CHEST Physician

For smokers, deaths with a cardiovascular or cancer-related cause, or ones that can be attributed to a respiratory disease such as chronic obstructive pulmonary disease, are significantly more common than for nonsmokers. It is widely recognized that stopping smoking leads to a reduction in mortality risk. To make reliable statements on the timeline of this reduction, researchers analyzed interview data and death rates from 438,015 adult US citizens from 1997 to the end of 2019.

The analyses show that it takes 30 years for the mortality risk of ex-smokers to resemble that of people who never regularly smoked. Blake Thomson, PhD, and Fahrad Islami, MD, PhD, both members of the Department of Surveillance and Health Equity Science of the American Cancer Society in Atlanta, Georgia, published their results as a research letter in JAMA Internal Medicine.
 

After Smoking Cessation

Overall, 11,860 cardiovascular, 10,935 cancer-related, and 2,060 respiratory-related deaths were considered from over 5 million patient years. Taken from these figures, the mortality risks of continuous smokers were 2.3 times (cardiovascular), 3.4 times (cancer-related), and 13.3 times (respiratory-related) higher than those of continuous nonsmokers.

Within 10 years of stopping smoking, the following occurred:

• The cardiovascular mortality risk fell by 1.47 times, compared with nonsmokers (by 36% compared with smokers).
• The cancer-related mortality risk fell by 2.13 times, compared with nonsmokers (by 47% compared with smokers).
• The respiratory-related mortality risk fell by 6.35 times, compared with nonsmokers (by 43% compared with smokers).

In the second decade after stopping smoking, the risk dropped even further. The researchers observed the following trends:

• The cardiovascular mortality risk fell by 1.26 times.
• The cancer-related mortality risk fell by 1.59 times.
• The respiratory-related mortality risk fell by 3.63 times — each time compared with nonsmokers.

During the third decade after stopping smoking, the risk continued to decrease. The trends were as follows:

• The cardiovascular mortality risk fell by 1.07 times.
• The cancer-related mortality risk fell by 1.34 times.
• The respiratory-related mortality risk fell by 2.34 times, compared with nonsmokers.

30 Years Later

Only after more than 30 years of not smoking was the cardiovascular-related mortality risk 0.96 and, therefore, no longer significant. Compared with nonsmokers, the cancer-related mortality risk was 1.16, and the respiratory-related mortality risk was 1.31.

Therefore, former smokers can reduce their cardiovascular mortality risk by 100%, the cancer-related by 93%, and the respiratory-related mortality risk by 97%.

The result reinforces earlier analyses on the reduction in mortality risks by stopping smoking, with fewer participants. Smokers, therefore, benefit more the longer that they can refrain from using tobacco. “The earlier in life that smoking is given up, the better,” the authors wrote. But even in the first 10 years, the mortality risks examined decreased by a statistically significant 36% (cardiovascular) to 47% (cancer-related).
 

An Underestimation?

One disadvantage of the study is that the participants’ data were collected using personal questionnaires. For this reason, participants may have reported their tobacco consumption as being lower than it was, particularly because these questionnaires are often answered in hindsight, the authors pointed out.

In addition, some of the participants who reported stopping smoking completely may have only reduced their consumption. However, both circumstances would cause the results of the analysis to be even clearer, compared with reality, and therefore better.

This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

For smokers, deaths with a cardiovascular or cancer-related cause, or ones that can be attributed to a respiratory disease such as chronic obstructive pulmonary disease, are significantly more common than for nonsmokers. It is widely recognized that stopping smoking leads to a reduction in mortality risk. To make reliable statements on the timeline of this reduction, researchers analyzed interview data and death rates from 438,015 adult US citizens from 1997 to the end of 2019.

The analyses show that it takes 30 years for the mortality risk of ex-smokers to resemble that of people who never regularly smoked. Blake Thomson, PhD, and Fahrad Islami, MD, PhD, both members of the Department of Surveillance and Health Equity Science of the American Cancer Society in Atlanta, Georgia, published their results as a research letter in JAMA Internal Medicine.
 

After Smoking Cessation

Overall, 11,860 cardiovascular, 10,935 cancer-related, and 2,060 respiratory-related deaths were considered from over 5 million patient years. Taken from these figures, the mortality risks of continuous smokers were 2.3 times (cardiovascular), 3.4 times (cancer-related), and 13.3 times (respiratory-related) higher than those of continuous nonsmokers.

Within 10 years of stopping smoking, the following occurred:

• The cardiovascular mortality risk fell by 1.47 times, compared with nonsmokers (by 36% compared with smokers).
• The cancer-related mortality risk fell by 2.13 times, compared with nonsmokers (by 47% compared with smokers).
• The respiratory-related mortality risk fell by 6.35 times, compared with nonsmokers (by 43% compared with smokers).

In the second decade after stopping smoking, the risk dropped even further. The researchers observed the following trends:

• The cardiovascular mortality risk fell by 1.26 times.
• The cancer-related mortality risk fell by 1.59 times.
• The respiratory-related mortality risk fell by 3.63 times — each time compared with nonsmokers.

During the third decade after stopping smoking, the risk continued to decrease. The trends were as follows:

• The cardiovascular mortality risk fell by 1.07 times.
• The cancer-related mortality risk fell by 1.34 times.
• The respiratory-related mortality risk fell by 2.34 times, compared with nonsmokers.

30 Years Later

Only after more than 30 years of not smoking was the cardiovascular-related mortality risk 0.96 and, therefore, no longer significant. Compared with nonsmokers, the cancer-related mortality risk was 1.16, and the respiratory-related mortality risk was 1.31.

Therefore, former smokers can reduce their cardiovascular mortality risk by 100%, the cancer-related by 93%, and the respiratory-related mortality risk by 97%.

The result reinforces earlier analyses on the reduction in mortality risks by stopping smoking, with fewer participants. Smokers, therefore, benefit more the longer that they can refrain from using tobacco. “The earlier in life that smoking is given up, the better,” the authors wrote. But even in the first 10 years, the mortality risks examined decreased by a statistically significant 36% (cardiovascular) to 47% (cancer-related).
 

An Underestimation?

One disadvantage of the study is that the participants’ data were collected using personal questionnaires. For this reason, participants may have reported their tobacco consumption as being lower than it was, particularly because these questionnaires are often answered in hindsight, the authors pointed out.

In addition, some of the participants who reported stopping smoking completely may have only reduced their consumption. However, both circumstances would cause the results of the analysis to be even clearer, compared with reality, and therefore better.

This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

For smokers, deaths with a cardiovascular or cancer-related cause, or ones that can be attributed to a respiratory disease such as chronic obstructive pulmonary disease, are significantly more common than for nonsmokers. It is widely recognized that stopping smoking leads to a reduction in mortality risk. To make reliable statements on the timeline of this reduction, researchers analyzed interview data and death rates from 438,015 adult US citizens from 1997 to the end of 2019.

The analyses show that it takes 30 years for the mortality risk of ex-smokers to resemble that of people who never regularly smoked. Blake Thomson, PhD, and Fahrad Islami, MD, PhD, both members of the Department of Surveillance and Health Equity Science of the American Cancer Society in Atlanta, Georgia, published their results as a research letter in JAMA Internal Medicine.
 

After Smoking Cessation

Overall, 11,860 cardiovascular, 10,935 cancer-related, and 2,060 respiratory-related deaths were considered from over 5 million patient years. Taken from these figures, the mortality risks of continuous smokers were 2.3 times (cardiovascular), 3.4 times (cancer-related), and 13.3 times (respiratory-related) higher than those of continuous nonsmokers.

Within 10 years of stopping smoking, the following occurred:

• The cardiovascular mortality risk fell by 1.47 times, compared with nonsmokers (by 36% compared with smokers).
• The cancer-related mortality risk fell by 2.13 times, compared with nonsmokers (by 47% compared with smokers).
• The respiratory-related mortality risk fell by 6.35 times, compared with nonsmokers (by 43% compared with smokers).

In the second decade after stopping smoking, the risk dropped even further. The researchers observed the following trends:

• The cardiovascular mortality risk fell by 1.26 times.
• The cancer-related mortality risk fell by 1.59 times.
• The respiratory-related mortality risk fell by 3.63 times — each time compared with nonsmokers.

During the third decade after stopping smoking, the risk continued to decrease. The trends were as follows:

• The cardiovascular mortality risk fell by 1.07 times.
• The cancer-related mortality risk fell by 1.34 times.
• The respiratory-related mortality risk fell by 2.34 times, compared with nonsmokers.

30 Years Later

Only after more than 30 years of not smoking was the cardiovascular-related mortality risk 0.96 and, therefore, no longer significant. Compared with nonsmokers, the cancer-related mortality risk was 1.16, and the respiratory-related mortality risk was 1.31.

Therefore, former smokers can reduce their cardiovascular mortality risk by 100%, the cancer-related by 93%, and the respiratory-related mortality risk by 97%.

The result reinforces earlier analyses on the reduction in mortality risks by stopping smoking, with fewer participants. Smokers, therefore, benefit more the longer that they can refrain from using tobacco. “The earlier in life that smoking is given up, the better,” the authors wrote. But even in the first 10 years, the mortality risks examined decreased by a statistically significant 36% (cardiovascular) to 47% (cancer-related).
 

An Underestimation?

One disadvantage of the study is that the participants’ data were collected using personal questionnaires. For this reason, participants may have reported their tobacco consumption as being lower than it was, particularly because these questionnaires are often answered in hindsight, the authors pointed out.

In addition, some of the participants who reported stopping smoking completely may have only reduced their consumption. However, both circumstances would cause the results of the analysis to be even clearer, compared with reality, and therefore better.

This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

Continuous positive airway pressure (CPAP) is first-line therapy for sleep-related breathing disorders (SRBDs). Obstructive sleep apnea (OSA) is the major player in the SRBDs space, with a prevalence approaching 100% in adult men using current diagnostic criteria. Patients with OSA and comorbid cardiovascular disease (CVD) are diagnosed with OSA syndrome, and CPAP is prescribed. Primary care physicians and cardiologists are quick to refer patients with CVD to sleep docs to see whether CPAP can improve CVD-related outcomes.

What the Studies Show

There’s a problem though. CPAP doesn’t seem to improve CVD-related outcomes. In some cases, it’s even harmful. Let’s do a quick review. In 2005, the CANPAP study found CPAP didn’t improve a composite CVD outcome that included mortality. A post hoc analysis found that it actually increased mortality if central apneas weren’t eliminated. The post hoc analysis also found benefit when central apneas were eliminated, but for all-comers, CPAP didn’t improve outcomes. Strike one.

Enter adaptive servo-ventilation (ASV). If CANPAP showed that success depended on eliminating central apneas, why not use ASV for all patients with CVD and central apneas or Cheyne-Stokes respirations? ASV eliminates central apneas and Cheyne-Stokes. Well, that didn’t work either. The randomized, controlled SERVE-HF trial, published in 2015, showed that ASV increases all-cause and CVD-specific mortality. Oops. That’s two trials showing that CPAP and ASV can increase mortality in patients with heart failure. Strike two.

Alright. But that’s heart failure. What about hypertension or coronary artery disease (CAD)? Shouldn’t such patients be treated with CPAP to reduce CVD risk? After all, there’s all those surrogate outcomes data for CPAP — it improves vascular tone and lowers catecholamines and all that stuff. Doesn’t it lower blood pressure too? Surely CPAP benefits patients with CVD who don’t have heart failure, right?

Not really. The RICCADSA study, published in 2016, found that CPAP didn’t reduce a composite of CVD outcomes in patients with newly revascularized CAD. The SAVE trial published the same year had a similar design with similar results. CPAP did not improve CVD-related outcomes. Most recently, the ISAACC study was negative. That’s three negative randomized controlled trials in less than 5 years showing CPAP doesn’t affect CVD-related outcomes in high-risk populations with known disease. Strike three?

