Latest News

Even before the presidential election, the Federal Trade Commission’s (FTC) national ban on noncompete clauses faced a tough battle for survival in the courts. 

Now, legal specialists forecast a grim prognosis for the ban under Donald Trump’s return to the White House.

In April 2024, a divided FTC board approved a rule that would ban most noncompete agreements, which are the bane of many physicians in the states where they’re allowed. 

But a federal district’s court ruling put the ban on hold, and the Trump administration isn’t expected to support lifting the ban. 

“It is likely that the Trump administration will decline to defend the rule and may not even appeal the district court’s ruling, which means that the ban on noncompetes will not go into effect,” Steven Lubet, JD, a professor emeritus at Northwestern University Pritzker School of Law, Chicago, Illinois, said in an interview.

 

What’s in a Noncompete Clause?

Noncompete clauses in employee contracts typically restrict when and where workers can take future jobs. In medicine, supporters argue that the clauses are fair. Hospitals and practices provide a base of patients to physicians, they say, in return for their agreement not to go work for a competitor. 

But those opposed to these clauses argue that the restrictions harm careers and hurt patients by unfairly preventing physicians from moving to new jobs where they’re needed. 

At an April meeting, the FTC board voted 3 to 2 to ban noncompete clauses; some nonprofit organizations and senior executives were expected to be exempt. The FTC estimated that the move would save the healthcare system alone as much as $194 billion over 10 years. 

“A pandemic killed a million people in this country, and there are doctors who cannot work because of a noncompete,” declared FTC Commissioner Alvaro Bedoya. 

Hospitals protested the move. In a statement, the general counsel for the American Hospital Association called it “bad law, bad policy, and a clear sign of an agency run amok” and said the FTC ignored “mountains of contrary legal precedent and evidence about its adverse impacts on the health care markets.”

Although the American Medical Association does not support a total ban, its House of Delegates adopted policies in 2023 to support the prohibition of noncompete contracts for physicians employed by for-profit and nonprofit hospitals, hospital systems, or staffing companies. 

 

Texas Federal Judge Intervenes to Halt Ban

The ban was supposed to take effect on Sept. 4, 2024. But Texas federal judge Ada E. Brown struck down the ban in an Aug. 20 decision. She ruled that the FTC went beyond its authority.

“The district court based its ruling on a very dubious distinction between ‘unfair practices,’ which the FTC may prohibit, and ‘unfair competition,’ which, according to the court, it may not,” said Lubet. 

In fact, the ban should stand, he said. “This is a classic case of the government intervening on behalf of consumers/patients by prohibiting an unfair and harmful employment practice,” Lubet said. 

Amanda Hill, an attorney in Austin, Texas, who trains physicians about how to negotiate contracts, has a different take. “The Federal Trade Commission came down hard, and honestly, it really overstepped,” she said in an interview. “Congress needs to write laws, not regulatory bodies. I think all the lawyers went: ‘Good try, but you’re not going to get anywhere with that.’ ”

She noted that physicians themselves are divided over the value of noncompete clauses. “I would say 80% of my clients can’t stand noncompetes.” But another 20% own their own practices and hate the idea of losing their physicians to competitors, she said. 

 

Trump Isn’t Seen as Likely to Support Ban

While the Biden administration firmly supported a ban on noncompete clauses, there isn’t a strict Democratic-Republican divide over whether the agreements are a good idea. Some red states have embraced bans, and Hill said this can make sense from a Republican point of view: “We don’t want to run doctors out of town and out of the state because they think they’re going to be bound by big hospitals and corporate interests.”

In fact, former Florida congressman Matt Gaetz, a Republican briefly tapped as President-elect Trump’s nominee for attorney general, supports noncompete clauses. He filed a friend-of-the-court brief with the Texas judge that supported the FTC’s ruling, saying it is a “vindication of economic freedom and free enterprise.” 

But Republicans generally “believe that federal agencies are going too far and beyond the power granted to them by Congress,” Atlanta, Georgia, attorney Benjamin Fink, Esq., said in an interview.

And Trump is no fan of the FTC and its chair, Lina Khan, who may step down. Observers don’t expect that the Trump administration or a newly constituted FTC board will support an appeal of the Texas judge’s ruling.

“I don’t think anybody else — another agency or a private party — could step in place of the FTC if the FTC declines to defend the ban,” Atlanta attorney Neal F. Weinrich, Esq., said in an interview. In that case, “I think it ends.”

Attorneys Weinrich and Fink work at the same firm, which handles noncompete agreements for physicians. 

 

Noncompete Ban Advocates Turn to States 

Even if Kamala Harris had won the presidency, a national ban on noncompete clauses would have faced an uphill battle at the Supreme Court. 

“The Supreme Court majority has been unsympathetic to administrative agencies, interpreting their authority very narrowly,” said Lubet.

So what happens to noncompete clauses now? While bipartisan bills in Congress have tried to ban them, legislation is unlikely to pass now that Republicans will control both the House and Senate, Fink said. 

According to a recent article, 12 states prohibit noncompete clauses for physicians: Alabama, California, Colorado, Delaware, Massachusetts, Montana, New Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, and South Dakota. 

The remaining states allow noncompetes in some form, often excluding them for employees earning below a certain threshold. For example, in Oregon, noncompete agreements may apply to employees earning more than $113,241. Most states have provisions to adjust the threshold annually. The District of Columbia permits 2-year noncompetes for “medical specialists” earning over $250,000 annually. 

Indiana employers can no longer enter into noncompete agreements with primary care providers. Other specialties may be subject to the clauses, except when the physician terminates the contract for cause or when an employer terminates the contract without cause. 

“I definitely think states are going to continue to restrict the use of noncompetes,” Fink said. 

Lubet has no disclosures. Hill, Fink, and Weinrich represent physicians in contract negotiations.

A version of this article appeared on Medscape.com.

Even before the presidential election, the Federal Trade Commission’s (FTC) national ban on noncompete clauses faced a tough battle for survival in the courts. 

Now, legal specialists forecast a grim prognosis for the ban under Donald Trump’s return to the White House.

In April 2024, a divided FTC board approved a rule that would ban most noncompete agreements, which are the bane of many physicians in the states where they’re allowed. 

But a federal district’s court ruling put the ban on hold, and the Trump administration isn’t expected to support lifting the ban. 

“It is likely that the Trump administration will decline to defend the rule and may not even appeal the district court’s ruling, which means that the ban on noncompetes will not go into effect,” Steven Lubet, JD, a professor emeritus at Northwestern University Pritzker School of Law, Chicago, Illinois, said in an interview.

 

What’s in a Noncompete Clause?

Noncompete clauses in employee contracts typically restrict when and where workers can take future jobs. In medicine, supporters argue that the clauses are fair. Hospitals and practices provide a base of patients to physicians, they say, in return for their agreement not to go work for a competitor. 

But those opposed to these clauses argue that the restrictions harm careers and hurt patients by unfairly preventing physicians from moving to new jobs where they’re needed. 

At an April meeting, the FTC board voted 3 to 2 to ban noncompete clauses; some nonprofit organizations and senior executives were expected to be exempt. The FTC estimated that the move would save the healthcare system alone as much as $194 billion over 10 years. 

“A pandemic killed a million people in this country, and there are doctors who cannot work because of a noncompete,” declared FTC Commissioner Alvaro Bedoya. 

Hospitals protested the move. In a statement, the general counsel for the American Hospital Association called it “bad law, bad policy, and a clear sign of an agency run amok” and said the FTC ignored “mountains of contrary legal precedent and evidence about its adverse impacts on the health care markets.”

Although the American Medical Association does not support a total ban, its House of Delegates adopted policies in 2023 to support the prohibition of noncompete contracts for physicians employed by for-profit and nonprofit hospitals, hospital systems, or staffing companies. 

 

Texas Federal Judge Intervenes to Halt Ban

The ban was supposed to take effect on Sept. 4, 2024. But Texas federal judge Ada E. Brown struck down the ban in an Aug. 20 decision. She ruled that the FTC went beyond its authority.

“The district court based its ruling on a very dubious distinction between ‘unfair practices,’ which the FTC may prohibit, and ‘unfair competition,’ which, according to the court, it may not,” said Lubet. 

In fact, the ban should stand, he said. “This is a classic case of the government intervening on behalf of consumers/patients by prohibiting an unfair and harmful employment practice,” Lubet said. 

Amanda Hill, an attorney in Austin, Texas, who trains physicians about how to negotiate contracts, has a different take. “The Federal Trade Commission came down hard, and honestly, it really overstepped,” she said in an interview. “Congress needs to write laws, not regulatory bodies. I think all the lawyers went: ‘Good try, but you’re not going to get anywhere with that.’ ”

She noted that physicians themselves are divided over the value of noncompete clauses. “I would say 80% of my clients can’t stand noncompetes.” But another 20% own their own practices and hate the idea of losing their physicians to competitors, she said. 

 

Trump Isn’t Seen as Likely to Support Ban

While the Biden administration firmly supported a ban on noncompete clauses, there isn’t a strict Democratic-Republican divide over whether the agreements are a good idea. Some red states have embraced bans, and Hill said this can make sense from a Republican point of view: “We don’t want to run doctors out of town and out of the state because they think they’re going to be bound by big hospitals and corporate interests.”

In fact, former Florida congressman Matt Gaetz, a Republican briefly tapped as President-elect Trump’s nominee for attorney general, supports noncompete clauses. He filed a friend-of-the-court brief with the Texas judge that supported the FTC’s ruling, saying it is a “vindication of economic freedom and free enterprise.” 

But Republicans generally “believe that federal agencies are going too far and beyond the power granted to them by Congress,” Atlanta, Georgia, attorney Benjamin Fink, Esq., said in an interview.

And Trump is no fan of the FTC and its chair, Lina Khan, who may step down. Observers don’t expect that the Trump administration or a newly constituted FTC board will support an appeal of the Texas judge’s ruling.

“I don’t think anybody else — another agency or a private party — could step in place of the FTC if the FTC declines to defend the ban,” Atlanta attorney Neal F. Weinrich, Esq., said in an interview. In that case, “I think it ends.”

Attorneys Weinrich and Fink work at the same firm, which handles noncompete agreements for physicians. 

 

Noncompete Ban Advocates Turn to States 

Even if Kamala Harris had won the presidency, a national ban on noncompete clauses would have faced an uphill battle at the Supreme Court. 

“The Supreme Court majority has been unsympathetic to administrative agencies, interpreting their authority very narrowly,” said Lubet.

So what happens to noncompete clauses now? While bipartisan bills in Congress have tried to ban them, legislation is unlikely to pass now that Republicans will control both the House and Senate, Fink said. 

According to a recent article, 12 states prohibit noncompete clauses for physicians: Alabama, California, Colorado, Delaware, Massachusetts, Montana, New Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, and South Dakota. 

The remaining states allow noncompetes in some form, often excluding them for employees earning below a certain threshold. For example, in Oregon, noncompete agreements may apply to employees earning more than $113,241. Most states have provisions to adjust the threshold annually. The District of Columbia permits 2-year noncompetes for “medical specialists” earning over $250,000 annually. 

Indiana employers can no longer enter into noncompete agreements with primary care providers. Other specialties may be subject to the clauses, except when the physician terminates the contract for cause or when an employer terminates the contract without cause. 

“I definitely think states are going to continue to restrict the use of noncompetes,” Fink said. 

Lubet has no disclosures. Hill, Fink, and Weinrich represent physicians in contract negotiations.

A version of this article appeared on Medscape.com.

Even before the presidential election, the Federal Trade Commission’s (FTC) national ban on noncompete clauses faced a tough battle for survival in the courts. 

Now, legal specialists forecast a grim prognosis for the ban under Donald Trump’s return to the White House.

In April 2024, a divided FTC board approved a rule that would ban most noncompete agreements, which are the bane of many physicians in the states where they’re allowed. 

But a federal district’s court ruling put the ban on hold, and the Trump administration isn’t expected to support lifting the ban. 

“It is likely that the Trump administration will decline to defend the rule and may not even appeal the district court’s ruling, which means that the ban on noncompetes will not go into effect,” Steven Lubet, JD, a professor emeritus at Northwestern University Pritzker School of Law, Chicago, Illinois, said in an interview.

 

What’s in a Noncompete Clause?

Noncompete clauses in employee contracts typically restrict when and where workers can take future jobs. In medicine, supporters argue that the clauses are fair. Hospitals and practices provide a base of patients to physicians, they say, in return for their agreement not to go work for a competitor. 

But those opposed to these clauses argue that the restrictions harm careers and hurt patients by unfairly preventing physicians from moving to new jobs where they’re needed. 

At an April meeting, the FTC board voted 3 to 2 to ban noncompete clauses; some nonprofit organizations and senior executives were expected to be exempt. The FTC estimated that the move would save the healthcare system alone as much as $194 billion over 10 years. 

“A pandemic killed a million people in this country, and there are doctors who cannot work because of a noncompete,” declared FTC Commissioner Alvaro Bedoya. 

Hospitals protested the move. In a statement, the general counsel for the American Hospital Association called it “bad law, bad policy, and a clear sign of an agency run amok” and said the FTC ignored “mountains of contrary legal precedent and evidence about its adverse impacts on the health care markets.”

Although the American Medical Association does not support a total ban, its House of Delegates adopted policies in 2023 to support the prohibition of noncompete contracts for physicians employed by for-profit and nonprofit hospitals, hospital systems, or staffing companies. 

 

Texas Federal Judge Intervenes to Halt Ban

The ban was supposed to take effect on Sept. 4, 2024. But Texas federal judge Ada E. Brown struck down the ban in an Aug. 20 decision. She ruled that the FTC went beyond its authority.

“The district court based its ruling on a very dubious distinction between ‘unfair practices,’ which the FTC may prohibit, and ‘unfair competition,’ which, according to the court, it may not,” said Lubet. 

In fact, the ban should stand, he said. “This is a classic case of the government intervening on behalf of consumers/patients by prohibiting an unfair and harmful employment practice,” Lubet said. 

Amanda Hill, an attorney in Austin, Texas, who trains physicians about how to negotiate contracts, has a different take. “The Federal Trade Commission came down hard, and honestly, it really overstepped,” she said in an interview. “Congress needs to write laws, not regulatory bodies. I think all the lawyers went: ‘Good try, but you’re not going to get anywhere with that.’ ”

She noted that physicians themselves are divided over the value of noncompete clauses. “I would say 80% of my clients can’t stand noncompetes.” But another 20% own their own practices and hate the idea of losing their physicians to competitors, she said. 

 

Trump Isn’t Seen as Likely to Support Ban

While the Biden administration firmly supported a ban on noncompete clauses, there isn’t a strict Democratic-Republican divide over whether the agreements are a good idea. Some red states have embraced bans, and Hill said this can make sense from a Republican point of view: “We don’t want to run doctors out of town and out of the state because they think they’re going to be bound by big hospitals and corporate interests.”

In fact, former Florida congressman Matt Gaetz, a Republican briefly tapped as President-elect Trump’s nominee for attorney general, supports noncompete clauses. He filed a friend-of-the-court brief with the Texas judge that supported the FTC’s ruling, saying it is a “vindication of economic freedom and free enterprise.” 

