had at least 1 hour of irregular rhythms. Among patients without HF, 40% had at least 6 minutes of irregular rhythms daily, and 18% had at least 1 hour.

Among patients with HF, the daily average AF burden increased from a baseline of 158 min/d 30 days before an admission to 170 min/d at admission, returning to baseline by 20 days after hospitalization.

For patients without HF, the AF burden increased from 107 min/d at baseline to 113 min/d during hospitalization and returned to baseline by 20 days after hospitalization.
 

Confounding Factor?

In the Q&A, session moderator Krishna Sundar, MBBS, MD, FCCP, a pulmonary, sleep medicine, and critical care medicine specialist at St. John’s Medical Center in Jackson, Wyoming, said that when patients with HF get admitted for COPD exacerbations, their HF typically worsens and asked Dr. Fischer how he could tell the difference.

“I know there’s a lot of interaction between heart failure and COPD. They’re well-know comorbidities, and the exacerbation of one can bring on worsening of the other. At least with this database, we can’t really tease out any sort of differences,” Dr. Fischer replied.

“I think that a diagnosis of COPD exacerbation is pretty well laid out, but it’s sometimes difficult to separate worsening of heart failure in these patients, and often these patients get treated for both problems. It’s clear that it’s the heart failure patients who are having more atrial fibrillation episodes, which is not surprising, but the question is how much is the COPD exacerbation contributing to the atrial fibrillation?” said Dr. Sundar.

The study was supported by Medtronic. Dr. Fischer is employed by the company. Dr. Sundar reported no relevant financial relationships.



A version of this article appeared on Medscape.com.

BOSTON — Patients with COPD who have exacerbations requiring hospitalization should be monitored for cardiac arrhythmias, investigators said.

This recommendation is based on results of a study of medical records showing that among more than 20,000 hospitalizations for patients with COPD without concurrent heart failure (HF), 40% patients had at least 6 minutes of daily atrial fibrillation (AF) burden, and nearly half of these patients had at least an hour of daily AF burden; patients with COPD and concurrent HF had similar daily AF burdens, reported Trent Fischer, MD, MS, senior principal scientist at Medtronic in Minneapolis.

“We can conclude that AF burden increases in the weeks after a hospitalization for COPD if they don’t have a concurrent diagnosis of heart failure. Also, having concurrent heart failure increases the risk of atrial fibrillation and increases the atrial fibrillation burden around the time of COPD hospitalization,” he said in a rapid-fire oral abstract session at the CHEST Annual Meeting.

The findings indicated a need for increased vigilance for AF around the time of a serious COPD exacerbation and may explain at least some of the increased risks for stroke observed in patients who are hospitalized for COPD exacerbations, he said.
 

Retrospective Study

Dr. Fischer and colleagues conducted the study to characterize the AF burden among patients both with and without HF who were hospitalized for acute COPD exacerbation and to determine the temporal relationship between AF and hospitalization.

They drew data from 2007 through 2021 on patients with implantable cardioverter defibrillators, cardiac resynchronization therapy devices, pacemakers, and implantable cardiac monitors, using the Optum de-identified electronic health record dataset linked with Medtronic’s CareLink database to conduct a retrospective analysis.

They looked at admissions for COPD linked to available device diagnostic parameters between 30 days prior to and 60 days after admission for COPD.

They identified a total of 20,056 COPD hospitalizations for patients with concurrent HF and 3877 for those without HF.

Among patients with HF, 43% had a daily AF burden of at least 6 minutes, and 22% had at least 1 hour of irregular rhythms. Among patients without HF, 40% had at least 6 minutes of irregular rhythms daily, and 18% had at least 1 hour.

Among patients with HF, the daily average AF burden increased from a baseline of 158 min/d 30 days before an admission to 170 min/d at admission, returning to baseline by 20 days after hospitalization.

For patients without HF, the AF burden increased from 107 min/d at baseline to 113 min/d during hospitalization and returned to baseline by 20 days after hospitalization.
 

Confounding Factor?

In the Q&A, session moderator Krishna Sundar, MBBS, MD, FCCP, a pulmonary, sleep medicine, and critical care medicine specialist at St. John’s Medical Center in Jackson, Wyoming, said that when patients with HF get admitted for COPD exacerbations, their HF typically worsens and asked Dr. Fischer how he could tell the difference.