CPAP provides no benefit for CVD and possible harm when treating heart failure. Surely CPAP is useful for patients with hypertension. Let’s see. The American Academy of Sleep Medicine (AASM) conducted meta-analyses for the guideline it produced recommending CPAP for patients with comorbid hypertension. They note that 24-hour blood pressure measurements are best correlated with outcomes. CPAP did lead to significant 24-hour blood pressure reduction, but guess how large it was? For systolic blood pressure, it was 1.5 mm Hg; for diastolic pressure, it was 1.6 mm Hg. That’s it.

How did the AASM summarize and interpret the above data in their 2019 guidelines for prescribing CPAP? Although covered in their detailed review, both heart failure and CVD are left out of their primary recommendations . They do provide a conditional recommendation for prescribing CPAP to patients with comorbid hypertension that states, “The majority of well-informed patients would choose the intervention over no treatment.” Really? If you were told that CPAP provides less reduction in blood pressure than dietary changes and/or medications, would you choose to wear it or take a pill once a day? Remember, you have to take the pill anyway to get your blood pressure to target unless your pressure is only 1.5-1.6 mm Hg above normal. Where does one find patients who are anxious to wear a mask to bed for minimal benefit and a 20% copay? I’ve yet to meet one.

As always, the pressure pushers are undeterred by inconvenient evidence. A secondary analysis of adherent patients in RICCADSA resorts to the “bait and switch” that’s propped up CPAP enthusiasts for decades: Compare adherent patients versus those who are not (or those who refuse treatment) to prove benefit. The flaws to this approach are obvious. First, performing a post hoc analysis that reintroduces all of the confounding that plagues existing CPAP data negates the benefits of randomization, fancy statistics notwithstanding. Second, it belies the reality that in well-controlled, well-conducted randomized trials where patients get far more support than those in the community (and sometimes are preselected for adherence), a majority simply won’t use CPAP . Excluding the nonadherent or comparing them with the adherent is the epitome of selection bias.

The editorial accompanying the ISAACC study is a tour de force in CPAP apologies. The apnea-hypopnea index (AHI) isn’t the right metric — this one’s invoked often. Never mind that the very premise that OSA causes CVD is from observational data based on the AHI. If you abandon the AHI, don’t you lose your justification for prospective trials targeting CVD with CPAP?

Even better, in an argument fit for a Twitter ban, the author suggests that patients in ISAACC, SAVE, and RICCADSA couldn’t benefit because they already have CVD. The very concept, refuted by decades of secondary prevention research in cardiology, implies that CPAP should be used for primary prevention. Only a sleep researcher could spin a negative study into an expansion of CPAP indications. Others in the AASM have made similar proposals.

Final Thoughts

The sleep field lacks unblinded realists capable of choosing wisely. A little therapeutic underconfidence is warranted. Diseases and therapies will always have champions. Prudence and restraint? Not so much. The AASM could summarize the CPAP literature in a single recommendation: “If your patient is sleepy, CPAP might help them feel better if their disease is moderate or severe.” All other indications are soft.

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

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He covers a  wide range of topics in pulmonary, critical care, and sleep medicine .

Continuous positive airway pressure (CPAP) is first-line therapy for sleep-related breathing disorders (SRBDs). Obstructive sleep apnea (OSA) is the major player in the SRBDs space, with a prevalence approaching 100% in adult men using current diagnostic criteria. Patients with OSA and comorbid cardiovascular disease (CVD) are diagnosed with OSA syndrome, and CPAP is prescribed. Primary care physicians and cardiologists are quick to refer patients with CVD to sleep docs to see whether CPAP can improve CVD-related outcomes.

What the Studies Show

There’s a problem though. CPAP doesn’t seem to improve CVD-related outcomes. In some cases, it’s even harmful. Let’s do a quick review. In 2005, the CANPAP study found CPAP didn’t improve a composite CVD outcome that included mortality. A post hoc analysis found that it actually increased mortality if central apneas weren’t eliminated. The post hoc analysis also found benefit when central apneas were eliminated, but for all-comers, CPAP didn’t improve outcomes. Strike one.

Enter adaptive servo-ventilation (ASV). If CANPAP showed that success depended on eliminating central apneas, why not use ASV for all patients with CVD and central apneas or Cheyne-Stokes respirations? ASV eliminates central apneas and Cheyne-Stokes. Well, that didn’t work either. The randomized, controlled SERVE-HF trial, published in 2015, showed that ASV increases all-cause and CVD-specific mortality. Oops. That’s two trials showing that CPAP and ASV can increase mortality in patients with heart failure. Strike two.

Alright. But that’s heart failure. What about hypertension or coronary artery disease (CAD)? Shouldn’t such patients be treated with CPAP to reduce CVD risk? After all, there’s all those surrogate outcomes data for CPAP — it improves vascular tone and lowers catecholamines and all that stuff. Doesn’t it lower blood pressure too? Surely CPAP benefits patients with CVD who don’t have heart failure, right?

Not really. The RICCADSA study, published in 2016, found that CPAP didn’t reduce a composite of CVD outcomes in patients with newly revascularized CAD. The SAVE trial published the same year had a similar design with similar results. CPAP did not improve CVD-related outcomes. Most recently, the ISAACC study was negative. That’s three negative randomized controlled trials in less than 5 years showing CPAP doesn’t affect CVD-related outcomes in high-risk populations with known disease. Strike three?

CPAP provides no benefit for CVD and possible harm when treating heart failure. Surely CPAP is useful for patients with hypertension. Let’s see. The American Academy of Sleep Medicine (AASM) conducted meta-analyses for the guideline it produced recommending CPAP for patients with comorbid hypertension. They note that 24-hour blood pressure measurements are best correlated with outcomes. CPAP did lead to significant 24-hour blood pressure reduction, but guess how large it was? For systolic blood pressure, it was 1.5 mm Hg; for diastolic pressure, it was 1.6 mm Hg. That’s it.

How did the AASM summarize and interpret the above data in their 2019 guidelines for prescribing CPAP? Although covered in their detailed review, both heart failure and CVD are left out of their primary recommendations . They do provide a conditional recommendation for prescribing CPAP to patients with comorbid hypertension that states, “The majority of well-informed patients would choose the intervention over no treatment.” Really? If you were told that CPAP provides less reduction in blood pressure than dietary changes and/or medications, would you choose to wear it or take a pill once a day? Remember, you have to take the pill anyway to get your blood pressure to target unless your pressure is only 1.5-1.6 mm Hg above normal. Where does one find patients who are anxious to wear a mask to bed for minimal benefit and a 20% copay? I’ve yet to meet one.

As always, the pressure pushers are undeterred by inconvenient evidence. A secondary analysis of adherent patients in RICCADSA resorts to the “bait and switch” that’s propped up CPAP enthusiasts for decades: Compare adherent patients versus those who are not (or those who refuse treatment) to prove benefit. The flaws to this approach are obvious. First, performing a post hoc analysis that reintroduces all of the confounding that plagues existing CPAP data negates the benefits of randomization, fancy statistics notwithstanding. Second, it belies the reality that in well-controlled, well-conducted randomized trials where patients get far more support than those in the community (and sometimes are preselected for adherence), a majority simply won’t use CPAP . Excluding the nonadherent or comparing them with the adherent is the epitome of selection bias.

The editorial accompanying the ISAACC study is a tour de force in CPAP apologies. The apnea-hypopnea index (AHI) isn’t the right metric — this one’s invoked often. Never mind that the very premise that OSA causes CVD is from observational data based on the AHI. If you abandon the AHI, don’t you lose your justification for prospective trials targeting CVD with CPAP?

Even better, in an argument fit for a Twitter ban, the author suggests that patients in ISAACC, SAVE, and RICCADSA couldn’t benefit because they already have CVD. The very concept, refuted by decades of secondary prevention research in cardiology, implies that CPAP should be used for primary prevention. Only a sleep researcher could spin a negative study into an expansion of CPAP indications. Others in the AASM have made similar proposals.

Final Thoughts

The sleep field lacks unblinded realists capable of choosing wisely. A little therapeutic underconfidence is warranted. Diseases and therapies will always have champions. Prudence and restraint? Not so much. The AASM could summarize the CPAP literature in a single recommendation: “If your patient is sleepy, CPAP might help them feel better if their disease is moderate or severe.” All other indications are soft.

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

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He covers a  wide range of topics in pulmonary, critical care, and sleep medicine .

Continuous positive airway pressure (CPAP) is first-line therapy for sleep-related breathing disorders (SRBDs). Obstructive sleep apnea (OSA) is the major player in the SRBDs space, with a prevalence approaching 100% in adult men using current diagnostic criteria. Patients with OSA and comorbid cardiovascular disease (CVD) are diagnosed with OSA syndrome, and CPAP is prescribed. Primary care physicians and cardiologists are quick to refer patients with CVD to sleep docs to see whether CPAP can improve CVD-related outcomes.

What the Studies Show

There’s a problem though. CPAP doesn’t seem to improve CVD-related outcomes. In some cases, it’s even harmful. Let’s do a quick review. In 2005, the CANPAP study found CPAP didn’t improve a composite CVD outcome that included mortality. A post hoc analysis found that it actually increased mortality if central apneas weren’t eliminated. The post hoc analysis also found benefit when central apneas were eliminated, but for all-comers, CPAP didn’t improve outcomes. Strike one.

Enter adaptive servo-ventilation (ASV). If CANPAP showed that success depended on eliminating central apneas, why not use ASV for all patients with CVD and central apneas or Cheyne-Stokes respirations? ASV eliminates central apneas and Cheyne-Stokes. Well, that didn’t work either. The randomized, controlled SERVE-HF trial, published in 2015, showed that ASV increases all-cause and CVD-specific mortality. Oops. That’s two trials showing that CPAP and ASV can increase mortality in patients with heart failure. Strike two.

Alright. But that’s heart failure. What about hypertension or coronary artery disease (CAD)? Shouldn’t such patients be treated with CPAP to reduce CVD risk? After all, there’s all those surrogate outcomes data for CPAP — it improves vascular tone and lowers catecholamines and all that stuff. Doesn’t it lower blood pressure too? Surely CPAP benefits patients with CVD who don’t have heart failure, right?

Not really. The RICCADSA study, published in 2016, found that CPAP didn’t reduce a composite of CVD outcomes in patients with newly revascularized CAD. The SAVE trial published the same year had a similar design with similar results. CPAP did not improve CVD-related outcomes. Most recently, the ISAACC study was negative. That’s three negative randomized controlled trials in less than 5 years showing CPAP doesn’t affect CVD-related outcomes in high-risk populations with known disease. Strike three?

CPAP provides no benefit for CVD and possible harm when treating heart failure. Surely CPAP is useful for patients with hypertension. Let’s see. The American Academy of Sleep Medicine (AASM) conducted meta-analyses for the guideline it produced recommending CPAP for patients with comorbid hypertension. They note that 24-hour blood pressure measurements are best correlated with outcomes. CPAP did lead to significant 24-hour blood pressure reduction, but guess how large it was? For systolic blood pressure, it was 1.5 mm Hg; for diastolic pressure, it was 1.6 mm Hg. That’s it.

How did the AASM summarize and interpret the above data in their 2019 guidelines for prescribing CPAP? Although covered in their detailed review, both heart failure and CVD are left out of their primary recommendations . They do provide a conditional recommendation for prescribing CPAP to patients with comorbid hypertension that states, “The majority of well-informed patients would choose the intervention over no treatment.” Really? If you were told that CPAP provides less reduction in blood pressure than dietary changes and/or medications, would you choose to wear it or take a pill once a day? Remember, you have to take the pill anyway to get your blood pressure to target unless your pressure is only 1.5-1.6 mm Hg above normal. Where does one find patients who are anxious to wear a mask to bed for minimal benefit and a 20% copay? I’ve yet to meet one.