But Republicans generally “believe that federal agencies are going too far and beyond the power granted to them by Congress,” Atlanta, Georgia, attorney Benjamin Fink, Esq., said in an interview.

And Trump is no fan of the FTC and its chair, Lina Khan, who may step down. Observers don’t expect that the Trump administration or a newly constituted FTC board will support an appeal of the Texas judge’s ruling.

“I don’t think anybody else — another agency or a private party — could step in place of the FTC if the FTC declines to defend the ban,” Atlanta attorney Neal F. Weinrich, Esq., said in an interview. In that case, “I think it ends.”

Attorneys Weinrich and Fink work at the same firm, which handles noncompete agreements for physicians. 

 

Noncompete Ban Advocates Turn to States 

Even if Kamala Harris had won the presidency, a national ban on noncompete clauses would have faced an uphill battle at the Supreme Court. 

“The Supreme Court majority has been unsympathetic to administrative agencies, interpreting their authority very narrowly,” said Lubet.

So what happens to noncompete clauses now? While bipartisan bills in Congress have tried to ban them, legislation is unlikely to pass now that Republicans will control both the House and Senate, Fink said. 

According to a recent article, 12 states prohibit noncompete clauses for physicians: Alabama, California, Colorado, Delaware, Massachusetts, Montana, New Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, and South Dakota. 

The remaining states allow noncompetes in some form, often excluding them for employees earning below a certain threshold. For example, in Oregon, noncompete agreements may apply to employees earning more than $113,241. Most states have provisions to adjust the threshold annually. The District of Columbia permits 2-year noncompetes for “medical specialists” earning over $250,000 annually. 

Indiana employers can no longer enter into noncompete agreements with primary care providers. Other specialties may be subject to the clauses, except when the physician terminates the contract for cause or when an employer terminates the contract without cause. 

“I definitely think states are going to continue to restrict the use of noncompetes,” Fink said. 

Lubet has no disclosures. Hill, Fink, and Weinrich represent physicians in contract negotiations.

A version of this article appeared on Medscape.com.

WASHINGTON — Investigational treatments aimed specifically at reducing pain in knee osteoarthritis (OA) are moving forward in parallel with disease-modifying approaches.

“We still have very few treatments for the pain of osteoarthritis…It worries me that people think the only way forward is structure modification. I think while we’re waiting for some drugs to be structure modifying, we still need more pain relief. About 70% of people can’t tolerate or shouldn’t be on a [nonsteroidal anti-inflammatory drug], and that leaves a large number of people with pain,” Philip Conaghan, MBBS, PhD, Chair of Musculoskeletal Medicine at the University of Leeds in England, said in an interview.

At the annual meeting of the American College of Rheumatology, Conaghan, who is also honorary consultant rheumatologist for the Leeds Teaching Hospitals NHS Trust, presented new data for two novel approaches, both targeting peripheral nociceptive pain signaling.

In a late-breaking poster, he presented phase 2 trial data on RTX-GRT7039 (resiniferatoxin [RTX]), an agonist of the transient receptor potential vanilloid 1 that is a driver of OA pain. The trial investigated the efficacy and safety of a single intra-articular injection of RTX-GRT7039 in people with knee OA.

And separately, in a late-breaking oral abstract session, Conaghan presented phase 2 trial safety and efficacy data for another investigational agent called LEVI-04, a first-in-class neurotrophin receptor fusion protein (p75NTR-Fc) that supplements the endogenous protein and provides analgesia via inhibition of NT-3 activity.

“I think both have potential to provide good pain relief, through slightly different mechanisms,” Conaghan said in an interview.

Asked to comment, session moderator Gregory C. Gardner, MD, emeritus professor in the Division of Rheumatology at the University of Washington, Seattle, said in an interview: “I think the results are really exciting terms of the ability to control pain to a significant degree in patients with osteoarthritis.”

However, Gardner also said, “The molecules can be very expensive ... so who do we give them to? Will insurance companies pay for this simply for OA pain? They improve function ... so clearly, [they] will be a boon to treating osteoarthritis, but do we give them to people with only more advanced forms of osteoarthritis or earlier on?”

Moreover, Gardner said, “One of my concerns about treating osteoarthritis is I don’t want to do too good of a job treating pain in somebody who has a biomechanically abnormal joint. ... You’ve got a knee that’s worn out some of the cartilage, and now you feel like you can go out and play soccer again. That’s not a good thing. That joint will wear out very quickly, even though it doesn’t feel pain.”

Another OA expert, Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, said in an interview, “I think we don’t focus nearly enough on pain, and that’s [partly] because the [Food and Drug Administration] has defined endpoints for knee OA trials that are radiographic. ... Patients do not care what their joint space narrowing is. They care what their pain is. And joint space changes and pain do not correlate in knee OA. ... About 20% or 30% of patients who have completely normal x-rays have a lot of pain…I hope that we’ll have some new OA pain therapeutics in the future because that’s what patients actually care about.”

But Jeffries noted that it will be very important to ensure that these agents don’t produce significant side effects, as had been seen previously in several large industry-sponsored trials of drugs targeting nerve growth factors.

“The big concern that we have in the field ... is that the nerve growth factor antibody trials were all stopped because there was a low but persistent risk of rapidly progressive OA in a small percent of patients. I think one of the questions in the field is whether targeting other things having to do with OA pain is going to result in similar bad outcomes. I think the answer is probably not, but that’s one thing that people do worry about, and they never really figured out why the [rapidly progressive OA] was happening.”

 

‘Potential to Provide Meaningful and Sustained Analgesia’

The phase 2 trial of RTX-GRT7039, funded by manufacturer Grünenthal, enrolled 40 patients with a baseline visual analog pain score (VAS) of > 40 mm on motion for average joint pain in the target knee over the past 2 days with or without analgesic medication and Kellgren-Lawrence grades 2-4.

They were randomized to receive a single intra-articular injection of 2 mg or 4 mg RTX-GRT7039 within 1 minute after receiving 5 mL ropivacaine (0.5%) or 4 mg or 8 mg RTX-GRT7039 administered 15 minutes after 5 mL ropivacaine pretreatment, or equivalent placebo treatments plus ropivacaine.

Plasma samples were collected for up to 2 hours, and VAS pain scores were collected for up to 3 hours post injection.

Reductions in VAS scores from baseline in the treated knee were seen in all RTX treatment groups as early as day 8 post injection and were maintained up to 6 months, while no reductions in VAS pain on motion scores were seen in the placebo group.

At 3 months, the absolute baseline-adjusted reductions in VAS scores were similar for RTX 2 mg (–39.75), RTX 4 mg (–40.20), and RTX 8 mg (–30.25), while the reduction in the placebo group was just –8.50. At 6 months, the mean absolute reduction in VAS score was numerically greater in the RTX 2-mg (–46.49), RTX 4-mg (–43.40), and RTX 8-mg (–38.60) groups vs the group that received RTX 4 mg within 1 minute after receiving ropivacaine (–22.00).

At both 3 and 6 months, a higher proportion of patients receiving any dose of RTX-GRT7039 achieved ≥ 50% and ≥ 70% reduction in pain on motion, compared with those who received placebo. All RTX-GRT7039 treatment groups reported a greater improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score than the placebo group at both 3 and 6 months.

Rates of treatment-emergent adverse events were similar between the RTX groups (85.7%-90.9%) and placebo (85.7%) and slightly lower in the group that received RTX 4 mg within 1 minute of receiving ropivacaine (60.0%).

There was a trend toward greater procedural/injection site pain in the RTX treatment groups, compared with placebo, most commonly arthralgia (37.5%), headache (17.5%), and back pain (10%). This tended to peak around 0.5 hours post injection and resolve by 1.5-3.0 hours.

No treatment-related serious adverse events occurred, and no treatment-emergent adverse events led to discontinuation or death.

“This early-phase trial indicates that RTX-GRT7039 has the potential to provide meaningful and sustained analgesia for patients with knee OA pain,” Conaghan and colleagues wrote in their poster.

The drug is now being evaluated in three phase 3 trials (NCT05248386, NCT05449132, and NCT05377489).

 

LEVI-04: Modulation of NT-3 Appears to Work Safely

LEVI-04 was evaluated in a phase 2, 20-week, 13-center (Europe and Hong Kong) randomized, double-blind, placebo-controlled trial in 518 people with knee OA who had WOMAC pain subscale scores ≥ 20, mean average daily pain numeric rating scale score of 4-9, and radiographic Kellgren-Lawrence grade ≥ 2.

They were randomized to a total of five infusions of placebo or 0.3 mg/kg, 0.1 mg/kg, or 2 mg/kg LEVI-04 from baseline through week 16, with safety follow-up to week 30.

The primary endpoint, change in WOMAC pain from baseline to weeks 5 and 17, was met for all three doses. At 17 weeks, those were –2.79, –2.89, and –3.08 for 0.3 mg, 1.0 mg, and 2 mg, respectively, vs –2.28 for placebo (all P < .05).

Secondary endpoints, including WOMAC physical function, WOMAC stiffness, and Patient Global Assessment, and > 50% pain responders, were also all met at weeks 5 and 17. More than 50% of the LEVI-04–treated patients reported ≥ 50% reduction in pain, and > 25% reported ≥ 75% reduction at weeks 5 and 17.

“So, this modulation of NT-3 is working,” Conaghan commented.

There were no increased incidences of severe adverse events, treatment-emergent adverse events, or joint pathologies, including rapidly progressive OA, compared with placebo.

There were more paresthesias reported with the active drug, 2-4 vs 1 with placebo. “That says to me that the drug is working and that it’s having an effect on peripheral nerves, but luckily these were all mild or moderate and didn’t lead to any study withdrawal or discontinuation,” Conaghan said.

Phase 3 trials are in the planning stages, he noted.

 

Other Approaches to Treating OA Pain

Other approaches to treating OA pain have included methotrexate, for which Conaghan was also a coauthor on one paper that came out earlier in 2024. “This presumably works by treating inflammation, but it’s not clear if that is within-joint inflammation or systemic inflammation,” he said in an interview.

Another approach, using the weight loss drug semaglutide, was presented in April 2024 at the 2024 World Congress on Osteoarthritis annual meeting and published in October 2024 in The New England Journal of Medicine

The trial involving RTX-GRT7039 was funded by Grünenthal, and some study coauthors are employees of the company. The trial involving LEVI-04 was funded by Levicept, and some study coauthors are employees of the company. Conaghan is a consultant and/or speaker for Eli Lilly, Eupraxia Pharmaceuticals, Formation Bio, Galapagos, Genascence, GlaxoSmithKline, Grünenthal, Janssen Pharmaceuticals, Kolon TissueGene, Levicept, Medipost, Moebius, Novartis, Pacira, Sandoz, Stryker Corporation, and Takeda. Gardner and Jeffries had no disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — Investigational treatments aimed specifically at reducing pain in knee osteoarthritis (OA) are moving forward in parallel with disease-modifying approaches.

“We still have very few treatments for the pain of osteoarthritis…It worries me that people think the only way forward is structure modification. I think while we’re waiting for some drugs to be structure modifying, we still need more pain relief. About 70% of people can’t tolerate or shouldn’t be on a [nonsteroidal anti-inflammatory drug], and that leaves a large number of people with pain,” Philip Conaghan, MBBS, PhD, Chair of Musculoskeletal Medicine at the University of Leeds in England, said in an interview.

At the annual meeting of the American College of Rheumatology, Conaghan, who is also honorary consultant rheumatologist for the Leeds Teaching Hospitals NHS Trust, presented new data for two novel approaches, both targeting peripheral nociceptive pain signaling.

In a late-breaking poster, he presented phase 2 trial data on RTX-GRT7039 (resiniferatoxin [RTX]), an agonist of the transient receptor potential vanilloid 1 that is a driver of OA pain. The trial investigated the efficacy and safety of a single intra-articular injection of RTX-GRT7039 in people with knee OA.

And separately, in a late-breaking oral abstract session, Conaghan presented phase 2 trial safety and efficacy data for another investigational agent called LEVI-04, a first-in-class neurotrophin receptor fusion protein (p75NTR-Fc) that supplements the endogenous protein and provides analgesia via inhibition of NT-3 activity.

“I think both have potential to provide good pain relief, through slightly different mechanisms,” Conaghan said in an interview.

Asked to comment, session moderator Gregory C. Gardner, MD, emeritus professor in the Division of Rheumatology at the University of Washington, Seattle, said in an interview: “I think the results are really exciting terms of the ability to control pain to a significant degree in patients with osteoarthritis.”

However, Gardner also said, “The molecules can be very expensive ... so who do we give them to? Will insurance companies pay for this simply for OA pain? They improve function ... so clearly, [they] will be a boon to treating osteoarthritis, but do we give them to people with only more advanced forms of osteoarthritis or earlier on?”

Moreover, Gardner said, “One of my concerns about treating osteoarthritis is I don’t want to do too good of a job treating pain in somebody who has a biomechanically abnormal joint. ... You’ve got a knee that’s worn out some of the cartilage, and now you feel like you can go out and play soccer again. That’s not a good thing. That joint will wear out very quickly, even though it doesn’t feel pain.”

Another OA expert, Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, said in an interview, “I think we don’t focus nearly enough on pain, and that’s [partly] because the [Food and Drug Administration] has defined endpoints for knee OA trials that are radiographic. ... Patients do not care what their joint space narrowing is. They care what their pain is. And joint space changes and pain do not correlate in knee OA. ... About 20% or 30% of patients who have completely normal x-rays have a lot of pain…I hope that we’ll have some new OA pain therapeutics in the future because that’s what patients actually care about.”

But Jeffries noted that it will be very important to ensure that these agents don’t produce significant side effects, as had been seen previously in several large industry-sponsored trials of drugs targeting nerve growth factors.

“The big concern that we have in the field ... is that the nerve growth factor antibody trials were all stopped because there was a low but persistent risk of rapidly progressive OA in a small percent of patients. I think one of the questions in the field is whether targeting other things having to do with OA pain is going to result in similar bad outcomes. I think the answer is probably not, but that’s one thing that people do worry about, and they never really figured out why the [rapidly progressive OA] was happening.”

 

‘Potential to Provide Meaningful and Sustained Analgesia’

The phase 2 trial of RTX-GRT7039, funded by manufacturer Grünenthal, enrolled 40 patients with a baseline visual analog pain score (VAS) of > 40 mm on motion for average joint pain in the target knee over the past 2 days with or without analgesic medication and Kellgren-Lawrence grades 2-4.

They were randomized to receive a single intra-articular injection of 2 mg or 4 mg RTX-GRT7039 within 1 minute after receiving 5 mL ropivacaine (0.5%) or 4 mg or 8 mg RTX-GRT7039 administered 15 minutes after 5 mL ropivacaine pretreatment, or equivalent placebo treatments plus ropivacaine.

Plasma samples were collected for up to 2 hours, and VAS pain scores were collected for up to 3 hours post injection.