“I know there’s a lot of interaction between heart failure and COPD. They’re well-know comorbidities, and the exacerbation of one can bring on worsening of the other. At least with this database, we can’t really tease out any sort of differences,” Dr. Fischer replied.

“I think that a diagnosis of COPD exacerbation is pretty well laid out, but it’s sometimes difficult to separate worsening of heart failure in these patients, and often these patients get treated for both problems. It’s clear that it’s the heart failure patients who are having more atrial fibrillation episodes, which is not surprising, but the question is how much is the COPD exacerbation contributing to the atrial fibrillation?” said Dr. Sundar.

The study was supported by Medtronic. Dr. Fischer is employed by the company. Dr. Sundar reported no relevant financial relationships.



A version of this article appeared on Medscape.com.

BOSTON — Patients with COPD who have exacerbations requiring hospitalization should be monitored for cardiac arrhythmias, investigators said.

This recommendation is based on results of a study of medical records showing that among more than 20,000 hospitalizations for patients with COPD without concurrent heart failure (HF), 40% patients had at least 6 minutes of daily atrial fibrillation (AF) burden, and nearly half of these patients had at least an hour of daily AF burden; patients with COPD and concurrent HF had similar daily AF burdens, reported Trent Fischer, MD, MS, senior principal scientist at Medtronic in Minneapolis.

“We can conclude that AF burden increases in the weeks after a hospitalization for COPD if they don’t have a concurrent diagnosis of heart failure. Also, having concurrent heart failure increases the risk of atrial fibrillation and increases the atrial fibrillation burden around the time of COPD hospitalization,” he said in a rapid-fire oral abstract session at the CHEST Annual Meeting.

The findings indicated a need for increased vigilance for AF around the time of a serious COPD exacerbation and may explain at least some of the increased risks for stroke observed in patients who are hospitalized for COPD exacerbations, he said.
 

Retrospective Study

Dr. Fischer and colleagues conducted the study to characterize the AF burden among patients both with and without HF who were hospitalized for acute COPD exacerbation and to determine the temporal relationship between AF and hospitalization.

They drew data from 2007 through 2021 on patients with implantable cardioverter defibrillators, cardiac resynchronization therapy devices, pacemakers, and implantable cardiac monitors, using the Optum de-identified electronic health record dataset linked with Medtronic’s CareLink database to conduct a retrospective analysis.

They looked at admissions for COPD linked to available device diagnostic parameters between 30 days prior to and 60 days after admission for COPD.

They identified a total of 20,056 COPD hospitalizations for patients with concurrent HF and 3877 for those without HF.

Among patients with HF, 43% had a daily AF burden of at least 6 minutes, and 22% had at least 1 hour of irregular rhythms. Among patients without HF, 40% had at least 6 minutes of irregular rhythms daily, and 18% had at least 1 hour.

Among patients with HF, the daily average AF burden increased from a baseline of 158 min/d 30 days before an admission to 170 min/d at admission, returning to baseline by 20 days after hospitalization.

For patients without HF, the AF burden increased from 107 min/d at baseline to 113 min/d during hospitalization and returned to baseline by 20 days after hospitalization.
 

Confounding Factor?

In the Q&A, session moderator Krishna Sundar, MBBS, MD, FCCP, a pulmonary, sleep medicine, and critical care medicine specialist at St. John’s Medical Center in Jackson, Wyoming, said that when patients with HF get admitted for COPD exacerbations, their HF typically worsens and asked Dr. Fischer how he could tell the difference.

“I know there’s a lot of interaction between heart failure and COPD. They’re well-know comorbidities, and the exacerbation of one can bring on worsening of the other. At least with this database, we can’t really tease out any sort of differences,” Dr. Fischer replied.

“I think that a diagnosis of COPD exacerbation is pretty well laid out, but it’s sometimes difficult to separate worsening of heart failure in these patients, and often these patients get treated for both problems. It’s clear that it’s the heart failure patients who are having more atrial fibrillation episodes, which is not surprising, but the question is how much is the COPD exacerbation contributing to the atrial fibrillation?” said Dr. Sundar.