As always, the pressure pushers are undeterred by inconvenient evidence. A secondary analysis of adherent patients in RICCADSA resorts to the “bait and switch” that’s propped up CPAP enthusiasts for decades: Compare adherent patients versus those who are not (or those who refuse treatment) to prove benefit. The flaws to this approach are obvious. First, performing a post hoc analysis that reintroduces all of the confounding that plagues existing CPAP data negates the benefits of randomization, fancy statistics notwithstanding. Second, it belies the reality that in well-controlled, well-conducted randomized trials where patients get far more support than those in the community (and sometimes are preselected for adherence), a majority simply won’t use CPAP . Excluding the nonadherent or comparing them with the adherent is the epitome of selection bias.

The editorial accompanying the ISAACC study is a tour de force in CPAP apologies. The apnea-hypopnea index (AHI) isn’t the right metric — this one’s invoked often. Never mind that the very premise that OSA causes CVD is from observational data based on the AHI. If you abandon the AHI, don’t you lose your justification for prospective trials targeting CVD with CPAP?

Even better, in an argument fit for a Twitter ban, the author suggests that patients in ISAACC, SAVE, and RICCADSA couldn’t benefit because they already have CVD. The very concept, refuted by decades of secondary prevention research in cardiology, implies that CPAP should be used for primary prevention. Only a sleep researcher could spin a negative study into an expansion of CPAP indications. Others in the AASM have made similar proposals.

Final Thoughts

The sleep field lacks unblinded realists capable of choosing wisely. A little therapeutic underconfidence is warranted. Diseases and therapies will always have champions. Prudence and restraint? Not so much. The AASM could summarize the CPAP literature in a single recommendation: “If your patient is sleepy, CPAP might help them feel better if their disease is moderate or severe.” All other indications are soft.

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

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He covers a  wide range of topics in pulmonary, critical care, and sleep medicine .

A treatment used to treat acute COVID-19 infection has also been found to be effective against long COVID, a new small study has found. The research, which assessed the benefits of monoclonal antibodies, suggests relief may finally be ahead for millions of Americans with long COVID for whom treatment has remained elusive.

The study, published in the American Journal of Emergency Medicine, found three Florida patients with long COVID made complete — and sudden — recoveries after they were given the monoclonal antibody cocktail casirivimab/imdevimab (Regeneron).

“We were struck by how rapid and complete the remissions were,” said study coauthor Paul Pepe, MD, MPH, a professor of management, policy, and community health at the School of Public Health at the University of Texas Health Sciences Center. “We found that no matter how long the patients were sick for — whether it was 5, 8, or 18 months — within 5 days, they appeared to be completely cured.”

All three patients had been initially infected with COVID-19 early in the pandemic, in 2020 or the first half of 2021. They were given Regeneron either after a reinfection or exposure to COVID-19, as a preventative, at state-run COVID clinics in Florida.

“In each case, the infusions were given to help prevent their long COVID from worsening,” said Dr. Pepe.

The researchers collected medical histories for all three patients, asking about symptoms such as physical fatigue, exercise intolerance, chest pain, heart palpitations, shortness of breath, cognitive fatigue, and memory problems. They asked patients to rate symptoms pre-COVID (baseline), during the long COVID phase, post-vaccine, and finally a week after their monoclonal antibody treatment. They also interviewed family members.

They found that across the board, symptoms improved significantly and often completely vanished. Their loved ones corroborated these reports as well.

One of the patients, a 63-year-old Floridian woman, came down with a mild case of COVID-19 at the start of the pandemic in March 2020 that lasted about 2 weeks. But several weeks later, she developed extreme, debilitating fatigue, along with chest pain and shortness of breath.

“I was chasing my 6-pound Yorkie one day after she got loose, and I was struck with such intense chest pain I fell down,” the woman, asking not to be identified, said in an interview.

Her symptoms progressed to the point where she no longer felt safe babysitting her grandchildren or driving to the grocery store.

“My short-term memory was completely gone. I couldn’t even read more than a paragraph at a time,” she said.

When she was exposed to COVID-19 in October 2021, her doctor suggested Regeneron as a preventative. She agreed to it.

“I was terrified that a second round would leave me permanently disabled and stuck in bed for the rest of my life,” she said.

About 4 days after her monoclonal antibody treatment, she noticed that some of the brain fog that had persisted after COVID was lifting.

“By day 5, it felt almost like a heavy-weighted blanket had been lifted off of me,” she recalled. “I was able to take my dog for a walk and go to the grocery store. It felt like I had gone from 0 to 100. As quickly as I went downhill, I quickly went back up.”

Reasons for Recovery

Researchers have come up with a few theories about why monoclonal antibodies may help treat long COVID, said study coauthor Aileen Marty, MD, professor of translational medicine at the Herbert Wertheim College of Medicine at Florida International University. Among them:

• It stimulates the body to fight off any residual virus. “We suspect that many of these patients simply have levels of virus that are so low they can’t be picked up by conventional testing,” said Dr. Marty. “The virus lingers in their body and causes long COVID symptoms. The monoclonal antibodies can zero in on them and knock them out.” This may also help explain why some patients with long COVID reported a temporary improvement of symptoms after their COVID-19 vaccination.
• It combats dysfunctional antibodies. Another theory is that people with long COVID have symptoms “not because of residual virus but because of junky antibodies,” said Dr. Marty. These antibodies go into overdrive and attack your own cells, which is what causes long COVID symptoms. “This may be why monoclonal antibodies work because they displace the dysfunctional antibodies that are attached to a patient’s cells,” she explained.
• Reactivation of other viruses. Long COVID is very similar to chronic fatigue syndrome, which is often thought to be triggered by reactivation of viruses like the Epstein-Barr virus, noted coauthor Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Fort Lauderdale. “It may not explain all of the cases of long COVID, but it could make up a subgroup,” she said. It’s thought that the monoclonal antibodies may perhaps neutralize this reactivation.

Where Research Is Headed

While Regeneron worked well in all three patients, it may be because they developed long COVID from either the initial virus or from early variants like Alpha, Beta, and Delta, said Dr. Pepe. As a result, it’s unclear whether this treatment would work for patients who developed long COVID from newer strains like Omicron.

“What concerns me is I believe there may be many people walking around with mild long COVID from these strains who don’t realize it,” he said. “They may assume that if they have difficulty walking upstairs, or forget why they went into another room, that it’s age related.”

The next step, the researchers said, is to create a registry of volunteer patients with severe long COVID. Dr. Klimas plans to enroll 20 volunteers who were infected before September 2022 to see how they respond to another monoclonal antibody initially used to treat COVID-19, bebtelovimab. (Like Regeneron, bebtelovimab is no longer approved for use against COVID-19 by the US Food and Drug Administration because it is no longer effective against variants of the virus circulating today.)

As for patients who developed long COVID after September 2022, research is ongoing to see if they respond to other monoclonal antibodies that are in development. One such study is currently enrolling participants at the University of California San Francisco. The center is recruiting 30 patients with long COVID to try a monoclonal antibody developed by Aerium Therapeutics.

“They created an investigational monoclonal antibody to treat acute COVID, but it proved less effective against variants that emerged in late 2022,” said lead investigator Michael Peluso, MD, an assistant professor of medicine in the Division of HIV, Infectious Diseases, and Global Medicine at the University of California San Francisco. The hope is it may still work to fight long COVID among patients infected with those variants.

In the meantime, the three patients with long COVID who responded to Regeneron have resumed life as they knew it pre-COVID. Although two subsequently became infected with COVID again, they recovered quickly and did not see symptoms return, something which, for them, seems nothing short of miraculous.

“I had prepared myself to be disabled for life,” said one of the patients, a 46-year-old Floridian woman who developed long COVID after an infection in January 2021. “I had crippling fatigue and dizziness so intense I felt like I was walking on a trampoline. My brain fog was so pronounced I had to write everything down constantly. Otherwise, I’d forget.”

When she became infected with COVID again in September 2021, “I thought I was going to die because I had no idea how I could possibly get worse,” she recalled. Her doctors recommended Regeneron infusion treatment. Forty-eight hours later, her symptoms improved significantly.

“I was able to go out to a cocktail party and dinner for the first time in months,” she said. “I would not have been able to do either of those things a week before.”

It’s also profoundly affected her husband, who had had to take over running the household and raising their five children, aged 11-22 years, for months.

“I can’t tell you how many school events and sports games I missed because I physically didn’t have the strength to get to them,” she noted. “To this day, my husband gets upset whenever we talk about that time. Long COVID literally took over all of our lives. It was devastating to me, but it’s just as devastating for loved ones, too. My family is just grateful to have me back.”

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

A treatment used to treat acute COVID-19 infection has also been found to be effective against long COVID, a new small study has found. The research, which assessed the benefits of monoclonal antibodies, suggests relief may finally be ahead for millions of Americans with long COVID for whom treatment has remained elusive.

The study, published in the American Journal of Emergency Medicine, found three Florida patients with long COVID made complete — and sudden — recoveries after they were given the monoclonal antibody cocktail casirivimab/imdevimab (Regeneron).

“We were struck by how rapid and complete the remissions were,” said study coauthor Paul Pepe, MD, MPH, a professor of management, policy, and community health at the School of Public Health at the University of Texas Health Sciences Center. “We found that no matter how long the patients were sick for — whether it was 5, 8, or 18 months — within 5 days, they appeared to be completely cured.”

All three patients had been initially infected with COVID-19 early in the pandemic, in 2020 or the first half of 2021. They were given Regeneron either after a reinfection or exposure to COVID-19, as a preventative, at state-run COVID clinics in Florida.

“In each case, the infusions were given to help prevent their long COVID from worsening,” said Dr. Pepe.

The researchers collected medical histories for all three patients, asking about symptoms such as physical fatigue, exercise intolerance, chest pain, heart palpitations, shortness of breath, cognitive fatigue, and memory problems. They asked patients to rate symptoms pre-COVID (baseline), during the long COVID phase, post-vaccine, and finally a week after their monoclonal antibody treatment. They also interviewed family members.

They found that across the board, symptoms improved significantly and often completely vanished. Their loved ones corroborated these reports as well.

One of the patients, a 63-year-old Floridian woman, came down with a mild case of COVID-19 at the start of the pandemic in March 2020 that lasted about 2 weeks. But several weeks later, she developed extreme, debilitating fatigue, along with chest pain and shortness of breath.

“I was chasing my 6-pound Yorkie one day after she got loose, and I was struck with such intense chest pain I fell down,” the woman, asking not to be identified, said in an interview.

Her symptoms progressed to the point where she no longer felt safe babysitting her grandchildren or driving to the grocery store.

“My short-term memory was completely gone. I couldn’t even read more than a paragraph at a time,” she said.

When she was exposed to COVID-19 in October 2021, her doctor suggested Regeneron as a preventative. She agreed to it.

“I was terrified that a second round would leave me permanently disabled and stuck in bed for the rest of my life,” she said.

About 4 days after her monoclonal antibody treatment, she noticed that some of the brain fog that had persisted after COVID was lifting.

“By day 5, it felt almost like a heavy-weighted blanket had been lifted off of me,” she recalled. “I was able to take my dog for a walk and go to the grocery store. It felt like I had gone from 0 to 100. As quickly as I went downhill, I quickly went back up.”

Reasons for Recovery

Researchers have come up with a few theories about why monoclonal antibodies may help treat long COVID, said study coauthor Aileen Marty, MD, professor of translational medicine at the Herbert Wertheim College of Medicine at Florida International University. Among them:

• It stimulates the body to fight off any residual virus. “We suspect that many of these patients simply have levels of virus that are so low they can’t be picked up by conventional testing,” said Dr. Marty. “The virus lingers in their body and causes long COVID symptoms. The monoclonal antibodies can zero in on them and knock them out.” This may also help explain why some patients with long COVID reported a temporary improvement of symptoms after their COVID-19 vaccination.
• It combats dysfunctional antibodies. Another theory is that people with long COVID have symptoms “not because of residual virus but because of junky antibodies,” said Dr. Marty. These antibodies go into overdrive and attack your own cells, which is what causes long COVID symptoms. “This may be why monoclonal antibodies work because they displace the dysfunctional antibodies that are attached to a patient’s cells,” she explained.
• Reactivation of other viruses. Long COVID is very similar to chronic fatigue syndrome, which is often thought to be triggered by reactivation of viruses like the Epstein-Barr virus, noted coauthor Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Fort Lauderdale. “It may not explain all of the cases of long COVID, but it could make up a subgroup,” she said. It’s thought that the monoclonal antibodies may perhaps neutralize this reactivation.