Reductions in VAS scores from baseline in the treated knee were seen in all RTX treatment groups as early as day 8 post injection and were maintained up to 6 months, while no reductions in VAS pain on motion scores were seen in the placebo group.

At 3 months, the absolute baseline-adjusted reductions in VAS scores were similar for RTX 2 mg (–39.75), RTX 4 mg (–40.20), and RTX 8 mg (–30.25), while the reduction in the placebo group was just –8.50. At 6 months, the mean absolute reduction in VAS score was numerically greater in the RTX 2-mg (–46.49), RTX 4-mg (–43.40), and RTX 8-mg (–38.60) groups vs the group that received RTX 4 mg within 1 minute after receiving ropivacaine (–22.00).

At both 3 and 6 months, a higher proportion of patients receiving any dose of RTX-GRT7039 achieved ≥ 50% and ≥ 70% reduction in pain on motion, compared with those who received placebo. All RTX-GRT7039 treatment groups reported a greater improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score than the placebo group at both 3 and 6 months.

Rates of treatment-emergent adverse events were similar between the RTX groups (85.7%-90.9%) and placebo (85.7%) and slightly lower in the group that received RTX 4 mg within 1 minute of receiving ropivacaine (60.0%).

There was a trend toward greater procedural/injection site pain in the RTX treatment groups, compared with placebo, most commonly arthralgia (37.5%), headache (17.5%), and back pain (10%). This tended to peak around 0.5 hours post injection and resolve by 1.5-3.0 hours.

No treatment-related serious adverse events occurred, and no treatment-emergent adverse events led to discontinuation or death.

“This early-phase trial indicates that RTX-GRT7039 has the potential to provide meaningful and sustained analgesia for patients with knee OA pain,” Conaghan and colleagues wrote in their poster.

The drug is now being evaluated in three phase 3 trials (NCT05248386, NCT05449132, and NCT05377489).

 

LEVI-04: Modulation of NT-3 Appears to Work Safely

LEVI-04 was evaluated in a phase 2, 20-week, 13-center (Europe and Hong Kong) randomized, double-blind, placebo-controlled trial in 518 people with knee OA who had WOMAC pain subscale scores ≥ 20, mean average daily pain numeric rating scale score of 4-9, and radiographic Kellgren-Lawrence grade ≥ 2.

They were randomized to a total of five infusions of placebo or 0.3 mg/kg, 0.1 mg/kg, or 2 mg/kg LEVI-04 from baseline through week 16, with safety follow-up to week 30.

The primary endpoint, change in WOMAC pain from baseline to weeks 5 and 17, was met for all three doses. At 17 weeks, those were –2.79, –2.89, and –3.08 for 0.3 mg, 1.0 mg, and 2 mg, respectively, vs –2.28 for placebo (all P < .05).

Secondary endpoints, including WOMAC physical function, WOMAC stiffness, and Patient Global Assessment, and > 50% pain responders, were also all met at weeks 5 and 17. More than 50% of the LEVI-04–treated patients reported ≥ 50% reduction in pain, and > 25% reported ≥ 75% reduction at weeks 5 and 17.

“So, this modulation of NT-3 is working,” Conaghan commented.

There were no increased incidences of severe adverse events, treatment-emergent adverse events, or joint pathologies, including rapidly progressive OA, compared with placebo.

There were more paresthesias reported with the active drug, 2-4 vs 1 with placebo. “That says to me that the drug is working and that it’s having an effect on peripheral nerves, but luckily these were all mild or moderate and didn’t lead to any study withdrawal or discontinuation,” Conaghan said.

Phase 3 trials are in the planning stages, he noted.

 

Other Approaches to Treating OA Pain

Other approaches to treating OA pain have included methotrexate, for which Conaghan was also a coauthor on one paper that came out earlier in 2024. “This presumably works by treating inflammation, but it’s not clear if that is within-joint inflammation or systemic inflammation,” he said in an interview.

Another approach, using the weight loss drug semaglutide, was presented in April 2024 at the 2024 World Congress on Osteoarthritis annual meeting and published in October 2024 in The New England Journal of Medicine

The trial involving RTX-GRT7039 was funded by Grünenthal, and some study coauthors are employees of the company. The trial involving LEVI-04 was funded by Levicept, and some study coauthors are employees of the company. Conaghan is a consultant and/or speaker for Eli Lilly, Eupraxia Pharmaceuticals, Formation Bio, Galapagos, Genascence, GlaxoSmithKline, Grünenthal, Janssen Pharmaceuticals, Kolon TissueGene, Levicept, Medipost, Moebius, Novartis, Pacira, Sandoz, Stryker Corporation, and Takeda. Gardner and Jeffries had no disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — Investigational treatments aimed specifically at reducing pain in knee osteoarthritis (OA) are moving forward in parallel with disease-modifying approaches.

“We still have very few treatments for the pain of osteoarthritis…It worries me that people think the only way forward is structure modification. I think while we’re waiting for some drugs to be structure modifying, we still need more pain relief. About 70% of people can’t tolerate or shouldn’t be on a [nonsteroidal anti-inflammatory drug], and that leaves a large number of people with pain,” Philip Conaghan, MBBS, PhD, Chair of Musculoskeletal Medicine at the University of Leeds in England, said in an interview.

At the annual meeting of the American College of Rheumatology, Conaghan, who is also honorary consultant rheumatologist for the Leeds Teaching Hospitals NHS Trust, presented new data for two novel approaches, both targeting peripheral nociceptive pain signaling.

In a late-breaking poster, he presented phase 2 trial data on RTX-GRT7039 (resiniferatoxin [RTX]), an agonist of the transient receptor potential vanilloid 1 that is a driver of OA pain. The trial investigated the efficacy and safety of a single intra-articular injection of RTX-GRT7039 in people with knee OA.

And separately, in a late-breaking oral abstract session, Conaghan presented phase 2 trial safety and efficacy data for another investigational agent called LEVI-04, a first-in-class neurotrophin receptor fusion protein (p75NTR-Fc) that supplements the endogenous protein and provides analgesia via inhibition of NT-3 activity.

“I think both have potential to provide good pain relief, through slightly different mechanisms,” Conaghan said in an interview.

Asked to comment, session moderator Gregory C. Gardner, MD, emeritus professor in the Division of Rheumatology at the University of Washington, Seattle, said in an interview: “I think the results are really exciting terms of the ability to control pain to a significant degree in patients with osteoarthritis.”

However, Gardner also said, “The molecules can be very expensive ... so who do we give them to? Will insurance companies pay for this simply for OA pain? They improve function ... so clearly, [they] will be a boon to treating osteoarthritis, but do we give them to people with only more advanced forms of osteoarthritis or earlier on?”

Moreover, Gardner said, “One of my concerns about treating osteoarthritis is I don’t want to do too good of a job treating pain in somebody who has a biomechanically abnormal joint. ... You’ve got a knee that’s worn out some of the cartilage, and now you feel like you can go out and play soccer again. That’s not a good thing. That joint will wear out very quickly, even though it doesn’t feel pain.”

Another OA expert, Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, said in an interview, “I think we don’t focus nearly enough on pain, and that’s [partly] because the [Food and Drug Administration] has defined endpoints for knee OA trials that are radiographic. ... Patients do not care what their joint space narrowing is. They care what their pain is. And joint space changes and pain do not correlate in knee OA. ... About 20% or 30% of patients who have completely normal x-rays have a lot of pain…I hope that we’ll have some new OA pain therapeutics in the future because that’s what patients actually care about.”

But Jeffries noted that it will be very important to ensure that these agents don’t produce significant side effects, as had been seen previously in several large industry-sponsored trials of drugs targeting nerve growth factors.

“The big concern that we have in the field ... is that the nerve growth factor antibody trials were all stopped because there was a low but persistent risk of rapidly progressive OA in a small percent of patients. I think one of the questions in the field is whether targeting other things having to do with OA pain is going to result in similar bad outcomes. I think the answer is probably not, but that’s one thing that people do worry about, and they never really figured out why the [rapidly progressive OA] was happening.”

 

‘Potential to Provide Meaningful and Sustained Analgesia’

The phase 2 trial of RTX-GRT7039, funded by manufacturer Grünenthal, enrolled 40 patients with a baseline visual analog pain score (VAS) of > 40 mm on motion for average joint pain in the target knee over the past 2 days with or without analgesic medication and Kellgren-Lawrence grades 2-4.

They were randomized to receive a single intra-articular injection of 2 mg or 4 mg RTX-GRT7039 within 1 minute after receiving 5 mL ropivacaine (0.5%) or 4 mg or 8 mg RTX-GRT7039 administered 15 minutes after 5 mL ropivacaine pretreatment, or equivalent placebo treatments plus ropivacaine.

Plasma samples were collected for up to 2 hours, and VAS pain scores were collected for up to 3 hours post injection.

Reductions in VAS scores from baseline in the treated knee were seen in all RTX treatment groups as early as day 8 post injection and were maintained up to 6 months, while no reductions in VAS pain on motion scores were seen in the placebo group.

At 3 months, the absolute baseline-adjusted reductions in VAS scores were similar for RTX 2 mg (–39.75), RTX 4 mg (–40.20), and RTX 8 mg (–30.25), while the reduction in the placebo group was just –8.50. At 6 months, the mean absolute reduction in VAS score was numerically greater in the RTX 2-mg (–46.49), RTX 4-mg (–43.40), and RTX 8-mg (–38.60) groups vs the group that received RTX 4 mg within 1 minute after receiving ropivacaine (–22.00).

At both 3 and 6 months, a higher proportion of patients receiving any dose of RTX-GRT7039 achieved ≥ 50% and ≥ 70% reduction in pain on motion, compared with those who received placebo. All RTX-GRT7039 treatment groups reported a greater improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score than the placebo group at both 3 and 6 months.

Rates of treatment-emergent adverse events were similar between the RTX groups (85.7%-90.9%) and placebo (85.7%) and slightly lower in the group that received RTX 4 mg within 1 minute of receiving ropivacaine (60.0%).

There was a trend toward greater procedural/injection site pain in the RTX treatment groups, compared with placebo, most commonly arthralgia (37.5%), headache (17.5%), and back pain (10%). This tended to peak around 0.5 hours post injection and resolve by 1.5-3.0 hours.

No treatment-related serious adverse events occurred, and no treatment-emergent adverse events led to discontinuation or death.

“This early-phase trial indicates that RTX-GRT7039 has the potential to provide meaningful and sustained analgesia for patients with knee OA pain,” Conaghan and colleagues wrote in their poster.

The drug is now being evaluated in three phase 3 trials (NCT05248386, NCT05449132, and NCT05377489).

 

LEVI-04: Modulation of NT-3 Appears to Work Safely

LEVI-04 was evaluated in a phase 2, 20-week, 13-center (Europe and Hong Kong) randomized, double-blind, placebo-controlled trial in 518 people with knee OA who had WOMAC pain subscale scores ≥ 20, mean average daily pain numeric rating scale score of 4-9, and radiographic Kellgren-Lawrence grade ≥ 2.

They were randomized to a total of five infusions of placebo or 0.3 mg/kg, 0.1 mg/kg, or 2 mg/kg LEVI-04 from baseline through week 16, with safety follow-up to week 30.

The primary endpoint, change in WOMAC pain from baseline to weeks 5 and 17, was met for all three doses. At 17 weeks, those were –2.79, –2.89, and –3.08 for 0.3 mg, 1.0 mg, and 2 mg, respectively, vs –2.28 for placebo (all P < .05).

Secondary endpoints, including WOMAC physical function, WOMAC stiffness, and Patient Global Assessment, and > 50% pain responders, were also all met at weeks 5 and 17. More than 50% of the LEVI-04–treated patients reported ≥ 50% reduction in pain, and > 25% reported ≥ 75% reduction at weeks 5 and 17.

“So, this modulation of NT-3 is working,” Conaghan commented.

There were no increased incidences of severe adverse events, treatment-emergent adverse events, or joint pathologies, including rapidly progressive OA, compared with placebo.

There were more paresthesias reported with the active drug, 2-4 vs 1 with placebo. “That says to me that the drug is working and that it’s having an effect on peripheral nerves, but luckily these were all mild or moderate and didn’t lead to any study withdrawal or discontinuation,” Conaghan said.

Phase 3 trials are in the planning stages, he noted.

 

Other Approaches to Treating OA Pain

Other approaches to treating OA pain have included methotrexate, for which Conaghan was also a coauthor on one paper that came out earlier in 2024. “This presumably works by treating inflammation, but it’s not clear if that is within-joint inflammation or systemic inflammation,” he said in an interview.

Another approach, using the weight loss drug semaglutide, was presented in April 2024 at the 2024 World Congress on Osteoarthritis annual meeting and published in October 2024 in The New England Journal of Medicine

The trial involving RTX-GRT7039 was funded by Grünenthal, and some study coauthors are employees of the company. The trial involving LEVI-04 was funded by Levicept, and some study coauthors are employees of the company. Conaghan is a consultant and/or speaker for Eli Lilly, Eupraxia Pharmaceuticals, Formation Bio, Galapagos, Genascence, GlaxoSmithKline, Grünenthal, Janssen Pharmaceuticals, Kolon TissueGene, Levicept, Medipost, Moebius, Novartis, Pacira, Sandoz, Stryker Corporation, and Takeda. Gardner and Jeffries had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with serum ferritin levels higher than 1000 μg/L show a 91% increased risk for any fracture, with a doubled risk for vertebral and humerus fractures compared with those without iron overload.

 

METHODOLOGY:

• Iron overload’s association with decreased bone mineral density is established, but its relationship to osteoporotic fracture risk has remained understudied and inconsistent across fracture sites.
• Researchers conducted a population-based cohort study using a UK general practice database to evaluate the fracture risk in 20,264 patients with iron overload and 192,956 matched controls without elevated ferritin (mean age, 57 years; about 40% women).
• Patients with iron overload were identified as those with laboratory-confirmed iron overload (serum ferritin levels > 1000 μg/L; n = 13,510) or a diagnosis of an iron overloading disorder, such as thalassemia major, sickle cell disease, or hemochromatosis (n = 6754).
• The primary outcome of interest was the first occurrence of an osteoporotic fracture after the diagnosis of iron overload or first record of high ferritin.
• A sensitivity analysis was conducted to check the impact of laboratory-confirmed iron overload on the risk for osteoporotic fracture compared with a diagnosis code without elevated ferritin.

TAKEAWAY:

• In the overall cohort, patients with iron overload had a 55% higher risk for any osteoporotic fracture than control individuals (adjusted hazard ratio [aHR], 1.55; 95% CI, 1.42-1.68), with the highest risk observed for vertebral fractures (aHR, 1.97; 95% CI, 1.63-2.37) and humerus fractures (aHR, 1.91; 95% CI, 1.61-2.26).
• Patients with laboratory-confirmed iron overload showed a 91% increased risk for any fracture (aHR, 1.91; 95% CI, 1.73-2.10), with a 2.5-fold higher risk observed for vertebral fractures (aHR, 2.51; 95% CI, 2.01-3.12), followed by humerus fractures (aHR, 2.41; 95% CI, 1.96-2.95).
• There was no increased risk for fracture at any site in patients with a diagnosis of an iron overloading disorder but no laboratory-confirmed iron overload.
• No sex-specific differences were identified in the association between iron overload and fracture risk.

