Federal Practitioner

Contact allergy to cobalt, chromium, and especially nickel, may be higher in European metalworkers than in all European male patients with allergic contact dermatitis, a systematic review and meta-analysis reports.

“Metal allergy to all three metals was significantly more common in European metalworkers with dermatitis attending patch test clinics as compared to ESSCA [European Surveillance System on Contact Allergies] data, indicating a relationship to occupational exposures,” senior study author Jeanne D. Johansen, MD, professor, department of dermatology and allergy, Copenhagen University Hospital, Hellerup, Denmark, and colleagues at the University of Copenhagen wrote in Contact Dermatitis. “However, confounders could not be accounted for.”

How common is metal allergy in metalworkers?

Occupational hand eczema is known to be common in metalworkers. Touching oils, greases, metals, leather gloves, rubber materials, and metalworking fluids as they repeatedly cut, shape, and process raw metals and minerals derived from ore mining exposes metalworkers to allergens and skin irritants, the authors wrote. But the prevalence of allergy to certain metals has not been well characterized.

So they searched PubMed for full-text studies in English that reported metal allergy prevalence in metalworkers, from the database’s inception through April 2022.

They included studies with absolute numbers or proportions of metal allergy to cobalt, chromium, or nickel, in all metalworkers with suspected allergic contact dermatitis who attended outpatient clinics or who worked at metalworking plants participating in workplace studies.

The researchers performed a random-effects meta-analysis to calculate the pooled prevalence of metal allergy. Because 85%-90% of metalworkers in Denmark are male, they compared the estimates they found with ESSCA data on 13,382 consecutively patch-tested males with dermatitis between 2015 and 2018.

Of the 1,667 records they screened, they analyzed data from 29 that met their inclusion criteria: 22 patient studies and 7 workplace studies involving 5,691 patients overall from 22 studies from Europe, 5 studies from Asia, and 1 from Africa. Regarding European metalworkers, the authors found:

• Pooled proportions of allergy in European metalworkers with dermatitis referred to patch test clinics were 8.2% to cobalt (95% confidence interval, 5.3%-11.7%), 8.0% to chromium (95% CI, 5.1%-11.4%), and 11.0% to nickel (95% CI, 7.3%-15.4%).
• In workplace studies, the pooled proportions of allergy in unselected European metalworkers were 4.9% to cobalt, (95% CI, 2.4%-8.1%), 5.2% to chromium (95% CI, 1.0% - 12.6%), and 7.6% to nickel (95% CI, 3.8%-12.6%).
• By comparison, ESSCA data on metal allergy prevalence showed 3.9% allergic to cobalt (95% CI, 3.6%-4.2%), 4.4% allergic to chromium (95% CI, 4.1%-4.8%), and 6.7% allergic to nickel (95% CI, 6.3%-7.0%).
• Data on sex, age, body piercings, and atopic dermatitis were scant.

Thorough histories, protective regulations and equipment

Providers need to ask their dermatitis patients about current and past occupations and hobbies, and employers need to provide employees with equipment that protects them from exposure, Kelly Tyler, MD, associate professor of dermatology, Ohio State University Wexner Medical Center, Columbus, said in an interview.

“Repeated exposure to an allergen is required for sensitization to develop,” said Dr. Tyler, who was not involved in the study. “Metalworkers, who are continually exposed to metals and metalworking fluids, have a higher risk of allergic contact dermatitis to cobalt, chromium, and nickel.”

“The primary treatment for allergic contact dermatitis is preventing continued exposure to the allergen,” she added. “This study highlights the importance of asking about metal or metalworking fluid in the workplace and of elucidating whether the employer is providing appropriate protective gear.”

To prevent occupational dermatitis, workplaces need to apply regulatory measures and provide their employees with protective equipment, Dr. Tyler advised.

“Body piercings are a common sensitizer in patients with metal allergy, and the prevalence of body piercings among metalworkers was not included in the study,” she noted.

The results of the study may not be generalizable to patients in the United States, she added, because regulations and requirements to provide protective gear here may differ.

“Taking a thorough patient history is crucial when investigating potential causes of dermatitis, especially in patients with suspected allergic contact dermatitis,” Dr. Tyler urged.

Funding and conflict-of-interest details were not provided. Dr. Tyler reported no relevant financial relationships.

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

Contact allergy to cobalt, chromium, and especially nickel, may be higher in European metalworkers than in all European male patients with allergic contact dermatitis, a systematic review and meta-analysis reports.

“Metal allergy to all three metals was significantly more common in European metalworkers with dermatitis attending patch test clinics as compared to ESSCA [European Surveillance System on Contact Allergies] data, indicating a relationship to occupational exposures,” senior study author Jeanne D. Johansen, MD, professor, department of dermatology and allergy, Copenhagen University Hospital, Hellerup, Denmark, and colleagues at the University of Copenhagen wrote in Contact Dermatitis. “However, confounders could not be accounted for.”

How common is metal allergy in metalworkers?

Occupational hand eczema is known to be common in metalworkers. Touching oils, greases, metals, leather gloves, rubber materials, and metalworking fluids as they repeatedly cut, shape, and process raw metals and minerals derived from ore mining exposes metalworkers to allergens and skin irritants, the authors wrote. But the prevalence of allergy to certain metals has not been well characterized.

So they searched PubMed for full-text studies in English that reported metal allergy prevalence in metalworkers, from the database’s inception through April 2022.

They included studies with absolute numbers or proportions of metal allergy to cobalt, chromium, or nickel, in all metalworkers with suspected allergic contact dermatitis who attended outpatient clinics or who worked at metalworking plants participating in workplace studies.

The researchers performed a random-effects meta-analysis to calculate the pooled prevalence of metal allergy. Because 85%-90% of metalworkers in Denmark are male, they compared the estimates they found with ESSCA data on 13,382 consecutively patch-tested males with dermatitis between 2015 and 2018.

Of the 1,667 records they screened, they analyzed data from 29 that met their inclusion criteria: 22 patient studies and 7 workplace studies involving 5,691 patients overall from 22 studies from Europe, 5 studies from Asia, and 1 from Africa. Regarding European metalworkers, the authors found:

• Pooled proportions of allergy in European metalworkers with dermatitis referred to patch test clinics were 8.2% to cobalt (95% confidence interval, 5.3%-11.7%), 8.0% to chromium (95% CI, 5.1%-11.4%), and 11.0% to nickel (95% CI, 7.3%-15.4%).
• In workplace studies, the pooled proportions of allergy in unselected European metalworkers were 4.9% to cobalt, (95% CI, 2.4%-8.1%), 5.2% to chromium (95% CI, 1.0% - 12.6%), and 7.6% to nickel (95% CI, 3.8%-12.6%).
• By comparison, ESSCA data on metal allergy prevalence showed 3.9% allergic to cobalt (95% CI, 3.6%-4.2%), 4.4% allergic to chromium (95% CI, 4.1%-4.8%), and 6.7% allergic to nickel (95% CI, 6.3%-7.0%).
• Data on sex, age, body piercings, and atopic dermatitis were scant.

Thorough histories, protective regulations and equipment

Providers need to ask their dermatitis patients about current and past occupations and hobbies, and employers need to provide employees with equipment that protects them from exposure, Kelly Tyler, MD, associate professor of dermatology, Ohio State University Wexner Medical Center, Columbus, said in an interview.

“Repeated exposure to an allergen is required for sensitization to develop,” said Dr. Tyler, who was not involved in the study. “Metalworkers, who are continually exposed to metals and metalworking fluids, have a higher risk of allergic contact dermatitis to cobalt, chromium, and nickel.”

“The primary treatment for allergic contact dermatitis is preventing continued exposure to the allergen,” she added. “This study highlights the importance of asking about metal or metalworking fluid in the workplace and of elucidating whether the employer is providing appropriate protective gear.”

To prevent occupational dermatitis, workplaces need to apply regulatory measures and provide their employees with protective equipment, Dr. Tyler advised.

“Body piercings are a common sensitizer in patients with metal allergy, and the prevalence of body piercings among metalworkers was not included in the study,” she noted.

The results of the study may not be generalizable to patients in the United States, she added, because regulations and requirements to provide protective gear here may differ.

“Taking a thorough patient history is crucial when investigating potential causes of dermatitis, especially in patients with suspected allergic contact dermatitis,” Dr. Tyler urged.

Funding and conflict-of-interest details were not provided. Dr. Tyler reported no relevant financial relationships.

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

Contact allergy to cobalt, chromium, and especially nickel, may be higher in European metalworkers than in all European male patients with allergic contact dermatitis, a systematic review and meta-analysis reports.

“Metal allergy to all three metals was significantly more common in European metalworkers with dermatitis attending patch test clinics as compared to ESSCA [European Surveillance System on Contact Allergies] data, indicating a relationship to occupational exposures,” senior study author Jeanne D. Johansen, MD, professor, department of dermatology and allergy, Copenhagen University Hospital, Hellerup, Denmark, and colleagues at the University of Copenhagen wrote in Contact Dermatitis. “However, confounders could not be accounted for.”

How common is metal allergy in metalworkers?

Occupational hand eczema is known to be common in metalworkers. Touching oils, greases, metals, leather gloves, rubber materials, and metalworking fluids as they repeatedly cut, shape, and process raw metals and minerals derived from ore mining exposes metalworkers to allergens and skin irritants, the authors wrote. But the prevalence of allergy to certain metals has not been well characterized.

So they searched PubMed for full-text studies in English that reported metal allergy prevalence in metalworkers, from the database’s inception through April 2022.

They included studies with absolute numbers or proportions of metal allergy to cobalt, chromium, or nickel, in all metalworkers with suspected allergic contact dermatitis who attended outpatient clinics or who worked at metalworking plants participating in workplace studies.

The researchers performed a random-effects meta-analysis to calculate the pooled prevalence of metal allergy. Because 85%-90% of metalworkers in Denmark are male, they compared the estimates they found with ESSCA data on 13,382 consecutively patch-tested males with dermatitis between 2015 and 2018.

Of the 1,667 records they screened, they analyzed data from 29 that met their inclusion criteria: 22 patient studies and 7 workplace studies involving 5,691 patients overall from 22 studies from Europe, 5 studies from Asia, and 1 from Africa. Regarding European metalworkers, the authors found:

• Pooled proportions of allergy in European metalworkers with dermatitis referred to patch test clinics were 8.2% to cobalt (95% confidence interval, 5.3%-11.7%), 8.0% to chromium (95% CI, 5.1%-11.4%), and 11.0% to nickel (95% CI, 7.3%-15.4%).
• In workplace studies, the pooled proportions of allergy in unselected European metalworkers were 4.9% to cobalt, (95% CI, 2.4%-8.1%), 5.2% to chromium (95% CI, 1.0% - 12.6%), and 7.6% to nickel (95% CI, 3.8%-12.6%).
• By comparison, ESSCA data on metal allergy prevalence showed 3.9% allergic to cobalt (95% CI, 3.6%-4.2%), 4.4% allergic to chromium (95% CI, 4.1%-4.8%), and 6.7% allergic to nickel (95% CI, 6.3%-7.0%).
• Data on sex, age, body piercings, and atopic dermatitis were scant.

