Rheumatology News

Interleukin (IL)–23 inhibition may still have a role to play in the treatment of patients with axial spondyloarthritis (SpA), suggests research presented at the 12th International Congress on Spondyloarthritides.

There is a strong rationale for using IL-23 inhibitors in patients with axial SpA, and the IL-23/IL-17 axis has been proposed as a critical player in the pathophysiology of the disease. But around 2018 it became clear from randomized, controlled trials that IL-23 inhibition was ineffective at improving key clinical outcomes, at least in patients with axial disease.

Although the overall results of a systematic review and meta-analysis that was presented at the meeting corroborated the negative results seen with IL-23–inhibiting agents in clinical trials, there were some data showing benefits of the IL-23 inhibitor risankizumab on secondary outcomes in one trial.

To look at the available evidence, Louise Vanhoutte, a 2nd-year internal medicine student at University Hospitals Leuven (Belgium) worked under the guidance of Rik Lories, MD, PhD, head of the division of rheumatology at University Hospitals Leuven. Together they searched known databases for randomized, controlled trials investigating the use of IL-23 and IL-17 inhibitors for the treatment of adults with axial SpA or psoriatic arthritis. Studies could be either phase 2 or phase 3, but had to have included a placebo and used the ASAS40 (40% Improvement in Assessment of SpondyloArthritis International Society Response criteria), ASAS20, Bath Ankylosing Spondylitis Disease Activity Index, or SPARCC (Spondyloarthritis Research Consortium of Canada) index score to assess outcomes.

The systematic review whittled the number of clinical trials in the meta-analysis to 12, which concerned the use of ustekinumab, an IL-12/23 inhibitor, and risankizumab, along with two IL-17 inhibitors, ixekizumab and secukinumab. Data for the IL-23 inhibitors guselkumab and tildrakizumab were not available.

“To no surprise, Forest plots showed that there was a lack of efficacy for IL-23 agents in the treatment of axial spondyloarthritis and a superior efficacy for IL-17 inhibitors in the treatment of axial spondyloarthritis,” Ms. Vanhoutte reported.

The respective odds ratios for IL-23 and IL-17 inhibitors in getting patients to meet ASAS40 response criteria in comparison to baseline were 1.51 (95% confidence interval, 0.98-2.31) and 2.54 (95% CI, 2.02-3.19).

“Does this mean it is a dead-end street for all IL-23 inhibition?” she asked. Not necessarily. In the meta-analysis, not only did risankizumab lower the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) by a mean difference (MD) of –0.30 (95% CI, –0.41 to –0.19) from baseline values, but it also led to statistically significant reductions in SPARCC index score for the spine (MD, –3.10; 95% CI, –4.50 to –1.70) and high-sensitivity CRP (MD, –2.10; 95% CI, –2.56 to –1.64). The risankizumab findings might suggest there are potential disease-modifying properties for specifically targeting IL-23p19. There could also be a window of opportunity to use IL-23 inhibitors earlier.

“These are only results from one randomized, controlled trial in a small sample size where outcomes were reported as medians and interquartile ranges, so they had to be converted to means and standard deviations to have an odds ratio in the end,” she explained.

“Also, these were results from a radiographic axial spondyloarthritis population and not a nonradiographic axial spondyloarthritis population,” she added.

While that might limit the interpretation of the findings, “what we see here is both reduction in inflammation and reduction in structural disease progression as [measured] by SPARCC,” Ms. Vanhoutte said.

“Since IL-23 is an upstream molecule from IL-17 it’s probable that IL-23 is present in the prephase of the disease, in a prephase inflammation state,” she hypothesized. “This is especially interesting because there are very few randomized, controlled trials that examine therapeutic agents in nonradiographic axial spondyloarthritis,” she observed. Looking at IL-23 in radiographic, or established, disease therefore may not be as useful.

“I’m thinking you’re making actually a very important point for us,” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center.

“We are discussing whether or not IL-23 is important in inhibiting the disease activity of patients with axial spondyloarthritis, and we are surprised that it is not shown in RCTs.

“Why is it completely ineffective in axial spondyloarthritis? You show us that that is probably not the case,” Dr. Landewé suggested.

“What you make very clear here is that indeed there is some efficacy, and from a pathophysiological way of thinking it might be slightly different as compared with what most clinicians nowadays think.”

The study had no specific funding, and no disclosures were reported.

Interleukin (IL)–23 inhibition may still have a role to play in the treatment of patients with axial spondyloarthritis (SpA), suggests research presented at the 12th International Congress on Spondyloarthritides.

There is a strong rationale for using IL-23 inhibitors in patients with axial SpA, and the IL-23/IL-17 axis has been proposed as a critical player in the pathophysiology of the disease. But around 2018 it became clear from randomized, controlled trials that IL-23 inhibition was ineffective at improving key clinical outcomes, at least in patients with axial disease.

Although the overall results of a systematic review and meta-analysis that was presented at the meeting corroborated the negative results seen with IL-23–inhibiting agents in clinical trials, there were some data showing benefits of the IL-23 inhibitor risankizumab on secondary outcomes in one trial.

To look at the available evidence, Louise Vanhoutte, a 2nd-year internal medicine student at University Hospitals Leuven (Belgium) worked under the guidance of Rik Lories, MD, PhD, head of the division of rheumatology at University Hospitals Leuven. Together they searched known databases for randomized, controlled trials investigating the use of IL-23 and IL-17 inhibitors for the treatment of adults with axial SpA or psoriatic arthritis. Studies could be either phase 2 or phase 3, but had to have included a placebo and used the ASAS40 (40% Improvement in Assessment of SpondyloArthritis International Society Response criteria), ASAS20, Bath Ankylosing Spondylitis Disease Activity Index, or SPARCC (Spondyloarthritis Research Consortium of Canada) index score to assess outcomes.

The systematic review whittled the number of clinical trials in the meta-analysis to 12, which concerned the use of ustekinumab, an IL-12/23 inhibitor, and risankizumab, along with two IL-17 inhibitors, ixekizumab and secukinumab. Data for the IL-23 inhibitors guselkumab and tildrakizumab were not available.

“To no surprise, Forest plots showed that there was a lack of efficacy for IL-23 agents in the treatment of axial spondyloarthritis and a superior efficacy for IL-17 inhibitors in the treatment of axial spondyloarthritis,” Ms. Vanhoutte reported.

The respective odds ratios for IL-23 and IL-17 inhibitors in getting patients to meet ASAS40 response criteria in comparison to baseline were 1.51 (95% confidence interval, 0.98-2.31) and 2.54 (95% CI, 2.02-3.19).

“Does this mean it is a dead-end street for all IL-23 inhibition?” she asked. Not necessarily. In the meta-analysis, not only did risankizumab lower the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) by a mean difference (MD) of –0.30 (95% CI, –0.41 to –0.19) from baseline values, but it also led to statistically significant reductions in SPARCC index score for the spine (MD, –3.10; 95% CI, –4.50 to –1.70) and high-sensitivity CRP (MD, –2.10; 95% CI, –2.56 to –1.64). The risankizumab findings might suggest there are potential disease-modifying properties for specifically targeting IL-23p19. There could also be a window of opportunity to use IL-23 inhibitors earlier.

“These are only results from one randomized, controlled trial in a small sample size where outcomes were reported as medians and interquartile ranges, so they had to be converted to means and standard deviations to have an odds ratio in the end,” she explained.

“Also, these were results from a radiographic axial spondyloarthritis population and not a nonradiographic axial spondyloarthritis population,” she added.

While that might limit the interpretation of the findings, “what we see here is both reduction in inflammation and reduction in structural disease progression as [measured] by SPARCC,” Ms. Vanhoutte said.

“Since IL-23 is an upstream molecule from IL-17 it’s probable that IL-23 is present in the prephase of the disease, in a prephase inflammation state,” she hypothesized. “This is especially interesting because there are very few randomized, controlled trials that examine therapeutic agents in nonradiographic axial spondyloarthritis,” she observed. Looking at IL-23 in radiographic, or established, disease therefore may not be as useful.

“I’m thinking you’re making actually a very important point for us,” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center.

“We are discussing whether or not IL-23 is important in inhibiting the disease activity of patients with axial spondyloarthritis, and we are surprised that it is not shown in RCTs.

“Why is it completely ineffective in axial spondyloarthritis? You show us that that is probably not the case,” Dr. Landewé suggested.

“What you make very clear here is that indeed there is some efficacy, and from a pathophysiological way of thinking it might be slightly different as compared with what most clinicians nowadays think.”

The study had no specific funding, and no disclosures were reported.

Interleukin (IL)–23 inhibition may still have a role to play in the treatment of patients with axial spondyloarthritis (SpA), suggests research presented at the 12th International Congress on Spondyloarthritides.

There is a strong rationale for using IL-23 inhibitors in patients with axial SpA, and the IL-23/IL-17 axis has been proposed as a critical player in the pathophysiology of the disease. But around 2018 it became clear from randomized, controlled trials that IL-23 inhibition was ineffective at improving key clinical outcomes, at least in patients with axial disease.

Although the overall results of a systematic review and meta-analysis that was presented at the meeting corroborated the negative results seen with IL-23–inhibiting agents in clinical trials, there were some data showing benefits of the IL-23 inhibitor risankizumab on secondary outcomes in one trial.

To look at the available evidence, Louise Vanhoutte, a 2nd-year internal medicine student at University Hospitals Leuven (Belgium) worked under the guidance of Rik Lories, MD, PhD, head of the division of rheumatology at University Hospitals Leuven. Together they searched known databases for randomized, controlled trials investigating the use of IL-23 and IL-17 inhibitors for the treatment of adults with axial SpA or psoriatic arthritis. Studies could be either phase 2 or phase 3, but had to have included a placebo and used the ASAS40 (40% Improvement in Assessment of SpondyloArthritis International Society Response criteria), ASAS20, Bath Ankylosing Spondylitis Disease Activity Index, or SPARCC (Spondyloarthritis Research Consortium of Canada) index score to assess outcomes.

The systematic review whittled the number of clinical trials in the meta-analysis to 12, which concerned the use of ustekinumab, an IL-12/23 inhibitor, and risankizumab, along with two IL-17 inhibitors, ixekizumab and secukinumab. Data for the IL-23 inhibitors guselkumab and tildrakizumab were not available.

“To no surprise, Forest plots showed that there was a lack of efficacy for IL-23 agents in the treatment of axial spondyloarthritis and a superior efficacy for IL-17 inhibitors in the treatment of axial spondyloarthritis,” Ms. Vanhoutte reported.

The respective odds ratios for IL-23 and IL-17 inhibitors in getting patients to meet ASAS40 response criteria in comparison to baseline were 1.51 (95% confidence interval, 0.98-2.31) and 2.54 (95% CI, 2.02-3.19).