Where Research Is Headed

While Regeneron worked well in all three patients, it may be because they developed long COVID from either the initial virus or from early variants like Alpha, Beta, and Delta, said Dr. Pepe. As a result, it’s unclear whether this treatment would work for patients who developed long COVID from newer strains like Omicron.

“What concerns me is I believe there may be many people walking around with mild long COVID from these strains who don’t realize it,” he said. “They may assume that if they have difficulty walking upstairs, or forget why they went into another room, that it’s age related.”

The next step, the researchers said, is to create a registry of volunteer patients with severe long COVID. Dr. Klimas plans to enroll 20 volunteers who were infected before September 2022 to see how they respond to another monoclonal antibody initially used to treat COVID-19, bebtelovimab. (Like Regeneron, bebtelovimab is no longer approved for use against COVID-19 by the US Food and Drug Administration because it is no longer effective against variants of the virus circulating today.)

As for patients who developed long COVID after September 2022, research is ongoing to see if they respond to other monoclonal antibodies that are in development. One such study is currently enrolling participants at the University of California San Francisco. The center is recruiting 30 patients with long COVID to try a monoclonal antibody developed by Aerium Therapeutics.

“They created an investigational monoclonal antibody to treat acute COVID, but it proved less effective against variants that emerged in late 2022,” said lead investigator Michael Peluso, MD, an assistant professor of medicine in the Division of HIV, Infectious Diseases, and Global Medicine at the University of California San Francisco. The hope is it may still work to fight long COVID among patients infected with those variants.

In the meantime, the three patients with long COVID who responded to Regeneron have resumed life as they knew it pre-COVID. Although two subsequently became infected with COVID again, they recovered quickly and did not see symptoms return, something which, for them, seems nothing short of miraculous.

“I had prepared myself to be disabled for life,” said one of the patients, a 46-year-old Floridian woman who developed long COVID after an infection in January 2021. “I had crippling fatigue and dizziness so intense I felt like I was walking on a trampoline. My brain fog was so pronounced I had to write everything down constantly. Otherwise, I’d forget.”

When she became infected with COVID again in September 2021, “I thought I was going to die because I had no idea how I could possibly get worse,” she recalled. Her doctors recommended Regeneron infusion treatment. Forty-eight hours later, her symptoms improved significantly.

“I was able to go out to a cocktail party and dinner for the first time in months,” she said. “I would not have been able to do either of those things a week before.”

It’s also profoundly affected her husband, who had had to take over running the household and raising their five children, aged 11-22 years, for months.

“I can’t tell you how many school events and sports games I missed because I physically didn’t have the strength to get to them,” she noted. “To this day, my husband gets upset whenever we talk about that time. Long COVID literally took over all of our lives. It was devastating to me, but it’s just as devastating for loved ones, too. My family is just grateful to have me back.”

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

A treatment used to treat acute COVID-19 infection has also been found to be effective against long COVID, a new small study has found. The research, which assessed the benefits of monoclonal antibodies, suggests relief may finally be ahead for millions of Americans with long COVID for whom treatment has remained elusive.

The study, published in the American Journal of Emergency Medicine, found three Florida patients with long COVID made complete — and sudden — recoveries after they were given the monoclonal antibody cocktail casirivimab/imdevimab (Regeneron).

“We were struck by how rapid and complete the remissions were,” said study coauthor Paul Pepe, MD, MPH, a professor of management, policy, and community health at the School of Public Health at the University of Texas Health Sciences Center. “We found that no matter how long the patients were sick for — whether it was 5, 8, or 18 months — within 5 days, they appeared to be completely cured.”

All three patients had been initially infected with COVID-19 early in the pandemic, in 2020 or the first half of 2021. They were given Regeneron either after a reinfection or exposure to COVID-19, as a preventative, at state-run COVID clinics in Florida.

“In each case, the infusions were given to help prevent their long COVID from worsening,” said Dr. Pepe.

The researchers collected medical histories for all three patients, asking about symptoms such as physical fatigue, exercise intolerance, chest pain, heart palpitations, shortness of breath, cognitive fatigue, and memory problems. They asked patients to rate symptoms pre-COVID (baseline), during the long COVID phase, post-vaccine, and finally a week after their monoclonal antibody treatment. They also interviewed family members.

They found that across the board, symptoms improved significantly and often completely vanished. Their loved ones corroborated these reports as well.

One of the patients, a 63-year-old Floridian woman, came down with a mild case of COVID-19 at the start of the pandemic in March 2020 that lasted about 2 weeks. But several weeks later, she developed extreme, debilitating fatigue, along with chest pain and shortness of breath.

“I was chasing my 6-pound Yorkie one day after she got loose, and I was struck with such intense chest pain I fell down,” the woman, asking not to be identified, said in an interview.

Her symptoms progressed to the point where she no longer felt safe babysitting her grandchildren or driving to the grocery store.

“My short-term memory was completely gone. I couldn’t even read more than a paragraph at a time,” she said.

When she was exposed to COVID-19 in October 2021, her doctor suggested Regeneron as a preventative. She agreed to it.

“I was terrified that a second round would leave me permanently disabled and stuck in bed for the rest of my life,” she said.

About 4 days after her monoclonal antibody treatment, she noticed that some of the brain fog that had persisted after COVID was lifting.

“By day 5, it felt almost like a heavy-weighted blanket had been lifted off of me,” she recalled. “I was able to take my dog for a walk and go to the grocery store. It felt like I had gone from 0 to 100. As quickly as I went downhill, I quickly went back up.”

Reasons for Recovery

Researchers have come up with a few theories about why monoclonal antibodies may help treat long COVID, said study coauthor Aileen Marty, MD, professor of translational medicine at the Herbert Wertheim College of Medicine at Florida International University. Among them:

• It stimulates the body to fight off any residual virus. “We suspect that many of these patients simply have levels of virus that are so low they can’t be picked up by conventional testing,” said Dr. Marty. “The virus lingers in their body and causes long COVID symptoms. The monoclonal antibodies can zero in on them and knock them out.” This may also help explain why some patients with long COVID reported a temporary improvement of symptoms after their COVID-19 vaccination.
• It combats dysfunctional antibodies. Another theory is that people with long COVID have symptoms “not because of residual virus but because of junky antibodies,” said Dr. Marty. These antibodies go into overdrive and attack your own cells, which is what causes long COVID symptoms. “This may be why monoclonal antibodies work because they displace the dysfunctional antibodies that are attached to a patient’s cells,” she explained.
• Reactivation of other viruses. Long COVID is very similar to chronic fatigue syndrome, which is often thought to be triggered by reactivation of viruses like the Epstein-Barr virus, noted coauthor Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Fort Lauderdale. “It may not explain all of the cases of long COVID, but it could make up a subgroup,” she said. It’s thought that the monoclonal antibodies may perhaps neutralize this reactivation.

Where Research Is Headed

While Regeneron worked well in all three patients, it may be because they developed long COVID from either the initial virus or from early variants like Alpha, Beta, and Delta, said Dr. Pepe. As a result, it’s unclear whether this treatment would work for patients who developed long COVID from newer strains like Omicron.

“What concerns me is I believe there may be many people walking around with mild long COVID from these strains who don’t realize it,” he said. “They may assume that if they have difficulty walking upstairs, or forget why they went into another room, that it’s age related.”

The next step, the researchers said, is to create a registry of volunteer patients with severe long COVID. Dr. Klimas plans to enroll 20 volunteers who were infected before September 2022 to see how they respond to another monoclonal antibody initially used to treat COVID-19, bebtelovimab. (Like Regeneron, bebtelovimab is no longer approved for use against COVID-19 by the US Food and Drug Administration because it is no longer effective against variants of the virus circulating today.)

As for patients who developed long COVID after September 2022, research is ongoing to see if they respond to other monoclonal antibodies that are in development. One such study is currently enrolling participants at the University of California San Francisco. The center is recruiting 30 patients with long COVID to try a monoclonal antibody developed by Aerium Therapeutics.

“They created an investigational monoclonal antibody to treat acute COVID, but it proved less effective against variants that emerged in late 2022,” said lead investigator Michael Peluso, MD, an assistant professor of medicine in the Division of HIV, Infectious Diseases, and Global Medicine at the University of California San Francisco. The hope is it may still work to fight long COVID among patients infected with those variants.

In the meantime, the three patients with long COVID who responded to Regeneron have resumed life as they knew it pre-COVID. Although two subsequently became infected with COVID again, they recovered quickly and did not see symptoms return, something which, for them, seems nothing short of miraculous.

“I had prepared myself to be disabled for life,” said one of the patients, a 46-year-old Floridian woman who developed long COVID after an infection in January 2021. “I had crippling fatigue and dizziness so intense I felt like I was walking on a trampoline. My brain fog was so pronounced I had to write everything down constantly. Otherwise, I’d forget.”

When she became infected with COVID again in September 2021, “I thought I was going to die because I had no idea how I could possibly get worse,” she recalled. Her doctors recommended Regeneron infusion treatment. Forty-eight hours later, her symptoms improved significantly.

“I was able to go out to a cocktail party and dinner for the first time in months,” she said. “I would not have been able to do either of those things a week before.”

It’s also profoundly affected her husband, who had had to take over running the household and raising their five children, aged 11-22 years, for months.

“I can’t tell you how many school events and sports games I missed because I physically didn’t have the strength to get to them,” she noted. “To this day, my husband gets upset whenever we talk about that time. Long COVID literally took over all of our lives. It was devastating to me, but it’s just as devastating for loved ones, too. My family is just grateful to have me back.”

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

The World Health Organization called the COVID-19 variant JN.1 a standalone “variant of interest” and said JN.1 will drive an increase in cases of the virus, the global health agency has announced.

JN.1 was previously grouped with its relative, BA.2.86, but has increased so much in the past 4 weeks that the WHO moved it to standalone status, according to a summary published by the agency. The prevalence of JN.1 worldwide jumped from 3% for the week ending November 5 to 27% for the week ending December 3. During that same period, JN.1 rose from 1% to 66% of cases in the Western Pacific, which stretches across 37 countries, from China and Mongolia to Australia and New Zealand.

In the United States, JN.1 has been increasing rapidly. The variant accounted for an estimated 21% of cases for the 2-week period ending December 9, up from 8% during the 2 weeks prior.

SARS-CoV-2 is the virus that causes COVID, and like other viruses, it evolves over time, sometimes changing how the virus affects people or how well existing treatments and vaccines work against it.

The WHO and CDC have said the current COVID vaccine appears to protect people against severe symptoms due to JN.1, and the WHO called the rising variant’s public health risk “low.”

“As we observe the rise of the JN.1 variant, it’s important to note that while it may be spreading more widely, there is currently no significant evidence suggesting it is more severe or that it poses a substantial public health risk,” John Brownstein, PhD, chief innovation officer at Boston Children’s Hospital, told ABC News.

In its recent risk analysis, the WHO did acknowledge that it’s not certain whether JN.1 has a higher risk of evading immunity or causing more severe symptoms than other strains. The WHO advised countries to further study how much JN.1 can evade existing antibodies and whether the variant results in more severe disease.

The latest CDC data show that 11% of COVID tests reported to the agency are positive, and 23,432 people were hospitalized with severe symptoms within a 7-day period. The CDC urgently asked people to get vaccinated against respiratory illnesses like the flu and COVID-19 ahead of the holidays as cases rise nationwide.

“Getting vaccinated now can help prevent hospitalizations and save lives,” the agency advised.