Thorough histories, protective regulations and equipment

Providers need to ask their dermatitis patients about current and past occupations and hobbies, and employers need to provide employees with equipment that protects them from exposure, Kelly Tyler, MD, associate professor of dermatology, Ohio State University Wexner Medical Center, Columbus, said in an interview.

“Repeated exposure to an allergen is required for sensitization to develop,” said Dr. Tyler, who was not involved in the study. “Metalworkers, who are continually exposed to metals and metalworking fluids, have a higher risk of allergic contact dermatitis to cobalt, chromium, and nickel.”

“The primary treatment for allergic contact dermatitis is preventing continued exposure to the allergen,” she added. “This study highlights the importance of asking about metal or metalworking fluid in the workplace and of elucidating whether the employer is providing appropriate protective gear.”

To prevent occupational dermatitis, workplaces need to apply regulatory measures and provide their employees with protective equipment, Dr. Tyler advised.

“Body piercings are a common sensitizer in patients with metal allergy, and the prevalence of body piercings among metalworkers was not included in the study,” she noted.

The results of the study may not be generalizable to patients in the United States, she added, because regulations and requirements to provide protective gear here may differ.

“Taking a thorough patient history is crucial when investigating potential causes of dermatitis, especially in patients with suspected allergic contact dermatitis,” Dr. Tyler urged.

Funding and conflict-of-interest details were not provided. Dr. Tyler reported no relevant financial relationships.

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

CHICAGO – Clinicians who prescribe heart failure meds are holding the best hand they’ve ever had, but with so much underuse and suboptimal dosing in actual practice, it seems many may not appreciate the value of their cards. But a major randomized trial that has captured the field’s attention may embolden them to go all in.

Results showed that a strategy of early, rapid up-titration of multiple guideline-directed meds in patients hospitalized with heart failure, compared with a usual-care approach, cut their 6-month risk for death or HF readmission by a steep 34% (P = .002).

The drugs had been started and partly up-titrated in the hospital with the goal of full up-titration within 2 weeks after discharge.

Patients well tolerated the high-intensity approach, researchers said. Their quality-of-life scores improved (P < .0001) compared with the usual-care group, and adverse events were considered few and manageable in the international trial with more than 1,000 patients.

Safety on the high-intensity strategy depended on close patient monitoring at frequently planned clinic visits along with guidance for the up-titrations from clinical signs and natriuretic peptide levels, observed Alexandre Mebazaa, MD, PhD, University of Paris and Public Hospitals of Paris.

Dr. Mebazaa is principal investigator on the trial, called STRONG-HF, which he presented at the American Heart Association scientific sessions, held in Chicago and virtually. He is also lead author on the study’s same-day publication in the Lancet.

The high-intensity strategy’s superiority emerged early in the trial, which was halted early on the data safety monitoring board’s recommendation, with about 90% of follow-ups completed. The board “felt it was unethical to keep patients in usual care,” Dr. Mebazaa said at a press conference.
 

A dramatic change

The next step, he said, will be to educate the heart failure community on the high-intensity care technique so it can swiftly enter clinical practice. Currently in acute heart failure, “very few patients are monitored after discharge and treated with full doses of heart failure therapies.”

Adoption of the strategy “would be a dramatic change from what’s currently being done,” said Martin B. Leon, MD, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, who moderated the press conference.

Only an estimated 5% of patients with HF in the United States receive full guideline-directed medical therapy, Dr. Leon said, “so the generalizability of this strategy, with careful follow-up that has safety involved in it, is absolutely crucial.”

But the potential impact of this high-intensity approach on resource use is unknown, raising questions about how widely and consistently it could be implemented, said Dr. Leon, who is not connected with STRONG-HF.

The trial called for in-hospital initiation of the three distinct drug classes that, at the time, were the core of guideline-directed HF therapy, with up-titration to 50% of recommended dosage by hospital discharge, and then to 100% within 2 weeks later.

The meds included a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system inhibitor (RASI). The latter could be an ACE inhibitor, angiotensin-receptor blocker (ARB), or angiotensin receptor-neprilysin inhibitor (ARNI).
 

How about a fourth drug?

Conspicuously absent from the list, for contemporary practice, was an SGLT2 inhibitor, a class that entered the HF guidelines well after STRONG-HF was designed. They would undoubtedly join the other three agents were the high-intensity strategy to enter practice, potentially changing its complexity and safety profile.

But Dr. Mebazaa and other experts don’t see that as a big challenge and would expect a smooth transition to a high-intensity approach that also includes the SGLT2 inhibitors.

STRONG-HF was necessary in part because many clinicians have been “reluctant” to take full advantage of three agents that had been the basis of guideline-directed therapy, he told this news organization.

That reluctance stemmed from concerns that beta-blockers might worsen the heart failure, ACE inhibitors could hurt the kidneys, or MRAs might cause hyperkalemia, Dr. Mebazaa said. The STRONG-HF high-intensity regimen, therefore, demanded multiple clinic visits for close follow-up.

But the SGLT2 inhibitors “are known to be rather safe drugs, at least much safer than the three others,” he said. So, it seems unlikely that their addition to a beta-blocker, RASI, and MRA in patients with HF would worsen the risk of adverse events.

John G.F. Cleland, MD, PhD, agrees. With addition of the fourth agent, “You may need to be a little bit more careful with renal function, just in that first couple of weeks,” he told this news organization. “But I think it would be easy to add an SGLT2 inhibitor into this regimen. And in general, there’s no titration with an SGLT2 inhibitor, so they’ll all be on full dose predischarge.”

Given the drugs’ diuretic-like action, moreover, some patients might be able to pull back on their loop diuretics, speculated Dr. Cleland, from the University of Glasgow’s School of Health and Wellbeing.

The prospect of a high-intensity strategy’s wide implementation in practice presents both “challenges and opportunities,” Amanda R. Vest, MBBS, MPH, Tufts University, Boston, told this news organization.

“There may be additional challenges in terms of ensuring we avoid hypotension or acute kidney injury in the up-titration phase,” said Dr. Vest, who is medical director of her center’s cardiac transplantation program but not connected with STRONG-HF.

“But it also gives us opportunities,” she added, “because there are some patients, especially in that vulnerable postdischarge phase, who are actually much more able to tolerate introduction of an SGLT2 inhibitor than, for example, an ACE inhibitor, ARB, or ARNI – or maybe a beta-blocker if they’ve been in a low cardiac-output state.” Effective dosing would depend on “the personalization and skill of the clinician in optimizing the medications in their correct sequence,” Dr. Vest said.

“It’s challenging to think that we would ever get to 100% up-titration,” she added, “and even in this excellent study, they didn’t get to 100%.” But as clinicians gain experience with the high-intensity strategy, especially as the SGLT2 inhibitors are included, “I think we can reasonably expect more progress to be made in these up-titration skills.”
 

No restrictions on LVEF

The researchers entered 1,078 patients hospitalized with acute HF in 14 countries across Africa, Europe, the Middle East, and South America, and randomly assigned them to the high-intensity management strategy or usual care.

About 60% of the patients were male and 77% were White. There were no entry restrictions based on left ventricular ejection fraction (LVEF), which exceeded 40% in almost a third of cases.

In the high-intensity care group’s 542 patients, the three agents were up-titrated to 50% of the maximum guideline-recommended dosage prior to hospital discharge, and to 100% within 2 weeks after discharge. Symptoms and laboratory biomarkers, including natriuretic peptides, were monitored closely at four planned clinical visits over the following 6 weeks.

The 536 patients assigned to usual care were discharged and managed according to local standards, with their meds handled by their own primary care doctors or cardiologists, the published report notes. They were reevaluated by STRONG-HF clinicians 90 days after discharge.

The number of clinic visits in the first 90 postdischarge days averaged 4.8 in the high-intensity care group and 1.0 for those receiving usual care. Full up-titration was far more likely in the high-intensity care group: 55% vs. 2% for RASI agents, 49% vs. 4% for beta-blockers, and 84% vs. 46% for MRAs.

They also fared significantly better on all measured parameters associated with decongestion, including weight, prevalence of peripheral edema, jugular venous pressure, NYHA functional class, and natriuretic peptide levels, the researchers said.

The primary endpoint of 180-day death from any cause or HF readmission was met by 15.2% of the high-intensity care group and 23.3% of usual-care patients, for an adjusted risk ratio (RR) of 0.66 (95% CI, 0.50-0.86; P = .0021).

Subgroup analyses saw no significant interactions by age, sex, race, geography, or baseline blood pressure, renal function, or LVEF. Patients with higher vs. lower baseline natriuretic peptide levels trend toward better responses to high-intensity care (P = .08)
 

The COVID effect

The group performed a sensitivity analysis that excluded deaths attributed to COVID-19 in STRONG-HF, which launched prior to the pandemic. The high-intensity strategy’s benefit for the primary endpoint grew, with an adjusted RR of 0.61 (95% CI, 0.46-0.82; P = .0005). There was no corresponding effect on death from any cause (P = .15).

Treatment-related adverse effects in the overall trial were seen in 41.1% of the high-intensity care group and in 29.5% of those assigned to usual care.

The higher rate in the high-intensity care arm “may be related to their higher number of [clinic] visits compared to usual care,” Dr. Mebazaa said. “However, serious adverse events and fatal adverse events were similar in both arms.”

Cardiac failure was the most common adverse event, developing in about 15% in both groups. It was followed by hypotension, hyperkalemia, and renal impairment, according to the published report.

Dr. Cleland cautioned that the risk of adverse events would potentially be higher should the high-intensity strategy become common clinical practice. The median age in STRONG-HF was 63, which is “10-15 years younger, on average, than the population with recently admitted heart failure that we see. There’s no doubt that older people have more multimorbidity.”

STRONG-HF was funded by Roche Diagnostics. Dr. Mebazaa discloses receiving grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics; honoraria for lectures from Roche Diagnostics, Bayer, and Merck, Sharp & Dohme; and consulting for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and to being a co-inventor on a patent involving combination therapy for patients having acute or persistent dyspnea.

Dr. Vest reports modest relationships with Boehringer Ingelheim, Corvia, and CareDx; and receiving research grants from the American Heart Association and the National Institutes of Health. Dr. Cleland discloses receiving honoraria from Idorsia; and research grants from Vifor Pharma, Medtronic, Bayer, and Bristol-Myers Squibb. Dr. Leon had no disclosures.

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

CHICAGO – Clinicians who prescribe heart failure meds are holding the best hand they’ve ever had, but with so much underuse and suboptimal dosing in actual practice, it seems many may not appreciate the value of their cards. But a major randomized trial that has captured the field’s attention may embolden them to go all in.

Results showed that a strategy of early, rapid up-titration of multiple guideline-directed meds in patients hospitalized with heart failure, compared with a usual-care approach, cut their 6-month risk for death or HF readmission by a steep 34% (P = .002).