The study was supported by Medtronic. Dr. Fischer is employed by the company. Dr. Sundar reported no relevant financial relationships.



A version of this article appeared on Medscape.com.

Combining cognitive remediation with transcranial direct current stimulation (tDCS) was associated with slower cognitive decline for up to 6 years in older adults with major depressive disorder that is in remission (rMDD), mild cognitive impairment (MCI), or both, new research suggests.

The cognitive remediation intervention included a series of progressively difficult computer-based and facilitator-monitored mental exercises designed to sharpen cognitive function. 

Researchers found that using cognitive remediation with tDCS slowed decline in executive function and verbal memory more than other cognitive functions. The effect was stronger among people with rMDD versus those with MCI and in those at low genetic risk for Alzheimer’s disease. 

“We have developed a novel intervention, combining two interventions that if used separately have a weak effect but together have substantial and clinically meaningful effect of slowing the progression of cognitive decline,” said study author Benoit H. Mulsant, MD, chair of the Department of Psychiatry, University of Toronto, Ontario, Canada, and senior scientist at the Center for Addiction and Mental Health, also in Toronto. 

The findings were published online in JAMA Psychiatry. 
 

High-Risk Group

Research shows that older adults with MDD or MCI are at high risk for cognitive decline and dementia. Evidence also suggests that depression in early or mid-life significantly increases the risk for dementia in late life, even if the depression has been in remission for decades.

A potential mechanism underlying this increased risk for dementia could be impaired cortical plasticity, or the ability of the brain to compensate for damage.

The PACt-MD trial included 375 older adults with rMDD, MCI, or both (mean age, 72 years; 62% women) at five academic hospitals in Toronto.

Participants received either cognitive remediation plus tDCS or sham intervention 5 days per week for 8 weeks (acute phase), followed by 5-day “boosters” every 6 months.

tDCS was administered by trained personnel and involved active stimulation for 30 minutes at the beginning of each cognitive remediation group session. The intervention targets the prefrontal cortex, a critical region for cognitive compensation in normal cognitive aging.

The sham group received a weakened version of cognitive remediation, with exercises that did not get progressively more difficult. For the sham stimulation, the current flowed at full intensity for only 54 seconds before and after 30-second ramp-up and ramp-down phases, to create a blinding effect, the authors noted. 

A geriatric psychiatrist followed all participants throughout the study, conducting assessments at baseline, month 2, and yearly for 3-7 years (mean follow-up, 48.3 months). 

Participants’ depressive symptoms were evaluated at baseline and at all follow-ups and underwent neuropsychological testing to assess six cognitive domains: processing speed, working memory, executive functioning, verbal memory, visual memory, and language.

To get a norm for the cognitive tests, researchers recruited a comparator group of 75 subjects similar in age, gender, and years of education, with no neuropsychiatric disorder or cognitive impairment. They completed the same assessments but not the intervention.

Study participants and assessors were blinded to treatment assignment.
 

Slower Cognitive Decline

Participants in the intervention group had a significantly slower decline in cognitive function, compared with those in the sham group (adjusted z score difference [active – sham] at month 60, 0.21; P = .006). This is equivalent to slowing cognitive decline by about 4 years, researchers reported. The intervention also showed a positive effect on executive function and verbal memory. 

“If I can push dementia from 85 to 89 years and you die at 86, in practice, I have prevented you from ever developing dementia,” Mulsant said.

The efficacy of cognitive remediation plus tDCS in rMDD could be tied to enhanced neuroplasticity, said Mulsant. 

The treatment worked well in people with a history of depression, regardless of MCI status, but was not as effective for people with just MCI, researchers noted. The intervention also did not work as well among people at genetic risk for Alzheimer’s disease.

“We don’t believe we have discovered an intervention to prevent dementia in people who are at high risk for Alzheimer disease, but we have discovered an intervention that could prevent dementia in people who have an history of depression,” said Mulsant. 

These results suggest the pathways to dementia among people with MCI and rMDD are different, he added. 

Because previous research showed either treatment alone demonstrated little efficacy, researchers said the new results indicate that there may be a synergistic effect of combining the two. 