“Does this mean it is a dead-end street for all IL-23 inhibition?” she asked. Not necessarily. In the meta-analysis, not only did risankizumab lower the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) by a mean difference (MD) of –0.30 (95% CI, –0.41 to –0.19) from baseline values, but it also led to statistically significant reductions in SPARCC index score for the spine (MD, –3.10; 95% CI, –4.50 to –1.70) and high-sensitivity CRP (MD, –2.10; 95% CI, –2.56 to –1.64). The risankizumab findings might suggest there are potential disease-modifying properties for specifically targeting IL-23p19. There could also be a window of opportunity to use IL-23 inhibitors earlier.

“These are only results from one randomized, controlled trial in a small sample size where outcomes were reported as medians and interquartile ranges, so they had to be converted to means and standard deviations to have an odds ratio in the end,” she explained.

“Also, these were results from a radiographic axial spondyloarthritis population and not a nonradiographic axial spondyloarthritis population,” she added.

While that might limit the interpretation of the findings, “what we see here is both reduction in inflammation and reduction in structural disease progression as [measured] by SPARCC,” Ms. Vanhoutte said.

“Since IL-23 is an upstream molecule from IL-17 it’s probable that IL-23 is present in the prephase of the disease, in a prephase inflammation state,” she hypothesized. “This is especially interesting because there are very few randomized, controlled trials that examine therapeutic agents in nonradiographic axial spondyloarthritis,” she observed. Looking at IL-23 in radiographic, or established, disease therefore may not be as useful.

“I’m thinking you’re making actually a very important point for us,” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center.

“We are discussing whether or not IL-23 is important in inhibiting the disease activity of patients with axial spondyloarthritis, and we are surprised that it is not shown in RCTs.

“Why is it completely ineffective in axial spondyloarthritis? You show us that that is probably not the case,” Dr. Landewé suggested.

“What you make very clear here is that indeed there is some efficacy, and from a pathophysiological way of thinking it might be slightly different as compared with what most clinicians nowadays think.”

The study had no specific funding, and no disclosures were reported.

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended marketing authorization this week for two new adalimumab biosimilars, Hukyndra and Libmyris.

The biosimilars, both developed by STADA Arzneimittel AG, will be available as a 40-mg solution for injection in a pre-filled syringe and pre-filled pen and 80-mg solution for injection in a pre-filled syringe. Both biosimilars will have 15 indications:

• rheumatoid arthritis
• polyarticular juvenile idiopathic arthritis
• enthesitis-related arthritis
• ankylosing spondylitis
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• psoriatic arthritis
• chronic plaque psoriasis (adults and children)
• hidradenitis suppurativa
• Crohn’s disease (adults and children)
• ulcerative colitis (adults and children)
• uveitis (adults and children)

Data show that both Hukyndra and Libmyris are highly similar to the reference product Humira (adalimumab), a monoclonal antibody to tumor necrosis factor alpha, and have comparable quality, safety, and efficacy.

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

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended marketing authorization this week for two new adalimumab biosimilars, Hukyndra and Libmyris.

The biosimilars, both developed by STADA Arzneimittel AG, will be available as a 40-mg solution for injection in a pre-filled syringe and pre-filled pen and 80-mg solution for injection in a pre-filled syringe. Both biosimilars will have 15 indications:

• rheumatoid arthritis
• polyarticular juvenile idiopathic arthritis
• enthesitis-related arthritis
• ankylosing spondylitis
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• psoriatic arthritis
• chronic plaque psoriasis (adults and children)
• hidradenitis suppurativa
• Crohn’s disease (adults and children)
• ulcerative colitis (adults and children)
• uveitis (adults and children)

Data show that both Hukyndra and Libmyris are highly similar to the reference product Humira (adalimumab), a monoclonal antibody to tumor necrosis factor alpha, and have comparable quality, safety, and efficacy.

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

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended marketing authorization this week for two new adalimumab biosimilars, Hukyndra and Libmyris.

The biosimilars, both developed by STADA Arzneimittel AG, will be available as a 40-mg solution for injection in a pre-filled syringe and pre-filled pen and 80-mg solution for injection in a pre-filled syringe. Both biosimilars will have 15 indications:

• rheumatoid arthritis
• polyarticular juvenile idiopathic arthritis
• enthesitis-related arthritis
• ankylosing spondylitis
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• psoriatic arthritis
• chronic plaque psoriasis (adults and children)
• hidradenitis suppurativa
• Crohn’s disease (adults and children)
• ulcerative colitis (adults and children)
• uveitis (adults and children)

Data show that both Hukyndra and Libmyris are highly similar to the reference product Humira (adalimumab), a monoclonal antibody to tumor necrosis factor alpha, and have comparable quality, safety, and efficacy.

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

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

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

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

Opioid-related drug overdose deaths in the United States exploded to an estimated record high of 69,031 people in 2020, topping the 49,860 deaths logged in 2019, according to a new report from the Centers for Disease Control and Prevention. Most of the deaths involved synthetic opioids such as fentanyl.

President Joe Biden has pledged more than $10 billion to expand access to prevention, treatment, and recovery services. The money is important as people receiving treatment for opioid use disorder have a high risk for relapse, and that means a high risk for opioid overdose.

Now, researchers are studying a possible bridge to successful recovery: A vaccine that could blunt the drugs’ ability to cause harm.

The first such vaccines are now entering clinical trials, raising hopes of adding another tool to the antiaddiction armamentarium. But even if the vaccines prove safe and effective, their success could generate some new problems to solve.

An advantage of vaccines is that their effects can last for several months, said trial investigator Sandra Comer, PhD, professor of neurobiology and psychiatry at Columbia University Irving Medical Center, New York. Dropout rates for existing medical therapies for opioid use disorder are as high as 50% at 6 months, and a vaccine could protect people from overdose and give them time to re-enter treatment.

“It serves as a bit of a safety net,” she said.

The first vaccine to enter a trial targets oxycodone. Volunteers are being recruited who have a diagnosis of opioid use disorder but are not being medically treated and are still using opioids. A third of them will receive a placebo vaccine, a third will receive a low-dose injection of vaccine, and the other third will receive a high-dose vaccine.
 

A shot against oxycodone

Researchers are primarily tracking the safety of the shot, but they’re also looking at whether vaccination prevents the euphoria that opioids usually produce. They expect to enroll 24 people initially but expand to 45 if results look promising.

In response to the shot, the body produces antibodies, proteins that tag oxycodone and keep it from reaching the brain. If the drug can’t reach brain cells, it can’t produce euphoria. And more important for lifesaving effects, it can’t block the brain’s signals to the body to breathe. The vaccine has already performed well in animal studies.

Previous trials of vaccines for cocaine and nicotine failed. Those vaccines made it to the last clinical trial stage, but didn’t prove effective overall. So this time, investigators plan to track antibody levels in participants, examining blood samples for signs of a good immune response to the vaccine.

But even though earlier cocaine and nicotine vaccines didn’t work for everybody, there were some people they seemed to help. This is why investigators involved in opioid vaccine trials want to track immune responses, said Marco Pravetoni, PhD, associate professor of pharmacology and medicine at the University of Minnesota, Minneapolis, whose team will be assessing the blood samples. Ultimately, a doctor might even be able to use this information to tailor vaccine selection to a specific person.

Dr. Pravetoni also said that oxycodone is one of three vaccine targets – the other two are heroin and fentanyl – that researchers hope to combine into a single shot. Recipients might need to have one shot a month for the first 3 to 4 months and then receive annual boosters.
 

Stopping the pain

The vaccines also raise some issues that need attention, said Cody Wenthur, PharmD, PhD, assistant professor of pharmacy at the University of Wisconsin–Madison, who is not involved in the vaccine trials.

“If you’re vaccinated against oxycodone, you might not have access to adequate pain control if you get into a car accident, for example,” he said.

Clinicians could use other opioids for pain management, but limiting the opioids that the vaccine targets is a “double-edged sword,” said Dr. Wenthur, because vaccinated people could just switch their opioid of choice to one that a vaccine does not inhibit.

Although these issues need to be addressed, vaccines, if successful, will have an important role. Dr. Wenthur noted a survey of pharmacists and pharmacy students that he and his group conducted showing that respondents “overwhelmingly” viewed a potential vaccine as helpful.

If the vaccines do become available, their application could extend beyond people who have opioid use disorder, said Dr. Pravetoni. He mentioned the 2002 incident when terrorists took over a theater in Moscow and Russian special forces are thought to have used an aerosolized form of fentanyl to incapacitate everyone in the room. More than 100 of the hostages died, and the episode raised the specter of opioids being used in chemical attacks.

Dr. Pravetoni said vaccination could offer protection for first responders, law enforcement or other people whose professions place them at risk for inhalation, either accidentally or through such attacks.

These or other real-world applications for people at risk for exposure are several years away. Dr. Pravetoni said it took 10 years to get to this phase and estimates that, in about 5 years, a vaccine that targets multiple opioid drugs might enter the first clinical trial.

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

Opioid-related drug overdose deaths in the United States exploded to an estimated record high of 69,031 people in 2020, topping the 49,860 deaths logged in 2019, according to a new report from the Centers for Disease Control and Prevention. Most of the deaths involved synthetic opioids such as fentanyl.

President Joe Biden has pledged more than $10 billion to expand access to prevention, treatment, and recovery services. The money is important as people receiving treatment for opioid use disorder have a high risk for relapse, and that means a high risk for opioid overdose.

Now, researchers are studying a possible bridge to successful recovery: A vaccine that could blunt the drugs’ ability to cause harm.

The first such vaccines are now entering clinical trials, raising hopes of adding another tool to the antiaddiction armamentarium. But even if the vaccines prove safe and effective, their success could generate some new problems to solve.

An advantage of vaccines is that their effects can last for several months, said trial investigator Sandra Comer, PhD, professor of neurobiology and psychiatry at Columbia University Irving Medical Center, New York. Dropout rates for existing medical therapies for opioid use disorder are as high as 50% at 6 months, and a vaccine could protect people from overdose and give them time to re-enter treatment.

“It serves as a bit of a safety net,” she said.

The first vaccine to enter a trial targets oxycodone. Volunteers are being recruited who have a diagnosis of opioid use disorder but are not being medically treated and are still using opioids. A third of them will receive a placebo vaccine, a third will receive a low-dose injection of vaccine, and the other third will receive a high-dose vaccine.
 

A shot against oxycodone

Researchers are primarily tracking the safety of the shot, but they’re also looking at whether vaccination prevents the euphoria that opioids usually produce. They expect to enroll 24 people initially but expand to 45 if results look promising.

In response to the shot, the body produces antibodies, proteins that tag oxycodone and keep it from reaching the brain. If the drug can’t reach brain cells, it can’t produce euphoria. And more important for lifesaving effects, it can’t block the brain’s signals to the body to breathe. The vaccine has already performed well in animal studies.