The drugs had been started and partly up-titrated in the hospital with the goal of full up-titration within 2 weeks after discharge.

Patients well tolerated the high-intensity approach, researchers said. Their quality-of-life scores improved (P < .0001) compared with the usual-care group, and adverse events were considered few and manageable in the international trial with more than 1,000 patients.

Safety on the high-intensity strategy depended on close patient monitoring at frequently planned clinic visits along with guidance for the up-titrations from clinical signs and natriuretic peptide levels, observed Alexandre Mebazaa, MD, PhD, University of Paris and Public Hospitals of Paris.

Dr. Mebazaa is principal investigator on the trial, called STRONG-HF, which he presented at the American Heart Association scientific sessions, held in Chicago and virtually. He is also lead author on the study’s same-day publication in the Lancet.

The high-intensity strategy’s superiority emerged early in the trial, which was halted early on the data safety monitoring board’s recommendation, with about 90% of follow-ups completed. The board “felt it was unethical to keep patients in usual care,” Dr. Mebazaa said at a press conference.
 

A dramatic change

The next step, he said, will be to educate the heart failure community on the high-intensity care technique so it can swiftly enter clinical practice. Currently in acute heart failure, “very few patients are monitored after discharge and treated with full doses of heart failure therapies.”

Adoption of the strategy “would be a dramatic change from what’s currently being done,” said Martin B. Leon, MD, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, who moderated the press conference.

Only an estimated 5% of patients with HF in the United States receive full guideline-directed medical therapy, Dr. Leon said, “so the generalizability of this strategy, with careful follow-up that has safety involved in it, is absolutely crucial.”

But the potential impact of this high-intensity approach on resource use is unknown, raising questions about how widely and consistently it could be implemented, said Dr. Leon, who is not connected with STRONG-HF.

The trial called for in-hospital initiation of the three distinct drug classes that, at the time, were the core of guideline-directed HF therapy, with up-titration to 50% of recommended dosage by hospital discharge, and then to 100% within 2 weeks later.

The meds included a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system inhibitor (RASI). The latter could be an ACE inhibitor, angiotensin-receptor blocker (ARB), or angiotensin receptor-neprilysin inhibitor (ARNI).
 

How about a fourth drug?

Conspicuously absent from the list, for contemporary practice, was an SGLT2 inhibitor, a class that entered the HF guidelines well after STRONG-HF was designed. They would undoubtedly join the other three agents were the high-intensity strategy to enter practice, potentially changing its complexity and safety profile.

But Dr. Mebazaa and other experts don’t see that as a big challenge and would expect a smooth transition to a high-intensity approach that also includes the SGLT2 inhibitors.

STRONG-HF was necessary in part because many clinicians have been “reluctant” to take full advantage of three agents that had been the basis of guideline-directed therapy, he told this news organization.

That reluctance stemmed from concerns that beta-blockers might worsen the heart failure, ACE inhibitors could hurt the kidneys, or MRAs might cause hyperkalemia, Dr. Mebazaa said. The STRONG-HF high-intensity regimen, therefore, demanded multiple clinic visits for close follow-up.

But the SGLT2 inhibitors “are known to be rather safe drugs, at least much safer than the three others,” he said. So, it seems unlikely that their addition to a beta-blocker, RASI, and MRA in patients with HF would worsen the risk of adverse events.

John G.F. Cleland, MD, PhD, agrees. With addition of the fourth agent, “You may need to be a little bit more careful with renal function, just in that first couple of weeks,” he told this news organization. “But I think it would be easy to add an SGLT2 inhibitor into this regimen. And in general, there’s no titration with an SGLT2 inhibitor, so they’ll all be on full dose predischarge.”

Given the drugs’ diuretic-like action, moreover, some patients might be able to pull back on their loop diuretics, speculated Dr. Cleland, from the University of Glasgow’s School of Health and Wellbeing.

The prospect of a high-intensity strategy’s wide implementation in practice presents both “challenges and opportunities,” Amanda R. Vest, MBBS, MPH, Tufts University, Boston, told this news organization.

“There may be additional challenges in terms of ensuring we avoid hypotension or acute kidney injury in the up-titration phase,” said Dr. Vest, who is medical director of her center’s cardiac transplantation program but not connected with STRONG-HF.

“But it also gives us opportunities,” she added, “because there are some patients, especially in that vulnerable postdischarge phase, who are actually much more able to tolerate introduction of an SGLT2 inhibitor than, for example, an ACE inhibitor, ARB, or ARNI – or maybe a beta-blocker if they’ve been in a low cardiac-output state.” Effective dosing would depend on “the personalization and skill of the clinician in optimizing the medications in their correct sequence,” Dr. Vest said.

“It’s challenging to think that we would ever get to 100% up-titration,” she added, “and even in this excellent study, they didn’t get to 100%.” But as clinicians gain experience with the high-intensity strategy, especially as the SGLT2 inhibitors are included, “I think we can reasonably expect more progress to be made in these up-titration skills.”
 

No restrictions on LVEF

The researchers entered 1,078 patients hospitalized with acute HF in 14 countries across Africa, Europe, the Middle East, and South America, and randomly assigned them to the high-intensity management strategy or usual care.

About 60% of the patients were male and 77% were White. There were no entry restrictions based on left ventricular ejection fraction (LVEF), which exceeded 40% in almost a third of cases.

In the high-intensity care group’s 542 patients, the three agents were up-titrated to 50% of the maximum guideline-recommended dosage prior to hospital discharge, and to 100% within 2 weeks after discharge. Symptoms and laboratory biomarkers, including natriuretic peptides, were monitored closely at four planned clinical visits over the following 6 weeks.

The 536 patients assigned to usual care were discharged and managed according to local standards, with their meds handled by their own primary care doctors or cardiologists, the published report notes. They were reevaluated by STRONG-HF clinicians 90 days after discharge.

The number of clinic visits in the first 90 postdischarge days averaged 4.8 in the high-intensity care group and 1.0 for those receiving usual care. Full up-titration was far more likely in the high-intensity care group: 55% vs. 2% for RASI agents, 49% vs. 4% for beta-blockers, and 84% vs. 46% for MRAs.

They also fared significantly better on all measured parameters associated with decongestion, including weight, prevalence of peripheral edema, jugular venous pressure, NYHA functional class, and natriuretic peptide levels, the researchers said.

The primary endpoint of 180-day death from any cause or HF readmission was met by 15.2% of the high-intensity care group and 23.3% of usual-care patients, for an adjusted risk ratio (RR) of 0.66 (95% CI, 0.50-0.86; P = .0021).

Subgroup analyses saw no significant interactions by age, sex, race, geography, or baseline blood pressure, renal function, or LVEF. Patients with higher vs. lower baseline natriuretic peptide levels trend toward better responses to high-intensity care (P = .08)
 

The COVID effect

The group performed a sensitivity analysis that excluded deaths attributed to COVID-19 in STRONG-HF, which launched prior to the pandemic. The high-intensity strategy’s benefit for the primary endpoint grew, with an adjusted RR of 0.61 (95% CI, 0.46-0.82; P = .0005). There was no corresponding effect on death from any cause (P = .15).

Treatment-related adverse effects in the overall trial were seen in 41.1% of the high-intensity care group and in 29.5% of those assigned to usual care.

The higher rate in the high-intensity care arm “may be related to their higher number of [clinic] visits compared to usual care,” Dr. Mebazaa said. “However, serious adverse events and fatal adverse events were similar in both arms.”

Cardiac failure was the most common adverse event, developing in about 15% in both groups. It was followed by hypotension, hyperkalemia, and renal impairment, according to the published report.

Dr. Cleland cautioned that the risk of adverse events would potentially be higher should the high-intensity strategy become common clinical practice. The median age in STRONG-HF was 63, which is “10-15 years younger, on average, than the population with recently admitted heart failure that we see. There’s no doubt that older people have more multimorbidity.”

STRONG-HF was funded by Roche Diagnostics. Dr. Mebazaa discloses receiving grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics; honoraria for lectures from Roche Diagnostics, Bayer, and Merck, Sharp & Dohme; and consulting for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and to being a co-inventor on a patent involving combination therapy for patients having acute or persistent dyspnea.

Dr. Vest reports modest relationships with Boehringer Ingelheim, Corvia, and CareDx; and receiving research grants from the American Heart Association and the National Institutes of Health. Dr. Cleland discloses receiving honoraria from Idorsia; and research grants from Vifor Pharma, Medtronic, Bayer, and Bristol-Myers Squibb. Dr. Leon had no disclosures.

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

CHICAGO – Clinicians who prescribe heart failure meds are holding the best hand they’ve ever had, but with so much underuse and suboptimal dosing in actual practice, it seems many may not appreciate the value of their cards. But a major randomized trial that has captured the field’s attention may embolden them to go all in.

Results showed that a strategy of early, rapid up-titration of multiple guideline-directed meds in patients hospitalized with heart failure, compared with a usual-care approach, cut their 6-month risk for death or HF readmission by a steep 34% (P = .002).

The drugs had been started and partly up-titrated in the hospital with the goal of full up-titration within 2 weeks after discharge.

Patients well tolerated the high-intensity approach, researchers said. Their quality-of-life scores improved (P < .0001) compared with the usual-care group, and adverse events were considered few and manageable in the international trial with more than 1,000 patients.

Safety on the high-intensity strategy depended on close patient monitoring at frequently planned clinic visits along with guidance for the up-titrations from clinical signs and natriuretic peptide levels, observed Alexandre Mebazaa, MD, PhD, University of Paris and Public Hospitals of Paris.

Dr. Mebazaa is principal investigator on the trial, called STRONG-HF, which he presented at the American Heart Association scientific sessions, held in Chicago and virtually. He is also lead author on the study’s same-day publication in the Lancet.

The high-intensity strategy’s superiority emerged early in the trial, which was halted early on the data safety monitoring board’s recommendation, with about 90% of follow-ups completed. The board “felt it was unethical to keep patients in usual care,” Dr. Mebazaa said at a press conference.
 

A dramatic change

The next step, he said, will be to educate the heart failure community on the high-intensity care technique so it can swiftly enter clinical practice. Currently in acute heart failure, “very few patients are monitored after discharge and treated with full doses of heart failure therapies.”

Adoption of the strategy “would be a dramatic change from what’s currently being done,” said Martin B. Leon, MD, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, who moderated the press conference.

Only an estimated 5% of patients with HF in the United States receive full guideline-directed medical therapy, Dr. Leon said, “so the generalizability of this strategy, with careful follow-up that has safety involved in it, is absolutely crucial.”

But the potential impact of this high-intensity approach on resource use is unknown, raising questions about how widely and consistently it could be implemented, said Dr. Leon, who is not connected with STRONG-HF.

The trial called for in-hospital initiation of the three distinct drug classes that, at the time, were the core of guideline-directed HF therapy, with up-titration to 50% of recommended dosage by hospital discharge, and then to 100% within 2 weeks later.