IN PRACTICE:

“The main clinical message from our findings is that clinicians should consider iron overloading as a risk factor for fracture. Importantly, among high-risk patients presenting with serum ferritin values exceeding 1000 μg/L, osteoporosis screening and treatment strategies should be initiated in accordance with the guidelines for patients with hepatic disease,” the authors wrote.

 

SOURCE:

The study was led by Andrea Michelle Burden, PhD, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich in Switzerland, and was published online in The Journal of Clinical Endocrinology & Metabolism.

 

LIMITATIONS:

The study could not assess the duration of iron overload on fracture risk, and thus, patients could enter the cohort with a single elevated serum ferritin value that may not have reflected systemic iron overload. The authors also acknowledged potential exposure misclassification among matched control individuals because only 2.9% had a serum ferritin value available at baseline. Also, researchers were unable to adjust for inflammation status due to the limited availability of C-reactive protein measurements and the lack of leukocyte count data in primary care settings.

 

DISCLOSURES:

This study received support through grants from the German Research Foundation. The authors declared no conflicts of interest.

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

TOPLINE:

Patients with serum ferritin levels higher than 1000 μg/L show a 91% increased risk for any fracture, with a doubled risk for vertebral and humerus fractures compared with those without iron overload.

 

METHODOLOGY:

• Iron overload’s association with decreased bone mineral density is established, but its relationship to osteoporotic fracture risk has remained understudied and inconsistent across fracture sites.
• Researchers conducted a population-based cohort study using a UK general practice database to evaluate the fracture risk in 20,264 patients with iron overload and 192,956 matched controls without elevated ferritin (mean age, 57 years; about 40% women).
• Patients with iron overload were identified as those with laboratory-confirmed iron overload (serum ferritin levels > 1000 μg/L; n = 13,510) or a diagnosis of an iron overloading disorder, such as thalassemia major, sickle cell disease, or hemochromatosis (n = 6754).
• The primary outcome of interest was the first occurrence of an osteoporotic fracture after the diagnosis of iron overload or first record of high ferritin.
• A sensitivity analysis was conducted to check the impact of laboratory-confirmed iron overload on the risk for osteoporotic fracture compared with a diagnosis code without elevated ferritin.

TAKEAWAY:

• In the overall cohort, patients with iron overload had a 55% higher risk for any osteoporotic fracture than control individuals (adjusted hazard ratio [aHR], 1.55; 95% CI, 1.42-1.68), with the highest risk observed for vertebral fractures (aHR, 1.97; 95% CI, 1.63-2.37) and humerus fractures (aHR, 1.91; 95% CI, 1.61-2.26).
• Patients with laboratory-confirmed iron overload showed a 91% increased risk for any fracture (aHR, 1.91; 95% CI, 1.73-2.10), with a 2.5-fold higher risk observed for vertebral fractures (aHR, 2.51; 95% CI, 2.01-3.12), followed by humerus fractures (aHR, 2.41; 95% CI, 1.96-2.95).
• There was no increased risk for fracture at any site in patients with a diagnosis of an iron overloading disorder but no laboratory-confirmed iron overload.
• No sex-specific differences were identified in the association between iron overload and fracture risk.

IN PRACTICE:

“The main clinical message from our findings is that clinicians should consider iron overloading as a risk factor for fracture. Importantly, among high-risk patients presenting with serum ferritin values exceeding 1000 μg/L, osteoporosis screening and treatment strategies should be initiated in accordance with the guidelines for patients with hepatic disease,” the authors wrote.

 

SOURCE:

The study was led by Andrea Michelle Burden, PhD, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich in Switzerland, and was published online in The Journal of Clinical Endocrinology & Metabolism.

 

LIMITATIONS:

The study could not assess the duration of iron overload on fracture risk, and thus, patients could enter the cohort with a single elevated serum ferritin value that may not have reflected systemic iron overload. The authors also acknowledged potential exposure misclassification among matched control individuals because only 2.9% had a serum ferritin value available at baseline. Also, researchers were unable to adjust for inflammation status due to the limited availability of C-reactive protein measurements and the lack of leukocyte count data in primary care settings.

 

DISCLOSURES:

This study received support through grants from the German Research Foundation. The authors declared no conflicts of interest.

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

TOPLINE:

Patients with serum ferritin levels higher than 1000 μg/L show a 91% increased risk for any fracture, with a doubled risk for vertebral and humerus fractures compared with those without iron overload.

 

METHODOLOGY:

• Iron overload’s association with decreased bone mineral density is established, but its relationship to osteoporotic fracture risk has remained understudied and inconsistent across fracture sites.
• Researchers conducted a population-based cohort study using a UK general practice database to evaluate the fracture risk in 20,264 patients with iron overload and 192,956 matched controls without elevated ferritin (mean age, 57 years; about 40% women).
• Patients with iron overload were identified as those with laboratory-confirmed iron overload (serum ferritin levels > 1000 μg/L; n = 13,510) or a diagnosis of an iron overloading disorder, such as thalassemia major, sickle cell disease, or hemochromatosis (n = 6754).
• The primary outcome of interest was the first occurrence of an osteoporotic fracture after the diagnosis of iron overload or first record of high ferritin.
• A sensitivity analysis was conducted to check the impact of laboratory-confirmed iron overload on the risk for osteoporotic fracture compared with a diagnosis code without elevated ferritin.

TAKEAWAY:

• In the overall cohort, patients with iron overload had a 55% higher risk for any osteoporotic fracture than control individuals (adjusted hazard ratio [aHR], 1.55; 95% CI, 1.42-1.68), with the highest risk observed for vertebral fractures (aHR, 1.97; 95% CI, 1.63-2.37) and humerus fractures (aHR, 1.91; 95% CI, 1.61-2.26).
• Patients with laboratory-confirmed iron overload showed a 91% increased risk for any fracture (aHR, 1.91; 95% CI, 1.73-2.10), with a 2.5-fold higher risk observed for vertebral fractures (aHR, 2.51; 95% CI, 2.01-3.12), followed by humerus fractures (aHR, 2.41; 95% CI, 1.96-2.95).
• There was no increased risk for fracture at any site in patients with a diagnosis of an iron overloading disorder but no laboratory-confirmed iron overload.
• No sex-specific differences were identified in the association between iron overload and fracture risk.

IN PRACTICE:

“The main clinical message from our findings is that clinicians should consider iron overloading as a risk factor for fracture. Importantly, among high-risk patients presenting with serum ferritin values exceeding 1000 μg/L, osteoporosis screening and treatment strategies should be initiated in accordance with the guidelines for patients with hepatic disease,” the authors wrote.

 

SOURCE:

The study was led by Andrea Michelle Burden, PhD, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich in Switzerland, and was published online in The Journal of Clinical Endocrinology & Metabolism.

 

LIMITATIONS:

The study could not assess the duration of iron overload on fracture risk, and thus, patients could enter the cohort with a single elevated serum ferritin value that may not have reflected systemic iron overload. The authors also acknowledged potential exposure misclassification among matched control individuals because only 2.9% had a serum ferritin value available at baseline. Also, researchers were unable to adjust for inflammation status due to the limited availability of C-reactive protein measurements and the lack of leukocyte count data in primary care settings.

 

DISCLOSURES:

This study received support through grants from the German Research Foundation. The authors declared no conflicts of interest.

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

TOPLINE:

Exposure to individual or mixed per- and polyfluoroalkyl substances (PFASs) is associated with changes in peripheral rather than central thyroid hormone sensitivity.

METHODOLOGY:

• PFASs are widely recognized for their persistence in the environment and potential endocrine-disrupting effects.
• A cross-sectional study investigated associations between PFAS exposures and thyroid homeostasis parameters in adult participants in two National Health and Nutrition Examination Survey cycles (2007-2008 and 2011-2012).
• Participants were required to have complete thyroid hormone profiles and measurements of PFAS concentration, not be pregnant, and not have thyroid disease or a history of using thyroid drugs such as thyroxine, methimazole, and propylthiouracil.
• Levels of six PFASs were measured in the serum: Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid, perfluorohexane sulfonic acid (PFHxS), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid.
• Thyroid homeostasis parameters were assessed using serum concentrations of thyroid hormones.
• Peripheral sensitivity was calculated using the ratio of free triiodothyronine to free thyroxine (FT3/FT4) and the sum activity of peripheral deiodinases (SPINA-GD).
• Central sensitivity was assessed with thyrotroph thyroxine resistance index, thyroid-stimulating hormone index, thyroid feedback quantile–based index (TFQI), and parametric TFQI.

TAKEAWAY:

• Researchers included 2386 adults (mean age, 47.59 years; 53.94% men; 42.88% White).
• FT3/FT4 and SPINA-GD were positively associated with PFOA, PFOS, PFNA, and PFHxS (P < .05 for all) in an adjusted analysis; however, no link was found between central thyroid sensitivity parameters and PFAS exposures.
• Specifically, higher quartiles of PFOA and PFOS concentrations were associated with an increased FT3/FT4 and SPINA-GD, indicating an increased conversion efficiency of FT4 to FT3 or peripheral deiodinase.
• Exposure to a mixture of different PFASs was also positively correlated with FT3/FT4 (beta, 0.013; P < .001) and SPINA-GD (beta, 1.230; P < .001), with PFOA showing the highest contribution.
• Men and smokers showed higher correlations of PFOA with peripheral thyroid hormone sensitivity indicators than women and nonsmokers, respectively.

IN PRACTICE:

“PFAS exposure, especially PFOA and PFOS, mainly impacted peripheral sensitivity to thyroid hormones, instead of central sensitivity,” the authors wrote, adding that their results may support, “taking more steps to prevent and reduce” the harmful effects of PFASs.

SOURCE:

This study was led by Xinwen Yu and Yufei Liu, Department of Endocrinology, The Second Affiliated Hospital of Air Force Medical University, Xi’an, China. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The cross-sectional design of this study limited the ability to establish causal relationships between PFAS exposure and thyroid function. The assessment of thyroid homeostasis parameters was conducted indirectly by measuring thyroid hormone levels. Inaccuracies in self-reported data on long-term exposure to PFASs and the exclusion of other endocrine-disrupting chemicals may have affected the study’s conclusions.

DISCLOSURES:

This study was supported by grants from the Natural Science Foundation of Shaanxi Province, China; the Key Research and Development Project of Shaanxi Province; and the Clinical Research Program of Air Force Medical University. The authors reported having no relevant conflicts of interest.

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

TOPLINE:

Exposure to individual or mixed per- and polyfluoroalkyl substances (PFASs) is associated with changes in peripheral rather than central thyroid hormone sensitivity.

METHODOLOGY:

• PFASs are widely recognized for their persistence in the environment and potential endocrine-disrupting effects.
• A cross-sectional study investigated associations between PFAS exposures and thyroid homeostasis parameters in adult participants in two National Health and Nutrition Examination Survey cycles (2007-2008 and 2011-2012).
• Participants were required to have complete thyroid hormone profiles and measurements of PFAS concentration, not be pregnant, and not have thyroid disease or a history of using thyroid drugs such as thyroxine, methimazole, and propylthiouracil.
• Levels of six PFASs were measured in the serum: Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid, perfluorohexane sulfonic acid (PFHxS), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid.
• Thyroid homeostasis parameters were assessed using serum concentrations of thyroid hormones.
• Peripheral sensitivity was calculated using the ratio of free triiodothyronine to free thyroxine (FT3/FT4) and the sum activity of peripheral deiodinases (SPINA-GD).
• Central sensitivity was assessed with thyrotroph thyroxine resistance index, thyroid-stimulating hormone index, thyroid feedback quantile–based index (TFQI), and parametric TFQI.

TAKEAWAY:

• Researchers included 2386 adults (mean age, 47.59 years; 53.94% men; 42.88% White).
• FT3/FT4 and SPINA-GD were positively associated with PFOA, PFOS, PFNA, and PFHxS (P < .05 for all) in an adjusted analysis; however, no link was found between central thyroid sensitivity parameters and PFAS exposures.
• Specifically, higher quartiles of PFOA and PFOS concentrations were associated with an increased FT3/FT4 and SPINA-GD, indicating an increased conversion efficiency of FT4 to FT3 or peripheral deiodinase.
• Exposure to a mixture of different PFASs was also positively correlated with FT3/FT4 (beta, 0.013; P < .001) and SPINA-GD (beta, 1.230; P < .001), with PFOA showing the highest contribution.
• Men and smokers showed higher correlations of PFOA with peripheral thyroid hormone sensitivity indicators than women and nonsmokers, respectively.

IN PRACTICE:

“PFAS exposure, especially PFOA and PFOS, mainly impacted peripheral sensitivity to thyroid hormones, instead of central sensitivity,” the authors wrote, adding that their results may support, “taking more steps to prevent and reduce” the harmful effects of PFASs.

SOURCE:

This study was led by Xinwen Yu and Yufei Liu, Department of Endocrinology, The Second Affiliated Hospital of Air Force Medical University, Xi’an, China. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The cross-sectional design of this study limited the ability to establish causal relationships between PFAS exposure and thyroid function. The assessment of thyroid homeostasis parameters was conducted indirectly by measuring thyroid hormone levels. Inaccuracies in self-reported data on long-term exposure to PFASs and the exclusion of other endocrine-disrupting chemicals may have affected the study’s conclusions.

DISCLOSURES:

This study was supported by grants from the Natural Science Foundation of Shaanxi Province, China; the Key Research and Development Project of Shaanxi Province; and the Clinical Research Program of Air Force Medical University. The authors reported having no relevant conflicts of interest.

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

TOPLINE:

Exposure to individual or mixed per- and polyfluoroalkyl substances (PFASs) is associated with changes in peripheral rather than central thyroid hormone sensitivity.

METHODOLOGY:

• PFASs are widely recognized for their persistence in the environment and potential endocrine-disrupting effects.
• A cross-sectional study investigated associations between PFAS exposures and thyroid homeostasis parameters in adult participants in two National Health and Nutrition Examination Survey cycles (2007-2008 and 2011-2012).
• Participants were required to have complete thyroid hormone profiles and measurements of PFAS concentration, not be pregnant, and not have thyroid disease or a history of using thyroid drugs such as thyroxine, methimazole, and propylthiouracil.
• Levels of six PFASs were measured in the serum: Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid, perfluorohexane sulfonic acid (PFHxS), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid.
• Thyroid homeostasis parameters were assessed using serum concentrations of thyroid hormones.
• Peripheral sensitivity was calculated using the ratio of free triiodothyronine to free thyroxine (FT3/FT4) and the sum activity of peripheral deiodinases (SPINA-GD).
• Central sensitivity was assessed with thyrotroph thyroxine resistance index, thyroid-stimulating hormone index, thyroid feedback quantile–based index (TFQI), and parametric TFQI.