Previous trials of vaccines for cocaine and nicotine failed. Those vaccines made it to the last clinical trial stage, but didn’t prove effective overall. So this time, investigators plan to track antibody levels in participants, examining blood samples for signs of a good immune response to the vaccine.

But even though earlier cocaine and nicotine vaccines didn’t work for everybody, there were some people they seemed to help. This is why investigators involved in opioid vaccine trials want to track immune responses, said Marco Pravetoni, PhD, associate professor of pharmacology and medicine at the University of Minnesota, Minneapolis, whose team will be assessing the blood samples. Ultimately, a doctor might even be able to use this information to tailor vaccine selection to a specific person.

Dr. Pravetoni also said that oxycodone is one of three vaccine targets – the other two are heroin and fentanyl – that researchers hope to combine into a single shot. Recipients might need to have one shot a month for the first 3 to 4 months and then receive annual boosters.
 

Stopping the pain

The vaccines also raise some issues that need attention, said Cody Wenthur, PharmD, PhD, assistant professor of pharmacy at the University of Wisconsin–Madison, who is not involved in the vaccine trials.

“If you’re vaccinated against oxycodone, you might not have access to adequate pain control if you get into a car accident, for example,” he said.

Clinicians could use other opioids for pain management, but limiting the opioids that the vaccine targets is a “double-edged sword,” said Dr. Wenthur, because vaccinated people could just switch their opioid of choice to one that a vaccine does not inhibit.

Although these issues need to be addressed, vaccines, if successful, will have an important role. Dr. Wenthur noted a survey of pharmacists and pharmacy students that he and his group conducted showing that respondents “overwhelmingly” viewed a potential vaccine as helpful.

If the vaccines do become available, their application could extend beyond people who have opioid use disorder, said Dr. Pravetoni. He mentioned the 2002 incident when terrorists took over a theater in Moscow and Russian special forces are thought to have used an aerosolized form of fentanyl to incapacitate everyone in the room. More than 100 of the hostages died, and the episode raised the specter of opioids being used in chemical attacks.

Dr. Pravetoni said vaccination could offer protection for first responders, law enforcement or other people whose professions place them at risk for inhalation, either accidentally or through such attacks.

These or other real-world applications for people at risk for exposure are several years away. Dr. Pravetoni said it took 10 years to get to this phase and estimates that, in about 5 years, a vaccine that targets multiple opioid drugs might enter the first clinical trial.

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

Opioid-related drug overdose deaths in the United States exploded to an estimated record high of 69,031 people in 2020, topping the 49,860 deaths logged in 2019, according to a new report from the Centers for Disease Control and Prevention. Most of the deaths involved synthetic opioids such as fentanyl.

President Joe Biden has pledged more than $10 billion to expand access to prevention, treatment, and recovery services. The money is important as people receiving treatment for opioid use disorder have a high risk for relapse, and that means a high risk for opioid overdose.

Now, researchers are studying a possible bridge to successful recovery: A vaccine that could blunt the drugs’ ability to cause harm.

The first such vaccines are now entering clinical trials, raising hopes of adding another tool to the antiaddiction armamentarium. But even if the vaccines prove safe and effective, their success could generate some new problems to solve.

An advantage of vaccines is that their effects can last for several months, said trial investigator Sandra Comer, PhD, professor of neurobiology and psychiatry at Columbia University Irving Medical Center, New York. Dropout rates for existing medical therapies for opioid use disorder are as high as 50% at 6 months, and a vaccine could protect people from overdose and give them time to re-enter treatment.

“It serves as a bit of a safety net,” she said.

The first vaccine to enter a trial targets oxycodone. Volunteers are being recruited who have a diagnosis of opioid use disorder but are not being medically treated and are still using opioids. A third of them will receive a placebo vaccine, a third will receive a low-dose injection of vaccine, and the other third will receive a high-dose vaccine.
 

A shot against oxycodone

Researchers are primarily tracking the safety of the shot, but they’re also looking at whether vaccination prevents the euphoria that opioids usually produce. They expect to enroll 24 people initially but expand to 45 if results look promising.

In response to the shot, the body produces antibodies, proteins that tag oxycodone and keep it from reaching the brain. If the drug can’t reach brain cells, it can’t produce euphoria. And more important for lifesaving effects, it can’t block the brain’s signals to the body to breathe. The vaccine has already performed well in animal studies.

Previous trials of vaccines for cocaine and nicotine failed. Those vaccines made it to the last clinical trial stage, but didn’t prove effective overall. So this time, investigators plan to track antibody levels in participants, examining blood samples for signs of a good immune response to the vaccine.

But even though earlier cocaine and nicotine vaccines didn’t work for everybody, there were some people they seemed to help. This is why investigators involved in opioid vaccine trials want to track immune responses, said Marco Pravetoni, PhD, associate professor of pharmacology and medicine at the University of Minnesota, Minneapolis, whose team will be assessing the blood samples. Ultimately, a doctor might even be able to use this information to tailor vaccine selection to a specific person.

Dr. Pravetoni also said that oxycodone is one of three vaccine targets – the other two are heroin and fentanyl – that researchers hope to combine into a single shot. Recipients might need to have one shot a month for the first 3 to 4 months and then receive annual boosters.
 

Stopping the pain

The vaccines also raise some issues that need attention, said Cody Wenthur, PharmD, PhD, assistant professor of pharmacy at the University of Wisconsin–Madison, who is not involved in the vaccine trials.

“If you’re vaccinated against oxycodone, you might not have access to adequate pain control if you get into a car accident, for example,” he said.

Clinicians could use other opioids for pain management, but limiting the opioids that the vaccine targets is a “double-edged sword,” said Dr. Wenthur, because vaccinated people could just switch their opioid of choice to one that a vaccine does not inhibit.

Although these issues need to be addressed, vaccines, if successful, will have an important role. Dr. Wenthur noted a survey of pharmacists and pharmacy students that he and his group conducted showing that respondents “overwhelmingly” viewed a potential vaccine as helpful.

If the vaccines do become available, their application could extend beyond people who have opioid use disorder, said Dr. Pravetoni. He mentioned the 2002 incident when terrorists took over a theater in Moscow and Russian special forces are thought to have used an aerosolized form of fentanyl to incapacitate everyone in the room. More than 100 of the hostages died, and the episode raised the specter of opioids being used in chemical attacks.

Dr. Pravetoni said vaccination could offer protection for first responders, law enforcement or other people whose professions place them at risk for inhalation, either accidentally or through such attacks.

These or other real-world applications for people at risk for exposure are several years away. Dr. Pravetoni said it took 10 years to get to this phase and estimates that, in about 5 years, a vaccine that targets multiple opioid drugs might enter the first clinical trial.

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

Heidi Erickson, MD, is tired. As a pulmonary and critical care physician at Hennepin Healthcare in Minneapolis, she has been providing care for patients with COVID-19 since the start of the pandemic.

rclassenlayouts/Getty Images

It was exhausting from the beginning, as she and her colleagues scrambled to understand how to deal with this new disease. But lately, she has noticed a different kind of exhaustion arising from the knowledge that with vaccines widely available, the latest surge was preventable.

Her intensive care unit is currently as full as it has ever been with COVID-19 patients, many of them young adults and most of them unvaccinated. After the recent death of one patient, an unvaccinated man with teenage children, she had to face his family’s questions about why ivermectin, an antiparasitic medication that was falsely promoted as a COVID-19 treatment, was not administered.

“I’m fatigued because I’m working more than ever, but more people don’t have to die,” Dr. Erickson said in an interview . “It’s been very hard physically, mentally, emotionally.”

Amid yet another surge in COVID-19 cases around the United States, clinicians are speaking out about their growing frustration with this preventable crisis.

Some are using the terms “empathy fatigue” and “compassion fatigue” – a sense that they are losing empathy for unvaccinated individuals who are fueling the pandemic.

Dr. Erickson says she is frustrated not by individual patients but by a system that has allowed disinformation to proliferate. Experts say these types of feelings fit into a widespread pattern of physician burnout that has taken a new turn at this stage of the pandemic.

Paradoxical choices

Empathy is a cornerstone of what clinicians do, and the ability to understand and share a patient’s feelings is an essential skill for providing effective care, says Kaz Nelson, MD, a psychiatrist at the University of Minnesota, Minneapolis.

Practitioners face paradoxical situations all the time, she notes. These include individuals who break bones and go skydiving again, people who have high cholesterol but continue to eat fried foods, and those with advanced lung cancer who continue to smoke.

To treat patients with compassion, practitioners learn to set aside judgment by acknowledging the complexity of human behavior. They may lament the addictive nature of nicotine and advertising that targets children, for example, while still listening and caring.

Empathy requires high-level brain function, but as stress levels rise, brain function that drives empathy tends to shut down. It’s a survival mechanism, Dr. Nelson says.

When health care workers feel overwhelmed, trapped, or threatened by patients demanding unproven treatments or by ICUs with more patients than ventilators, they may experience a fight-or-flight response that makes them defensive, frustrated, angry, or uncaring, notes Mona Masood, DO, a Philadelphia-area psychiatrist and founder of Physician Support Line, a free mental health hotline for doctors.

Some clinicians have taken to Twitter and other social media platforms to post about these types of experiences.

These feelings, which have been brewing for months, have been exacerbated by the complexity of the current situation. Clinicians see a disconnect between what is and what could be, Dr. Nelson notes.

“Prior to vaccines, there weren’t other options, and so we had toxic stress and we had fatigue, but we could still maintain little bits of empathy by saying, ‘You know, people didn’t choose to get infected, and we are in a pandemic.’ We could kind of hate the virus. Now with access to vaccines, that last connection to empathy is removed for many people,” she says.

Self-preservation vs. empathy

Compassion fatigue or empathy fatigue is just one reaction to feeling completely maxed out and overstressed, Dr. Nelson says. Anger at society, such as what Dr. Erickson experienced, is another response.

Practitioners may also feel as if they are just going through the motions of their job, or they might disassociate, ceasing to feel that their patients are human. Plenty of doctors and nurses have cried in their cars after shifts and have posted tearful videos on social media.

Early in the pandemic, Dr. Masood says, physicians who called the support hotline expressed sadness and grief. Now, she had her colleagues hear frustration and anger, along with guilt and shame for having feelings they believe they shouldn’t be having, especially toward patients. They may feel unprofessional or worse – unworthy of being physicians, she says.

One recent caller to the hotline was a long-time ICU physician who had been told so many times by patients that ivermectin was the only medicine that would cure them that he began to doubt himself, says Dr. Masood. This caller needed to be reassured by another physician that he was doing the right thing.