The meds included a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system inhibitor (RASI). The latter could be an ACE inhibitor, angiotensin-receptor blocker (ARB), or angiotensin receptor-neprilysin inhibitor (ARNI).
 

How about a fourth drug?

Conspicuously absent from the list, for contemporary practice, was an SGLT2 inhibitor, a class that entered the HF guidelines well after STRONG-HF was designed. They would undoubtedly join the other three agents were the high-intensity strategy to enter practice, potentially changing its complexity and safety profile.

But Dr. Mebazaa and other experts don’t see that as a big challenge and would expect a smooth transition to a high-intensity approach that also includes the SGLT2 inhibitors.

STRONG-HF was necessary in part because many clinicians have been “reluctant” to take full advantage of three agents that had been the basis of guideline-directed therapy, he told this news organization.

That reluctance stemmed from concerns that beta-blockers might worsen the heart failure, ACE inhibitors could hurt the kidneys, or MRAs might cause hyperkalemia, Dr. Mebazaa said. The STRONG-HF high-intensity regimen, therefore, demanded multiple clinic visits for close follow-up.

But the SGLT2 inhibitors “are known to be rather safe drugs, at least much safer than the three others,” he said. So, it seems unlikely that their addition to a beta-blocker, RASI, and MRA in patients with HF would worsen the risk of adverse events.

John G.F. Cleland, MD, PhD, agrees. With addition of the fourth agent, “You may need to be a little bit more careful with renal function, just in that first couple of weeks,” he told this news organization. “But I think it would be easy to add an SGLT2 inhibitor into this regimen. And in general, there’s no titration with an SGLT2 inhibitor, so they’ll all be on full dose predischarge.”

Given the drugs’ diuretic-like action, moreover, some patients might be able to pull back on their loop diuretics, speculated Dr. Cleland, from the University of Glasgow’s School of Health and Wellbeing.

The prospect of a high-intensity strategy’s wide implementation in practice presents both “challenges and opportunities,” Amanda R. Vest, MBBS, MPH, Tufts University, Boston, told this news organization.

“There may be additional challenges in terms of ensuring we avoid hypotension or acute kidney injury in the up-titration phase,” said Dr. Vest, who is medical director of her center’s cardiac transplantation program but not connected with STRONG-HF.

“But it also gives us opportunities,” she added, “because there are some patients, especially in that vulnerable postdischarge phase, who are actually much more able to tolerate introduction of an SGLT2 inhibitor than, for example, an ACE inhibitor, ARB, or ARNI – or maybe a beta-blocker if they’ve been in a low cardiac-output state.” Effective dosing would depend on “the personalization and skill of the clinician in optimizing the medications in their correct sequence,” Dr. Vest said.

“It’s challenging to think that we would ever get to 100% up-titration,” she added, “and even in this excellent study, they didn’t get to 100%.” But as clinicians gain experience with the high-intensity strategy, especially as the SGLT2 inhibitors are included, “I think we can reasonably expect more progress to be made in these up-titration skills.”
 

No restrictions on LVEF

The researchers entered 1,078 patients hospitalized with acute HF in 14 countries across Africa, Europe, the Middle East, and South America, and randomly assigned them to the high-intensity management strategy or usual care.

About 60% of the patients were male and 77% were White. There were no entry restrictions based on left ventricular ejection fraction (LVEF), which exceeded 40% in almost a third of cases.

In the high-intensity care group’s 542 patients, the three agents were up-titrated to 50% of the maximum guideline-recommended dosage prior to hospital discharge, and to 100% within 2 weeks after discharge. Symptoms and laboratory biomarkers, including natriuretic peptides, were monitored closely at four planned clinical visits over the following 6 weeks.

The 536 patients assigned to usual care were discharged and managed according to local standards, with their meds handled by their own primary care doctors or cardiologists, the published report notes. They were reevaluated by STRONG-HF clinicians 90 days after discharge.

The number of clinic visits in the first 90 postdischarge days averaged 4.8 in the high-intensity care group and 1.0 for those receiving usual care. Full up-titration was far more likely in the high-intensity care group: 55% vs. 2% for RASI agents, 49% vs. 4% for beta-blockers, and 84% vs. 46% for MRAs.

They also fared significantly better on all measured parameters associated with decongestion, including weight, prevalence of peripheral edema, jugular venous pressure, NYHA functional class, and natriuretic peptide levels, the researchers said.

The primary endpoint of 180-day death from any cause or HF readmission was met by 15.2% of the high-intensity care group and 23.3% of usual-care patients, for an adjusted risk ratio (RR) of 0.66 (95% CI, 0.50-0.86; P = .0021).

Subgroup analyses saw no significant interactions by age, sex, race, geography, or baseline blood pressure, renal function, or LVEF. Patients with higher vs. lower baseline natriuretic peptide levels trend toward better responses to high-intensity care (P = .08)
 

The COVID effect

The group performed a sensitivity analysis that excluded deaths attributed to COVID-19 in STRONG-HF, which launched prior to the pandemic. The high-intensity strategy’s benefit for the primary endpoint grew, with an adjusted RR of 0.61 (95% CI, 0.46-0.82; P = .0005). There was no corresponding effect on death from any cause (P = .15).

Treatment-related adverse effects in the overall trial were seen in 41.1% of the high-intensity care group and in 29.5% of those assigned to usual care.

The higher rate in the high-intensity care arm “may be related to their higher number of [clinic] visits compared to usual care,” Dr. Mebazaa said. “However, serious adverse events and fatal adverse events were similar in both arms.”

Cardiac failure was the most common adverse event, developing in about 15% in both groups. It was followed by hypotension, hyperkalemia, and renal impairment, according to the published report.

Dr. Cleland cautioned that the risk of adverse events would potentially be higher should the high-intensity strategy become common clinical practice. The median age in STRONG-HF was 63, which is “10-15 years younger, on average, than the population with recently admitted heart failure that we see. There’s no doubt that older people have more multimorbidity.”

STRONG-HF was funded by Roche Diagnostics. Dr. Mebazaa discloses receiving grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics; honoraria for lectures from Roche Diagnostics, Bayer, and Merck, Sharp & Dohme; and consulting for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and to being a co-inventor on a patent involving combination therapy for patients having acute or persistent dyspnea.

Dr. Vest reports modest relationships with Boehringer Ingelheim, Corvia, and CareDx; and receiving research grants from the American Heart Association and the National Institutes of Health. Dr. Cleland discloses receiving honoraria from Idorsia; and research grants from Vifor Pharma, Medtronic, Bayer, and Bristol-Myers Squibb. Dr. Leon had no disclosures.

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

Influenza vaccination is associated with a reduced risk of stroke among adults, even if they aren’t at high risk for stroke, according to new research.

The risk of stroke was about 23% lower in the 6 months following a flu shot, regardless of the patient’s age, sex, or underlying health conditions.

“There is an established link between upper respiratory infection and both heart attack and stroke. This has been very salient in the past few years throughout the COVID-19 pandemic,” study author Jessalyn Holodinsky, PhD, a stroke epidemiologist and postdoctoral fellow in clinical neurosciences at the University of Calgary (Alta.) told this news organization.

“It is also known that the flu shot can reduce risk of heart attack and hospitalization for those with heart disease,” she said. “Given both of these [observations], we thought it prudent to study whether there is a link between vaccination for influenza and stroke.”

The study was published in the Lancet Public Health.
 

Large effect size

The investigators analyzed administrative data from 2009 through 2018 from the Alberta Health Care Insurance Plan, which covers all residents of Alberta. The province provides free seasonal influenza vaccines to residents under the insurance plan.

The research team looked for stroke events such as acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and transient ischemic attack. They then analyzed the risk of stroke events among those with or without a flu shot in the previous 6 months. They accounted for multiple factors, including age, sex, income, location, and factors related to stroke risk, such as anticoagulant use, atrial fibrillation, chronic obstructive pulmonary disease, diabetes, and hypertension.

Among the 4.1 million adults included in the researchers’ analysis, about 1.8 million (43%) received at least one vaccination during the study period. Nearly 97,000 people received a flu vaccine in each year they were in the study, including 29,288 who received a shot in all 10 flu seasons included in the study.

About 38,000 stroke events were recorded, including about 34,000 (90%) first stroke events. Among the 10% of strokes that were recurrent events, the maximum number of stroke events in one person was nine.

Overall, patients who received at least one influenza vaccine were more likely to be older, be women, and have higher rates of comorbidities. The vaccinated group had a slightly higher proportion of people who lived in urban areas, but the income levels were similar between the vaccinated and unvaccinated groups.

The crude incidence of stroke was higher among people who had ever received an influenza vaccination, at 1.25%, compared with 0.52% among those who hadn’t been vaccinated. However, after adjusting for age, sex, underlying conditions, and socioeconomic status, recent flu vaccination (that is, in the previous 6 months) was associated with a 23% reduced risk of stroke.

The significant reduction in risk applied to all stroke types, particularly acute ischemic stroke and intracerebral hemorrhage. In addition, influenza vaccination was associated with a reduced risk across all ages and risk profiles, except patients without hypertension.

“What we were most surprised by was the sheer magnitude of the effect and that it existed across different adult age groups, for both sexes, and for those with and without risk factors for stroke,” said Dr. Holodinsky.

Vaccination was associated with a larger reduction in stroke risk in men than in women, perhaps because unvaccinated men had a significantly higher baseline risk for stroke than unvaccinated women, the study authors write.
 

Promoting cardiovascular health

In addition, vaccination was associated with a greater relative reduction in stroke risk in younger age groups, lower income groups, and those with diabetes, chronic obstructive pulmonary disease, and anticoagulant use.

Among 2.4 million people observed for the entire study period, vaccination protection increased with the number of vaccines received. People who were vaccinated serially each year had a significantly lower risk of stroke than those who received one shot.

Dr. Holodinsky and colleagues are conducting additional research into influenza vaccination, including stroke risk in children. They’re also investigating whether the reduced risk applies to other vaccinations for respiratory illnesses, such as COVID-19 and pneumonia.

“We hope that this added effect of vaccination encourages more adults to receive the flu shot,” she said. “One day, vaccinations might be considered a key pillar of cardiovascular health, along with diet, exercise, control of hypertension and high cholesterol, and smoking cessation.”

Future research should also investigate the reasons why adults – particularly people at high risk with underlying conditions – don’t receive recommended influenza vaccines, the study authors wrote.
 

‘Call to action’

Bahar Behrouzi, an MD-PhD candidate focused on clinical epidemiology at the Institute of Health Policy, Management, and Evaluation, University of Toronto, said: “There are a variety of observational studies around the world that show that flu vaccine uptake is low among the general population and high-risk persons. In studying these questions, our hope is that we can continue to build confidence in viral respiratory vaccines like the influenza vaccine by continuing to generate rigorous evidence with the latest data.”

Ms. Behrouzi, who wasn’t involved with this study, has researched influenza vaccination and cardiovascular risk. She and her colleagues have found that flu vaccines were associated with a 34% lower risk of major adverse cardiovascular events, including a 45% reduced risk among patients with recent acute coronary syndrome.