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

The World Health Organization called the COVID-19 variant JN.1 a standalone “variant of interest” and said JN.1 will drive an increase in cases of the virus, the global health agency has announced.

JN.1 was previously grouped with its relative, BA.2.86, but has increased so much in the past 4 weeks that the WHO moved it to standalone status, according to a summary published by the agency. The prevalence of JN.1 worldwide jumped from 3% for the week ending November 5 to 27% for the week ending December 3. During that same period, JN.1 rose from 1% to 66% of cases in the Western Pacific, which stretches across 37 countries, from China and Mongolia to Australia and New Zealand.

In the United States, JN.1 has been increasing rapidly. The variant accounted for an estimated 21% of cases for the 2-week period ending December 9, up from 8% during the 2 weeks prior.

SARS-CoV-2 is the virus that causes COVID, and like other viruses, it evolves over time, sometimes changing how the virus affects people or how well existing treatments and vaccines work against it.

The WHO and CDC have said the current COVID vaccine appears to protect people against severe symptoms due to JN.1, and the WHO called the rising variant’s public health risk “low.”

“As we observe the rise of the JN.1 variant, it’s important to note that while it may be spreading more widely, there is currently no significant evidence suggesting it is more severe or that it poses a substantial public health risk,” John Brownstein, PhD, chief innovation officer at Boston Children’s Hospital, told ABC News.

In its recent risk analysis, the WHO did acknowledge that it’s not certain whether JN.1 has a higher risk of evading immunity or causing more severe symptoms than other strains. The WHO advised countries to further study how much JN.1 can evade existing antibodies and whether the variant results in more severe disease.

The latest CDC data show that 11% of COVID tests reported to the agency are positive, and 23,432 people were hospitalized with severe symptoms within a 7-day period. The CDC urgently asked people to get vaccinated against respiratory illnesses like the flu and COVID-19 ahead of the holidays as cases rise nationwide.

“Getting vaccinated now can help prevent hospitalizations and save lives,” the agency advised.


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

The World Health Organization called the COVID-19 variant JN.1 a standalone “variant of interest” and said JN.1 will drive an increase in cases of the virus, the global health agency has announced.

JN.1 was previously grouped with its relative, BA.2.86, but has increased so much in the past 4 weeks that the WHO moved it to standalone status, according to a summary published by the agency. The prevalence of JN.1 worldwide jumped from 3% for the week ending November 5 to 27% for the week ending December 3. During that same period, JN.1 rose from 1% to 66% of cases in the Western Pacific, which stretches across 37 countries, from China and Mongolia to Australia and New Zealand.

In the United States, JN.1 has been increasing rapidly. The variant accounted for an estimated 21% of cases for the 2-week period ending December 9, up from 8% during the 2 weeks prior.

SARS-CoV-2 is the virus that causes COVID, and like other viruses, it evolves over time, sometimes changing how the virus affects people or how well existing treatments and vaccines work against it.

The WHO and CDC have said the current COVID vaccine appears to protect people against severe symptoms due to JN.1, and the WHO called the rising variant’s public health risk “low.”

“As we observe the rise of the JN.1 variant, it’s important to note that while it may be spreading more widely, there is currently no significant evidence suggesting it is more severe or that it poses a substantial public health risk,” John Brownstein, PhD, chief innovation officer at Boston Children’s Hospital, told ABC News.

In its recent risk analysis, the WHO did acknowledge that it’s not certain whether JN.1 has a higher risk of evading immunity or causing more severe symptoms than other strains. The WHO advised countries to further study how much JN.1 can evade existing antibodies and whether the variant results in more severe disease.

The latest CDC data show that 11% of COVID tests reported to the agency are positive, and 23,432 people were hospitalized with severe symptoms within a 7-day period. The CDC urgently asked people to get vaccinated against respiratory illnesses like the flu and COVID-19 ahead of the holidays as cases rise nationwide.

“Getting vaccinated now can help prevent hospitalizations and save lives,” the agency advised.


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

The smartphone and smartwatch have spun off multiple apps and platforms for remotely monitoring a host of disease states, including pulmonary diseases and sleep disorders, but, as with any emergent technology, pitfalls come along with the promise and potential.

Meanwhile, technology to remotely monitor respiratory diseases is advancing into other modalities. In recent months, researchers have reported on an artificial intelligence–aided home stethoscope to monitor asthma exacerbations and an ingestible electronic capsule, which has shown some facility for continuous, remote monitoring of sleep apnea and opioid induced respiratory depression.

American College of Chest Physicians

“Smartphones and wearable technology in health care are here to stay,” Mariam Louis, MD, pulmonologist and sleep medicine physician at the University of Florida Health and chair of the nonrespiratory sleep section of the Sleep Medicine Network with the American College of Chest Physicians, said in an interview.

“It is an exciting field, as it encourages patients to be actively involved in their medical care and can potentially offer more real-time feedback regarding the patient’s medical conditions,” she said. “There are currently many apps that are being used to monitor sleep and other diseases. However, the technology is still rudimentary, and much more research is needed to see if these apps are accurate and dependable.”

Studies in the past few months have reported on the accuracy of 18 wearable sleep-tracker devices, finding they overestimated sleep duration by 19 minutes on average (Sleep. 2023 Nov 8. doi: 10.1093/sleep/zsad288). Researchers in the United States also recently reported on the first human trial of an ingestible pill for monitoring sleep apnea that sends data to a receiving device up to six feet away (Device. 2023 Nov 17. doi: 10.1016/j.device.2023.100125), and a group in Poland reported than an AI-aided home stethoscope provided reliable information on asthma exacerbations in 149 patients (Ann Fam Med. 2023;21:517-25).

Targeting Challenges With Polysomnography

All of these technologies aim to overcome challenges with traditional devices, such as polysomnography (PSG) for evaluating sleep. Jaques Reifman, PhD, a senior research scientist at the U.S. Army Medical Research and Development Command in Fort Detrick, Maryland, led the study of 18 wearable sleep trackers. “Both polysomnography and sleep tracking devices in a sense are attempting to reach the same goal: they’re trying to estimate certain sleep parameters,” Dr. Reifman said in an interview.

U.S. Army Medical Research and Development Command

“But they use very different signals,” he added, noting that PSG uses electroencephalography (EEG) to measure electrical signals in the skull whereas most sleep trackers used an accelerometer to measure body movement. “As your wrist moves around, it determines if you are moving or not,” Dr. Reifman said.

“Each of them have their plusses and minuses,” he added. PSG, while it’s considered the gold standard for measuring sleep, isn’t a consumer product. “It generally requires a very sophisticated data acquisition system; they are laden with motion artifacts and you have to have software to remove them before you analyze the data,” Dr. Reifman said. “They generally require an expert to interpret the results, although lately there are a few AI-based algorithms that you can provide the EEG signals to and it does score those stages for you”

Sleep trackers, on the other hand, are consumer products. “They can be used outside the lab, and you can use them to record for long periods of time, which is not really possible with PSG,” Dr. Reifman said. “They are low cost, they are easy to use, small size, and folks have developed algorithms that can directly tell the consumer you slept seven hours last night.

“In that sense, they’re comfortable to use as opposed to using an almost-like shower cap with the EEG and face sensors as part of the PSG montage.”

However, what sleep trackers offer in convenience, they lack in accuracy. “There are things they just cannot do based on the limitations of the signals that they use,” Dr. Reifman said.

The study was actually a meta-analysis of 14 different studies that evaluated 18 different sleep-tracking devices in 364 patients. The meta-analysis found wide variability in accuracy between devices; for example, a 75-minute overestimation of sleep with one device and a one-minute overestimation with another.

And different studies reported variations with the same tracker or different models of a tracker. The Fitbit Charge 2, for example, was found to underestimate sleep by 12 minutes in one study and overestimate sleep by 9 minutes in another, while the Fitbit HR Charge was found to overestimate sleep by 52 minutes in a third study.

The meta-analysis found while sleep trackers have high sensitivity (>90%), they had a relatively low specificity (<50%), Dr. Reifman noted.

“Because they are mainly based on the acceleration of your wrist, if you are laying down in bed and motionless after a few minutes the device is going to think you’re asleep when in reality you’re just motionless, daydreaming or trying to go to sleep but not sleeping, so the specificity to sleep is not that high,” he said.

These types of devices still have obstacles to overcome before they’re more widely used, Dr. Louis said. “All of these technologies are proprietary,” she said. “As such, little is known about the algorithms used to come up with the diagnosis or other conclusions. In addition, the majority of the data cannot be analyzed independently by the providers, limiting some of the usage of these devices for now.”

 

Early Study of Ingestible Capsule

To overcome some of those challenges with collecting data from wearables, researchers from the Massachusetts Institute of Technology and West Virginia University have worked with Celero Systems to develop a pill-sized capsule the patient swallows and which then collects vitals data from inside the gastrointestinal tract. The first in-human study evaluated the device, called the vitals-monitoring (VM) pill, in 10 patients. The study reported the data captured by the pill aligned with that gathered with standard sleep metrics and that it could detect sleep apnea episodes.

The study described the pill as a wireless device that uses a custom configuration of four off-the shelf integrated circuits — a microcontroller, accelerometer, memory component and radio signal — and electronic sensors for ballistic measurements from within the GI tract. The accelerometer measures movement of the abdomen during breathing.

Ingestible devices have actually been around for a couple of decades. The most common, the PillCam, is mostly used by gastroenterologists to capture images of the small intestine.

In the VM pill study, 3 of the 10 human volunteers had a diagnosis of either central or obstructive sleep apnea and wore a continuous positive airway pressure device during the study. The patients also had PSG. The study found that the heart rate accuracy of the VM pill was within 2.5 beats per minute of the PSG measure. The study found no significant difference in the ability of the VM pill to accurately measure respiratory rate with or without CPAP.

Since study completion, the device has been evaluated in another 10 patients, Ben Pless, CEO of Celero Systems, the company developing the VM pill and a coauthor of the study, said in an interview. All patients passed the capsule without any adverse events, he said.

Celero Systems

The capsule carries the advantages of an implantable device without the surgery, Mr. Pless said. “In addition to the product being inside body, it is very good at measuring core temperature and, of course, there are diurnal variations in core temperature,” he said. “Even though this was not in the paper, we found the combination of  monitoring respiration and core temperature is a very powerful way to do sleep staging in a completely unobtrusive and discrete way.”

The first study evaluated the overnight use of the VM pill, but future studies will evaluate longer duration of the device, first up to a week and then extending out to a month, with the goal of collecting data through the entire duration, Mr. Pless said.

“If you want to do ongoing monitoring for events that may have a low incidence, for example COPD exacerbations or some asthma which does not occur every day and you want to do long-term monitoring, an ingestible format where you ultimately take one capsule and you’re monitored for a month in a completely unobtrusive way would be a great way to do patient monitoring,” he said.

This platform could also collect multinight data for sleep studies, he added.

“While this is an exciting technology, there is much more to diagnosing sleep apnea than just heart rate and breathing,” Dr. Louis said. “During a sleep study, we look at oxygen levels, snoring, and many other variables.”

 
 

AI-Aided Stethoscope

The AI-aided stethoscope demonstrated an ability to collect reliable information on asthma exacerbations, the study in Poland found. “The parameters provided are effective for children, especially those younger than 5 years of age,” the study authors wrote.

The study enrolled patients of various ages with asthma, using the AI-aided stethoscope to monitor asthma-related physiologic parameters at home for six months. The stethoscope recorded auscultatory sounds from standard chest point and sent them to a dedicated mobile phone application in which an AI module automatically analyzed the recordings and displayed the results. The researchers trained the AI module using more than 10,000 recordings of respiratory sounds.

The study showed that a host of parameters — wheezes, rhonchi, coarse and fine crackles, heart rate, respiratory rate and inspiration-to-expiration duration ration — measured with the AI-aided stethoscope can detect asthma exacerbations without the need for obtaining peak expiratory flow measurements. It also showed a potential to make asthma diagnosis more straightforward in younger children.