Another emergency department physician told Dr. Masood about a young child who had arrived at the hospital with COVID-19 symptoms. When asked whether the family had been exposed to anyone with COVID-19, the child’s parent lied so that they could be triaged faster.

The physician, who needed to step away from the situation, reached out to Dr. Masood to express her frustration so that she wouldn’t “let it out” on the patient.

“It’s hard to have empathy for people who, for all intents and purposes, are very self-centered,” Dr. Masood says. “We’re at a place where we’re having to choose between self-preservation and empathy.”
 

How to cope

To help practitioners cope, Dr. Masood offers words that describe what they’re experiencing. She often hears clinicians say things such as, “This is a type of burnout that I feel to my bones,” or “This makes me want to quit,” or “I feel like I’m at the end of my rope.”

She encourages them to consider the terms “empathy fatigue,” and “moral injury” in order to reconcile how their sense of responsibility to take care of people is compromised by factors outside of their control.

It is not shameful to acknowledge that they experience emotions, including difficult ones such as frustration, anger, sadness, and anxiety, Dr. Masood adds.

Being frustrated with a patient doesn’t make someone a bad doctor, and admitting those emotions is the first step toward dealing with them, she says.

Dr. Nelson adds that taking breaks from work can help. She also recommends setting boundaries, seeking therapy, and acknowledging feelings early before they cause a sense of callousness or other consequences that become harder to heal from as time goes on.

“We’re trained to just go, go, go and sometimes not pause and check in,” she says. Clinicians who open up are likely to find they are not the only ones feeling tired or frustrated right now, she adds.

“Connect with peers and colleagues, because chances are, they can relate,” Dr. Nelson says.

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

Heidi Erickson, MD, is tired. As a pulmonary and critical care physician at Hennepin Healthcare in Minneapolis, she has been providing care for patients with COVID-19 since the start of the pandemic.

rclassenlayouts/Getty Images

It was exhausting from the beginning, as she and her colleagues scrambled to understand how to deal with this new disease. But lately, she has noticed a different kind of exhaustion arising from the knowledge that with vaccines widely available, the latest surge was preventable.

Her intensive care unit is currently as full as it has ever been with COVID-19 patients, many of them young adults and most of them unvaccinated. After the recent death of one patient, an unvaccinated man with teenage children, she had to face his family’s questions about why ivermectin, an antiparasitic medication that was falsely promoted as a COVID-19 treatment, was not administered.

“I’m fatigued because I’m working more than ever, but more people don’t have to die,” Dr. Erickson said in an interview . “It’s been very hard physically, mentally, emotionally.”

Amid yet another surge in COVID-19 cases around the United States, clinicians are speaking out about their growing frustration with this preventable crisis.

Some are using the terms “empathy fatigue” and “compassion fatigue” – a sense that they are losing empathy for unvaccinated individuals who are fueling the pandemic.

Dr. Erickson says she is frustrated not by individual patients but by a system that has allowed disinformation to proliferate. Experts say these types of feelings fit into a widespread pattern of physician burnout that has taken a new turn at this stage of the pandemic.

Paradoxical choices

Empathy is a cornerstone of what clinicians do, and the ability to understand and share a patient’s feelings is an essential skill for providing effective care, says Kaz Nelson, MD, a psychiatrist at the University of Minnesota, Minneapolis.

Practitioners face paradoxical situations all the time, she notes. These include individuals who break bones and go skydiving again, people who have high cholesterol but continue to eat fried foods, and those with advanced lung cancer who continue to smoke.

To treat patients with compassion, practitioners learn to set aside judgment by acknowledging the complexity of human behavior. They may lament the addictive nature of nicotine and advertising that targets children, for example, while still listening and caring.

Empathy requires high-level brain function, but as stress levels rise, brain function that drives empathy tends to shut down. It’s a survival mechanism, Dr. Nelson says.

When health care workers feel overwhelmed, trapped, or threatened by patients demanding unproven treatments or by ICUs with more patients than ventilators, they may experience a fight-or-flight response that makes them defensive, frustrated, angry, or uncaring, notes Mona Masood, DO, a Philadelphia-area psychiatrist and founder of Physician Support Line, a free mental health hotline for doctors.

Some clinicians have taken to Twitter and other social media platforms to post about these types of experiences.

These feelings, which have been brewing for months, have been exacerbated by the complexity of the current situation. Clinicians see a disconnect between what is and what could be, Dr. Nelson notes.

“Prior to vaccines, there weren’t other options, and so we had toxic stress and we had fatigue, but we could still maintain little bits of empathy by saying, ‘You know, people didn’t choose to get infected, and we are in a pandemic.’ We could kind of hate the virus. Now with access to vaccines, that last connection to empathy is removed for many people,” she says.

Self-preservation vs. empathy

Compassion fatigue or empathy fatigue is just one reaction to feeling completely maxed out and overstressed, Dr. Nelson says. Anger at society, such as what Dr. Erickson experienced, is another response.

Practitioners may also feel as if they are just going through the motions of their job, or they might disassociate, ceasing to feel that their patients are human. Plenty of doctors and nurses have cried in their cars after shifts and have posted tearful videos on social media.

Early in the pandemic, Dr. Masood says, physicians who called the support hotline expressed sadness and grief. Now, she had her colleagues hear frustration and anger, along with guilt and shame for having feelings they believe they shouldn’t be having, especially toward patients. They may feel unprofessional or worse – unworthy of being physicians, she says.

One recent caller to the hotline was a long-time ICU physician who had been told so many times by patients that ivermectin was the only medicine that would cure them that he began to doubt himself, says Dr. Masood. This caller needed to be reassured by another physician that he was doing the right thing.

Another emergency department physician told Dr. Masood about a young child who had arrived at the hospital with COVID-19 symptoms. When asked whether the family had been exposed to anyone with COVID-19, the child’s parent lied so that they could be triaged faster.

The physician, who needed to step away from the situation, reached out to Dr. Masood to express her frustration so that she wouldn’t “let it out” on the patient.

“It’s hard to have empathy for people who, for all intents and purposes, are very self-centered,” Dr. Masood says. “We’re at a place where we’re having to choose between self-preservation and empathy.”
 

How to cope

To help practitioners cope, Dr. Masood offers words that describe what they’re experiencing. She often hears clinicians say things such as, “This is a type of burnout that I feel to my bones,” or “This makes me want to quit,” or “I feel like I’m at the end of my rope.”

She encourages them to consider the terms “empathy fatigue,” and “moral injury” in order to reconcile how their sense of responsibility to take care of people is compromised by factors outside of their control.

It is not shameful to acknowledge that they experience emotions, including difficult ones such as frustration, anger, sadness, and anxiety, Dr. Masood adds.

Being frustrated with a patient doesn’t make someone a bad doctor, and admitting those emotions is the first step toward dealing with them, she says.

Dr. Nelson adds that taking breaks from work can help. She also recommends setting boundaries, seeking therapy, and acknowledging feelings early before they cause a sense of callousness or other consequences that become harder to heal from as time goes on.

“We’re trained to just go, go, go and sometimes not pause and check in,” she says. Clinicians who open up are likely to find they are not the only ones feeling tired or frustrated right now, she adds.

“Connect with peers and colleagues, because chances are, they can relate,” Dr. Nelson says.

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

Heidi Erickson, MD, is tired. As a pulmonary and critical care physician at Hennepin Healthcare in Minneapolis, she has been providing care for patients with COVID-19 since the start of the pandemic.

rclassenlayouts/Getty Images

It was exhausting from the beginning, as she and her colleagues scrambled to understand how to deal with this new disease. But lately, she has noticed a different kind of exhaustion arising from the knowledge that with vaccines widely available, the latest surge was preventable.

Her intensive care unit is currently as full as it has ever been with COVID-19 patients, many of them young adults and most of them unvaccinated. After the recent death of one patient, an unvaccinated man with teenage children, she had to face his family’s questions about why ivermectin, an antiparasitic medication that was falsely promoted as a COVID-19 treatment, was not administered.

“I’m fatigued because I’m working more than ever, but more people don’t have to die,” Dr. Erickson said in an interview . “It’s been very hard physically, mentally, emotionally.”

Amid yet another surge in COVID-19 cases around the United States, clinicians are speaking out about their growing frustration with this preventable crisis.

Some are using the terms “empathy fatigue” and “compassion fatigue” – a sense that they are losing empathy for unvaccinated individuals who are fueling the pandemic.

Dr. Erickson says she is frustrated not by individual patients but by a system that has allowed disinformation to proliferate. Experts say these types of feelings fit into a widespread pattern of physician burnout that has taken a new turn at this stage of the pandemic.

Paradoxical choices

Empathy is a cornerstone of what clinicians do, and the ability to understand and share a patient’s feelings is an essential skill for providing effective care, says Kaz Nelson, MD, a psychiatrist at the University of Minnesota, Minneapolis.

Practitioners face paradoxical situations all the time, she notes. These include individuals who break bones and go skydiving again, people who have high cholesterol but continue to eat fried foods, and those with advanced lung cancer who continue to smoke.

To treat patients with compassion, practitioners learn to set aside judgment by acknowledging the complexity of human behavior. They may lament the addictive nature of nicotine and advertising that targets children, for example, while still listening and caring.

Empathy requires high-level brain function, but as stress levels rise, brain function that drives empathy tends to shut down. It’s a survival mechanism, Dr. Nelson says.

When health care workers feel overwhelmed, trapped, or threatened by patients demanding unproven treatments or by ICUs with more patients than ventilators, they may experience a fight-or-flight response that makes them defensive, frustrated, angry, or uncaring, notes Mona Masood, DO, a Philadelphia-area psychiatrist and founder of Physician Support Line, a free mental health hotline for doctors.

Some clinicians have taken to Twitter and other social media platforms to post about these types of experiences.

These feelings, which have been brewing for months, have been exacerbated by the complexity of the current situation. Clinicians see a disconnect between what is and what could be, Dr. Nelson notes.

“Prior to vaccines, there weren’t other options, and so we had toxic stress and we had fatigue, but we could still maintain little bits of empathy by saying, ‘You know, people didn’t choose to get infected, and we are in a pandemic.’ We could kind of hate the virus. Now with access to vaccines, that last connection to empathy is removed for many people,” she says.

Self-preservation vs. empathy

Compassion fatigue or empathy fatigue is just one reaction to feeling completely maxed out and overstressed, Dr. Nelson says. Anger at society, such as what Dr. Erickson experienced, is another response.

Practitioners may also feel as if they are just going through the motions of their job, or they might disassociate, ceasing to feel that their patients are human. Plenty of doctors and nurses have cried in their cars after shifts and have posted tearful videos on social media.

Early in the pandemic, Dr. Masood says, physicians who called the support hotline expressed sadness and grief. Now, she had her colleagues hear frustration and anger, along with guilt and shame for having feelings they believe they shouldn’t be having, especially toward patients. They may feel unprofessional or worse – unworthy of being physicians, she says.