“The broader public health message is for people to advocate for themselves and get the seasonal flu vaccine, especially if they are part of an at-risk group,” she said. “In our studies, we have positioned this message as a call to action not only for the public, but also for health care professionals – particularly specialists such as cardiologists or neurologists – to encourage or remind them to engage in conversation about the broad benefits of vaccination beyond just preventing or reducing the severity of flu infection.”

The study was conducted without outside funding. Dr. Holodinsky and Ms. Behrouzi have reported no relevant disclosures.

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

Influenza vaccination is associated with a reduced risk of stroke among adults, even if they aren’t at high risk for stroke, according to new research.

The risk of stroke was about 23% lower in the 6 months following a flu shot, regardless of the patient’s age, sex, or underlying health conditions.

“There is an established link between upper respiratory infection and both heart attack and stroke. This has been very salient in the past few years throughout the COVID-19 pandemic,” study author Jessalyn Holodinsky, PhD, a stroke epidemiologist and postdoctoral fellow in clinical neurosciences at the University of Calgary (Alta.) told this news organization.

“It is also known that the flu shot can reduce risk of heart attack and hospitalization for those with heart disease,” she said. “Given both of these [observations], we thought it prudent to study whether there is a link between vaccination for influenza and stroke.”

The study was published in the Lancet Public Health.
 

Large effect size

The investigators analyzed administrative data from 2009 through 2018 from the Alberta Health Care Insurance Plan, which covers all residents of Alberta. The province provides free seasonal influenza vaccines to residents under the insurance plan.

The research team looked for stroke events such as acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and transient ischemic attack. They then analyzed the risk of stroke events among those with or without a flu shot in the previous 6 months. They accounted for multiple factors, including age, sex, income, location, and factors related to stroke risk, such as anticoagulant use, atrial fibrillation, chronic obstructive pulmonary disease, diabetes, and hypertension.

Among the 4.1 million adults included in the researchers’ analysis, about 1.8 million (43%) received at least one vaccination during the study period. Nearly 97,000 people received a flu vaccine in each year they were in the study, including 29,288 who received a shot in all 10 flu seasons included in the study.

About 38,000 stroke events were recorded, including about 34,000 (90%) first stroke events. Among the 10% of strokes that were recurrent events, the maximum number of stroke events in one person was nine.

Overall, patients who received at least one influenza vaccine were more likely to be older, be women, and have higher rates of comorbidities. The vaccinated group had a slightly higher proportion of people who lived in urban areas, but the income levels were similar between the vaccinated and unvaccinated groups.

The crude incidence of stroke was higher among people who had ever received an influenza vaccination, at 1.25%, compared with 0.52% among those who hadn’t been vaccinated. However, after adjusting for age, sex, underlying conditions, and socioeconomic status, recent flu vaccination (that is, in the previous 6 months) was associated with a 23% reduced risk of stroke.

The significant reduction in risk applied to all stroke types, particularly acute ischemic stroke and intracerebral hemorrhage. In addition, influenza vaccination was associated with a reduced risk across all ages and risk profiles, except patients without hypertension.

“What we were most surprised by was the sheer magnitude of the effect and that it existed across different adult age groups, for both sexes, and for those with and without risk factors for stroke,” said Dr. Holodinsky.

Vaccination was associated with a larger reduction in stroke risk in men than in women, perhaps because unvaccinated men had a significantly higher baseline risk for stroke than unvaccinated women, the study authors write.
 

Promoting cardiovascular health

In addition, vaccination was associated with a greater relative reduction in stroke risk in younger age groups, lower income groups, and those with diabetes, chronic obstructive pulmonary disease, and anticoagulant use.

Among 2.4 million people observed for the entire study period, vaccination protection increased with the number of vaccines received. People who were vaccinated serially each year had a significantly lower risk of stroke than those who received one shot.

Dr. Holodinsky and colleagues are conducting additional research into influenza vaccination, including stroke risk in children. They’re also investigating whether the reduced risk applies to other vaccinations for respiratory illnesses, such as COVID-19 and pneumonia.

“We hope that this added effect of vaccination encourages more adults to receive the flu shot,” she said. “One day, vaccinations might be considered a key pillar of cardiovascular health, along with diet, exercise, control of hypertension and high cholesterol, and smoking cessation.”

Future research should also investigate the reasons why adults – particularly people at high risk with underlying conditions – don’t receive recommended influenza vaccines, the study authors wrote.
 

‘Call to action’

Bahar Behrouzi, an MD-PhD candidate focused on clinical epidemiology at the Institute of Health Policy, Management, and Evaluation, University of Toronto, said: “There are a variety of observational studies around the world that show that flu vaccine uptake is low among the general population and high-risk persons. In studying these questions, our hope is that we can continue to build confidence in viral respiratory vaccines like the influenza vaccine by continuing to generate rigorous evidence with the latest data.”

Ms. Behrouzi, who wasn’t involved with this study, has researched influenza vaccination and cardiovascular risk. She and her colleagues have found that flu vaccines were associated with a 34% lower risk of major adverse cardiovascular events, including a 45% reduced risk among patients with recent acute coronary syndrome.

“The broader public health message is for people to advocate for themselves and get the seasonal flu vaccine, especially if they are part of an at-risk group,” she said. “In our studies, we have positioned this message as a call to action not only for the public, but also for health care professionals – particularly specialists such as cardiologists or neurologists – to encourage or remind them to engage in conversation about the broad benefits of vaccination beyond just preventing or reducing the severity of flu infection.”

The study was conducted without outside funding. Dr. Holodinsky and Ms. Behrouzi have reported no relevant disclosures.

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

Influenza vaccination is associated with a reduced risk of stroke among adults, even if they aren’t at high risk for stroke, according to new research.

The risk of stroke was about 23% lower in the 6 months following a flu shot, regardless of the patient’s age, sex, or underlying health conditions.

“There is an established link between upper respiratory infection and both heart attack and stroke. This has been very salient in the past few years throughout the COVID-19 pandemic,” study author Jessalyn Holodinsky, PhD, a stroke epidemiologist and postdoctoral fellow in clinical neurosciences at the University of Calgary (Alta.) told this news organization.

“It is also known that the flu shot can reduce risk of heart attack and hospitalization for those with heart disease,” she said. “Given both of these [observations], we thought it prudent to study whether there is a link between vaccination for influenza and stroke.”

The study was published in the Lancet Public Health.
 

Large effect size

The investigators analyzed administrative data from 2009 through 2018 from the Alberta Health Care Insurance Plan, which covers all residents of Alberta. The province provides free seasonal influenza vaccines to residents under the insurance plan.

The research team looked for stroke events such as acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and transient ischemic attack. They then analyzed the risk of stroke events among those with or without a flu shot in the previous 6 months. They accounted for multiple factors, including age, sex, income, location, and factors related to stroke risk, such as anticoagulant use, atrial fibrillation, chronic obstructive pulmonary disease, diabetes, and hypertension.

Among the 4.1 million adults included in the researchers’ analysis, about 1.8 million (43%) received at least one vaccination during the study period. Nearly 97,000 people received a flu vaccine in each year they were in the study, including 29,288 who received a shot in all 10 flu seasons included in the study.

About 38,000 stroke events were recorded, including about 34,000 (90%) first stroke events. Among the 10% of strokes that were recurrent events, the maximum number of stroke events in one person was nine.

Overall, patients who received at least one influenza vaccine were more likely to be older, be women, and have higher rates of comorbidities. The vaccinated group had a slightly higher proportion of people who lived in urban areas, but the income levels were similar between the vaccinated and unvaccinated groups.

The crude incidence of stroke was higher among people who had ever received an influenza vaccination, at 1.25%, compared with 0.52% among those who hadn’t been vaccinated. However, after adjusting for age, sex, underlying conditions, and socioeconomic status, recent flu vaccination (that is, in the previous 6 months) was associated with a 23% reduced risk of stroke.

The significant reduction in risk applied to all stroke types, particularly acute ischemic stroke and intracerebral hemorrhage. In addition, influenza vaccination was associated with a reduced risk across all ages and risk profiles, except patients without hypertension.

“What we were most surprised by was the sheer magnitude of the effect and that it existed across different adult age groups, for both sexes, and for those with and without risk factors for stroke,” said Dr. Holodinsky.

Vaccination was associated with a larger reduction in stroke risk in men than in women, perhaps because unvaccinated men had a significantly higher baseline risk for stroke than unvaccinated women, the study authors write.
 

Promoting cardiovascular health

In addition, vaccination was associated with a greater relative reduction in stroke risk in younger age groups, lower income groups, and those with diabetes, chronic obstructive pulmonary disease, and anticoagulant use.

Among 2.4 million people observed for the entire study period, vaccination protection increased with the number of vaccines received. People who were vaccinated serially each year had a significantly lower risk of stroke than those who received one shot.

Dr. Holodinsky and colleagues are conducting additional research into influenza vaccination, including stroke risk in children. They’re also investigating whether the reduced risk applies to other vaccinations for respiratory illnesses, such as COVID-19 and pneumonia.

“We hope that this added effect of vaccination encourages more adults to receive the flu shot,” she said. “One day, vaccinations might be considered a key pillar of cardiovascular health, along with diet, exercise, control of hypertension and high cholesterol, and smoking cessation.”

Future research should also investigate the reasons why adults – particularly people at high risk with underlying conditions – don’t receive recommended influenza vaccines, the study authors wrote.
 

‘Call to action’

Bahar Behrouzi, an MD-PhD candidate focused on clinical epidemiology at the Institute of Health Policy, Management, and Evaluation, University of Toronto, said: “There are a variety of observational studies around the world that show that flu vaccine uptake is low among the general population and high-risk persons. In studying these questions, our hope is that we can continue to build confidence in viral respiratory vaccines like the influenza vaccine by continuing to generate rigorous evidence with the latest data.”

Ms. Behrouzi, who wasn’t involved with this study, has researched influenza vaccination and cardiovascular risk. She and her colleagues have found that flu vaccines were associated with a 34% lower risk of major adverse cardiovascular events, including a 45% reduced risk among patients with recent acute coronary syndrome.

“The broader public health message is for people to advocate for themselves and get the seasonal flu vaccine, especially if they are part of an at-risk group,” she said. “In our studies, we have positioned this message as a call to action not only for the public, but also for health care professionals – particularly specialists such as cardiologists or neurologists – to encourage or remind them to engage in conversation about the broad benefits of vaccination beyond just preventing or reducing the severity of flu infection.”

The study was conducted without outside funding. Dr. Holodinsky and Ms. Behrouzi have reported no relevant disclosures.

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

PAU, FRANCE – Postpartum posttraumatic stress disorder tends to get worse over the months following the birth of a child. Therefore, it’s necessary to screen for it as early on as possible and to ensure that women who are affected are given the proper treatment. This was the message delivered during the Infogyn 2022 conference by Ludivine Franchitto, MD, a child psychiatrist at Toulouse University Hospital, France. Because postpartum PTSD is still not fully recognized, treatment remains inadequate and poorly documented.