TAKEAWAY:

• Researchers included 2386 adults (mean age, 47.59 years; 53.94% men; 42.88% White).
• FT3/FT4 and SPINA-GD were positively associated with PFOA, PFOS, PFNA, and PFHxS (P < .05 for all) in an adjusted analysis; however, no link was found between central thyroid sensitivity parameters and PFAS exposures.
• Specifically, higher quartiles of PFOA and PFOS concentrations were associated with an increased FT3/FT4 and SPINA-GD, indicating an increased conversion efficiency of FT4 to FT3 or peripheral deiodinase.
• Exposure to a mixture of different PFASs was also positively correlated with FT3/FT4 (beta, 0.013; P < .001) and SPINA-GD (beta, 1.230; P < .001), with PFOA showing the highest contribution.
• Men and smokers showed higher correlations of PFOA with peripheral thyroid hormone sensitivity indicators than women and nonsmokers, respectively.

IN PRACTICE:

“PFAS exposure, especially PFOA and PFOS, mainly impacted peripheral sensitivity to thyroid hormones, instead of central sensitivity,” the authors wrote, adding that their results may support, “taking more steps to prevent and reduce” the harmful effects of PFASs.

SOURCE:

This study was led by Xinwen Yu and Yufei Liu, Department of Endocrinology, The Second Affiliated Hospital of Air Force Medical University, Xi’an, China. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The cross-sectional design of this study limited the ability to establish causal relationships between PFAS exposure and thyroid function. The assessment of thyroid homeostasis parameters was conducted indirectly by measuring thyroid hormone levels. Inaccuracies in self-reported data on long-term exposure to PFASs and the exclusion of other endocrine-disrupting chemicals may have affected the study’s conclusions.

DISCLOSURES:

This study was supported by grants from the Natural Science Foundation of Shaanxi Province, China; the Key Research and Development Project of Shaanxi Province; and the Clinical Research Program of Air Force Medical University. The authors reported having no relevant conflicts of interest.

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

Most US adults continue to plan on skipping an annual COVID vaccine.

About 6 in 10 people say they probably won’t get an updated shot this year, despite the Centers for Disease Control and Prevention’s (CDC) recommendation that everyone do so, according to results of a new survey from the Pew Research Center.

When asked why people wouldn’t get an updated COVID vaccine, 61% said a major reason was that they don’t think they need it, and 60% said a major reason is that they are concerned about side effects. Cost was a factor for 14% of people, and 46% of people said they don’t get vaccines in general.

There were some differences in intention to get vaccinated based on a person’s age. Among people ages 65 and older, 27% said they had already gotten the vaccine, and another 27% said they probably will get the shot, leaving 45% who said they probably won’t roll up their sleeves. People ages 30-49 years old were the least likely to plan on getting a COVID shot – 66% said they probably won’t get one.

Public health officials say everyone should get an annual COVID vaccine, just as they should get a flu shot, because the vaccines are formulated each year to target virus strains predicted to be in wide circulation. Also, immunity – either from past vaccination or past infection – wanes over time. 

Research shows that the vaccines reduce the likelihood of hospitalization or death caused by severe illness, particularly among people who have risk factors, like being over age 65 or having health issues that are becoming increasingly common in the United States, like diabetes, heart problems, and lung conditions.

The survey included 9,593 adults who were asked about their COVID vaccine intentions with this question: “Public health officials recently recommended an updated vaccine for COVID-19. Do you think you will probably get an updated vaccine, probably not get an updated vaccine, or have you already received an updated vaccine?” The survey was done online and by telephone from October 21 to October 27.

So far in 2024, the CDC’s ongoing immunization survey shows that 17% of adults say that, as of November 2, they have gotten vaccinated for COVID-19 this season, and 14% said they will definitely get vaccinated. The Pew Research Center survey found that 15% of people said they’ve already gotten the shot this season.

Reports of positive COVID tests, emergency room visits, and hospitalizations remain very low. About 3.6% of test results shared with the CDC were positive for COVID the week ending November 9. Less than 1% of ER visits involve a COVID diagnosis, and hospitalizations are well below the rate seen at this time last year. Last year, COVID activity in the United States began rising around Thanksgiving and continued upward, peaking in early January.

The protection from a COVID-19 vaccination usually fully kicks in about 2 weeks after you get the shot, and the vaccines are most effective for the following 3 months.

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

Most US adults continue to plan on skipping an annual COVID vaccine.

About 6 in 10 people say they probably won’t get an updated shot this year, despite the Centers for Disease Control and Prevention’s (CDC) recommendation that everyone do so, according to results of a new survey from the Pew Research Center.

When asked why people wouldn’t get an updated COVID vaccine, 61% said a major reason was that they don’t think they need it, and 60% said a major reason is that they are concerned about side effects. Cost was a factor for 14% of people, and 46% of people said they don’t get vaccines in general.

There were some differences in intention to get vaccinated based on a person’s age. Among people ages 65 and older, 27% said they had already gotten the vaccine, and another 27% said they probably will get the shot, leaving 45% who said they probably won’t roll up their sleeves. People ages 30-49 years old were the least likely to plan on getting a COVID shot – 66% said they probably won’t get one.

Public health officials say everyone should get an annual COVID vaccine, just as they should get a flu shot, because the vaccines are formulated each year to target virus strains predicted to be in wide circulation. Also, immunity – either from past vaccination or past infection – wanes over time. 

Research shows that the vaccines reduce the likelihood of hospitalization or death caused by severe illness, particularly among people who have risk factors, like being over age 65 or having health issues that are becoming increasingly common in the United States, like diabetes, heart problems, and lung conditions.

The survey included 9,593 adults who were asked about their COVID vaccine intentions with this question: “Public health officials recently recommended an updated vaccine for COVID-19. Do you think you will probably get an updated vaccine, probably not get an updated vaccine, or have you already received an updated vaccine?” The survey was done online and by telephone from October 21 to October 27.

So far in 2024, the CDC’s ongoing immunization survey shows that 17% of adults say that, as of November 2, they have gotten vaccinated for COVID-19 this season, and 14% said they will definitely get vaccinated. The Pew Research Center survey found that 15% of people said they’ve already gotten the shot this season.

Reports of positive COVID tests, emergency room visits, and hospitalizations remain very low. About 3.6% of test results shared with the CDC were positive for COVID the week ending November 9. Less than 1% of ER visits involve a COVID diagnosis, and hospitalizations are well below the rate seen at this time last year. Last year, COVID activity in the United States began rising around Thanksgiving and continued upward, peaking in early January.

The protection from a COVID-19 vaccination usually fully kicks in about 2 weeks after you get the shot, and the vaccines are most effective for the following 3 months.

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

Most US adults continue to plan on skipping an annual COVID vaccine.

About 6 in 10 people say they probably won’t get an updated shot this year, despite the Centers for Disease Control and Prevention’s (CDC) recommendation that everyone do so, according to results of a new survey from the Pew Research Center.

When asked why people wouldn’t get an updated COVID vaccine, 61% said a major reason was that they don’t think they need it, and 60% said a major reason is that they are concerned about side effects. Cost was a factor for 14% of people, and 46% of people said they don’t get vaccines in general.

There were some differences in intention to get vaccinated based on a person’s age. Among people ages 65 and older, 27% said they had already gotten the vaccine, and another 27% said they probably will get the shot, leaving 45% who said they probably won’t roll up their sleeves. People ages 30-49 years old were the least likely to plan on getting a COVID shot – 66% said they probably won’t get one.

Public health officials say everyone should get an annual COVID vaccine, just as they should get a flu shot, because the vaccines are formulated each year to target virus strains predicted to be in wide circulation. Also, immunity – either from past vaccination or past infection – wanes over time. 

Research shows that the vaccines reduce the likelihood of hospitalization or death caused by severe illness, particularly among people who have risk factors, like being over age 65 or having health issues that are becoming increasingly common in the United States, like diabetes, heart problems, and lung conditions.

The survey included 9,593 adults who were asked about their COVID vaccine intentions with this question: “Public health officials recently recommended an updated vaccine for COVID-19. Do you think you will probably get an updated vaccine, probably not get an updated vaccine, or have you already received an updated vaccine?” The survey was done online and by telephone from October 21 to October 27.

So far in 2024, the CDC’s ongoing immunization survey shows that 17% of adults say that, as of November 2, they have gotten vaccinated for COVID-19 this season, and 14% said they will definitely get vaccinated. The Pew Research Center survey found that 15% of people said they’ve already gotten the shot this season.

Reports of positive COVID tests, emergency room visits, and hospitalizations remain very low. About 3.6% of test results shared with the CDC were positive for COVID the week ending November 9. Less than 1% of ER visits involve a COVID diagnosis, and hospitalizations are well below the rate seen at this time last year. Last year, COVID activity in the United States began rising around Thanksgiving and continued upward, peaking in early January.

The protection from a COVID-19 vaccination usually fully kicks in about 2 weeks after you get the shot, and the vaccines are most effective for the following 3 months.

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

Six times as many cases of pertussis were reported in the United States for the week ending November 16, 2024, as the same week in 2023, according to new data from the Centers for Disease Control and Prevention (CDC).

The numbers reflect a return to prepandemic trends, but overall, pertussis cases for 2024 so far have surpassed those seen prior to the pandemic in 2019, according to the CDC.

Of the 434 cases reported for the week ending November 16, 2024, a majority (109) occurred in the East North Central region, mostly in Ohio (93). Another 70 cases occurred in the West North Central region, with 32 cases and 37 cases in Missouri and Nebraska, respectively.

None of the 75 cases in the Middle Atlantic region occurred in New Jersey or New York City; 38 were reported elsewhere in New York, and 37 in Pennsylvania. The South Atlantic region reported 55 cases, including 29 in Florida. The East South Central and West South Central regions reported 11 and 20 cases, respectively. The Mountain and Pacific regions reported 31 (20 in Arizona) and 47 (20 in Washington State) cases, respectively.

The CDC tracks pertussis cases through a national surveillance system, but many cases are likely unrecognized and unreported, according to the CDC.

Although vaccines for pertussis (whooping cough) provide protection, their effectiveness decreases over time, and the CDC expects rates to increase in vaccinated and unvaccinated populations as case levels rebound with the lifting of pandemic mitigation strategies such as masking and remote learning.

Recent CDC data reported by Medscape Medical News showed an association between lower vaccination rates and 2024’s uptick in pertussis cases.

 

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

Six times as many cases of pertussis were reported in the United States for the week ending November 16, 2024, as the same week in 2023, according to new data from the Centers for Disease Control and Prevention (CDC).

The numbers reflect a return to prepandemic trends, but overall, pertussis cases for 2024 so far have surpassed those seen prior to the pandemic in 2019, according to the CDC.

Of the 434 cases reported for the week ending November 16, 2024, a majority (109) occurred in the East North Central region, mostly in Ohio (93). Another 70 cases occurred in the West North Central region, with 32 cases and 37 cases in Missouri and Nebraska, respectively.

None of the 75 cases in the Middle Atlantic region occurred in New Jersey or New York City; 38 were reported elsewhere in New York, and 37 in Pennsylvania. The South Atlantic region reported 55 cases, including 29 in Florida. The East South Central and West South Central regions reported 11 and 20 cases, respectively. The Mountain and Pacific regions reported 31 (20 in Arizona) and 47 (20 in Washington State) cases, respectively.

The CDC tracks pertussis cases through a national surveillance system, but many cases are likely unrecognized and unreported, according to the CDC.

Although vaccines for pertussis (whooping cough) provide protection, their effectiveness decreases over time, and the CDC expects rates to increase in vaccinated and unvaccinated populations as case levels rebound with the lifting of pandemic mitigation strategies such as masking and remote learning.

Recent CDC data reported by Medscape Medical News showed an association between lower vaccination rates and 2024’s uptick in pertussis cases.

 

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

Six times as many cases of pertussis were reported in the United States for the week ending November 16, 2024, as the same week in 2023, according to new data from the Centers for Disease Control and Prevention (CDC).

The numbers reflect a return to prepandemic trends, but overall, pertussis cases for 2024 so far have surpassed those seen prior to the pandemic in 2019, according to the CDC.

Of the 434 cases reported for the week ending November 16, 2024, a majority (109) occurred in the East North Central region, mostly in Ohio (93). Another 70 cases occurred in the West North Central region, with 32 cases and 37 cases in Missouri and Nebraska, respectively.

None of the 75 cases in the Middle Atlantic region occurred in New Jersey or New York City; 38 were reported elsewhere in New York, and 37 in Pennsylvania. The South Atlantic region reported 55 cases, including 29 in Florida. The East South Central and West South Central regions reported 11 and 20 cases, respectively. The Mountain and Pacific regions reported 31 (20 in Arizona) and 47 (20 in Washington State) cases, respectively.

The CDC tracks pertussis cases through a national surveillance system, but many cases are likely unrecognized and unreported, according to the CDC.

Although vaccines for pertussis (whooping cough) provide protection, their effectiveness decreases over time, and the CDC expects rates to increase in vaccinated and unvaccinated populations as case levels rebound with the lifting of pandemic mitigation strategies such as masking and remote learning.

Recent CDC data reported by Medscape Medical News showed an association between lower vaccination rates and 2024’s uptick in pertussis cases.

 

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

TOPLINE:

Administering the Bacillus Calmette-Guérin (BCG) vaccine during the active phase of COVID-19 may help protect against the development of long COVID.

METHODOLOGY:

• A phase 3 clinical trial initiated in early 2020 investigated the effect of the BCG vaccine injected during active infection on COVID-19 progression in adults with mild or moderate COVID-19. The current study summarizes the 6- and 12-month follow-up data with a focus on long-COVID symptoms.
• Patients who tested positive for severe acute respiratory syndrome coronavirus 2 were randomly assigned to receive either 0.1 mL of intradermal BCG (n = 191) or 0.9% saline placebo (n = 202) within 14 days of symptom onset and were followed up at 7, 14, 21, and 45 days and at 6 and 12 months postinjection.
• Overall, 157 BCG (median age, 40 years; 54.1% women) and 142 placebo (median age, 41 years; 65.5% women) recipients completed the 6-month follow-up, and 97 BCG (median age, 37 years; 49.5% women) and 95 placebo (median age, 40 years; 67.4% women) recipients completed the 12-month follow-up.
• The researchers primarily assessed the effect of the BCG vaccine on the development of the symptoms of long COVID at 6 and 12 months.

TAKEAWAY:

• Hearing problems were less frequent among BCG recipients at 6 months compared with those who received placebo (odds ratio [OR], 0.26; 95% CI, 0.045-1.0; P = .044).
• At 12 months, participants who received the BCG vaccine exhibited fewer issues with sleeping (P = .027), concentration (P = .009), memory (P = .009), and vision (P = .022) along with a lower long-COVID score (one-sided Wilcoxon test, P = .002) than those who received placebo.
• At 6 months, BCG demonstrated a sex-specific paradoxical effect on hair loss, decreasing it in men (P = .031), while causing a slight, though statistically nonsignificant, increase in women.
• Male sex was the strongest predictive factor for long COVID, cognitive dysfunction, and cardiopulmonary scores at both follow-up assessments.