“As we learn more and refine these technologies, we will be able to offer more patient centered and precise medicine to our patients, tailored specifically to their needs,” Dr. Louis said. “AI will certainly play a part in the future.”

Dr. Louis and Dr. Reifman have no relevant relationships to disclose. Mr. Pless is CEO of Celero Systems, a privately held company in Lincoln, Mass.

The smartphone and smartwatch have spun off multiple apps and platforms for remotely monitoring a host of disease states, including pulmonary diseases and sleep disorders, but, as with any emergent technology, pitfalls come along with the promise and potential.

Meanwhile, technology to remotely monitor respiratory diseases is advancing into other modalities. In recent months, researchers have reported on an artificial intelligence–aided home stethoscope to monitor asthma exacerbations and an ingestible electronic capsule, which has shown some facility for continuous, remote monitoring of sleep apnea and opioid induced respiratory depression.

American College of Chest Physicians

“Smartphones and wearable technology in health care are here to stay,” Mariam Louis, MD, pulmonologist and sleep medicine physician at the University of Florida Health and chair of the nonrespiratory sleep section of the Sleep Medicine Network with the American College of Chest Physicians, said in an interview.

“It is an exciting field, as it encourages patients to be actively involved in their medical care and can potentially offer more real-time feedback regarding the patient’s medical conditions,” she said. “There are currently many apps that are being used to monitor sleep and other diseases. However, the technology is still rudimentary, and much more research is needed to see if these apps are accurate and dependable.”

Studies in the past few months have reported on the accuracy of 18 wearable sleep-tracker devices, finding they overestimated sleep duration by 19 minutes on average (Sleep. 2023 Nov 8. doi: 10.1093/sleep/zsad288). Researchers in the United States also recently reported on the first human trial of an ingestible pill for monitoring sleep apnea that sends data to a receiving device up to six feet away (Device. 2023 Nov 17. doi: 10.1016/j.device.2023.100125), and a group in Poland reported than an AI-aided home stethoscope provided reliable information on asthma exacerbations in 149 patients (Ann Fam Med. 2023;21:517-25).

Targeting Challenges With Polysomnography

All of these technologies aim to overcome challenges with traditional devices, such as polysomnography (PSG) for evaluating sleep. Jaques Reifman, PhD, a senior research scientist at the U.S. Army Medical Research and Development Command in Fort Detrick, Maryland, led the study of 18 wearable sleep trackers. “Both polysomnography and sleep tracking devices in a sense are attempting to reach the same goal: they’re trying to estimate certain sleep parameters,” Dr. Reifman said in an interview.

U.S. Army Medical Research and Development Command

“But they use very different signals,” he added, noting that PSG uses electroencephalography (EEG) to measure electrical signals in the skull whereas most sleep trackers used an accelerometer to measure body movement. “As your wrist moves around, it determines if you are moving or not,” Dr. Reifman said.

“Each of them have their plusses and minuses,” he added. PSG, while it’s considered the gold standard for measuring sleep, isn’t a consumer product. “It generally requires a very sophisticated data acquisition system; they are laden with motion artifacts and you have to have software to remove them before you analyze the data,” Dr. Reifman said. “They generally require an expert to interpret the results, although lately there are a few AI-based algorithms that you can provide the EEG signals to and it does score those stages for you”

Sleep trackers, on the other hand, are consumer products. “They can be used outside the lab, and you can use them to record for long periods of time, which is not really possible with PSG,” Dr. Reifman said. “They are low cost, they are easy to use, small size, and folks have developed algorithms that can directly tell the consumer you slept seven hours last night.

“In that sense, they’re comfortable to use as opposed to using an almost-like shower cap with the EEG and face sensors as part of the PSG montage.”

However, what sleep trackers offer in convenience, they lack in accuracy. “There are things they just cannot do based on the limitations of the signals that they use,” Dr. Reifman said.

The study was actually a meta-analysis of 14 different studies that evaluated 18 different sleep-tracking devices in 364 patients. The meta-analysis found wide variability in accuracy between devices; for example, a 75-minute overestimation of sleep with one device and a one-minute overestimation with another.

And different studies reported variations with the same tracker or different models of a tracker. The Fitbit Charge 2, for example, was found to underestimate sleep by 12 minutes in one study and overestimate sleep by 9 minutes in another, while the Fitbit HR Charge was found to overestimate sleep by 52 minutes in a third study.

The meta-analysis found while sleep trackers have high sensitivity (>90%), they had a relatively low specificity (<50%), Dr. Reifman noted.

“Because they are mainly based on the acceleration of your wrist, if you are laying down in bed and motionless after a few minutes the device is going to think you’re asleep when in reality you’re just motionless, daydreaming or trying to go to sleep but not sleeping, so the specificity to sleep is not that high,” he said.

These types of devices still have obstacles to overcome before they’re more widely used, Dr. Louis said. “All of these technologies are proprietary,” she said. “As such, little is known about the algorithms used to come up with the diagnosis or other conclusions. In addition, the majority of the data cannot be analyzed independently by the providers, limiting some of the usage of these devices for now.”

 

Early Study of Ingestible Capsule

To overcome some of those challenges with collecting data from wearables, researchers from the Massachusetts Institute of Technology and West Virginia University have worked with Celero Systems to develop a pill-sized capsule the patient swallows and which then collects vitals data from inside the gastrointestinal tract. The first in-human study evaluated the device, called the vitals-monitoring (VM) pill, in 10 patients. The study reported the data captured by the pill aligned with that gathered with standard sleep metrics and that it could detect sleep apnea episodes.

The study described the pill as a wireless device that uses a custom configuration of four off-the shelf integrated circuits — a microcontroller, accelerometer, memory component and radio signal — and electronic sensors for ballistic measurements from within the GI tract. The accelerometer measures movement of the abdomen during breathing.

Ingestible devices have actually been around for a couple of decades. The most common, the PillCam, is mostly used by gastroenterologists to capture images of the small intestine.

In the VM pill study, 3 of the 10 human volunteers had a diagnosis of either central or obstructive sleep apnea and wore a continuous positive airway pressure device during the study. The patients also had PSG. The study found that the heart rate accuracy of the VM pill was within 2.5 beats per minute of the PSG measure. The study found no significant difference in the ability of the VM pill to accurately measure respiratory rate with or without CPAP.

Since study completion, the device has been evaluated in another 10 patients, Ben Pless, CEO of Celero Systems, the company developing the VM pill and a coauthor of the study, said in an interview. All patients passed the capsule without any adverse events, he said.

Celero Systems

The capsule carries the advantages of an implantable device without the surgery, Mr. Pless said. “In addition to the product being inside body, it is very good at measuring core temperature and, of course, there are diurnal variations in core temperature,” he said. “Even though this was not in the paper, we found the combination of  monitoring respiration and core temperature is a very powerful way to do sleep staging in a completely unobtrusive and discrete way.”

The first study evaluated the overnight use of the VM pill, but future studies will evaluate longer duration of the device, first up to a week and then extending out to a month, with the goal of collecting data through the entire duration, Mr. Pless said.

“If you want to do ongoing monitoring for events that may have a low incidence, for example COPD exacerbations or some asthma which does not occur every day and you want to do long-term monitoring, an ingestible format where you ultimately take one capsule and you’re monitored for a month in a completely unobtrusive way would be a great way to do patient monitoring,” he said.

This platform could also collect multinight data for sleep studies, he added.

“While this is an exciting technology, there is much more to diagnosing sleep apnea than just heart rate and breathing,” Dr. Louis said. “During a sleep study, we look at oxygen levels, snoring, and many other variables.”

 
 

AI-Aided Stethoscope

The AI-aided stethoscope demonstrated an ability to collect reliable information on asthma exacerbations, the study in Poland found. “The parameters provided are effective for children, especially those younger than 5 years of age,” the study authors wrote.

The study enrolled patients of various ages with asthma, using the AI-aided stethoscope to monitor asthma-related physiologic parameters at home for six months. The stethoscope recorded auscultatory sounds from standard chest point and sent them to a dedicated mobile phone application in which an AI module automatically analyzed the recordings and displayed the results. The researchers trained the AI module using more than 10,000 recordings of respiratory sounds.

The study showed that a host of parameters — wheezes, rhonchi, coarse and fine crackles, heart rate, respiratory rate and inspiration-to-expiration duration ration — measured with the AI-aided stethoscope can detect asthma exacerbations without the need for obtaining peak expiratory flow measurements. It also showed a potential to make asthma diagnosis more straightforward in younger children.

“As we learn more and refine these technologies, we will be able to offer more patient centered and precise medicine to our patients, tailored specifically to their needs,” Dr. Louis said. “AI will certainly play a part in the future.”

Dr. Louis and Dr. Reifman have no relevant relationships to disclose. Mr. Pless is CEO of Celero Systems, a privately held company in Lincoln, Mass.

The smartphone and smartwatch have spun off multiple apps and platforms for remotely monitoring a host of disease states, including pulmonary diseases and sleep disorders, but, as with any emergent technology, pitfalls come along with the promise and potential.

Meanwhile, technology to remotely monitor respiratory diseases is advancing into other modalities. In recent months, researchers have reported on an artificial intelligence–aided home stethoscope to monitor asthma exacerbations and an ingestible electronic capsule, which has shown some facility for continuous, remote monitoring of sleep apnea and opioid induced respiratory depression.

American College of Chest Physicians

“Smartphones and wearable technology in health care are here to stay,” Mariam Louis, MD, pulmonologist and sleep medicine physician at the University of Florida Health and chair of the nonrespiratory sleep section of the Sleep Medicine Network with the American College of Chest Physicians, said in an interview.

“It is an exciting field, as it encourages patients to be actively involved in their medical care and can potentially offer more real-time feedback regarding the patient’s medical conditions,” she said. “There are currently many apps that are being used to monitor sleep and other diseases. However, the technology is still rudimentary, and much more research is needed to see if these apps are accurate and dependable.”

Studies in the past few months have reported on the accuracy of 18 wearable sleep-tracker devices, finding they overestimated sleep duration by 19 minutes on average (Sleep. 2023 Nov 8. doi: 10.1093/sleep/zsad288). Researchers in the United States also recently reported on the first human trial of an ingestible pill for monitoring sleep apnea that sends data to a receiving device up to six feet away (Device. 2023 Nov 17. doi: 10.1016/j.device.2023.100125), and a group in Poland reported than an AI-aided home stethoscope provided reliable information on asthma exacerbations in 149 patients (Ann Fam Med. 2023;21:517-25).

Targeting Challenges With Polysomnography

All of these technologies aim to overcome challenges with traditional devices, such as polysomnography (PSG) for evaluating sleep. Jaques Reifman, PhD, a senior research scientist at the U.S. Army Medical Research and Development Command in Fort Detrick, Maryland, led the study of 18 wearable sleep trackers. “Both polysomnography and sleep tracking devices in a sense are attempting to reach the same goal: they’re trying to estimate certain sleep parameters,” Dr. Reifman said in an interview.

U.S. Army Medical Research and Development Command

“But they use very different signals,” he added, noting that PSG uses electroencephalography (EEG) to measure electrical signals in the skull whereas most sleep trackers used an accelerometer to measure body movement. “As your wrist moves around, it determines if you are moving or not,” Dr. Reifman said.

“Each of them have their plusses and minuses,” he added. PSG, while it’s considered the gold standard for measuring sleep, isn’t a consumer product. “It generally requires a very sophisticated data acquisition system; they are laden with motion artifacts and you have to have software to remove them before you analyze the data,” Dr. Reifman said. “They generally require an expert to interpret the results, although lately there are a few AI-based algorithms that you can provide the EEG signals to and it does score those stages for you”

Sleep trackers, on the other hand, are consumer products. “They can be used outside the lab, and you can use them to record for long periods of time, which is not really possible with PSG,” Dr. Reifman said. “They are low cost, they are easy to use, small size, and folks have developed algorithms that can directly tell the consumer you slept seven hours last night.