Impact on the caregivers as well

“The situation is the same as what we saw with postpartum depression. The debate went on for 20 years before its existence was formally declared,” Dr. Franchitto noted. But for her, the important thing is not knowing whether a traumatic stress state may be experienced by the mother who had complications during pregnancy or delivery. Instead, it’s about focusing on the repercussions for the child.

During her presentation, Dr. Franchitto also pointed out that it’s necessary to recognize that caregivers who work in maternity wards may also be negatively impacted, as they routinely see the complications that women have during pregnancy and delivery. These workers may also develop a PTSD state, requiring support so that they can properly carry out their duties.

According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), posttraumatic stress disorder arises after exposure to actual (or threatened) death, serious injury, or sexual violence. Individuals who have witnessed a traumatic event in person or who have experienced repeated (or extreme) exposure to aversive details of traumatic events may also develop PTSD.

Dr. Franchitto mentioned some of the criteria needed to make the diagnosis. “Intrusive distressing memories of the event, recurrent distressing dreams related to the event, persistent avoidance of stimuli associated with the traumatic event, or negative alterations in cognitions and mood associated with the traumatic event. And the duration of the disturbance is more than 1 month.” There may also be marked alterations in arousal and reactivity associated with the traumatic event (for example, irritable behavior, loss of awareness of present surroundings).
 

Prevalent in 18% of women in high-risk groups

According to the studies, there is a wide variability of PTSD rates. If referring only to traumatic symptoms (for example, depressive syndrome, suicidal ideation, hyperreactivity, and persistent avoidance), the rate could reach up to 40%. A 2016 meta-analysis of 59 studies found that the prevalence of childbirth-related PTSD was 5.9%.

The authors distinguished two groups of women: those without complications during pregnancy or during delivery and those with severe complications related to the pregnancy, a fear of giving birth, a difficult delivery, an emergency C-section, a baby born prematurely with birth defects, etc. Their analysis showed PTSD rates of 4% and 18.5%, respectively.

Surprisingly, the major risk factor for PTSD turned out to be uncontrollable vomiting during pregnancy (seen in 40% of postpartum PTSD cases). The birth of a baby with birth defects was the second risk factor (35%), and the third, a history of violence in the mother’s childhood (34%). Women who experienced depression during the delivery were also at higher risk.

Other risk factors identified were lack of communication with the health care team, lack of consent, lack of support from the medical staff, and a long labor. Conversely, a sense of control and the support of a partner play a protective role.
 

Early screening

“If the symptoms of posttraumatic stress disorder aren’t treated after delivery, they tend to get worse over the period of 1 to 6 months following the child’s birth,” Dr. Franchitto indicated. This is why it’s necessary to screen for it as early as possible – in particular, by having the women fill out the City Birth Trauma Scale questionnaire – and provide proper treatment accordingly. When seeking to limit the effects of stress, early intervention by a psychologist may be beneficial.

Psychotherapy is the recommended first-line treatment for PTSD, especially cognitive behavioral therapy and Eye Movement Desensitization and Reprocessing therapy. This approach aims to limit the mental and behavioral avoidance that prevents the traumatic memory from being integrated and processed as a regular memory.

The consequences that the mother’s PTSD state has on the child are well documented. “Children whose mothers had PTSD during pregnancy have a lower birth weight and a shorter breast-feeding duration,” Dr. Franchitto reported. With respect to the quality of the mother-child relationship and the long-term development of the child, “the studies have highly conflicting findings.”

At the end of the presentation, Professor Israël Nisand, MD, an ob.gyn. at the American Hospital of Paris and the former president of the National College of French Gynecologists and Obstetricians, made the following comment: “I often think that we underestimate the consequences that the mother’s posttraumatic stress has on the child postpartum.” He added, “Postpartum posttraumatic stress disorder is a reality. Yet it isn’t screened for, let alone treated, even though it has serious consequences for the child.”

Dr. Franchitto also brought up the impact on members of the health care staff, the “second victims” of the traumatic events that occur while caring for the women in the maternity ward. “The estimated prevalence of PTSD symptoms among midwives is 22.9%,” which could lead to “a loss of confidence and a desire to leave the profession.”
 

Providing psychoeducation to health care staff

Dr. Franchitto believes that it’s essential to also protect caregivers who work in maternity wards. “It’s important to have the support of colleagues” – in particular, of team leaders – “and to share one’s experiences,” as long as one knows how to recognize the symptoms of posttraumatic stress through one’s emotions and is able to verbalize them.

She went on to say that providing psychoeducation to health care staff is therefore to be encouraged, as is “simulation-based training, for learning how to manage problematic situations.”

This content was originally published on Medscape French edition. A translated version appeared on Medscape.com.

PAU, FRANCE – Postpartum posttraumatic stress disorder tends to get worse over the months following the birth of a child. Therefore, it’s necessary to screen for it as early on as possible and to ensure that women who are affected are given the proper treatment. This was the message delivered during the Infogyn 2022 conference by Ludivine Franchitto, MD, a child psychiatrist at Toulouse University Hospital, France. Because postpartum PTSD is still not fully recognized, treatment remains inadequate and poorly documented.

Impact on the caregivers as well

“The situation is the same as what we saw with postpartum depression. The debate went on for 20 years before its existence was formally declared,” Dr. Franchitto noted. But for her, the important thing is not knowing whether a traumatic stress state may be experienced by the mother who had complications during pregnancy or delivery. Instead, it’s about focusing on the repercussions for the child.

During her presentation, Dr. Franchitto also pointed out that it’s necessary to recognize that caregivers who work in maternity wards may also be negatively impacted, as they routinely see the complications that women have during pregnancy and delivery. These workers may also develop a PTSD state, requiring support so that they can properly carry out their duties.

According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), posttraumatic stress disorder arises after exposure to actual (or threatened) death, serious injury, or sexual violence. Individuals who have witnessed a traumatic event in person or who have experienced repeated (or extreme) exposure to aversive details of traumatic events may also develop PTSD.

Dr. Franchitto mentioned some of the criteria needed to make the diagnosis. “Intrusive distressing memories of the event, recurrent distressing dreams related to the event, persistent avoidance of stimuli associated with the traumatic event, or negative alterations in cognitions and mood associated with the traumatic event. And the duration of the disturbance is more than 1 month.” There may also be marked alterations in arousal and reactivity associated with the traumatic event (for example, irritable behavior, loss of awareness of present surroundings).
 

Prevalent in 18% of women in high-risk groups

According to the studies, there is a wide variability of PTSD rates. If referring only to traumatic symptoms (for example, depressive syndrome, suicidal ideation, hyperreactivity, and persistent avoidance), the rate could reach up to 40%. A 2016 meta-analysis of 59 studies found that the prevalence of childbirth-related PTSD was 5.9%.

The authors distinguished two groups of women: those without complications during pregnancy or during delivery and those with severe complications related to the pregnancy, a fear of giving birth, a difficult delivery, an emergency C-section, a baby born prematurely with birth defects, etc. Their analysis showed PTSD rates of 4% and 18.5%, respectively.

Surprisingly, the major risk factor for PTSD turned out to be uncontrollable vomiting during pregnancy (seen in 40% of postpartum PTSD cases). The birth of a baby with birth defects was the second risk factor (35%), and the third, a history of violence in the mother’s childhood (34%). Women who experienced depression during the delivery were also at higher risk.

Other risk factors identified were lack of communication with the health care team, lack of consent, lack of support from the medical staff, and a long labor. Conversely, a sense of control and the support of a partner play a protective role.
 

Early screening

“If the symptoms of posttraumatic stress disorder aren’t treated after delivery, they tend to get worse over the period of 1 to 6 months following the child’s birth,” Dr. Franchitto indicated. This is why it’s necessary to screen for it as early as possible – in particular, by having the women fill out the City Birth Trauma Scale questionnaire – and provide proper treatment accordingly. When seeking to limit the effects of stress, early intervention by a psychologist may be beneficial.

Psychotherapy is the recommended first-line treatment for PTSD, especially cognitive behavioral therapy and Eye Movement Desensitization and Reprocessing therapy. This approach aims to limit the mental and behavioral avoidance that prevents the traumatic memory from being integrated and processed as a regular memory.

The consequences that the mother’s PTSD state has on the child are well documented. “Children whose mothers had PTSD during pregnancy have a lower birth weight and a shorter breast-feeding duration,” Dr. Franchitto reported. With respect to the quality of the mother-child relationship and the long-term development of the child, “the studies have highly conflicting findings.”

At the end of the presentation, Professor Israël Nisand, MD, an ob.gyn. at the American Hospital of Paris and the former president of the National College of French Gynecologists and Obstetricians, made the following comment: “I often think that we underestimate the consequences that the mother’s posttraumatic stress has on the child postpartum.” He added, “Postpartum posttraumatic stress disorder is a reality. Yet it isn’t screened for, let alone treated, even though it has serious consequences for the child.”

Dr. Franchitto also brought up the impact on members of the health care staff, the “second victims” of the traumatic events that occur while caring for the women in the maternity ward. “The estimated prevalence of PTSD symptoms among midwives is 22.9%,” which could lead to “a loss of confidence and a desire to leave the profession.”
 

Providing psychoeducation to health care staff

Dr. Franchitto believes that it’s essential to also protect caregivers who work in maternity wards. “It’s important to have the support of colleagues” – in particular, of team leaders – “and to share one’s experiences,” as long as one knows how to recognize the symptoms of posttraumatic stress through one’s emotions and is able to verbalize them.

She went on to say that providing psychoeducation to health care staff is therefore to be encouraged, as is “simulation-based training, for learning how to manage problematic situations.”

This content was originally published on Medscape French edition. A translated version appeared on Medscape.com.

PAU, FRANCE – Postpartum posttraumatic stress disorder tends to get worse over the months following the birth of a child. Therefore, it’s necessary to screen for it as early on as possible and to ensure that women who are affected are given the proper treatment. This was the message delivered during the Infogyn 2022 conference by Ludivine Franchitto, MD, a child psychiatrist at Toulouse University Hospital, France. Because postpartum PTSD is still not fully recognized, treatment remains inadequate and poorly documented.

Impact on the caregivers as well

“The situation is the same as what we saw with postpartum depression. The debate went on for 20 years before its existence was formally declared,” Dr. Franchitto noted. But for her, the important thing is not knowing whether a traumatic stress state may be experienced by the mother who had complications during pregnancy or delivery. Instead, it’s about focusing on the repercussions for the child.

During her presentation, Dr. Franchitto also pointed out that it’s necessary to recognize that caregivers who work in maternity wards may also be negatively impacted, as they routinely see the complications that women have during pregnancy and delivery. These workers may also develop a PTSD state, requiring support so that they can properly carry out their duties.

According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), posttraumatic stress disorder arises after exposure to actual (or threatened) death, serious injury, or sexual violence. Individuals who have witnessed a traumatic event in person or who have experienced repeated (or extreme) exposure to aversive details of traumatic events may also develop PTSD.