IN PRACTICE:

“[The study] findings suggest that BCG immunotherapy for an existing ailment may be superior to prophylaxis in healthy individuals,” the authors wrote.

SOURCE:

The study was led by Mehrsa Jalalizadeh and Keini Buosi, UroScience, State University of Campinas, Unicamp, São Paulo, Brazil. It was published online on November 19, 2024, in the Journal of Internal Medicine.

LIMITATIONS:

Previous mycobacterial exposure was not tested among the study participants. A notable loss to follow-up, particularly at 12 months, may have introduced bias into the results.

DISCLOSURES:

The study was supported by the Coordination for the Improvement of Higher Education Personnel, Federal Government of Brazil, the General Coordination of the National Immunization Program, Ministry of Health (Brazil), and the National Council for Scientific and Technological Development-Research Productivity. The authors declared no conflicts of interest.

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

TOPLINE:

Administering the Bacillus Calmette-Guérin (BCG) vaccine during the active phase of COVID-19 may help protect against the development of long COVID.

METHODOLOGY:

• A phase 3 clinical trial initiated in early 2020 investigated the effect of the BCG vaccine injected during active infection on COVID-19 progression in adults with mild or moderate COVID-19. The current study summarizes the 6- and 12-month follow-up data with a focus on long-COVID symptoms.
• Patients who tested positive for severe acute respiratory syndrome coronavirus 2 were randomly assigned to receive either 0.1 mL of intradermal BCG (n = 191) or 0.9% saline placebo (n = 202) within 14 days of symptom onset and were followed up at 7, 14, 21, and 45 days and at 6 and 12 months postinjection.
• Overall, 157 BCG (median age, 40 years; 54.1% women) and 142 placebo (median age, 41 years; 65.5% women) recipients completed the 6-month follow-up, and 97 BCG (median age, 37 years; 49.5% women) and 95 placebo (median age, 40 years; 67.4% women) recipients completed the 12-month follow-up.
• The researchers primarily assessed the effect of the BCG vaccine on the development of the symptoms of long COVID at 6 and 12 months.

TAKEAWAY:

• Hearing problems were less frequent among BCG recipients at 6 months compared with those who received placebo (odds ratio [OR], 0.26; 95% CI, 0.045-1.0; P = .044).
• At 12 months, participants who received the BCG vaccine exhibited fewer issues with sleeping (P = .027), concentration (P = .009), memory (P = .009), and vision (P = .022) along with a lower long-COVID score (one-sided Wilcoxon test, P = .002) than those who received placebo.
• At 6 months, BCG demonstrated a sex-specific paradoxical effect on hair loss, decreasing it in men (P = .031), while causing a slight, though statistically nonsignificant, increase in women.
• Male sex was the strongest predictive factor for long COVID, cognitive dysfunction, and cardiopulmonary scores at both follow-up assessments.

IN PRACTICE:

“[The study] findings suggest that BCG immunotherapy for an existing ailment may be superior to prophylaxis in healthy individuals,” the authors wrote.

SOURCE:

The study was led by Mehrsa Jalalizadeh and Keini Buosi, UroScience, State University of Campinas, Unicamp, São Paulo, Brazil. It was published online on November 19, 2024, in the Journal of Internal Medicine.

LIMITATIONS:

Previous mycobacterial exposure was not tested among the study participants. A notable loss to follow-up, particularly at 12 months, may have introduced bias into the results.

DISCLOSURES:

The study was supported by the Coordination for the Improvement of Higher Education Personnel, Federal Government of Brazil, the General Coordination of the National Immunization Program, Ministry of Health (Brazil), and the National Council for Scientific and Technological Development-Research Productivity. The authors declared no conflicts of interest.

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

TOPLINE:

Administering the Bacillus Calmette-Guérin (BCG) vaccine during the active phase of COVID-19 may help protect against the development of long COVID.

METHODOLOGY:

• A phase 3 clinical trial initiated in early 2020 investigated the effect of the BCG vaccine injected during active infection on COVID-19 progression in adults with mild or moderate COVID-19. The current study summarizes the 6- and 12-month follow-up data with a focus on long-COVID symptoms.
• Patients who tested positive for severe acute respiratory syndrome coronavirus 2 were randomly assigned to receive either 0.1 mL of intradermal BCG (n = 191) or 0.9% saline placebo (n = 202) within 14 days of symptom onset and were followed up at 7, 14, 21, and 45 days and at 6 and 12 months postinjection.
• Overall, 157 BCG (median age, 40 years; 54.1% women) and 142 placebo (median age, 41 years; 65.5% women) recipients completed the 6-month follow-up, and 97 BCG (median age, 37 years; 49.5% women) and 95 placebo (median age, 40 years; 67.4% women) recipients completed the 12-month follow-up.
• The researchers primarily assessed the effect of the BCG vaccine on the development of the symptoms of long COVID at 6 and 12 months.

TAKEAWAY:

• Hearing problems were less frequent among BCG recipients at 6 months compared with those who received placebo (odds ratio [OR], 0.26; 95% CI, 0.045-1.0; P = .044).
• At 12 months, participants who received the BCG vaccine exhibited fewer issues with sleeping (P = .027), concentration (P = .009), memory (P = .009), and vision (P = .022) along with a lower long-COVID score (one-sided Wilcoxon test, P = .002) than those who received placebo.
• At 6 months, BCG demonstrated a sex-specific paradoxical effect on hair loss, decreasing it in men (P = .031), while causing a slight, though statistically nonsignificant, increase in women.
• Male sex was the strongest predictive factor for long COVID, cognitive dysfunction, and cardiopulmonary scores at both follow-up assessments.

IN PRACTICE:

“[The study] findings suggest that BCG immunotherapy for an existing ailment may be superior to prophylaxis in healthy individuals,” the authors wrote.

SOURCE:

The study was led by Mehrsa Jalalizadeh and Keini Buosi, UroScience, State University of Campinas, Unicamp, São Paulo, Brazil. It was published online on November 19, 2024, in the Journal of Internal Medicine.

LIMITATIONS:

Previous mycobacterial exposure was not tested among the study participants. A notable loss to follow-up, particularly at 12 months, may have introduced bias into the results.

DISCLOSURES:

The study was supported by the Coordination for the Improvement of Higher Education Personnel, Federal Government of Brazil, the General Coordination of the National Immunization Program, Ministry of Health (Brazil), and the National Council for Scientific and Technological Development-Research Productivity. The authors declared no conflicts of interest.

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

This transcript has been edited for clarity. 

It has always amazed me that our bodies require these tiny amounts of incredibly rare substances to function. Sure, we need oxygen. We need water. But we also need molybdenum, which makes up just 1.2 parts per million of the Earth’s crust. 

Without adequate molybdenum intake, we develop seizures, developmental delays, death. Fortunately, we need so little molybdenum that true molybdenum deficiency is incredibly rare — seen only in people on total parenteral nutrition without supplementation or those with certain rare genetic conditions. But still, molybdenum is necessary for life.

Many metals are. Figure 1 colors the essential minerals on the periodic table. You can see that to stay alive, we humans need not only things like sodium, but selenium, bromine, zinc, copper, and cobalt. 

 

Some metals are very clearly not essential; we can all do without lead and mercury, and probably should.

But just because something is essential for life does not mean that more is better. The dose is the poison, as they say. And this week, we explore whether metals — even essential metals — might be adversely affecting our brains.

It’s not a stretch to think that metal intake could have weird effects on our nervous system. Lead exposure, primarily due to leaded gasoline, has been blamed for an average reduction of about 3 points in our national IQ, for example . But not all metals are created equal. Researchers set out to find out which might be more strongly associated with performance on cognitive tests and dementia, and reported their results in this study in JAMA Network Open.

To do this, they leveraged the MESA cohort study. This is a longitudinal study of a relatively diverse group of 6300 adults who were enrolled from 2000 to 2002 around the United States. At enrollment, they gave a urine sample and took a variety of cognitive tests. Important for this study was the digit symbol substitution test, where participants are provided a code and need to replace a list of numbers with symbols as per that code. Performance on this test worsens with age, depression, and cognitive impairment. 

Participants were followed for more than a decade, and over that time, 559 (about 9%) were diagnosed with dementia.

Those baseline urine samples were assayed for a variety of metals — some essential, some very much not, as you can see in Figure 2.

 

Now, I have to put my kidney doctor hat on for a second and talk about urine measurement ... of anything. The problem with urine is that the concentration can change a lot — by more than 10-fold, in fact — based on how much water you drank recently. Researchers correct for this, and in the case of this study, they do what a lot of researchers do: divide the measured concentration by the urine creatinine level. 

 

This introduces a bit of a problem. Take two people with exactly the same kidney function, who drank exactly the same water, whose urine is exactly the same concentration. The person with more muscle mass will have more creatinine in that urine sample, since creatinine is a byproduct of muscle metabolism. Because people with more muscle mass are generally healthier, when you divide your metal concentration by urine creatinine, you get a lower number, which might lead you to believe that lower levels of the metal in the urine are protective. But in fact, what you’re seeing is that higher levels of creatinine are protective. I see this issue all the time and it will always color results of studies like this. 

Okay, I am doffing my kidney doctor hat now to show you the results.

The researchers first looked at the relationship between metal concentrations in the urine and performance on cognitive tests. The results were fairly equivocal, save for that digit substitution test which is shown in Figure 4. 

 

Even these results don’t ring major alarm bells for me. What you’re seeing here is the change in scores on the digit substitution test for each 25-percentile increase in urinary metal level — a pretty big change. And yet, you see really minor changes in the performance on the test. The digit substitution test is not an IQ test; but to give you a feeling for the magnitude of this change, if we looked at copper level, moving from the 25th to the 50th percentile would be associated with a loss of nine tenths of an IQ point.

You see two colors on the Figure 4 graph, by the way. That’s because the researchers stratified their findings based on whether the individual carried the ApoE4 gene allele, which is a risk factor for the development of dementia. There are reasons to believe that neurotoxic metals might be worse in this population, and I suppose you do see generally more adverse effects on scores in the red lines compared with the blue lines. But still, we’re not talking about a huge effect size here.

Let’s look at the relationship between these metals and the development of dementia itself, a clearly more important outcome than how well you can replace numeric digits with symbols. I’ll highlight a few of the results that are particularly telling.

First, the nonessential mineral cadmium, which displays the type of relationship we would expect if the metal were neurotoxic: a clear, roughly linear increase in risk for dementia as urinary concentration increases. 

 

We see roughly similar patterns with the nonessential minerals tungsten and uranium, and the essential mineral zinc (beloved of respiratory-virus avoiders everywhere).

 

But it is very much not what we see for all metals. Strangest of all, look at lead, which shows basically no relationship with dementia.

 

This concerns me a bit. Earlier, I discussed the issue of measuring stuff in urine and how standardizing levels to the urine creatinine level introduces a bias due to muscle mass. One way around this is to standardize urine levels to some other marker of urine dilution, like osmolality. But more fundamental than that, I like to see positive and negative controls in studies like this. For example, lead strikes me as a good positive control here. If the experimental framework were valid, I would think we’d see a relationship between lead level and dementia. 

For a negative control? Well, something we are quite sure is not neurotoxic — something like sulfur, which is relatively ubiquitous, used in a variety of biological processes, and efficiently eliminated. We don’t have that in this study.

The authors close their case by creating a model that combines all the metal levels, asking the question of whether higher levels of metals in the urine in general worsen cognitive scores. And they find that the relationship exists, as you can see in Figure 8, both in carriers and noncarriers of ApoE4. But, to me, this is even more argument for the creatinine problem. If it’s not a specific metal but just the sort of general concentration of all metals, the risk for confounding by muscle mass is even higher. 

 

So should we worry about ingesting metals? I suppose the answer is ... kind of.

I am sure we should be avoiding lead, despite the results of this study. It’s probably best to stay away from uranium too.

 

As for the essential metals, I’m sure there is some toxic dose; there’s a toxic dose for everything at some point. But I don’t see evidence in this study to make me worry that a significant chunk of the population is anywhere close to that.

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships. 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

It has always amazed me that our bodies require these tiny amounts of incredibly rare substances to function. Sure, we need oxygen. We need water. But we also need molybdenum, which makes up just 1.2 parts per million of the Earth’s crust. 

Without adequate molybdenum intake, we develop seizures, developmental delays, death. Fortunately, we need so little molybdenum that true molybdenum deficiency is incredibly rare — seen only in people on total parenteral nutrition without supplementation or those with certain rare genetic conditions. But still, molybdenum is necessary for life.

Many metals are. Figure 1 colors the essential minerals on the periodic table. You can see that to stay alive, we humans need not only things like sodium, but selenium, bromine, zinc, copper, and cobalt. 

 

Some metals are very clearly not essential; we can all do without lead and mercury, and probably should.

But just because something is essential for life does not mean that more is better. The dose is the poison, as they say. And this week, we explore whether metals — even essential metals — might be adversely affecting our brains.

It’s not a stretch to think that metal intake could have weird effects on our nervous system. Lead exposure, primarily due to leaded gasoline, has been blamed for an average reduction of about 3 points in our national IQ, for example . But not all metals are created equal. Researchers set out to find out which might be more strongly associated with performance on cognitive tests and dementia, and reported their results in this study in JAMA Network Open.

To do this, they leveraged the MESA cohort study. This is a longitudinal study of a relatively diverse group of 6300 adults who were enrolled from 2000 to 2002 around the United States. At enrollment, they gave a urine sample and took a variety of cognitive tests. Important for this study was the digit symbol substitution test, where participants are provided a code and need to replace a list of numbers with symbols as per that code. Performance on this test worsens with age, depression, and cognitive impairment. 

Participants were followed for more than a decade, and over that time, 559 (about 9%) were diagnosed with dementia.

Those baseline urine samples were assayed for a variety of metals — some essential, some very much not, as you can see in Figure 2.

 

Now, I have to put my kidney doctor hat on for a second and talk about urine measurement ... of anything. The problem with urine is that the concentration can change a lot — by more than 10-fold, in fact — based on how much water you drank recently. Researchers correct for this, and in the case of this study, they do what a lot of researchers do: divide the measured concentration by the urine creatinine level. 

 

This introduces a bit of a problem. Take two people with exactly the same kidney function, who drank exactly the same water, whose urine is exactly the same concentration. The person with more muscle mass will have more creatinine in that urine sample, since creatinine is a byproduct of muscle metabolism. Because people with more muscle mass are generally healthier, when you divide your metal concentration by urine creatinine, you get a lower number, which might lead you to believe that lower levels of the metal in the urine are protective. But in fact, what you’re seeing is that higher levels of creatinine are protective. I see this issue all the time and it will always color results of studies like this. 

Okay, I am doffing my kidney doctor hat now to show you the results.

The researchers first looked at the relationship between metal concentrations in the urine and performance on cognitive tests. The results were fairly equivocal, save for that digit substitution test which is shown in Figure 4. 