“In that sense, they’re comfortable to use as opposed to using an almost-like shower cap with the EEG and face sensors as part of the PSG montage.”

However, what sleep trackers offer in convenience, they lack in accuracy. “There are things they just cannot do based on the limitations of the signals that they use,” Dr. Reifman said.

The study was actually a meta-analysis of 14 different studies that evaluated 18 different sleep-tracking devices in 364 patients. The meta-analysis found wide variability in accuracy between devices; for example, a 75-minute overestimation of sleep with one device and a one-minute overestimation with another.

And different studies reported variations with the same tracker or different models of a tracker. The Fitbit Charge 2, for example, was found to underestimate sleep by 12 minutes in one study and overestimate sleep by 9 minutes in another, while the Fitbit HR Charge was found to overestimate sleep by 52 minutes in a third study.

The meta-analysis found while sleep trackers have high sensitivity (>90%), they had a relatively low specificity (<50%), Dr. Reifman noted.

“Because they are mainly based on the acceleration of your wrist, if you are laying down in bed and motionless after a few minutes the device is going to think you’re asleep when in reality you’re just motionless, daydreaming or trying to go to sleep but not sleeping, so the specificity to sleep is not that high,” he said.

These types of devices still have obstacles to overcome before they’re more widely used, Dr. Louis said. “All of these technologies are proprietary,” she said. “As such, little is known about the algorithms used to come up with the diagnosis or other conclusions. In addition, the majority of the data cannot be analyzed independently by the providers, limiting some of the usage of these devices for now.”

 

Early Study of Ingestible Capsule

To overcome some of those challenges with collecting data from wearables, researchers from the Massachusetts Institute of Technology and West Virginia University have worked with Celero Systems to develop a pill-sized capsule the patient swallows and which then collects vitals data from inside the gastrointestinal tract. The first in-human study evaluated the device, called the vitals-monitoring (VM) pill, in 10 patients. The study reported the data captured by the pill aligned with that gathered with standard sleep metrics and that it could detect sleep apnea episodes.

The study described the pill as a wireless device that uses a custom configuration of four off-the shelf integrated circuits — a microcontroller, accelerometer, memory component and radio signal — and electronic sensors for ballistic measurements from within the GI tract. The accelerometer measures movement of the abdomen during breathing.

Ingestible devices have actually been around for a couple of decades. The most common, the PillCam, is mostly used by gastroenterologists to capture images of the small intestine.

In the VM pill study, 3 of the 10 human volunteers had a diagnosis of either central or obstructive sleep apnea and wore a continuous positive airway pressure device during the study. The patients also had PSG. The study found that the heart rate accuracy of the VM pill was within 2.5 beats per minute of the PSG measure. The study found no significant difference in the ability of the VM pill to accurately measure respiratory rate with or without CPAP.

Since study completion, the device has been evaluated in another 10 patients, Ben Pless, CEO of Celero Systems, the company developing the VM pill and a coauthor of the study, said in an interview. All patients passed the capsule without any adverse events, he said.

Celero Systems

The capsule carries the advantages of an implantable device without the surgery, Mr. Pless said. “In addition to the product being inside body, it is very good at measuring core temperature and, of course, there are diurnal variations in core temperature,” he said. “Even though this was not in the paper, we found the combination of  monitoring respiration and core temperature is a very powerful way to do sleep staging in a completely unobtrusive and discrete way.”

The first study evaluated the overnight use of the VM pill, but future studies will evaluate longer duration of the device, first up to a week and then extending out to a month, with the goal of collecting data through the entire duration, Mr. Pless said.

“If you want to do ongoing monitoring for events that may have a low incidence, for example COPD exacerbations or some asthma which does not occur every day and you want to do long-term monitoring, an ingestible format where you ultimately take one capsule and you’re monitored for a month in a completely unobtrusive way would be a great way to do patient monitoring,” he said.

This platform could also collect multinight data for sleep studies, he added.

“While this is an exciting technology, there is much more to diagnosing sleep apnea than just heart rate and breathing,” Dr. Louis said. “During a sleep study, we look at oxygen levels, snoring, and many other variables.”

 
 

AI-Aided Stethoscope

The AI-aided stethoscope demonstrated an ability to collect reliable information on asthma exacerbations, the study in Poland found. “The parameters provided are effective for children, especially those younger than 5 years of age,” the study authors wrote.

The study enrolled patients of various ages with asthma, using the AI-aided stethoscope to monitor asthma-related physiologic parameters at home for six months. The stethoscope recorded auscultatory sounds from standard chest point and sent them to a dedicated mobile phone application in which an AI module automatically analyzed the recordings and displayed the results. The researchers trained the AI module using more than 10,000 recordings of respiratory sounds.

The study showed that a host of parameters — wheezes, rhonchi, coarse and fine crackles, heart rate, respiratory rate and inspiration-to-expiration duration ration — measured with the AI-aided stethoscope can detect asthma exacerbations without the need for obtaining peak expiratory flow measurements. It also showed a potential to make asthma diagnosis more straightforward in younger children.

“As we learn more and refine these technologies, we will be able to offer more patient centered and precise medicine to our patients, tailored specifically to their needs,” Dr. Louis said. “AI will certainly play a part in the future.”

Dr. Louis and Dr. Reifman have no relevant relationships to disclose. Mr. Pless is CEO of Celero Systems, a privately held company in Lincoln, Mass.

Systematically biased artificial intelligence (AI) models did not improve clinicians’ accuracy in diagnosing hospitalized patients, based on data from more than 450 clinicians.

“Artificial Intelligence (AI) could support clinicians in their diagnostic decisions of hospitalized patients but could also be biased and cause potential harm,” said Sarah Jabbour, MSE, a PhD candidate in computer science and engineering at the University of Michigan, Ann Arbor, in an interview.

“Regulatory guidance has suggested that the use of AI explanations could mitigate these harms, but the effectiveness of using AI explanations has not been established,” she said.

To examine whether AI explanations can be effective in mitigating the potential harms of systemic bias in AI models, Ms. Jabbour and colleagues conducted a randomized clinical vignette survey study. The survey was administered between April 2022 and January 2023 across 13 states, and the study population included hospitalist physicians, nurse practitioners, and physician assistants. The results were published in JAMA.

Participants were randomized to AI predictions with AI explanations (226 clinicians) or without AI explanations (231 clinicians).

The primary outcome was diagnostic accuracy for pneumonia, heart failure, and chronic obstructive pulmonary disease, defined as the number of correct diagnoses over the total number of assessments, the researchers wrote.

The clinicians viewed nine clinical vignettes of patients hospitalized with acute respiratory failure, including their presenting symptoms, physical examination, laboratory results, and chest radiographs. Clinicians viewed two vignettes with no AI model input to establish baseline diagnostic accuracy. They made three assessments in each vignette, one for each diagnosis. The order of the vignettes was two without AI predictions (to establish baseline diagnostic accuracy), six with AI predictions, and one with a clinical consultation by a hypothetical colleague. The vignettes included standard and systematically biased AI models.

The baseline diagnostic accuracy was 73% for the diagnoses of pneumonia, heart failure, and chronic obstructive pulmonary disease. Clinicians’ accuracy increased by 2.9% when they viewed a standard diagnostic AI model without explanations and by 4.4% when they viewed models with AI explanations.

However, clinicians’ accuracy decreased by 11.3% after viewing systematically biased AI model predictions without explanations compared with baseline, and biased AI model predictions with explanations decreased accuracy by 9.1%.

The decrease in accuracy with systematically biased AI predictions without explanations was mainly attributable to a decrease in the participants’ diagnostic specificity, the researchers noted, but the addition of explanations did little to improve it, the researchers said.

Potentially Useful but Still Imperfect

The findings were limited by several factors including the use of a web-based survey, which differs from surveys in a clinical setting, the researchers wrote. Other limitations included the younger than average study population, and the focus on the clinicians making treatment decisions, vs other clinicians who might have a better understanding of the AI explanations.

“In our study, explanations were presented in a way that were considered to be obvious, where the AI model was completely focused on areas of the chest X-rays unrelated to the clinical condition,” Ms. Jabbour told this news organization. “We hypothesized that if presented with such explanations, the participants in our study would notice that the model was behaving incorrectly and not rely on its predictions. This was surprisingly not the case, and the explanations when presented alongside biased AI predictions had seemingly no effect in mitigating clinicians’ overreliance on biased AI,” she said.

“AI is being developed at an extraordinary rate, and our study shows that it has the potential to improve clinical decision-making. At the same time, it could harm clinical decision-making when biased,” Ms. Jabbour said. “We must be thoughtful about how to carefully integrate AI into clinical workflows, with the goal of improving clinical care while not introducing systematic errors or harming patients,” she added.

Looking ahead, “There are several potential research areas that could be explored,” said Ms. Jabbour. “Researchers should focus on careful validation of AI models to identify biased model behavior prior to deployment. AI researchers should also continue including and communicating with clinicians during the development of AI tools to better understand clinicians’ needs and how they interact with AI,” she said. “This is not an exhaustive list of research directions, and it will take much discussion between experts across disciplines such as AI, human computer interaction, and medicine to ultimately deploy AI safely into clinical care.”

Don’t Overestimate AI

“With the increasing use of artificial intelligence and machine learning in other spheres, there has been an increase in interest in exploring how they can be utilized to improve clinical outcomes,” said Suman Pal, MD, assistant professor in the division of hospital medicine at the University of New Mexico, Albuquerque, in an interview. “However, concerns remain regarding the possible harms and ways to mitigate them,” said Dr. Pal, who was not involved in the current study.

In the current study, “It was interesting to note that explanations did not significantly mitigate the decrease in clinician accuracy from systematically biased AI model predictions,” Dr. Pal said.

“For the clinician, the findings of this study caution against overreliance on AI in clinical decision-making, especially because of the risk of exacerbating existing health disparities due to systemic inequities in existing literature,” Dr. Pal told this news organization.

“Additional research is needed to explore how clinicians can be better trained in identifying both the utility and the limitations of AI and into methods of validation and continuous quality checks with integration of AI into clinical workflows,” he noted.

The study was funded by the National Heart, Lung, and Blood Institute. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

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

Systematically biased artificial intelligence (AI) models did not improve clinicians’ accuracy in diagnosing hospitalized patients, based on data from more than 450 clinicians.

“Artificial Intelligence (AI) could support clinicians in their diagnostic decisions of hospitalized patients but could also be biased and cause potential harm,” said Sarah Jabbour, MSE, a PhD candidate in computer science and engineering at the University of Michigan, Ann Arbor, in an interview.

“Regulatory guidance has suggested that the use of AI explanations could mitigate these harms, but the effectiveness of using AI explanations has not been established,” she said.

To examine whether AI explanations can be effective in mitigating the potential harms of systemic bias in AI models, Ms. Jabbour and colleagues conducted a randomized clinical vignette survey study. The survey was administered between April 2022 and January 2023 across 13 states, and the study population included hospitalist physicians, nurse practitioners, and physician assistants. The results were published in JAMA.

Participants were randomized to AI predictions with AI explanations (226 clinicians) or without AI explanations (231 clinicians).

The primary outcome was diagnostic accuracy for pneumonia, heart failure, and chronic obstructive pulmonary disease, defined as the number of correct diagnoses over the total number of assessments, the researchers wrote.

The clinicians viewed nine clinical vignettes of patients hospitalized with acute respiratory failure, including their presenting symptoms, physical examination, laboratory results, and chest radiographs. Clinicians viewed two vignettes with no AI model input to establish baseline diagnostic accuracy. They made three assessments in each vignette, one for each diagnosis. The order of the vignettes was two without AI predictions (to establish baseline diagnostic accuracy), six with AI predictions, and one with a clinical consultation by a hypothetical colleague. The vignettes included standard and systematically biased AI models.