Dr. Franchitto mentioned some of the criteria needed to make the diagnosis. “Intrusive distressing memories of the event, recurrent distressing dreams related to the event, persistent avoidance of stimuli associated with the traumatic event, or negative alterations in cognitions and mood associated with the traumatic event. And the duration of the disturbance is more than 1 month.” There may also be marked alterations in arousal and reactivity associated with the traumatic event (for example, irritable behavior, loss of awareness of present surroundings).
 

Prevalent in 18% of women in high-risk groups

According to the studies, there is a wide variability of PTSD rates. If referring only to traumatic symptoms (for example, depressive syndrome, suicidal ideation, hyperreactivity, and persistent avoidance), the rate could reach up to 40%. A 2016 meta-analysis of 59 studies found that the prevalence of childbirth-related PTSD was 5.9%.

The authors distinguished two groups of women: those without complications during pregnancy or during delivery and those with severe complications related to the pregnancy, a fear of giving birth, a difficult delivery, an emergency C-section, a baby born prematurely with birth defects, etc. Their analysis showed PTSD rates of 4% and 18.5%, respectively.

Surprisingly, the major risk factor for PTSD turned out to be uncontrollable vomiting during pregnancy (seen in 40% of postpartum PTSD cases). The birth of a baby with birth defects was the second risk factor (35%), and the third, a history of violence in the mother’s childhood (34%). Women who experienced depression during the delivery were also at higher risk.

Other risk factors identified were lack of communication with the health care team, lack of consent, lack of support from the medical staff, and a long labor. Conversely, a sense of control and the support of a partner play a protective role.
 

Early screening

“If the symptoms of posttraumatic stress disorder aren’t treated after delivery, they tend to get worse over the period of 1 to 6 months following the child’s birth,” Dr. Franchitto indicated. This is why it’s necessary to screen for it as early as possible – in particular, by having the women fill out the City Birth Trauma Scale questionnaire – and provide proper treatment accordingly. When seeking to limit the effects of stress, early intervention by a psychologist may be beneficial.

Psychotherapy is the recommended first-line treatment for PTSD, especially cognitive behavioral therapy and Eye Movement Desensitization and Reprocessing therapy. This approach aims to limit the mental and behavioral avoidance that prevents the traumatic memory from being integrated and processed as a regular memory.

The consequences that the mother’s PTSD state has on the child are well documented. “Children whose mothers had PTSD during pregnancy have a lower birth weight and a shorter breast-feeding duration,” Dr. Franchitto reported. With respect to the quality of the mother-child relationship and the long-term development of the child, “the studies have highly conflicting findings.”

At the end of the presentation, Professor Israël Nisand, MD, an ob.gyn. at the American Hospital of Paris and the former president of the National College of French Gynecologists and Obstetricians, made the following comment: “I often think that we underestimate the consequences that the mother’s posttraumatic stress has on the child postpartum.” He added, “Postpartum posttraumatic stress disorder is a reality. Yet it isn’t screened for, let alone treated, even though it has serious consequences for the child.”

Dr. Franchitto also brought up the impact on members of the health care staff, the “second victims” of the traumatic events that occur while caring for the women in the maternity ward. “The estimated prevalence of PTSD symptoms among midwives is 22.9%,” which could lead to “a loss of confidence and a desire to leave the profession.”
 

Providing psychoeducation to health care staff

Dr. Franchitto believes that it’s essential to also protect caregivers who work in maternity wards. “It’s important to have the support of colleagues” – in particular, of team leaders – “and to share one’s experiences,” as long as one knows how to recognize the symptoms of posttraumatic stress through one’s emotions and is able to verbalize them.

She went on to say that providing psychoeducation to health care staff is therefore to be encouraged, as is “simulation-based training, for learning how to manage problematic situations.”

This content was originally published on Medscape French edition. A translated version appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

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

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

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

Global snapshot: Lasting symptoms, impact on activities

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

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

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

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

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

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

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

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

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

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

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

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

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

Reducing the risk

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Global snapshot: Lasting symptoms, impact on activities

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

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

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

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

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

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

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

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

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

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

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

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

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

Reducing the risk

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Global snapshot: Lasting symptoms, impact on activities

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

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

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

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

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

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

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

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

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

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

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

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

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

Reducing the risk

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

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

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

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

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

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

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

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

Dementia prevalence is dropping in the United States, new research shows. New data from the Health and Retirement Study, a nationally representative survey, show that the prevalence of dementia among individuals aged 65 and older dropped from 12.2% in 2000 to 8.5% in 2016 – a 30.1% decrease. In men, the prevalence of dementia fell from 10.2% to 7.0%, while for women, it declined from 13.6% to 9.7%, researchers reported. Their finding were published online in PNAS.

The study also revealed that the proportion of college-educated men in the sample increased from 21.5% in 2000 to 33.7% in 2016, while the proportion of college-educated women increased from 12.3% in 2000 to 23% in 2016.

The findings also show a decline in the dementia prevalence in non-Hispanic Black men, which dropped from 17.2% to 9.9%, a decrease of 42.6%. In non-Hispanic White men, dementia declined 9.3% to 6.6%, or 29.0%.

The investigators also found a substantial increase in the level of education between 2000 and 2016. In addition, they found that, among 74- to 84-year-old women in 2000, 29.5% had worked for more than 30 years during their lifetime versus 59.0% in 2016.

The investigators speculated that the decline in dementia prevalence reflects larger socioeconomic changes in the United States as well as prevention strategies to reduce cardiovascular disease.

A person born around 1920, for example, would have had greater exposure to the Great Depression, while someone born in 1936 would have benefited more from the changes in living standards in the years following World War II, they noted.

“There’s a need for more research on the effect of employment on cognitive reserve. It’s plausible that working is good for your mental cognitive abilities,” said study investigator Péter Hudomiet, PhD, from the RAND Corporation, adding that there may also be benefits that extend beyond working years. It’s possible that women’s greater participation in the workforce gives them more chances to establish relationships that in some cases last well into retirement and provide essential social connection. It’s well known that social isolation has a negative impact on cognition.

“It’s plausible that working is good for your mental cognitive abilities,” he added.

The investigators noted that it is beyond the scope of their study to draw definitive conclusions about the causes of the decline, but they observed that positive trends in employment and standard of living make sense. “They would suggest that as schooling levels continue to rise in the U.S. population in younger generations, the prevalence of dementia would continue to decrease.

The investigators report no relevant financial relationships.

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

Dementia prevalence is dropping in the United States, new research shows. New data from the Health and Retirement Study, a nationally representative survey, show that the prevalence of dementia among individuals aged 65 and older dropped from 12.2% in 2000 to 8.5% in 2016 – a 30.1% decrease. In men, the prevalence of dementia fell from 10.2% to 7.0%, while for women, it declined from 13.6% to 9.7%, researchers reported. Their finding were published online in PNAS.

The study also revealed that the proportion of college-educated men in the sample increased from 21.5% in 2000 to 33.7% in 2016, while the proportion of college-educated women increased from 12.3% in 2000 to 23% in 2016.

The findings also show a decline in the dementia prevalence in non-Hispanic Black men, which dropped from 17.2% to 9.9%, a decrease of 42.6%. In non-Hispanic White men, dementia declined 9.3% to 6.6%, or 29.0%.

The investigators also found a substantial increase in the level of education between 2000 and 2016. In addition, they found that, among 74- to 84-year-old women in 2000, 29.5% had worked for more than 30 years during their lifetime versus 59.0% in 2016.

The investigators speculated that the decline in dementia prevalence reflects larger socioeconomic changes in the United States as well as prevention strategies to reduce cardiovascular disease.

A person born around 1920, for example, would have had greater exposure to the Great Depression, while someone born in 1936 would have benefited more from the changes in living standards in the years following World War II, they noted.

“There’s a need for more research on the effect of employment on cognitive reserve. It’s plausible that working is good for your mental cognitive abilities,” said study investigator Péter Hudomiet, PhD, from the RAND Corporation, adding that there may also be benefits that extend beyond working years. It’s possible that women’s greater participation in the workforce gives them more chances to establish relationships that in some cases last well into retirement and provide essential social connection. It’s well known that social isolation has a negative impact on cognition.

“It’s plausible that working is good for your mental cognitive abilities,” he added.

The investigators noted that it is beyond the scope of their study to draw definitive conclusions about the causes of the decline, but they observed that positive trends in employment and standard of living make sense. “They would suggest that as schooling levels continue to rise in the U.S. population in younger generations, the prevalence of dementia would continue to decrease.

The investigators report no relevant financial relationships.

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

Dementia prevalence is dropping in the United States, new research shows. New data from the Health and Retirement Study, a nationally representative survey, show that the prevalence of dementia among individuals aged 65 and older dropped from 12.2% in 2000 to 8.5% in 2016 – a 30.1% decrease. In men, the prevalence of dementia fell from 10.2% to 7.0%, while for women, it declined from 13.6% to 9.7%, researchers reported. Their finding were published online in PNAS.

The study also revealed that the proportion of college-educated men in the sample increased from 21.5% in 2000 to 33.7% in 2016, while the proportion of college-educated women increased from 12.3% in 2000 to 23% in 2016.

The findings also show a decline in the dementia prevalence in non-Hispanic Black men, which dropped from 17.2% to 9.9%, a decrease of 42.6%. In non-Hispanic White men, dementia declined 9.3% to 6.6%, or 29.0%.

The investigators also found a substantial increase in the level of education between 2000 and 2016. In addition, they found that, among 74- to 84-year-old women in 2000, 29.5% had worked for more than 30 years during their lifetime versus 59.0% in 2016.

The investigators speculated that the decline in dementia prevalence reflects larger socioeconomic changes in the United States as well as prevention strategies to reduce cardiovascular disease.

A person born around 1920, for example, would have had greater exposure to the Great Depression, while someone born in 1936 would have benefited more from the changes in living standards in the years following World War II, they noted.

“There’s a need for more research on the effect of employment on cognitive reserve. It’s plausible that working is good for your mental cognitive abilities,” said study investigator Péter Hudomiet, PhD, from the RAND Corporation, adding that there may also be benefits that extend beyond working years. It’s possible that women’s greater participation in the workforce gives them more chances to establish relationships that in some cases last well into retirement and provide essential social connection. It’s well known that social isolation has a negative impact on cognition.

“It’s plausible that working is good for your mental cognitive abilities,” he added.

The investigators noted that it is beyond the scope of their study to draw definitive conclusions about the causes of the decline, but they observed that positive trends in employment and standard of living make sense. “They would suggest that as schooling levels continue to rise in the U.S. population in younger generations, the prevalence of dementia would continue to decrease.

The investigators report no relevant financial relationships.