 

Even these results don’t ring major alarm bells for me. What you’re seeing here is the change in scores on the digit substitution test for each 25-percentile increase in urinary metal level — a pretty big change. And yet, you see really minor changes in the performance on the test. The digit substitution test is not an IQ test; but to give you a feeling for the magnitude of this change, if we looked at copper level, moving from the 25th to the 50th percentile would be associated with a loss of nine tenths of an IQ point.

You see two colors on the Figure 4 graph, by the way. That’s because the researchers stratified their findings based on whether the individual carried the ApoE4 gene allele, which is a risk factor for the development of dementia. There are reasons to believe that neurotoxic metals might be worse in this population, and I suppose you do see generally more adverse effects on scores in the red lines compared with the blue lines. But still, we’re not talking about a huge effect size here.

Let’s look at the relationship between these metals and the development of dementia itself, a clearly more important outcome than how well you can replace numeric digits with symbols. I’ll highlight a few of the results that are particularly telling.

First, the nonessential mineral cadmium, which displays the type of relationship we would expect if the metal were neurotoxic: a clear, roughly linear increase in risk for dementia as urinary concentration increases. 

 

We see roughly similar patterns with the nonessential minerals tungsten and uranium, and the essential mineral zinc (beloved of respiratory-virus avoiders everywhere).

 

But it is very much not what we see for all metals. Strangest of all, look at lead, which shows basically no relationship with dementia.

 

This concerns me a bit. Earlier, I discussed the issue of measuring stuff in urine and how standardizing levels to the urine creatinine level introduces a bias due to muscle mass. One way around this is to standardize urine levels to some other marker of urine dilution, like osmolality. But more fundamental than that, I like to see positive and negative controls in studies like this. For example, lead strikes me as a good positive control here. If the experimental framework were valid, I would think we’d see a relationship between lead level and dementia. 

For a negative control? Well, something we are quite sure is not neurotoxic — something like sulfur, which is relatively ubiquitous, used in a variety of biological processes, and efficiently eliminated. We don’t have that in this study.

The authors close their case by creating a model that combines all the metal levels, asking the question of whether higher levels of metals in the urine in general worsen cognitive scores. And they find that the relationship exists, as you can see in Figure 8, both in carriers and noncarriers of ApoE4. But, to me, this is even more argument for the creatinine problem. If it’s not a specific metal but just the sort of general concentration of all metals, the risk for confounding by muscle mass is even higher. 

 

So should we worry about ingesting metals? I suppose the answer is ... kind of.

I am sure we should be avoiding lead, despite the results of this study. It’s probably best to stay away from uranium too.

 

As for the essential metals, I’m sure there is some toxic dose; there’s a toxic dose for everything at some point. But I don’t see evidence in this study to make me worry that a significant chunk of the population is anywhere close to that.

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships. 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

It has always amazed me that our bodies require these tiny amounts of incredibly rare substances to function. Sure, we need oxygen. We need water. But we also need molybdenum, which makes up just 1.2 parts per million of the Earth’s crust. 

Without adequate molybdenum intake, we develop seizures, developmental delays, death. Fortunately, we need so little molybdenum that true molybdenum deficiency is incredibly rare — seen only in people on total parenteral nutrition without supplementation or those with certain rare genetic conditions. But still, molybdenum is necessary for life.

Many metals are. Figure 1 colors the essential minerals on the periodic table. You can see that to stay alive, we humans need not only things like sodium, but selenium, bromine, zinc, copper, and cobalt. 

 

Some metals are very clearly not essential; we can all do without lead and mercury, and probably should.

But just because something is essential for life does not mean that more is better. The dose is the poison, as they say. And this week, we explore whether metals — even essential metals — might be adversely affecting our brains.

It’s not a stretch to think that metal intake could have weird effects on our nervous system. Lead exposure, primarily due to leaded gasoline, has been blamed for an average reduction of about 3 points in our national IQ, for example . But not all metals are created equal. Researchers set out to find out which might be more strongly associated with performance on cognitive tests and dementia, and reported their results in this study in JAMA Network Open.

To do this, they leveraged the MESA cohort study. This is a longitudinal study of a relatively diverse group of 6300 adults who were enrolled from 2000 to 2002 around the United States. At enrollment, they gave a urine sample and took a variety of cognitive tests. Important for this study was the digit symbol substitution test, where participants are provided a code and need to replace a list of numbers with symbols as per that code. Performance on this test worsens with age, depression, and cognitive impairment. 

Participants were followed for more than a decade, and over that time, 559 (about 9%) were diagnosed with dementia.

Those baseline urine samples were assayed for a variety of metals — some essential, some very much not, as you can see in Figure 2.

 

Now, I have to put my kidney doctor hat on for a second and talk about urine measurement ... of anything. The problem with urine is that the concentration can change a lot — by more than 10-fold, in fact — based on how much water you drank recently. Researchers correct for this, and in the case of this study, they do what a lot of researchers do: divide the measured concentration by the urine creatinine level. 

 

This introduces a bit of a problem. Take two people with exactly the same kidney function, who drank exactly the same water, whose urine is exactly the same concentration. The person with more muscle mass will have more creatinine in that urine sample, since creatinine is a byproduct of muscle metabolism. Because people with more muscle mass are generally healthier, when you divide your metal concentration by urine creatinine, you get a lower number, which might lead you to believe that lower levels of the metal in the urine are protective. But in fact, what you’re seeing is that higher levels of creatinine are protective. I see this issue all the time and it will always color results of studies like this. 

Okay, I am doffing my kidney doctor hat now to show you the results.

The researchers first looked at the relationship between metal concentrations in the urine and performance on cognitive tests. The results were fairly equivocal, save for that digit substitution test which is shown in Figure 4. 

 

Even these results don’t ring major alarm bells for me. What you’re seeing here is the change in scores on the digit substitution test for each 25-percentile increase in urinary metal level — a pretty big change. And yet, you see really minor changes in the performance on the test. The digit substitution test is not an IQ test; but to give you a feeling for the magnitude of this change, if we looked at copper level, moving from the 25th to the 50th percentile would be associated with a loss of nine tenths of an IQ point.

You see two colors on the Figure 4 graph, by the way. That’s because the researchers stratified their findings based on whether the individual carried the ApoE4 gene allele, which is a risk factor for the development of dementia. There are reasons to believe that neurotoxic metals might be worse in this population, and I suppose you do see generally more adverse effects on scores in the red lines compared with the blue lines. But still, we’re not talking about a huge effect size here.

Let’s look at the relationship between these metals and the development of dementia itself, a clearly more important outcome than how well you can replace numeric digits with symbols. I’ll highlight a few of the results that are particularly telling.

First, the nonessential mineral cadmium, which displays the type of relationship we would expect if the metal were neurotoxic: a clear, roughly linear increase in risk for dementia as urinary concentration increases. 

 

We see roughly similar patterns with the nonessential minerals tungsten and uranium, and the essential mineral zinc (beloved of respiratory-virus avoiders everywhere).

 

But it is very much not what we see for all metals. Strangest of all, look at lead, which shows basically no relationship with dementia.

 

This concerns me a bit. Earlier, I discussed the issue of measuring stuff in urine and how standardizing levels to the urine creatinine level introduces a bias due to muscle mass. One way around this is to standardize urine levels to some other marker of urine dilution, like osmolality. But more fundamental than that, I like to see positive and negative controls in studies like this. For example, lead strikes me as a good positive control here. If the experimental framework were valid, I would think we’d see a relationship between lead level and dementia. 

For a negative control? Well, something we are quite sure is not neurotoxic — something like sulfur, which is relatively ubiquitous, used in a variety of biological processes, and efficiently eliminated. We don’t have that in this study.

The authors close their case by creating a model that combines all the metal levels, asking the question of whether higher levels of metals in the urine in general worsen cognitive scores. And they find that the relationship exists, as you can see in Figure 8, both in carriers and noncarriers of ApoE4. But, to me, this is even more argument for the creatinine problem. If it’s not a specific metal but just the sort of general concentration of all metals, the risk for confounding by muscle mass is even higher. 

 

So should we worry about ingesting metals? I suppose the answer is ... kind of.

I am sure we should be avoiding lead, despite the results of this study. It’s probably best to stay away from uranium too.

 

As for the essential metals, I’m sure there is some toxic dose; there’s a toxic dose for everything at some point. But I don’t see evidence in this study to make me worry that a significant chunk of the population is anywhere close to that.

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships. 

A version of this article appeared on Medscape.com.

LAS VEGAS — For clinicians who rely on generic tretinoin 0.5% as their go-to treatment for patients with acne, Shanna Miranti, MPAS, PA-C, offers some straightforward advice: You can do better.

“Friends don’t let friends write generic tretinoin only because there are so many better options out there,” Miranti, who practices dermatology in Naples, Florida, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. “Don’t get lazy; your patients deserve better.”

 

In her wide-ranging presentation, Miranti described the four pillars of acne pathogenesis as increased sebum production caused by androgens, follicular hyperkeratinization in the pilosebaceous unit, colonization by Cutibacterium acnes (formerly Proprionibacterium acnes), and inflammation. Acne “starts with androgens, but this is a cascade, so you have to find treatment options that hit as many of these four pillars as possible,” Miranti explained. “If you’re only using generic tretinoin, you’re only hitting maybe two of the four pillars at best.”

She then discussed the best treatment options for each pillar:

Follicular plugging and hyperkeratinization. Topical retinoids, including tretinoin, adapalene, tazarotene, and trifarotene, are highly effective for this issue. Systemic isotretinoin is also a strong option. For patients who are pregnant or trying to conceive, azelaic acid is a helpful alternative.

Excessive sebum production and androgens. “This may be the genesis of when acne begins — during puberty,” Miranti said. “With rising androgens comes rising amounts of sebum.” The only topical treatment that specifically targets this is clascoterone (Winlevi), which should be applied twice daily. For systemic management of excessive sebum, isotretinoin is highly effective. In women, spironolactone (50 mg daily, or split into two doses) and oral contraceptives are also options.

Inflammation. Topical options include retinoids, antibiotics, benzoyl peroxide (BPO), topical dapsone, azelaic acid, and clascoterone. Systemic options include isotretinoin; the antibiotics doxycycline, minocycline, and sarecycline; spironolactone; and oral contraceptives. “So, when you see patients with intense inflammation, and they’re starting to get post-inflammatory erythema or post-inflammatory hyperpigmentation, you need something to address this inflammatory problem,” she noted.

C acnes. Topical treatment options include BPO and antibiotics. However, topical antibiotics should never be used alone, Miranti said; they must always be combined with BPO to prevent bacterial resistance. Oral options include sarecycline, “which has a low propensity for antibiotic resistance and spares the gut microbiome to some degree,” and the “old-school” antibiotics doxycycline, minocycline, and tetracycline. “But all oral antibiotics should be used concomitantly with BPO,” she added.

Regardless of which treatment is chosen for any pillar, Miranti emphasized that monotherapy with a single agent is often insufficient. “Historically, we have combined therapies to treat the multiple causes of acne,” she said. “The average number of acne products used per patient is 2.53, but that’s also the average number of copays. We have to be conscious of that. If you are a mom with four kids who are on acne medication, you want to minimize your copay burden. So, if you can find a topical medication that hits three out of the four pillars of acne pathogenesis, that would be fantastic.” The only topical that targets excess sebum is clascoterone, she noted, and the only medication that hits all four pillars is isotretinoin.

In October 2023, the Food and Drug Administration approved a once-daily topical gel for patients aged 12 years or older that contains clindamycin 1.2%, adapalene 0.15%, and BPO 3.1%. The first-ever triple combination therapy, known as Cabtreo, was released to pharmacies in March 2024. In a phase 2 trial, researchers randomized 394 patients aged 9 years or older with moderate to severe acne to once-daily IDP-126, one of three dyad combination gels, or vehicle gel for 12 weeks. Patients in the Cabtreo arm achieved significantly greater lesion reductions than those in the vehicle arm (inflammatory: 78.3% vs 45.1%; noninflammatory: 70.0% vs 37.6%; P < .001 for both). They also experienced lesion reductions that were 9.2%-16.6% greater than those observed with any of the dyad combination gels. Miranti characterized the study results as “pretty phenomenal,” noting that the ease of use makes Cabtreo stand out as a treatment option. “Simplicity drives compliance, and compliance drives results,” she said. “This is one product to apply once a day. Any of you who have a teenage son like me, you know it is hard to get them to brush their teeth twice a day, let alone take medicine before they leave the house in the morning. This can be a home run for a lot of patients, and not just our teenagers. Adult females have done very well with this medication.”

In a network meta-analysis, researchers reviewed 221 randomized controlled trials to compare the efficacy of pharmacologic treatment for acne. The most effective treatment in reducing inflammatory and noninflammatory lesions was oral isotretinoin, followed by Cabtreo.

Miranti disclosed being a speaker, consultant, and/or an advisory board member for Arcutis Biotherapeutics, Bausch Health, Dermavant Sciences, Galderma, Incyte, LEO Pharma, Eli Lilly, Sun Pharma, Swift USA, and Verrica Pharmaceuticals.

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

LAS VEGAS — For clinicians who rely on generic tretinoin 0.5% as their go-to treatment for patients with acne, Shanna Miranti, MPAS, PA-C, offers some straightforward advice: You can do better.

“Friends don’t let friends write generic tretinoin only because there are so many better options out there,” Miranti, who practices dermatology in Naples, Florida, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. “Don’t get lazy; your patients deserve better.”

 

In her wide-ranging presentation, Miranti described the four pillars of acne pathogenesis as increased sebum production caused by androgens, follicular hyperkeratinization in the pilosebaceous unit, colonization by Cutibacterium acnes (formerly Proprionibacterium acnes), and inflammation. Acne “starts with androgens, but this is a cascade, so you have to find treatment options that hit as many of these four pillars as possible,” Miranti explained. “If you’re only using generic tretinoin, you’re only hitting maybe two of the four pillars at best.”

She then discussed the best treatment options for each pillar:

Follicular plugging and hyperkeratinization. Topical retinoids, including tretinoin, adapalene, tazarotene, and trifarotene, are highly effective for this issue. Systemic isotretinoin is also a strong option. For patients who are pregnant or trying to conceive, azelaic acid is a helpful alternative.

Excessive sebum production and androgens. “This may be the genesis of when acne begins — during puberty,” Miranti said. “With rising androgens comes rising amounts of sebum.” The only topical treatment that specifically targets this is clascoterone (Winlevi), which should be applied twice daily. For systemic management of excessive sebum, isotretinoin is highly effective. In women, spironolactone (50 mg daily, or split into two doses) and oral contraceptives are also options.

Inflammation. Topical options include retinoids, antibiotics, benzoyl peroxide (BPO), topical dapsone, azelaic acid, and clascoterone. Systemic options include isotretinoin; the antibiotics doxycycline, minocycline, and sarecycline; spironolactone; and oral contraceptives. “So, when you see patients with intense inflammation, and they’re starting to get post-inflammatory erythema or post-inflammatory hyperpigmentation, you need something to address this inflammatory problem,” she noted.