The ideal amount of treatment and optimal age for initiation still need to be determined, said Mulsant. The study did not include a comparator group without rMDD or MCI, so the observed cognitive benefits might be specific to people with these high-risk conditions. Another study limitation is lack of diversity in terms of ethnicity, race, and education. 
 

Promising, Important Findings

Commenting on the research, Badr Ratnakaran, MD, assistant professor and division director of geriatric psychiatry at Carilion Clinic–Virginia Tech Carilion School of Medicine, Roanoke, said the results are promising and important because there are so few treatment options for the increasing number of older patients with depression and dementia.

The side-effect profile of the combined treatment is better than that of many pharmacologic treatments, Ratnakaran noted. As more research like this comes out, Ratnakaran predicts that cognitive remediation and tCDS will become more readily available.

“This is telling us that the field of psychiatry, and also dementia, is progressing beyond your usual pharmacotherapy treatments,” said Ratnakaran, who also is chair of the American Psychiatric Association’s Council on Geriatric Psychiatry. 

The study received support from the Canada Brain Research Fund of Brain Canada, Health Canada, the Chagnon Family, and the Centre for Addiction and Mental Health Discovery Fund. Mulsant reported holding and receiving support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto; being a member of the Center for Addiction and Mental Health Board of Trustees; research support from Brain Canada, Canadian Institutes of Health Research, Center for Addiction and Mental Health Foundation, Patient-Centered Outcomes Research Institute, and National Institutes of Health; and nonfinancial support from Capital Solution Design and HappyNeuron. Ratnakaran reported no relevant conflicts.

A version of this article appeared on Medscape.com.

Combining cognitive remediation with transcranial direct current stimulation (tDCS) was associated with slower cognitive decline for up to 6 years in older adults with major depressive disorder that is in remission (rMDD), mild cognitive impairment (MCI), or both, new research suggests.

The cognitive remediation intervention included a series of progressively difficult computer-based and facilitator-monitored mental exercises designed to sharpen cognitive function. 

Researchers found that using cognitive remediation with tDCS slowed decline in executive function and verbal memory more than other cognitive functions. The effect was stronger among people with rMDD versus those with MCI and in those at low genetic risk for Alzheimer’s disease. 

“We have developed a novel intervention, combining two interventions that if used separately have a weak effect but together have substantial and clinically meaningful effect of slowing the progression of cognitive decline,” said study author Benoit H. Mulsant, MD, chair of the Department of Psychiatry, University of Toronto, Ontario, Canada, and senior scientist at the Center for Addiction and Mental Health, also in Toronto. 

The findings were published online in JAMA Psychiatry. 
 

High-Risk Group

Research shows that older adults with MDD or MCI are at high risk for cognitive decline and dementia. Evidence also suggests that depression in early or mid-life significantly increases the risk for dementia in late life, even if the depression has been in remission for decades.

A potential mechanism underlying this increased risk for dementia could be impaired cortical plasticity, or the ability of the brain to compensate for damage.

The PACt-MD trial included 375 older adults with rMDD, MCI, or both (mean age, 72 years; 62% women) at five academic hospitals in Toronto.

Participants received either cognitive remediation plus tDCS or sham intervention 5 days per week for 8 weeks (acute phase), followed by 5-day “boosters” every 6 months.

tDCS was administered by trained personnel and involved active stimulation for 30 minutes at the beginning of each cognitive remediation group session. The intervention targets the prefrontal cortex, a critical region for cognitive compensation in normal cognitive aging.

The sham group received a weakened version of cognitive remediation, with exercises that did not get progressively more difficult. For the sham stimulation, the current flowed at full intensity for only 54 seconds before and after 30-second ramp-up and ramp-down phases, to create a blinding effect, the authors noted. 

A geriatric psychiatrist followed all participants throughout the study, conducting assessments at baseline, month 2, and yearly for 3-7 years (mean follow-up, 48.3 months). 

Participants’ depressive symptoms were evaluated at baseline and at all follow-ups and underwent neuropsychological testing to assess six cognitive domains: processing speed, working memory, executive functioning, verbal memory, visual memory, and language.

To get a norm for the cognitive tests, researchers recruited a comparator group of 75 subjects similar in age, gender, and years of education, with no neuropsychiatric disorder or cognitive impairment. They completed the same assessments but not the intervention.