One recent caller to the hotline was a long-time ICU physician who had been told so many times by patients that ivermectin was the only medicine that would cure them that he began to doubt himself, says Dr. Masood. This caller needed to be reassured by another physician that he was doing the right thing.

Another emergency department physician told Dr. Masood about a young child who had arrived at the hospital with COVID-19 symptoms. When asked whether the family had been exposed to anyone with COVID-19, the child’s parent lied so that they could be triaged faster.

The physician, who needed to step away from the situation, reached out to Dr. Masood to express her frustration so that she wouldn’t “let it out” on the patient.

“It’s hard to have empathy for people who, for all intents and purposes, are very self-centered,” Dr. Masood says. “We’re at a place where we’re having to choose between self-preservation and empathy.”
 

How to cope

To help practitioners cope, Dr. Masood offers words that describe what they’re experiencing. She often hears clinicians say things such as, “This is a type of burnout that I feel to my bones,” or “This makes me want to quit,” or “I feel like I’m at the end of my rope.”

She encourages them to consider the terms “empathy fatigue,” and “moral injury” in order to reconcile how their sense of responsibility to take care of people is compromised by factors outside of their control.

It is not shameful to acknowledge that they experience emotions, including difficult ones such as frustration, anger, sadness, and anxiety, Dr. Masood adds.

Being frustrated with a patient doesn’t make someone a bad doctor, and admitting those emotions is the first step toward dealing with them, she says.

Dr. Nelson adds that taking breaks from work can help. She also recommends setting boundaries, seeking therapy, and acknowledging feelings early before they cause a sense of callousness or other consequences that become harder to heal from as time goes on.

“We’re trained to just go, go, go and sometimes not pause and check in,” she says. Clinicians who open up are likely to find they are not the only ones feeling tired or frustrated right now, she adds.

“Connect with peers and colleagues, because chances are, they can relate,” Dr. Nelson says.

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

As private practices try to recover and rebuild in the wake of the COVID-19 pandemic, many have faced an unexpected challenge: a paucity of employees.

My own office is prime example: I have had job listings for both front- and back-office positions posted on all the major job boards and other employment portals for months, with a disappointing response. Of the few who do respond, many, incredibly, do not show up for their interviews!

It turns out that this is a widespread problem, and not just in medicine. A recent survey by the National Federation of Independent Business found that 42% of business owners, in all walks of life, had job openings that could not be filled, a record high. Over 90% of those hiring reported few or no qualified applicants and an increase in interview no-shows.

Clearly, this is a huge obstacle to growth – and even to conducting normal operations – for my practice and many others.

Reasons for the situation vary, but a big one has been the unfortunate fact that many open job positions actually pay less than the expanded unemployment benefits that many people have received under the March 2020 CARES Act. By one estimate, almost 70% of unemployed workers have been collecting more on unemployment than they earned while working. The CARES benefits expired in early September, but many potential workers continue to receive payments through a newer FEMA program, and some states have their own ongoing benefit programs.

Other reasons have been offered: Some candidates are unvaccinated (an immediate deal-breaker in my office), and some working parents continue to face a lack of childcare or in-person schooling for their children. Some applicants – regardless of vaccination status – have said they are hesitant to work in a medical office setting and risk getting COVID-19, despite all the precautions we have in place. Others have said they are waiting until the job market improves.

There are no easy solutions to this complicated problem, but here are a few suggestions culled from my research and conversations with HR professionals and others.

One obvious option is to offer higher wages, and perhaps even signing bonuses. “Whenever anyone says they can’t find the workers they need,” a consultant told me, “they are really saying they can’t find them at the wages they want to pay.” There are limits to the wages and benefits a private office with a very finite salary budget can offer, of course – but a few higher-paid employees may be preferable to no new workers at all.

For job candidates who fear COVID-19 exposure, assure them that their health and safety is a priority by spelling out the procedures your office is following (social distancing, reduced patient capacity, interaction barriers, face masks, avoidance of handshakes, enhanced cleaning procedures, symptom questionnaires, temperature checks, etc.) to minimize the risk of exposure.

You also may need to rework your interview process. In the Zoom era, most preliminary interviews can be conducted remotely. For on-site interviews, explain how you’re maintaining a safe interview environment by applying the same office safety policies to interactions with interviewees.

If a promising candidate doesn’t show up for an interview, the applicant could be making a token effort to obtain a job in order to perpetuate unemployment payments, but don’t jump to that conclusion. There may be extenuating circumstances, such as an emergency, illness, or traffic issues. Also, consider the possibility that it was your fault. If you waited too long to schedule the interview, another office could have lured them away. Or you may not have adequately explained your COVID-19 exposure safeguards. At the very least, a drawn-out process or a lack of transparency can make applicants apprehensive about accepting a job with you, particularly if other employers are pursuing them.

To counter the shortsighted appeal of collecting unemployment benefits, it may help to highlight the long-term growth opportunities available at your office. Consider outlining typical career tracks, or providing specific examples of how people have advanced their careers at your facility. I frequently cite the example of my current office manager, who began as an assistant receptionist almost 30 years ago.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

As private practices try to recover and rebuild in the wake of the COVID-19 pandemic, many have faced an unexpected challenge: a paucity of employees.

My own office is prime example: I have had job listings for both front- and back-office positions posted on all the major job boards and other employment portals for months, with a disappointing response. Of the few who do respond, many, incredibly, do not show up for their interviews!

It turns out that this is a widespread problem, and not just in medicine. A recent survey by the National Federation of Independent Business found that 42% of business owners, in all walks of life, had job openings that could not be filled, a record high. Over 90% of those hiring reported few or no qualified applicants and an increase in interview no-shows.

Clearly, this is a huge obstacle to growth – and even to conducting normal operations – for my practice and many others.

Reasons for the situation vary, but a big one has been the unfortunate fact that many open job positions actually pay less than the expanded unemployment benefits that many people have received under the March 2020 CARES Act. By one estimate, almost 70% of unemployed workers have been collecting more on unemployment than they earned while working. The CARES benefits expired in early September, but many potential workers continue to receive payments through a newer FEMA program, and some states have their own ongoing benefit programs.

Other reasons have been offered: Some candidates are unvaccinated (an immediate deal-breaker in my office), and some working parents continue to face a lack of childcare or in-person schooling for their children. Some applicants – regardless of vaccination status – have said they are hesitant to work in a medical office setting and risk getting COVID-19, despite all the precautions we have in place. Others have said they are waiting until the job market improves.

There are no easy solutions to this complicated problem, but here are a few suggestions culled from my research and conversations with HR professionals and others.

One obvious option is to offer higher wages, and perhaps even signing bonuses. “Whenever anyone says they can’t find the workers they need,” a consultant told me, “they are really saying they can’t find them at the wages they want to pay.” There are limits to the wages and benefits a private office with a very finite salary budget can offer, of course – but a few higher-paid employees may be preferable to no new workers at all.

For job candidates who fear COVID-19 exposure, assure them that their health and safety is a priority by spelling out the procedures your office is following (social distancing, reduced patient capacity, interaction barriers, face masks, avoidance of handshakes, enhanced cleaning procedures, symptom questionnaires, temperature checks, etc.) to minimize the risk of exposure.

You also may need to rework your interview process. In the Zoom era, most preliminary interviews can be conducted remotely. For on-site interviews, explain how you’re maintaining a safe interview environment by applying the same office safety policies to interactions with interviewees.

If a promising candidate doesn’t show up for an interview, the applicant could be making a token effort to obtain a job in order to perpetuate unemployment payments, but don’t jump to that conclusion. There may be extenuating circumstances, such as an emergency, illness, or traffic issues. Also, consider the possibility that it was your fault. If you waited too long to schedule the interview, another office could have lured them away. Or you may not have adequately explained your COVID-19 exposure safeguards. At the very least, a drawn-out process or a lack of transparency can make applicants apprehensive about accepting a job with you, particularly if other employers are pursuing them.

To counter the shortsighted appeal of collecting unemployment benefits, it may help to highlight the long-term growth opportunities available at your office. Consider outlining typical career tracks, or providing specific examples of how people have advanced their careers at your facility. I frequently cite the example of my current office manager, who began as an assistant receptionist almost 30 years ago.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

As private practices try to recover and rebuild in the wake of the COVID-19 pandemic, many have faced an unexpected challenge: a paucity of employees.

My own office is prime example: I have had job listings for both front- and back-office positions posted on all the major job boards and other employment portals for months, with a disappointing response. Of the few who do respond, many, incredibly, do not show up for their interviews!

It turns out that this is a widespread problem, and not just in medicine. A recent survey by the National Federation of Independent Business found that 42% of business owners, in all walks of life, had job openings that could not be filled, a record high. Over 90% of those hiring reported few or no qualified applicants and an increase in interview no-shows.

Clearly, this is a huge obstacle to growth – and even to conducting normal operations – for my practice and many others.

Reasons for the situation vary, but a big one has been the unfortunate fact that many open job positions actually pay less than the expanded unemployment benefits that many people have received under the March 2020 CARES Act. By one estimate, almost 70% of unemployed workers have been collecting more on unemployment than they earned while working. The CARES benefits expired in early September, but many potential workers continue to receive payments through a newer FEMA program, and some states have their own ongoing benefit programs.

Other reasons have been offered: Some candidates are unvaccinated (an immediate deal-breaker in my office), and some working parents continue to face a lack of childcare or in-person schooling for their children. Some applicants – regardless of vaccination status – have said they are hesitant to work in a medical office setting and risk getting COVID-19, despite all the precautions we have in place. Others have said they are waiting until the job market improves.

There are no easy solutions to this complicated problem, but here are a few suggestions culled from my research and conversations with HR professionals and others.

One obvious option is to offer higher wages, and perhaps even signing bonuses. “Whenever anyone says they can’t find the workers they need,” a consultant told me, “they are really saying they can’t find them at the wages they want to pay.” There are limits to the wages and benefits a private office with a very finite salary budget can offer, of course – but a few higher-paid employees may be preferable to no new workers at all.

For job candidates who fear COVID-19 exposure, assure them that their health and safety is a priority by spelling out the procedures your office is following (social distancing, reduced patient capacity, interaction barriers, face masks, avoidance of handshakes, enhanced cleaning procedures, symptom questionnaires, temperature checks, etc.) to minimize the risk of exposure.

You also may need to rework your interview process. In the Zoom era, most preliminary interviews can be conducted remotely. For on-site interviews, explain how you’re maintaining a safe interview environment by applying the same office safety policies to interactions with interviewees.