C acnes. Topical treatment options include BPO and antibiotics. However, topical antibiotics should never be used alone, Miranti said; they must always be combined with BPO to prevent bacterial resistance. Oral options include sarecycline, “which has a low propensity for antibiotic resistance and spares the gut microbiome to some degree,” and the “old-school” antibiotics doxycycline, minocycline, and tetracycline. “But all oral antibiotics should be used concomitantly with BPO,” she added.

Regardless of which treatment is chosen for any pillar, Miranti emphasized that monotherapy with a single agent is often insufficient. “Historically, we have combined therapies to treat the multiple causes of acne,” she said. “The average number of acne products used per patient is 2.53, but that’s also the average number of copays. We have to be conscious of that. If you are a mom with four kids who are on acne medication, you want to minimize your copay burden. So, if you can find a topical medication that hits three out of the four pillars of acne pathogenesis, that would be fantastic.” The only topical that targets excess sebum is clascoterone, she noted, and the only medication that hits all four pillars is isotretinoin.

In October 2023, the Food and Drug Administration approved a once-daily topical gel for patients aged 12 years or older that contains clindamycin 1.2%, adapalene 0.15%, and BPO 3.1%. The first-ever triple combination therapy, known as Cabtreo, was released to pharmacies in March 2024. In a phase 2 trial, researchers randomized 394 patients aged 9 years or older with moderate to severe acne to once-daily IDP-126, one of three dyad combination gels, or vehicle gel for 12 weeks. Patients in the Cabtreo arm achieved significantly greater lesion reductions than those in the vehicle arm (inflammatory: 78.3% vs 45.1%; noninflammatory: 70.0% vs 37.6%; P < .001 for both). They also experienced lesion reductions that were 9.2%-16.6% greater than those observed with any of the dyad combination gels. Miranti characterized the study results as “pretty phenomenal,” noting that the ease of use makes Cabtreo stand out as a treatment option. “Simplicity drives compliance, and compliance drives results,” she said. “This is one product to apply once a day. Any of you who have a teenage son like me, you know it is hard to get them to brush their teeth twice a day, let alone take medicine before they leave the house in the morning. This can be a home run for a lot of patients, and not just our teenagers. Adult females have done very well with this medication.”

In a network meta-analysis, researchers reviewed 221 randomized controlled trials to compare the efficacy of pharmacologic treatment for acne. The most effective treatment in reducing inflammatory and noninflammatory lesions was oral isotretinoin, followed by Cabtreo.

Miranti disclosed being a speaker, consultant, and/or an advisory board member for Arcutis Biotherapeutics, Bausch Health, Dermavant Sciences, Galderma, Incyte, LEO Pharma, Eli Lilly, Sun Pharma, Swift USA, and Verrica Pharmaceuticals.

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

LAS VEGAS — For clinicians who rely on generic tretinoin 0.5% as their go-to treatment for patients with acne, Shanna Miranti, MPAS, PA-C, offers some straightforward advice: You can do better.

“Friends don’t let friends write generic tretinoin only because there are so many better options out there,” Miranti, who practices dermatology in Naples, Florida, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. “Don’t get lazy; your patients deserve better.”

 

In her wide-ranging presentation, Miranti described the four pillars of acne pathogenesis as increased sebum production caused by androgens, follicular hyperkeratinization in the pilosebaceous unit, colonization by Cutibacterium acnes (formerly Proprionibacterium acnes), and inflammation. Acne “starts with androgens, but this is a cascade, so you have to find treatment options that hit as many of these four pillars as possible,” Miranti explained. “If you’re only using generic tretinoin, you’re only hitting maybe two of the four pillars at best.”

She then discussed the best treatment options for each pillar:

Follicular plugging and hyperkeratinization. Topical retinoids, including tretinoin, adapalene, tazarotene, and trifarotene, are highly effective for this issue. Systemic isotretinoin is also a strong option. For patients who are pregnant or trying to conceive, azelaic acid is a helpful alternative.

Excessive sebum production and androgens. “This may be the genesis of when acne begins — during puberty,” Miranti said. “With rising androgens comes rising amounts of sebum.” The only topical treatment that specifically targets this is clascoterone (Winlevi), which should be applied twice daily. For systemic management of excessive sebum, isotretinoin is highly effective. In women, spironolactone (50 mg daily, or split into two doses) and oral contraceptives are also options.

Inflammation. Topical options include retinoids, antibiotics, benzoyl peroxide (BPO), topical dapsone, azelaic acid, and clascoterone. Systemic options include isotretinoin; the antibiotics doxycycline, minocycline, and sarecycline; spironolactone; and oral contraceptives. “So, when you see patients with intense inflammation, and they’re starting to get post-inflammatory erythema or post-inflammatory hyperpigmentation, you need something to address this inflammatory problem,” she noted.

C acnes. Topical treatment options include BPO and antibiotics. However, topical antibiotics should never be used alone, Miranti said; they must always be combined with BPO to prevent bacterial resistance. Oral options include sarecycline, “which has a low propensity for antibiotic resistance and spares the gut microbiome to some degree,” and the “old-school” antibiotics doxycycline, minocycline, and tetracycline. “But all oral antibiotics should be used concomitantly with BPO,” she added.

Regardless of which treatment is chosen for any pillar, Miranti emphasized that monotherapy with a single agent is often insufficient. “Historically, we have combined therapies to treat the multiple causes of acne,” she said. “The average number of acne products used per patient is 2.53, but that’s also the average number of copays. We have to be conscious of that. If you are a mom with four kids who are on acne medication, you want to minimize your copay burden. So, if you can find a topical medication that hits three out of the four pillars of acne pathogenesis, that would be fantastic.” The only topical that targets excess sebum is clascoterone, she noted, and the only medication that hits all four pillars is isotretinoin.

In October 2023, the Food and Drug Administration approved a once-daily topical gel for patients aged 12 years or older that contains clindamycin 1.2%, adapalene 0.15%, and BPO 3.1%. The first-ever triple combination therapy, known as Cabtreo, was released to pharmacies in March 2024. In a phase 2 trial, researchers randomized 394 patients aged 9 years or older with moderate to severe acne to once-daily IDP-126, one of three dyad combination gels, or vehicle gel for 12 weeks. Patients in the Cabtreo arm achieved significantly greater lesion reductions than those in the vehicle arm (inflammatory: 78.3% vs 45.1%; noninflammatory: 70.0% vs 37.6%; P < .001 for both). They also experienced lesion reductions that were 9.2%-16.6% greater than those observed with any of the dyad combination gels. Miranti characterized the study results as “pretty phenomenal,” noting that the ease of use makes Cabtreo stand out as a treatment option. “Simplicity drives compliance, and compliance drives results,” she said. “This is one product to apply once a day. Any of you who have a teenage son like me, you know it is hard to get them to brush their teeth twice a day, let alone take medicine before they leave the house in the morning. This can be a home run for a lot of patients, and not just our teenagers. Adult females have done very well with this medication.”

In a network meta-analysis, researchers reviewed 221 randomized controlled trials to compare the efficacy of pharmacologic treatment for acne. The most effective treatment in reducing inflammatory and noninflammatory lesions was oral isotretinoin, followed by Cabtreo.

Miranti disclosed being a speaker, consultant, and/or an advisory board member for Arcutis Biotherapeutics, Bausch Health, Dermavant Sciences, Galderma, Incyte, LEO Pharma, Eli Lilly, Sun Pharma, Swift USA, and Verrica Pharmaceuticals.

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

TOPLINE:

About one in five people who live in the same household as an individual infected with the influenza virus develop secondary infections within a 7-day follow-up period, with children facing the highest risk. Vaccination lowers the risk of contracting the infection among household contacts.

METHODOLOGY:

• Researchers conducted a prospective cohort study of data between 2017 and 2020 to determine the estimated effectiveness of influenza vaccines in preventing secondary infections in household contacts.
• Overall, 699 people were primary contacts, or the first in a household to get infected (median age, 13 years; 54.5% women); there were 1581 household contacts (median age, 31 years; 52.7% women), and both groups were followed for 7 days.
• Participants collected daily symptom diaries and nasal swabs during the follow-up period.
• Participants also submitted their history of influenza vaccination; 50.1% of household contacts had received a shot at least 14 days before the first case of disease onset in the household.
• The risk for secondary infection and vaccine effectiveness in preventing infection among household contacts was estimated overall and by virus type, subtype, and lineage.

TAKEAWAY:

• Nearly half (48.2%) of primary cases were from children and teens between ages 5 and 17 years.
• Overall, 22% household contacts had laboratory-confirmed influenza during follow-up, of which 7% were asymptomatic.
• The overall risk for secondary infection among unvaccinated household contacts was 18.8%, with the highest risk observed among children younger than age 5 years (29.9%).
• The overall effectiveness of influenza vaccines in preventing laboratory-confirmed infections among household contacts was 21% (95% CI, 1.4%-36.7%).
• The vaccine demonstrated specific protection against influenza B infection (56.4%; 95% CI, 30.1%-72.8%), particularly among those between ages 5 and 17 years.

IN PRACTICE:

“Although complementary preventive strategies to prevent influenza in household settings may be considered, seasonal influenza vaccination is the primary strategy recommended for prevention of influenza illness and its complications,” the authors wrote.

SOURCE:

The study was led by Carlos G. Grijalva, MD, MPH, of Vanderbilt University Medical Center in Nashville, Tennessee, and was published online in JAMA Network Open.

LIMITATIONS:

The recruitment of infected individuals from clinical testing pools may have limited the generalizability of the risk for secondary infection in households in which the primary case had a milder or asymptomatic infection. The study was unable to assess the effectiveness of specific vaccine formulations, such as those receiving high doses. The stratification of estimates by influenza subtypes and lineages was challenging because of small cell sizes.

DISCLOSURES:

This study was supported by grants from the Centers for Disease Control and Prevention (CDC) and authors reported support from grants from the National Institute Of Allergy And Infectious Diseases. Some authors reported contracts, receiving personal fees and grants from the CDC and various pharmaceutical companies such as Merck and Sanofi.

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

TOPLINE:

About one in five people who live in the same household as an individual infected with the influenza virus develop secondary infections within a 7-day follow-up period, with children facing the highest risk. Vaccination lowers the risk of contracting the infection among household contacts.

METHODOLOGY:

• Researchers conducted a prospective cohort study of data between 2017 and 2020 to determine the estimated effectiveness of influenza vaccines in preventing secondary infections in household contacts.
• Overall, 699 people were primary contacts, or the first in a household to get infected (median age, 13 years; 54.5% women); there were 1581 household contacts (median age, 31 years; 52.7% women), and both groups were followed for 7 days.
• Participants collected daily symptom diaries and nasal swabs during the follow-up period.
• Participants also submitted their history of influenza vaccination; 50.1% of household contacts had received a shot at least 14 days before the first case of disease onset in the household.
• The risk for secondary infection and vaccine effectiveness in preventing infection among household contacts was estimated overall and by virus type, subtype, and lineage.

TAKEAWAY:

• Nearly half (48.2%) of primary cases were from children and teens between ages 5 and 17 years.
• Overall, 22% household contacts had laboratory-confirmed influenza during follow-up, of which 7% were asymptomatic.
• The overall risk for secondary infection among unvaccinated household contacts was 18.8%, with the highest risk observed among children younger than age 5 years (29.9%).
• The overall effectiveness of influenza vaccines in preventing laboratory-confirmed infections among household contacts was 21% (95% CI, 1.4%-36.7%).
• The vaccine demonstrated specific protection against influenza B infection (56.4%; 95% CI, 30.1%-72.8%), particularly among those between ages 5 and 17 years.

IN PRACTICE:

“Although complementary preventive strategies to prevent influenza in household settings may be considered, seasonal influenza vaccination is the primary strategy recommended for prevention of influenza illness and its complications,” the authors wrote.

SOURCE:

The study was led by Carlos G. Grijalva, MD, MPH, of Vanderbilt University Medical Center in Nashville, Tennessee, and was published online in JAMA Network Open.

LIMITATIONS:

The recruitment of infected individuals from clinical testing pools may have limited the generalizability of the risk for secondary infection in households in which the primary case had a milder or asymptomatic infection. The study was unable to assess the effectiveness of specific vaccine formulations, such as those receiving high doses. The stratification of estimates by influenza subtypes and lineages was challenging because of small cell sizes.

DISCLOSURES:

This study was supported by grants from the Centers for Disease Control and Prevention (CDC) and authors reported support from grants from the National Institute Of Allergy And Infectious Diseases. Some authors reported contracts, receiving personal fees and grants from the CDC and various pharmaceutical companies such as Merck and Sanofi.

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

TOPLINE:

About one in five people who live in the same household as an individual infected with the influenza virus develop secondary infections within a 7-day follow-up period, with children facing the highest risk. Vaccination lowers the risk of contracting the infection among household contacts.

METHODOLOGY:

• Researchers conducted a prospective cohort study of data between 2017 and 2020 to determine the estimated effectiveness of influenza vaccines in preventing secondary infections in household contacts.
• Overall, 699 people were primary contacts, or the first in a household to get infected (median age, 13 years; 54.5% women); there were 1581 household contacts (median age, 31 years; 52.7% women), and both groups were followed for 7 days.
• Participants collected daily symptom diaries and nasal swabs during the follow-up period.
• Participants also submitted their history of influenza vaccination; 50.1% of household contacts had received a shot at least 14 days before the first case of disease onset in the household.
• The risk for secondary infection and vaccine effectiveness in preventing infection among household contacts was estimated overall and by virus type, subtype, and lineage.

TAKEAWAY:

• Nearly half (48.2%) of primary cases were from children and teens between ages 5 and 17 years.
• Overall, 22% household contacts had laboratory-confirmed influenza during follow-up, of which 7% were asymptomatic.
• The overall risk for secondary infection among unvaccinated household contacts was 18.8%, with the highest risk observed among children younger than age 5 years (29.9%).
• The overall effectiveness of influenza vaccines in preventing laboratory-confirmed infections among household contacts was 21% (95% CI, 1.4%-36.7%).
• The vaccine demonstrated specific protection against influenza B infection (56.4%; 95% CI, 30.1%-72.8%), particularly among those between ages 5 and 17 years.

IN PRACTICE:

“Although complementary preventive strategies to prevent influenza in household settings may be considered, seasonal influenza vaccination is the primary strategy recommended for prevention of influenza illness and its complications,” the authors wrote.

SOURCE:

The study was led by Carlos G. Grijalva, MD, MPH, of Vanderbilt University Medical Center in Nashville, Tennessee, and was published online in JAMA Network Open.

LIMITATIONS:

The recruitment of infected individuals from clinical testing pools may have limited the generalizability of the risk for secondary infection in households in which the primary case had a milder or asymptomatic infection. The study was unable to assess the effectiveness of specific vaccine formulations, such as those receiving high doses. The stratification of estimates by influenza subtypes and lineages was challenging because of small cell sizes.

DISCLOSURES:

This study was supported by grants from the Centers for Disease Control and Prevention (CDC) and authors reported support from grants from the National Institute Of Allergy And Infectious Diseases. Some authors reported contracts, receiving personal fees and grants from the CDC and various pharmaceutical companies such as Merck and Sanofi.

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