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

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

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

Neil Osterweil/MDedge News

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

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

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

Pain despite disease control

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

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

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

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

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

Matched cohorts

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

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

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

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

Higher death rate in opioid users

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

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

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

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

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

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

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

‘Beautiful’ analysis

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

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

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

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

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

Neil Osterweil/MDedge News

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

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

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

Pain despite disease control

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

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

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

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

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

Matched cohorts

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

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

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

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

Higher death rate in opioid users

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

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

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

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

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

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

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

‘Beautiful’ analysis

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

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

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

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

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

Neil Osterweil/MDedge News

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

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

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

Pain despite disease control

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

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

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

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

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

Matched cohorts

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

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

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

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

Higher death rate in opioid users

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

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

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

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

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

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

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

‘Beautiful’ analysis

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

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

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

Numerous species of fungi exist in cancer cells and differ by tumor type, according to findings from a large study of multiple sample types across 35 different cancers.

The investigators characterized the cancer mycobiome within 17,401 tissue, blood, and plasma samples from four international cohorts, revealing new information about fungi distribution, association with immune cells, and potential prognostic value.

Fungi were detected in all cancer types studied and were often intracellular, reported Lian Narunsky-Haziza, PhD, of Weizmann Institute of Science, Rehovot, Israel, and colleagues.

Additionally, multiple fungal-bacterial-immune ecologies were detected across tumors, and intratumoral fungi stratified clinical outcomes, including immunotherapy response, they noted. Also, cell-free fungal DNA diagnosed healthy and cancer patients in early-stage disease.

The findings, published online in the journal Cell, have potential implications for cancer detection, diagnosis, and treatment, the researchers suggested.

The existence of fungi in most human cancers “is both a surprise and to be expected,” study coauthor Rob Knight, PhD, a professor at the University of California, San Diego, stated in a press release. “It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected, because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth, and skin, where bacteria and fungi interact as part of a complex community.”

Exploration of the associations between cancer and microbes are nothing new, but cancer-associated fungi have rarely been examined, the authors noted.

The findings from this pan-cancer analysis, which suggested “prognostic and diagnostic capacities of the tissue and plasma mycobiomes, even in stage I cancers,” complement current “understanding of the interaction between cancer cells and the bacteria that exist in tumors alongside fungi, bacteria that have been shown to affect cancer growth, metastasis, and response to therapy,” they explained.

Of note, the study revealed multiple correlations between the presence of specific fungi in tumors and conditions related to treatment. For example, patients with breast cancer whose tumors contained Malassezia globosa – a fungus found naturally on the skin – had a much lower survival rate than those whose tumors did not contain the fungus. Furthermore, specific fungi were more prevalent in breast tumors from older vs. younger patients, in lung tumors of smokers vs. nonsmokers, and in melanoma tumors that responded to immunotherapy vs. those that did not respond.

These findings suggest that fungal activity is “a new and emerging hallmark of cancer,” stated study coleader Ravid Straussman, PhD, of the Weizmann molecular cell biology department. “These findings should drive us to better explore the potential effects of tumor fungi and to re-examine almost everything we know about cancer through a ‘microbiome lens.’ ”

Unique relationships observed between fungi and bacteria – for example, tumors that contain Aspergillus fungi tended to have specific bacteria in them, whereas tumors that contain Malassezia fungi tended to have other bacteria in them – may have implications for treatment, as they correlated with both tumor immunity and patient survival, according to the authors.

“This study sheds new light on the complex biological environment within tumors, and future research will reveal how fungi affect cancerous growth,” said coauthor Yitzhak Pilpel, PhD, a principal investigator at the Weizmann molecular genetics department. “The fact that fungi can be found not only in cancer cells but also in immune cells implies that, in the future, we’ll probably find that fungi have some effect not only on the cancer cells but also on immune cells and their activity.”

A further finding related to the presence of fungal and bacterial DNA in human blood further suggests that measuring microbial DNA in the blood could lead to early detection of cancer, the authors noted.

Dr. Straussman’s research is supported by the Swiss Society Institute for Cancer Prevention Research, the Fabricant-Morse Families Research Fund for Humanity, the Dr. Chantal d’Adesky Scheinberg Research Fund, and the Dr. Dvora and Haim Teitelbaum Endowment Fund.
 

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

Numerous species of fungi exist in cancer cells and differ by tumor type, according to findings from a large study of multiple sample types across 35 different cancers.

The investigators characterized the cancer mycobiome within 17,401 tissue, blood, and plasma samples from four international cohorts, revealing new information about fungi distribution, association with immune cells, and potential prognostic value.

Fungi were detected in all cancer types studied and were often intracellular, reported Lian Narunsky-Haziza, PhD, of Weizmann Institute of Science, Rehovot, Israel, and colleagues.

Additionally, multiple fungal-bacterial-immune ecologies were detected across tumors, and intratumoral fungi stratified clinical outcomes, including immunotherapy response, they noted. Also, cell-free fungal DNA diagnosed healthy and cancer patients in early-stage disease.

The findings, published online in the journal Cell, have potential implications for cancer detection, diagnosis, and treatment, the researchers suggested.

The existence of fungi in most human cancers “is both a surprise and to be expected,” study coauthor Rob Knight, PhD, a professor at the University of California, San Diego, stated in a press release. “It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected, because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth, and skin, where bacteria and fungi interact as part of a complex community.”

Exploration of the associations between cancer and microbes are nothing new, but cancer-associated fungi have rarely been examined, the authors noted.

The findings from this pan-cancer analysis, which suggested “prognostic and diagnostic capacities of the tissue and plasma mycobiomes, even in stage I cancers,” complement current “understanding of the interaction between cancer cells and the bacteria that exist in tumors alongside fungi, bacteria that have been shown to affect cancer growth, metastasis, and response to therapy,” they explained.

Of note, the study revealed multiple correlations between the presence of specific fungi in tumors and conditions related to treatment. For example, patients with breast cancer whose tumors contained Malassezia globosa – a fungus found naturally on the skin – had a much lower survival rate than those whose tumors did not contain the fungus. Furthermore, specific fungi were more prevalent in breast tumors from older vs. younger patients, in lung tumors of smokers vs. nonsmokers, and in melanoma tumors that responded to immunotherapy vs. those that did not respond.

These findings suggest that fungal activity is “a new and emerging hallmark of cancer,” stated study coleader Ravid Straussman, PhD, of the Weizmann molecular cell biology department. “These findings should drive us to better explore the potential effects of tumor fungi and to re-examine almost everything we know about cancer through a ‘microbiome lens.’ ”

Unique relationships observed between fungi and bacteria – for example, tumors that contain Aspergillus fungi tended to have specific bacteria in them, whereas tumors that contain Malassezia fungi tended to have other bacteria in them – may have implications for treatment, as they correlated with both tumor immunity and patient survival, according to the authors.

“This study sheds new light on the complex biological environment within tumors, and future research will reveal how fungi affect cancerous growth,” said coauthor Yitzhak Pilpel, PhD, a principal investigator at the Weizmann molecular genetics department. “The fact that fungi can be found not only in cancer cells but also in immune cells implies that, in the future, we’ll probably find that fungi have some effect not only on the cancer cells but also on immune cells and their activity.”

A further finding related to the presence of fungal and bacterial DNA in human blood further suggests that measuring microbial DNA in the blood could lead to early detection of cancer, the authors noted.

Dr. Straussman’s research is supported by the Swiss Society Institute for Cancer Prevention Research, the Fabricant-Morse Families Research Fund for Humanity, the Dr. Chantal d’Adesky Scheinberg Research Fund, and the Dr. Dvora and Haim Teitelbaum Endowment Fund.
 

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

Numerous species of fungi exist in cancer cells and differ by tumor type, according to findings from a large study of multiple sample types across 35 different cancers.

The investigators characterized the cancer mycobiome within 17,401 tissue, blood, and plasma samples from four international cohorts, revealing new information about fungi distribution, association with immune cells, and potential prognostic value.

Fungi were detected in all cancer types studied and were often intracellular, reported Lian Narunsky-Haziza, PhD, of Weizmann Institute of Science, Rehovot, Israel, and colleagues.

Additionally, multiple fungal-bacterial-immune ecologies were detected across tumors, and intratumoral fungi stratified clinical outcomes, including immunotherapy response, they noted. Also, cell-free fungal DNA diagnosed healthy and cancer patients in early-stage disease.

The findings, published online in the journal Cell, have potential implications for cancer detection, diagnosis, and treatment, the researchers suggested.

The existence of fungi in most human cancers “is both a surprise and to be expected,” study coauthor Rob Knight, PhD, a professor at the University of California, San Diego, stated in a press release. “It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected, because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth, and skin, where bacteria and fungi interact as part of a complex community.”

Exploration of the associations between cancer and microbes are nothing new, but cancer-associated fungi have rarely been examined, the authors noted.

The findings from this pan-cancer analysis, which suggested “prognostic and diagnostic capacities of the tissue and plasma mycobiomes, even in stage I cancers,” complement current “understanding of the interaction between cancer cells and the bacteria that exist in tumors alongside fungi, bacteria that have been shown to affect cancer growth, metastasis, and response to therapy,” they explained.

Of note, the study revealed multiple correlations between the presence of specific fungi in tumors and conditions related to treatment. For example, patients with breast cancer whose tumors contained Malassezia globosa – a fungus found naturally on the skin – had a much lower survival rate than those whose tumors did not contain the fungus. Furthermore, specific fungi were more prevalent in breast tumors from older vs. younger patients, in lung tumors of smokers vs. nonsmokers, and in melanoma tumors that responded to immunotherapy vs. those that did not respond.

These findings suggest that fungal activity is “a new and emerging hallmark of cancer,” stated study coleader Ravid Straussman, PhD, of the Weizmann molecular cell biology department. “These findings should drive us to better explore the potential effects of tumor fungi and to re-examine almost everything we know about cancer through a ‘microbiome lens.’ ”

Unique relationships observed between fungi and bacteria – for example, tumors that contain Aspergillus fungi tended to have specific bacteria in them, whereas tumors that contain Malassezia fungi tended to have other bacteria in them – may have implications for treatment, as they correlated with both tumor immunity and patient survival, according to the authors.

“This study sheds new light on the complex biological environment within tumors, and future research will reveal how fungi affect cancerous growth,” said coauthor Yitzhak Pilpel, PhD, a principal investigator at the Weizmann molecular genetics department. “The fact that fungi can be found not only in cancer cells but also in immune cells implies that, in the future, we’ll probably find that fungi have some effect not only on the cancer cells but also on immune cells and their activity.”

A further finding related to the presence of fungal and bacterial DNA in human blood further suggests that measuring microbial DNA in the blood could lead to early detection of cancer, the authors noted.

Dr. Straussman’s research is supported by the Swiss Society Institute for Cancer Prevention Research, the Fabricant-Morse Families Research Fund for Humanity, the Dr. Chantal d’Adesky Scheinberg Research Fund, and the Dr. Dvora and Haim Teitelbaum Endowment Fund.
 

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

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

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

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

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

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

Screening, despite lack of consensus guidelines

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

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

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

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

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

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

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

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

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

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

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

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

Mounting evidence linking CD to autoimmune disorders

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

Going gluten free has preventive advantages

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

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

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

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

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

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

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

Other factors to consider

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

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

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

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

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

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

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