If a promising candidate doesn’t show up for an interview, the applicant could be making a token effort to obtain a job in order to perpetuate unemployment payments, but don’t jump to that conclusion. There may be extenuating circumstances, such as an emergency, illness, or traffic issues. Also, consider the possibility that it was your fault. If you waited too long to schedule the interview, another office could have lured them away. Or you may not have adequately explained your COVID-19 exposure safeguards. At the very least, a drawn-out process or a lack of transparency can make applicants apprehensive about accepting a job with you, particularly if other employers are pursuing them.

To counter the shortsighted appeal of collecting unemployment benefits, it may help to highlight the long-term growth opportunities available at your office. Consider outlining typical career tracks, or providing specific examples of how people have advanced their careers at your facility. I frequently cite the example of my current office manager, who began as an assistant receptionist almost 30 years ago.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

Opioid overdoses usually aren’t fatal, but a new review of numerous studies, mostly case reports and case series, suggests that they can have long-lasting effects on cognition, possibly because of hypoxia resulting from respiratory depression.

Erin L. Winstanley, PhD, MA, and associates noted in the review that opioids cause about 80% of worldwide deaths from illicit drug use, and the Centers for Disease Control and Prevention’s provisional August 2021 number of more than 88,000 opioid-caused deaths in the United States is the highest ever recorded – a 27% increase over what was reported last December. That number suggests that the opioid epidemic continues to rage, but the study results also show that the neurological consequences of nonfatal overdoses are an important public health problem.

And that’s something that may be overlooked, according to Mark S. Gold, MD, who was not involved with the study and was asked to comment on the review, which was published in the Journal of Addiction Science.

“Assuming that an overdose has no effect on the brain, mood, and behavior is not supported by experience or the literature. While reversing overdoses is life-saving, preventing overdose may be brain saving,” said Dr. Gold. He is a University of Florida, Gainesville, Emeritus Eminent Scholar, adjunct professor of psychiatry at Washington University in St. Louis, and a member of the clinical council of Washington University’s Public Health Institute.

A common pattern among patients with opioid use disorder (OUD) is that they undergo treatment with medication-assisted therapy (MAT), only to drop out of treatment and then repeat the treatment at a later date. That suggests that physicians should take a harder look at the limitations of MAT and other treatments, Dr. Gold said.

Although the review found some associations between neurocognitive deficits and opioid overdose, the authors point out that it is difficult to make direct comparisons because of biases and differences in methodology among the included studies. They were not able to reach conclusions about the prevalence of brain injuries following nonfatal opioid overdoses. Few included studies controlled for confounding factors that might contribute to or explain neurocognitive impairments, reported Dr. Winstanley, associate professor in the department of behavioral medicine and psychiatry at the University of West Virginia, Morgantown, and associates.

Still, distinct patterns emerged from the analysis of almost 3,500 subjects in 79 studies in 21 countries. Twenty-nine studies reported diagnoses of leukoencephalopathy, which affects white matter. Spongiform leukoencephalopathy is known to occur secondarily after exposure to a variety of toxic agents, including carbon monoxide poisoning and drugs of abuse. The damage can lead to erosion of higher cerebral function. The condition can occur from 2 to 180 days after a hypoxic brain injury, potentially complicating efforts to attribute it specifically to an opioid overdose. Amnestic syndrome was also reported in some studies. One study found that about 39% of people seeking buprenorphine treatment suffered from neurocognitive impairment.

Dr. Gold called the study’s findings novel and of public health importance. “Each overdose takes a toll on the body, and especially the brain,” he said.
 

Better documentation needed

The variability in symptoms, as well as their timing, present challenges to initial treatment, which often occur before a patient reaches the hospital. This is a vital window because the length of time of inadequate respiration because of opioid overdose is likely to predict the extent of brain injury. The duration of inadequate respiration may not be captured in electronic medical records, and emergency departments don’t typically collect toxicology information, which may lead health care providers to attribute neurocognitive impairments to ongoing drug use rather than an acute anoxic or hypoxic episode. Further neurocognitive damage may have a delayed onset, and better documentation of these events could help physicians determine whether those symptoms stem from the acute event.

Dr. Winstanley and associates called for more research, including prospective case-control studies to identify brain changes following opioid-related overdose.

The authors also suggested that physicians might want to consider screening patients who experience prolonged anoxia or hypoxia for neurocognitive impairments and brain injuries. Dr. Gold agreed.

“Clinicians working with OUD patients should take these data to heart and take a comprehensive history of previous overdoses, loss of consciousness, head trauma, and following up on the history with neuropsychological and other tests of brain function,” Dr. Gold said. “After an assessment, rehabilitation and treatment might then be more personalized and effective.”

Dr. Gold had no relevant financial disclosures.

Opioid overdoses usually aren’t fatal, but a new review of numerous studies, mostly case reports and case series, suggests that they can have long-lasting effects on cognition, possibly because of hypoxia resulting from respiratory depression.

Erin L. Winstanley, PhD, MA, and associates noted in the review that opioids cause about 80% of worldwide deaths from illicit drug use, and the Centers for Disease Control and Prevention’s provisional August 2021 number of more than 88,000 opioid-caused deaths in the United States is the highest ever recorded – a 27% increase over what was reported last December. That number suggests that the opioid epidemic continues to rage, but the study results also show that the neurological consequences of nonfatal overdoses are an important public health problem.

And that’s something that may be overlooked, according to Mark S. Gold, MD, who was not involved with the study and was asked to comment on the review, which was published in the Journal of Addiction Science.

“Assuming that an overdose has no effect on the brain, mood, and behavior is not supported by experience or the literature. While reversing overdoses is life-saving, preventing overdose may be brain saving,” said Dr. Gold. He is a University of Florida, Gainesville, Emeritus Eminent Scholar, adjunct professor of psychiatry at Washington University in St. Louis, and a member of the clinical council of Washington University’s Public Health Institute.

A common pattern among patients with opioid use disorder (OUD) is that they undergo treatment with medication-assisted therapy (MAT), only to drop out of treatment and then repeat the treatment at a later date. That suggests that physicians should take a harder look at the limitations of MAT and other treatments, Dr. Gold said.

Although the review found some associations between neurocognitive deficits and opioid overdose, the authors point out that it is difficult to make direct comparisons because of biases and differences in methodology among the included studies. They were not able to reach conclusions about the prevalence of brain injuries following nonfatal opioid overdoses. Few included studies controlled for confounding factors that might contribute to or explain neurocognitive impairments, reported Dr. Winstanley, associate professor in the department of behavioral medicine and psychiatry at the University of West Virginia, Morgantown, and associates.

Still, distinct patterns emerged from the analysis of almost 3,500 subjects in 79 studies in 21 countries. Twenty-nine studies reported diagnoses of leukoencephalopathy, which affects white matter. Spongiform leukoencephalopathy is known to occur secondarily after exposure to a variety of toxic agents, including carbon monoxide poisoning and drugs of abuse. The damage can lead to erosion of higher cerebral function. The condition can occur from 2 to 180 days after a hypoxic brain injury, potentially complicating efforts to attribute it specifically to an opioid overdose. Amnestic syndrome was also reported in some studies. One study found that about 39% of people seeking buprenorphine treatment suffered from neurocognitive impairment.

Dr. Gold called the study’s findings novel and of public health importance. “Each overdose takes a toll on the body, and especially the brain,” he said.
 

Better documentation needed

The variability in symptoms, as well as their timing, present challenges to initial treatment, which often occur before a patient reaches the hospital. This is a vital window because the length of time of inadequate respiration because of opioid overdose is likely to predict the extent of brain injury. The duration of inadequate respiration may not be captured in electronic medical records, and emergency departments don’t typically collect toxicology information, which may lead health care providers to attribute neurocognitive impairments to ongoing drug use rather than an acute anoxic or hypoxic episode. Further neurocognitive damage may have a delayed onset, and better documentation of these events could help physicians determine whether those symptoms stem from the acute event.

Dr. Winstanley and associates called for more research, including prospective case-control studies to identify brain changes following opioid-related overdose.

The authors also suggested that physicians might want to consider screening patients who experience prolonged anoxia or hypoxia for neurocognitive impairments and brain injuries. Dr. Gold agreed.

“Clinicians working with OUD patients should take these data to heart and take a comprehensive history of previous overdoses, loss of consciousness, head trauma, and following up on the history with neuropsychological and other tests of brain function,” Dr. Gold said. “After an assessment, rehabilitation and treatment might then be more personalized and effective.”

Dr. Gold had no relevant financial disclosures.

Opioid overdoses usually aren’t fatal, but a new review of numerous studies, mostly case reports and case series, suggests that they can have long-lasting effects on cognition, possibly because of hypoxia resulting from respiratory depression.

Erin L. Winstanley, PhD, MA, and associates noted in the review that opioids cause about 80% of worldwide deaths from illicit drug use, and the Centers for Disease Control and Prevention’s provisional August 2021 number of more than 88,000 opioid-caused deaths in the United States is the highest ever recorded – a 27% increase over what was reported last December. That number suggests that the opioid epidemic continues to rage, but the study results also show that the neurological consequences of nonfatal overdoses are an important public health problem.

And that’s something that may be overlooked, according to Mark S. Gold, MD, who was not involved with the study and was asked to comment on the review, which was published in the Journal of Addiction Science.

“Assuming that an overdose has no effect on the brain, mood, and behavior is not supported by experience or the literature. While reversing overdoses is life-saving, preventing overdose may be brain saving,” said Dr. Gold. He is a University of Florida, Gainesville, Emeritus Eminent Scholar, adjunct professor of psychiatry at Washington University in St. Louis, and a member of the clinical council of Washington University’s Public Health Institute.

A common pattern among patients with opioid use disorder (OUD) is that they undergo treatment with medication-assisted therapy (MAT), only to drop out of treatment and then repeat the treatment at a later date. That suggests that physicians should take a harder look at the limitations of MAT and other treatments, Dr. Gold said.

Although the review found some associations between neurocognitive deficits and opioid overdose, the authors point out that it is difficult to make direct comparisons because of biases and differences in methodology among the included studies. They were not able to reach conclusions about the prevalence of brain injuries following nonfatal opioid overdoses. Few included studies controlled for confounding factors that might contribute to or explain neurocognitive impairments, reported Dr. Winstanley, associate professor in the department of behavioral medicine and psychiatry at the University of West Virginia, Morgantown, and associates.

Still, distinct patterns emerged from the analysis of almost 3,500 subjects in 79 studies in 21 countries. Twenty-nine studies reported diagnoses of leukoencephalopathy, which affects white matter. Spongiform leukoencephalopathy is known to occur secondarily after exposure to a variety of toxic agents, including carbon monoxide poisoning and drugs of abuse. The damage can lead to erosion of higher cerebral function. The condition can occur from 2 to 180 days after a hypoxic brain injury, potentially complicating efforts to attribute it specifically to an opioid overdose. Amnestic syndrome was also reported in some studies. One study found that about 39% of people seeking buprenorphine treatment suffered from neurocognitive impairment.