Study participants and assessors were blinded to treatment assignment.
 

Slower Cognitive Decline

Participants in the intervention group had a significantly slower decline in cognitive function, compared with those in the sham group (adjusted z score difference [active – sham] at month 60, 0.21; P = .006). This is equivalent to slowing cognitive decline by about 4 years, researchers reported. The intervention also showed a positive effect on executive function and verbal memory. 

“If I can push dementia from 85 to 89 years and you die at 86, in practice, I have prevented you from ever developing dementia,” Mulsant said.

The efficacy of cognitive remediation plus tDCS in rMDD could be tied to enhanced neuroplasticity, said Mulsant. 

The treatment worked well in people with a history of depression, regardless of MCI status, but was not as effective for people with just MCI, researchers noted. The intervention also did not work as well among people at genetic risk for Alzheimer’s disease.

“We don’t believe we have discovered an intervention to prevent dementia in people who are at high risk for Alzheimer disease, but we have discovered an intervention that could prevent dementia in people who have an history of depression,” said Mulsant. 

These results suggest the pathways to dementia among people with MCI and rMDD are different, he added. 

Because previous research showed either treatment alone demonstrated little efficacy, researchers said the new results indicate that there may be a synergistic effect of combining the two. 

The ideal amount of treatment and optimal age for initiation still need to be determined, said Mulsant. The study did not include a comparator group without rMDD or MCI, so the observed cognitive benefits might be specific to people with these high-risk conditions. Another study limitation is lack of diversity in terms of ethnicity, race, and education. 
 

Promising, Important Findings

Commenting on the research, Badr Ratnakaran, MD, assistant professor and division director of geriatric psychiatry at Carilion Clinic–Virginia Tech Carilion School of Medicine, Roanoke, said the results are promising and important because there are so few treatment options for the increasing number of older patients with depression and dementia.

The side-effect profile of the combined treatment is better than that of many pharmacologic treatments, Ratnakaran noted. As more research like this comes out, Ratnakaran predicts that cognitive remediation and tCDS will become more readily available.

“This is telling us that the field of psychiatry, and also dementia, is progressing beyond your usual pharmacotherapy treatments,” said Ratnakaran, who also is chair of the American Psychiatric Association’s Council on Geriatric Psychiatry. 

The study received support from the Canada Brain Research Fund of Brain Canada, Health Canada, the Chagnon Family, and the Centre for Addiction and Mental Health Discovery Fund. Mulsant reported holding and receiving support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto; being a member of the Center for Addiction and Mental Health Board of Trustees; research support from Brain Canada, Canadian Institutes of Health Research, Center for Addiction and Mental Health Foundation, Patient-Centered Outcomes Research Institute, and National Institutes of Health; and nonfinancial support from Capital Solution Design and HappyNeuron. Ratnakaran reported no relevant conflicts.

A version of this article appeared on Medscape.com.

Combining cognitive remediation with transcranial direct current stimulation (tDCS) was associated with slower cognitive decline for up to 6 years in older adults with major depressive disorder that is in remission (rMDD), mild cognitive impairment (MCI), or both, new research suggests.

The cognitive remediation intervention included a series of progressively difficult computer-based and facilitator-monitored mental exercises designed to sharpen cognitive function. 

Researchers found that using cognitive remediation with tDCS slowed decline in executive function and verbal memory more than other cognitive functions. The effect was stronger among people with rMDD versus those with MCI and in those at low genetic risk for Alzheimer’s disease. 

“We have developed a novel intervention, combining two interventions that if used separately have a weak effect but together have substantial and clinically meaningful effect of slowing the progression of cognitive decline,” said study author Benoit H. Mulsant, MD, chair of the Department of Psychiatry, University of Toronto, Ontario, Canada, and senior scientist at the Center for Addiction and Mental Health, also in Toronto. 

The findings were published online in JAMA Psychiatry. 
 

High-Risk Group

Research shows that older adults with MDD or MCI are at high risk for cognitive decline and dementia. Evidence also suggests that depression in early or mid-life significantly increases the risk for dementia in late life, even if the depression has been in remission for decades.

A potential mechanism underlying this increased risk for dementia could be impaired cortical plasticity, or the ability of the brain to compensate for damage.