Dr. Gold called the study’s findings novel and of public health importance. “Each overdose takes a toll on the body, and especially the brain,” he said.
 

Better documentation needed

The variability in symptoms, as well as their timing, present challenges to initial treatment, which often occur before a patient reaches the hospital. This is a vital window because the length of time of inadequate respiration because of opioid overdose is likely to predict the extent of brain injury. The duration of inadequate respiration may not be captured in electronic medical records, and emergency departments don’t typically collect toxicology information, which may lead health care providers to attribute neurocognitive impairments to ongoing drug use rather than an acute anoxic or hypoxic episode. Further neurocognitive damage may have a delayed onset, and better documentation of these events could help physicians determine whether those symptoms stem from the acute event.

Dr. Winstanley and associates called for more research, including prospective case-control studies to identify brain changes following opioid-related overdose.

The authors also suggested that physicians might want to consider screening patients who experience prolonged anoxia or hypoxia for neurocognitive impairments and brain injuries. Dr. Gold agreed.

“Clinicians working with OUD patients should take these data to heart and take a comprehensive history of previous overdoses, loss of consciousness, head trauma, and following up on the history with neuropsychological and other tests of brain function,” Dr. Gold said. “After an assessment, rehabilitation and treatment might then be more personalized and effective.”

Dr. Gold had no relevant financial disclosures.

Subclinical or preclinical interstitial lung disease in patients with connective tissue diseases is not a benign entity, and many patients may experience progression of lung fibrosis before a diagnosis of ILD is made, investigators caution.

Among patients with connective tissue disease assessed with baseline and follow-up high-resolution CT scans for ILD, nearly one-fourth had evidence of ILD progression over a median of 4.5 years, reported Anna-Maria Hoffmann-Vold, MD, PhD, from Oslo University Hospital.

“Subclinical ILD is frequently present across all connective tissue diseases. It progresses over time in a substantial subgroup of people comparable to patients with clinical ILD, and our findings really question the terms ‘subclinical/preclinical ILD,’ which may potentially lead to a suboptimal watchful waiting management,” she said in an oral abstract presentation during the European Respiratory Society International Congress.

Jesse Roman, MD, CEO at the Jane & Leonard Korman Respiratory Institute at Thomas Jefferson University, Philadelphia, who was not involved in the study, commented that the findings regarding subclinical disease come as no surprise.

“The connective tissue disorders are linked to interstitial lung disease, and we believe that they are the primary causes of interstitial lung diseases in most countries,” he said in an interview.

“Basically, what you’re detecting is that if you can identify these people early, then you can see that they behave like any other patients with interstitial lung disease with progression, so most experts recommend that patients with any kind of connective tissue disorder be followed with either CT scans or pulmonary function tests, or carefully interviewed every time they come to identify any kind of very early interstitial lung disease – particularly in patients with rheumatoid arthritis, in patients with systemic sclerosis, and in patients with dermatomyositis,” Dr. Roman said.

He noted that when patients present with an idiopathic or undiagnosed condition suggestive of ILD, clinicians at his center will order serology tests to detect potential cases of subclinical connective tissue disorders.

Observational study

Dr. Hoffmann-Vold and colleagues looked at 525 patients with connective tissue diseases assessed for ILD at their center, including 296 with systemic sclerosis, 94 with anti-synthetase syndrome, and 135 with mixed connective tissue disease.

­­They used semiquantitative assessment to determine the prevalence of ILD, defining subclinical disease as ILD extent of less than 5% on high-resolution CT, preserved lung function with forced vital capacity (FVC) greater than 80% of predicted, and no respiratory symptoms.

Clinical ILD was defined as either ILD extent greater than 5%, or ILD extent below 5% but with respiratory symptoms and FVC below 80% of predicted.

They found that 44% of the patients had ILD on high-resolution CT, 43% had no evidence of ILD, and 13% had subclinical ILD.

In a comparison of patients without ILD and those with either clinical or subclinical ILD, they found that, while the mean patient age was about 51 in all three groups, men were more likely than women to have clinical ILD. A higher proportion of patients with clinical ILD (39%) died during the total observation period of about 13 years, compared with 22% of patients without ILD, and 18% of those with subclinical ILD.

As noted before, of 395 patients with baseline and follow-up high-resolution CT, 95 (24%) had evidence of lung fibrosis progression, with 38% of patients with subclinical ILD and 51% of patients with clinical ILD having progression during follow-up.

“In our connective tissue disease patients with ILD, the symptoms-define-disease argument would clearly lead to [the idea] that ILD is not a disease until patients become symptomatic, which we all know is frequently appearing in advanced stages of ILD,” Dr. Hoffmann-Vold said.

The study was funded by Oslo University Hospital. Dr. Hoffmann-Vold and Dr. Roman reported no relevant conflicts of interest to disclose.

Subclinical or preclinical interstitial lung disease in patients with connective tissue diseases is not a benign entity, and many patients may experience progression of lung fibrosis before a diagnosis of ILD is made, investigators caution.

Among patients with connective tissue disease assessed with baseline and follow-up high-resolution CT scans for ILD, nearly one-fourth had evidence of ILD progression over a median of 4.5 years, reported Anna-Maria Hoffmann-Vold, MD, PhD, from Oslo University Hospital.

“Subclinical ILD is frequently present across all connective tissue diseases. It progresses over time in a substantial subgroup of people comparable to patients with clinical ILD, and our findings really question the terms ‘subclinical/preclinical ILD,’ which may potentially lead to a suboptimal watchful waiting management,” she said in an oral abstract presentation during the European Respiratory Society International Congress.

Jesse Roman, MD, CEO at the Jane & Leonard Korman Respiratory Institute at Thomas Jefferson University, Philadelphia, who was not involved in the study, commented that the findings regarding subclinical disease come as no surprise.

“The connective tissue disorders are linked to interstitial lung disease, and we believe that they are the primary causes of interstitial lung diseases in most countries,” he said in an interview.

“Basically, what you’re detecting is that if you can identify these people early, then you can see that they behave like any other patients with interstitial lung disease with progression, so most experts recommend that patients with any kind of connective tissue disorder be followed with either CT scans or pulmonary function tests, or carefully interviewed every time they come to identify any kind of very early interstitial lung disease – particularly in patients with rheumatoid arthritis, in patients with systemic sclerosis, and in patients with dermatomyositis,” Dr. Roman said.

He noted that when patients present with an idiopathic or undiagnosed condition suggestive of ILD, clinicians at his center will order serology tests to detect potential cases of subclinical connective tissue disorders.

Observational study

Dr. Hoffmann-Vold and colleagues looked at 525 patients with connective tissue diseases assessed for ILD at their center, including 296 with systemic sclerosis, 94 with anti-synthetase syndrome, and 135 with mixed connective tissue disease.

­­They used semiquantitative assessment to determine the prevalence of ILD, defining subclinical disease as ILD extent of less than 5% on high-resolution CT, preserved lung function with forced vital capacity (FVC) greater than 80% of predicted, and no respiratory symptoms.

Clinical ILD was defined as either ILD extent greater than 5%, or ILD extent below 5% but with respiratory symptoms and FVC below 80% of predicted.

They found that 44% of the patients had ILD on high-resolution CT, 43% had no evidence of ILD, and 13% had subclinical ILD.

In a comparison of patients without ILD and those with either clinical or subclinical ILD, they found that, while the mean patient age was about 51 in all three groups, men were more likely than women to have clinical ILD. A higher proportion of patients with clinical ILD (39%) died during the total observation period of about 13 years, compared with 22% of patients without ILD, and 18% of those with subclinical ILD.

As noted before, of 395 patients with baseline and follow-up high-resolution CT, 95 (24%) had evidence of lung fibrosis progression, with 38% of patients with subclinical ILD and 51% of patients with clinical ILD having progression during follow-up.

“In our connective tissue disease patients with ILD, the symptoms-define-disease argument would clearly lead to [the idea] that ILD is not a disease until patients become symptomatic, which we all know is frequently appearing in advanced stages of ILD,” Dr. Hoffmann-Vold said.

The study was funded by Oslo University Hospital. Dr. Hoffmann-Vold and Dr. Roman reported no relevant conflicts of interest to disclose.

Subclinical or preclinical interstitial lung disease in patients with connective tissue diseases is not a benign entity, and many patients may experience progression of lung fibrosis before a diagnosis of ILD is made, investigators caution.

Among patients with connective tissue disease assessed with baseline and follow-up high-resolution CT scans for ILD, nearly one-fourth had evidence of ILD progression over a median of 4.5 years, reported Anna-Maria Hoffmann-Vold, MD, PhD, from Oslo University Hospital.

“Subclinical ILD is frequently present across all connective tissue diseases. It progresses over time in a substantial subgroup of people comparable to patients with clinical ILD, and our findings really question the terms ‘subclinical/preclinical ILD,’ which may potentially lead to a suboptimal watchful waiting management,” she said in an oral abstract presentation during the European Respiratory Society International Congress.

Jesse Roman, MD, CEO at the Jane & Leonard Korman Respiratory Institute at Thomas Jefferson University, Philadelphia, who was not involved in the study, commented that the findings regarding subclinical disease come as no surprise.

“The connective tissue disorders are linked to interstitial lung disease, and we believe that they are the primary causes of interstitial lung diseases in most countries,” he said in an interview.

“Basically, what you’re detecting is that if you can identify these people early, then you can see that they behave like any other patients with interstitial lung disease with progression, so most experts recommend that patients with any kind of connective tissue disorder be followed with either CT scans or pulmonary function tests, or carefully interviewed every time they come to identify any kind of very early interstitial lung disease – particularly in patients with rheumatoid arthritis, in patients with systemic sclerosis, and in patients with dermatomyositis,” Dr. Roman said.

He noted that when patients present with an idiopathic or undiagnosed condition suggestive of ILD, clinicians at his center will order serology tests to detect potential cases of subclinical connective tissue disorders.

Observational study

Dr. Hoffmann-Vold and colleagues looked at 525 patients with connective tissue diseases assessed for ILD at their center, including 296 with systemic sclerosis, 94 with anti-synthetase syndrome, and 135 with mixed connective tissue disease.

­­They used semiquantitative assessment to determine the prevalence of ILD, defining subclinical disease as ILD extent of less than 5% on high-resolution CT, preserved lung function with forced vital capacity (FVC) greater than 80% of predicted, and no respiratory symptoms.

Clinical ILD was defined as either ILD extent greater than 5%, or ILD extent below 5% but with respiratory symptoms and FVC below 80% of predicted.

They found that 44% of the patients had ILD on high-resolution CT, 43% had no evidence of ILD, and 13% had subclinical ILD.