The PACt-MD trial included 375 older adults with rMDD, MCI, or both (mean age, 72 years; 62% women) at five academic hospitals in Toronto.

Participants received either cognitive remediation plus tDCS or sham intervention 5 days per week for 8 weeks (acute phase), followed by 5-day “boosters” every 6 months.

tDCS was administered by trained personnel and involved active stimulation for 30 minutes at the beginning of each cognitive remediation group session. The intervention targets the prefrontal cortex, a critical region for cognitive compensation in normal cognitive aging.

The sham group received a weakened version of cognitive remediation, with exercises that did not get progressively more difficult. For the sham stimulation, the current flowed at full intensity for only 54 seconds before and after 30-second ramp-up and ramp-down phases, to create a blinding effect, the authors noted. 

A geriatric psychiatrist followed all participants throughout the study, conducting assessments at baseline, month 2, and yearly for 3-7 years (mean follow-up, 48.3 months). 

Participants’ depressive symptoms were evaluated at baseline and at all follow-ups and underwent neuropsychological testing to assess six cognitive domains: processing speed, working memory, executive functioning, verbal memory, visual memory, and language.

To get a norm for the cognitive tests, researchers recruited a comparator group of 75 subjects similar in age, gender, and years of education, with no neuropsychiatric disorder or cognitive impairment. They completed the same assessments but not the intervention.

Study participants and assessors were blinded to treatment assignment.
 

Slower Cognitive Decline

Participants in the intervention group had a significantly slower decline in cognitive function, compared with those in the sham group (adjusted z score difference [active – sham] at month 60, 0.21; P = .006). This is equivalent to slowing cognitive decline by about 4 years, researchers reported. The intervention also showed a positive effect on executive function and verbal memory. 

“If I can push dementia from 85 to 89 years and you die at 86, in practice, I have prevented you from ever developing dementia,” Mulsant said.

The efficacy of cognitive remediation plus tDCS in rMDD could be tied to enhanced neuroplasticity, said Mulsant. 

The treatment worked well in people with a history of depression, regardless of MCI status, but was not as effective for people with just MCI, researchers noted. The intervention also did not work as well among people at genetic risk for Alzheimer’s disease.

“We don’t believe we have discovered an intervention to prevent dementia in people who are at high risk for Alzheimer disease, but we have discovered an intervention that could prevent dementia in people who have an history of depression,” said Mulsant. 

These results suggest the pathways to dementia among people with MCI and rMDD are different, he added. 

Because previous research showed either treatment alone demonstrated little efficacy, researchers said the new results indicate that there may be a synergistic effect of combining the two. 

The ideal amount of treatment and optimal age for initiation still need to be determined, said Mulsant. The study did not include a comparator group without rMDD or MCI, so the observed cognitive benefits might be specific to people with these high-risk conditions. Another study limitation is lack of diversity in terms of ethnicity, race, and education. 
 

Promising, Important Findings

Commenting on the research, Badr Ratnakaran, MD, assistant professor and division director of geriatric psychiatry at Carilion Clinic–Virginia Tech Carilion School of Medicine, Roanoke, said the results are promising and important because there are so few treatment options for the increasing number of older patients with depression and dementia.

The side-effect profile of the combined treatment is better than that of many pharmacologic treatments, Ratnakaran noted. As more research like this comes out, Ratnakaran predicts that cognitive remediation and tCDS will become more readily available.

“This is telling us that the field of psychiatry, and also dementia, is progressing beyond your usual pharmacotherapy treatments,” said Ratnakaran, who also is chair of the American Psychiatric Association’s Council on Geriatric Psychiatry. 

The study received support from the Canada Brain Research Fund of Brain Canada, Health Canada, the Chagnon Family, and the Centre for Addiction and Mental Health Discovery Fund. Mulsant reported holding and receiving support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto; being a member of the Center for Addiction and Mental Health Board of Trustees; research support from Brain Canada, Canadian Institutes of Health Research, Center for Addiction and Mental Health Foundation, Patient-Centered Outcomes Research Institute, and National Institutes of Health; and nonfinancial support from Capital Solution Design and HappyNeuron. Ratnakaran reported no relevant conflicts.

A version of this article appeared on Medscape.com.