In a comparison of patients without ILD and those with either clinical or subclinical ILD, they found that, while the mean patient age was about 51 in all three groups, men were more likely than women to have clinical ILD. A higher proportion of patients with clinical ILD (39%) died during the total observation period of about 13 years, compared with 22% of patients without ILD, and 18% of those with subclinical ILD.

As noted before, of 395 patients with baseline and follow-up high-resolution CT, 95 (24%) had evidence of lung fibrosis progression, with 38% of patients with subclinical ILD and 51% of patients with clinical ILD having progression during follow-up.

“In our connective tissue disease patients with ILD, the symptoms-define-disease argument would clearly lead to [the idea] that ILD is not a disease until patients become symptomatic, which we all know is frequently appearing in advanced stages of ILD,” Dr. Hoffmann-Vold said.

The study was funded by Oslo University Hospital. Dr. Hoffmann-Vold and Dr. Roman reported no relevant conflicts of interest to disclose.

In the first revision to its guidance on the management of osteoporosis in a decade, the North American Menopause Society has issued an updated position statement addressing evolving evidence on osteoporosis issues ranging from screening and risk assessment to appropriate use of preventive therapy in postmenopausal women.

“Since the 2010 statement, there have been important new developments in our field, including better delineation of risk factors for fracture, resulting in better strategies for assessing fracture risk,” Michael R. McClung, MD, who is a NAMS board member and colead of the editorial panel for the 2021 position statement, told this news organization. Dr. McClung is also director emeritus of the Oregon Osteoporosis Center in Portland.

“There is much more information about the long-term safety of therapies,” he added. Dr. McClung also noted “the availability of four new drugs for the prevention and treatment of osteoporosis and clinical experience informing us of the effects of using different treatments in various sequences.”
 

Osteoporosis is substantially underdiagnosed and undertreated

A basis for the update, recently published in Menopause: The Journal of the North American Menopause Society, is the need to tackle the troubling fact that approximately half of postmenopausal women will experience a fracture related to osteoporosis in their lifetime, yet the condition is “substantially underdiagnosed and undertreated,” NAMS underscores.

With that in mind, osteoporosis should be considered by practitioners treating menopausal and postmenopausal women at all levels of care.

“All physicians and advanced care providers caring for postmenopausal women should be comfortable assessing and managing their patients with, or at risk for, fractures,” Dr. McClung added.
 

Osteoporosis prevention in young menopausal women

The NAMS statement covers a broad range of issues, and while most recommendations generally follow those of other societies’ guidelines, a unique aspect is the emphasis on preventing osteoporosis in young menopausal women with estrogen or other drugs.

While underscoring that all menopausal women should be encouraged to adopt healthy lifestyles, with good diets and physical activity to reduce the risk of bone loss and fractures, pharmacologic interventions also have a role, NAMS says.

Though long an issue of debate, NAMS voices support for estrogen therapy as having an important role in osteoporosis prevention, as estrogen deficiency is the principal cause of bone loss in postmenopausal women.

“Hormone therapy is the most appropriate choice to prevent bone loss at the time of menopause for healthy women, particularly those who have menopause symptoms,” the group states. Drug interventions are specifically supported in women with premature menopause, at least until the average age of natural menopause, in addition to those with low bone mineral density (BMD) (T-score < –1.0) and those experiencing relatively rapid bone loss related to acute estrogen deficiency in the menopause transition or on discontinuing estrogen therapy.

“Although using drugs to prevent osteoporosis is not included in national osteoporosis guidelines, a strong clinical argument can be made for doing so, especially in women who come to menopause with low bone mass,” the report states.

And therapy is also recommended if patients have a low BMD and other risk factors for fracture, such as family history, but do not meet the criteria for osteoporosis treatment.

Ultimately, clinicians should work with patients when deciding the options, Dr. McClung said. 

“After carefully weighing the small risks associated with hormone therapy or other therapies begun at the time of menopause, menopause practitioners and their patients can and should make informed decisions about the use of Food and Drug Administration–approved medications to prevent osteoporosis in women who are at risk for developing that condition,” he noted, adding that his view on the matter is his own and not necessarily that of NAMS.
 

New treatments endorsed for high-risk patients to avoid ‘bone attack’

While most patients are treated for osteoporosis with antiremodeling drugs such as bisphosphonates and denosumab, NAMS endorses “a new paradigm of beginning treatment with a bone-building agent followed by an antiremodeling agent” for women at very high risk of fracture.

“Consider osteoanabolic therapies for patients at very high risk of fracture, including older women with recent fractures, T-scores –3.0 and lower, or multiple other risk factors,” the statement suggests.

Among those at highest risk are women who have sustained a first fracture.

“A recent fracture in a postmenopausal woman is the strongest risk factor for another fracture,” Dr. McClung said.

In fact, “having a fracture should be thought of and assessed as a ‘bone attack,’ ” he asserted.

Therapy is recommended in such cases to rapidly increase bone density and reduce their subsequent fracture risk.

“For these patients, osteoanabolic or bone-building agents are more effective than bisphosphonates and are recommended as initial therapy,” Dr. McClung noted.

Treatment discontinuation?

On the issue of drug holidays and when or whether to stop therapy, as no therapies cure osteoporosis, medications should not be permanently stopped, even if bone density increases, NAMS recommends.

“By analogy, we do not stop diabetes therapy when A1c levels become normal,” Dr. McClung noted.

“Because the benefits of therapy on bone density and fracture protection wane, quickly for nonbisphosphonates and more slowly with bisphosphonates, short-term therapy, for instance 5 years, is not optimal treatment,” he said.

While the short-term interruption of bisphosphonate therapy may be considered in some patients, “the concept of ‘drug holidays’ does not pertain to nonbisphosphonate drugs,” Dr. McClung said.

NAMS adds that management of therapeutic choices should instead be ongoing.

“During therapy, reevaluate the treatment goals and the choice of medication on an ongoing basis through periodic medical examination and follow-up BMD testing,” NAMS recommends.

In terms of assessment, the measurement of bone mineral density while on treatment can gauge the current risk of fracture, and NAMS supports the use of the T-score at the hip as an appropriate clinical target in guiding choices of therapy.

Ultimately, “effective tools for diagnosing osteoporosis and assessing fracture risk are available, and well-studied strategies exist for managing bone health in women at both low and high risk of fracture,” NAMS concludes.

“By individualizing treatment approaches and monitoring and adjusting those approaches if the clinical picture changes, the consequences of osteoporosis on a menopausal woman’s activity and well-being can be minimized.”

Dr. McClung has reported receiving consulting fees from Amgen and Myovant, and honorarium for speaking from Amgen and Alexon. He serves on the boards of NAMS and the International Osteoporosis Foundation.

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

In the first revision to its guidance on the management of osteoporosis in a decade, the North American Menopause Society has issued an updated position statement addressing evolving evidence on osteoporosis issues ranging from screening and risk assessment to appropriate use of preventive therapy in postmenopausal women.

“Since the 2010 statement, there have been important new developments in our field, including better delineation of risk factors for fracture, resulting in better strategies for assessing fracture risk,” Michael R. McClung, MD, who is a NAMS board member and colead of the editorial panel for the 2021 position statement, told this news organization. Dr. McClung is also director emeritus of the Oregon Osteoporosis Center in Portland.

“There is much more information about the long-term safety of therapies,” he added. Dr. McClung also noted “the availability of four new drugs for the prevention and treatment of osteoporosis and clinical experience informing us of the effects of using different treatments in various sequences.”
 

Osteoporosis is substantially underdiagnosed and undertreated

A basis for the update, recently published in Menopause: The Journal of the North American Menopause Society, is the need to tackle the troubling fact that approximately half of postmenopausal women will experience a fracture related to osteoporosis in their lifetime, yet the condition is “substantially underdiagnosed and undertreated,” NAMS underscores.

With that in mind, osteoporosis should be considered by practitioners treating menopausal and postmenopausal women at all levels of care.

“All physicians and advanced care providers caring for postmenopausal women should be comfortable assessing and managing their patients with, or at risk for, fractures,” Dr. McClung added.
 

Osteoporosis prevention in young menopausal women

The NAMS statement covers a broad range of issues, and while most recommendations generally follow those of other societies’ guidelines, a unique aspect is the emphasis on preventing osteoporosis in young menopausal women with estrogen or other drugs.

While underscoring that all menopausal women should be encouraged to adopt healthy lifestyles, with good diets and physical activity to reduce the risk of bone loss and fractures, pharmacologic interventions also have a role, NAMS says.

Though long an issue of debate, NAMS voices support for estrogen therapy as having an important role in osteoporosis prevention, as estrogen deficiency is the principal cause of bone loss in postmenopausal women.

“Hormone therapy is the most appropriate choice to prevent bone loss at the time of menopause for healthy women, particularly those who have menopause symptoms,” the group states. Drug interventions are specifically supported in women with premature menopause, at least until the average age of natural menopause, in addition to those with low bone mineral density (BMD) (T-score < –1.0) and those experiencing relatively rapid bone loss related to acute estrogen deficiency in the menopause transition or on discontinuing estrogen therapy.

“Although using drugs to prevent osteoporosis is not included in national osteoporosis guidelines, a strong clinical argument can be made for doing so, especially in women who come to menopause with low bone mass,” the report states.

And therapy is also recommended if patients have a low BMD and other risk factors for fracture, such as family history, but do not meet the criteria for osteoporosis treatment.

Ultimately, clinicians should work with patients when deciding the options, Dr. McClung said. 

“After carefully weighing the small risks associated with hormone therapy or other therapies begun at the time of menopause, menopause practitioners and their patients can and should make informed decisions about the use of Food and Drug Administration–approved medications to prevent osteoporosis in women who are at risk for developing that condition,” he noted, adding that his view on the matter is his own and not necessarily that of NAMS.
 

New treatments endorsed for high-risk patients to avoid ‘bone attack’

While most patients are treated for osteoporosis with antiremodeling drugs such as bisphosphonates and denosumab, NAMS endorses “a new paradigm of beginning treatment with a bone-building agent followed by an antiremodeling agent” for women at very high risk of fracture.

“Consider osteoanabolic therapies for patients at very high risk of fracture, including older women with recent fractures, T-scores –3.0 and lower, or multiple other risk factors,” the statement suggests.

Among those at highest risk are women who have sustained a first fracture.

“A recent fracture in a postmenopausal woman is the strongest risk factor for another fracture,” Dr. McClung said.

In fact, “having a fracture should be thought of and assessed as a ‘bone attack,’ ” he asserted.

Therapy is recommended in such cases to rapidly increase bone density and reduce their subsequent fracture risk.

“For these patients, osteoanabolic or bone-building agents are more effective than bisphosphonates and are recommended as initial therapy,” Dr. McClung noted.