The baseline diagnostic accuracy was 73% for the diagnoses of pneumonia, heart failure, and chronic obstructive pulmonary disease. Clinicians’ accuracy increased by 2.9% when they viewed a standard diagnostic AI model without explanations and by 4.4% when they viewed models with AI explanations.

However, clinicians’ accuracy decreased by 11.3% after viewing systematically biased AI model predictions without explanations compared with baseline, and biased AI model predictions with explanations decreased accuracy by 9.1%.

The decrease in accuracy with systematically biased AI predictions without explanations was mainly attributable to a decrease in the participants’ diagnostic specificity, the researchers noted, but the addition of explanations did little to improve it, the researchers said.

Potentially Useful but Still Imperfect

The findings were limited by several factors including the use of a web-based survey, which differs from surveys in a clinical setting, the researchers wrote. Other limitations included the younger than average study population, and the focus on the clinicians making treatment decisions, vs other clinicians who might have a better understanding of the AI explanations.

“In our study, explanations were presented in a way that were considered to be obvious, where the AI model was completely focused on areas of the chest X-rays unrelated to the clinical condition,” Ms. Jabbour told this news organization. “We hypothesized that if presented with such explanations, the participants in our study would notice that the model was behaving incorrectly and not rely on its predictions. This was surprisingly not the case, and the explanations when presented alongside biased AI predictions had seemingly no effect in mitigating clinicians’ overreliance on biased AI,” she said.

“AI is being developed at an extraordinary rate, and our study shows that it has the potential to improve clinical decision-making. At the same time, it could harm clinical decision-making when biased,” Ms. Jabbour said. “We must be thoughtful about how to carefully integrate AI into clinical workflows, with the goal of improving clinical care while not introducing systematic errors or harming patients,” she added.

Looking ahead, “There are several potential research areas that could be explored,” said Ms. Jabbour. “Researchers should focus on careful validation of AI models to identify biased model behavior prior to deployment. AI researchers should also continue including and communicating with clinicians during the development of AI tools to better understand clinicians’ needs and how they interact with AI,” she said. “This is not an exhaustive list of research directions, and it will take much discussion between experts across disciplines such as AI, human computer interaction, and medicine to ultimately deploy AI safely into clinical care.”

Don’t Overestimate AI

“With the increasing use of artificial intelligence and machine learning in other spheres, there has been an increase in interest in exploring how they can be utilized to improve clinical outcomes,” said Suman Pal, MD, assistant professor in the division of hospital medicine at the University of New Mexico, Albuquerque, in an interview. “However, concerns remain regarding the possible harms and ways to mitigate them,” said Dr. Pal, who was not involved in the current study.

In the current study, “It was interesting to note that explanations did not significantly mitigate the decrease in clinician accuracy from systematically biased AI model predictions,” Dr. Pal said.

“For the clinician, the findings of this study caution against overreliance on AI in clinical decision-making, especially because of the risk of exacerbating existing health disparities due to systemic inequities in existing literature,” Dr. Pal told this news organization.

“Additional research is needed to explore how clinicians can be better trained in identifying both the utility and the limitations of AI and into methods of validation and continuous quality checks with integration of AI into clinical workflows,” he noted.

The study was funded by the National Heart, Lung, and Blood Institute. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

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

Systematically biased artificial intelligence (AI) models did not improve clinicians’ accuracy in diagnosing hospitalized patients, based on data from more than 450 clinicians.

“Artificial Intelligence (AI) could support clinicians in their diagnostic decisions of hospitalized patients but could also be biased and cause potential harm,” said Sarah Jabbour, MSE, a PhD candidate in computer science and engineering at the University of Michigan, Ann Arbor, in an interview.

“Regulatory guidance has suggested that the use of AI explanations could mitigate these harms, but the effectiveness of using AI explanations has not been established,” she said.

To examine whether AI explanations can be effective in mitigating the potential harms of systemic bias in AI models, Ms. Jabbour and colleagues conducted a randomized clinical vignette survey study. The survey was administered between April 2022 and January 2023 across 13 states, and the study population included hospitalist physicians, nurse practitioners, and physician assistants. The results were published in JAMA.

Participants were randomized to AI predictions with AI explanations (226 clinicians) or without AI explanations (231 clinicians).

The primary outcome was diagnostic accuracy for pneumonia, heart failure, and chronic obstructive pulmonary disease, defined as the number of correct diagnoses over the total number of assessments, the researchers wrote.

The clinicians viewed nine clinical vignettes of patients hospitalized with acute respiratory failure, including their presenting symptoms, physical examination, laboratory results, and chest radiographs. Clinicians viewed two vignettes with no AI model input to establish baseline diagnostic accuracy. They made three assessments in each vignette, one for each diagnosis. The order of the vignettes was two without AI predictions (to establish baseline diagnostic accuracy), six with AI predictions, and one with a clinical consultation by a hypothetical colleague. The vignettes included standard and systematically biased AI models.

The baseline diagnostic accuracy was 73% for the diagnoses of pneumonia, heart failure, and chronic obstructive pulmonary disease. Clinicians’ accuracy increased by 2.9% when they viewed a standard diagnostic AI model without explanations and by 4.4% when they viewed models with AI explanations.

However, clinicians’ accuracy decreased by 11.3% after viewing systematically biased AI model predictions without explanations compared with baseline, and biased AI model predictions with explanations decreased accuracy by 9.1%.

The decrease in accuracy with systematically biased AI predictions without explanations was mainly attributable to a decrease in the participants’ diagnostic specificity, the researchers noted, but the addition of explanations did little to improve it, the researchers said.

Potentially Useful but Still Imperfect

The findings were limited by several factors including the use of a web-based survey, which differs from surveys in a clinical setting, the researchers wrote. Other limitations included the younger than average study population, and the focus on the clinicians making treatment decisions, vs other clinicians who might have a better understanding of the AI explanations.

“In our study, explanations were presented in a way that were considered to be obvious, where the AI model was completely focused on areas of the chest X-rays unrelated to the clinical condition,” Ms. Jabbour told this news organization. “We hypothesized that if presented with such explanations, the participants in our study would notice that the model was behaving incorrectly and not rely on its predictions. This was surprisingly not the case, and the explanations when presented alongside biased AI predictions had seemingly no effect in mitigating clinicians’ overreliance on biased AI,” she said.

“AI is being developed at an extraordinary rate, and our study shows that it has the potential to improve clinical decision-making. At the same time, it could harm clinical decision-making when biased,” Ms. Jabbour said. “We must be thoughtful about how to carefully integrate AI into clinical workflows, with the goal of improving clinical care while not introducing systematic errors or harming patients,” she added.

Looking ahead, “There are several potential research areas that could be explored,” said Ms. Jabbour. “Researchers should focus on careful validation of AI models to identify biased model behavior prior to deployment. AI researchers should also continue including and communicating with clinicians during the development of AI tools to better understand clinicians’ needs and how they interact with AI,” she said. “This is not an exhaustive list of research directions, and it will take much discussion between experts across disciplines such as AI, human computer interaction, and medicine to ultimately deploy AI safely into clinical care.”

Don’t Overestimate AI

“With the increasing use of artificial intelligence and machine learning in other spheres, there has been an increase in interest in exploring how they can be utilized to improve clinical outcomes,” said Suman Pal, MD, assistant professor in the division of hospital medicine at the University of New Mexico, Albuquerque, in an interview. “However, concerns remain regarding the possible harms and ways to mitigate them,” said Dr. Pal, who was not involved in the current study.

In the current study, “It was interesting to note that explanations did not significantly mitigate the decrease in clinician accuracy from systematically biased AI model predictions,” Dr. Pal said.

“For the clinician, the findings of this study caution against overreliance on AI in clinical decision-making, especially because of the risk of exacerbating existing health disparities due to systemic inequities in existing literature,” Dr. Pal told this news organization.

“Additional research is needed to explore how clinicians can be better trained in identifying both the utility and the limitations of AI and into methods of validation and continuous quality checks with integration of AI into clinical workflows,” he noted.

The study was funded by the National Heart, Lung, and Blood Institute. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

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

TOPLINE:

Both blood eosinophil-directed treatment (BET) and standard care treatment (ST) similarly reduced treatment failure following acute exacerbations in chronic obstructive pulmonary disease (COPD).

METHODOLOGY:

• The researchers randomized 152 adults with a mean age of 70 years to BET or a placebo (if eosinophil counts were less than 2%) or to standard care treatment regardless of baseline eosinophil counts; the final population available for analysis included 47 patients in the blood eosinophil group and 46 in the primary care group, with 73 and 71 exacerbations, respectively.
• Participants were assessed at baseline and at day 14, day 30, and day 90 after exacerbation; the primary outcome was the rate of treatment failure at 30 days post exacerbation, defined as any need for retreatment with antibiotics or steroids, hospitalization, or death; secondary outcomes included health-related quality of life, forced expiratory volume in 1 second, and visual analogue score respiratory symptoms.
• Participants were recruited from 14 general practices between November 6, 2017, and April 30, 2020; the study was terminated on April 30, 2023, because of the COVID-19 pandemic.

TAKEAWAY:

• BET was noninferior to ST in a noninferiority analysis.
• At 30 days post exacerbation, 14 treatment failures had occurred in the BET group and 23 in the ST group; the relative risk was 0.60 (P = .070).
• The frequency of adverse events was similar between the groups; the most common adverse events were glycosuria and hospital admission for COPD exacerbation (2% in the BET group and 1% in the ST group for both event types), and no deaths occurred during the study period.
• Subgroup analysis showed the greatest benefit in both groups was to patients with higher eosinophil counts who received prednisolone.

IN PRACTICE: 

“There was improvement of lung function, quality of life, and symptoms in exacerbations with low eosinophil count independent of whether placebo or prednisolone was prescribed,” the authors wrote in their discussion.

SOURCE:

The lead author on the study was Sanjay Ramakrishnan, MBBS, University of Oxford, United Kingdom. The study was published online in Lancet Respiratory Medicine .

LIMITATIONS:

A key limitation was an error in the randomization code that prevented the trial’s completion as a superiority study; other limitations included the relatively low number of exacerbations associated with low eosinophil counts and reduction in the recommended length of treatment with prednisolone during the study period.

DISCLOSURES:

The study was supported by the National Institute for Health and Care Research. Dr. Ramakrishnan disclosed personal salary support from the National Institute for Health and Care Research, an unrestricted research grant from AstraZeneca to his institution, and speaker fees and conference travel support from AstraZeneca, all unrelated to the current study.

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

TOPLINE:

Both blood eosinophil-directed treatment (BET) and standard care treatment (ST) similarly reduced treatment failure following acute exacerbations in chronic obstructive pulmonary disease (COPD).

METHODOLOGY:

• The researchers randomized 152 adults with a mean age of 70 years to BET or a placebo (if eosinophil counts were less than 2%) or to standard care treatment regardless of baseline eosinophil counts; the final population available for analysis included 47 patients in the blood eosinophil group and 46 in the primary care group, with 73 and 71 exacerbations, respectively.
• Participants were assessed at baseline and at day 14, day 30, and day 90 after exacerbation; the primary outcome was the rate of treatment failure at 30 days post exacerbation, defined as any need for retreatment with antibiotics or steroids, hospitalization, or death; secondary outcomes included health-related quality of life, forced expiratory volume in 1 second, and visual analogue score respiratory symptoms.
• Participants were recruited from 14 general practices between November 6, 2017, and April 30, 2020; the study was terminated on April 30, 2023, because of the COVID-19 pandemic.

TAKEAWAY:

• BET was noninferior to ST in a noninferiority analysis.
• At 30 days post exacerbation, 14 treatment failures had occurred in the BET group and 23 in the ST group; the relative risk was 0.60 (P = .070).
• The frequency of adverse events was similar between the groups; the most common adverse events were glycosuria and hospital admission for COPD exacerbation (2% in the BET group and 1% in the ST group for both event types), and no deaths occurred during the study period.
• Subgroup analysis showed the greatest benefit in both groups was to patients with higher eosinophil counts who received prednisolone.

IN PRACTICE: 

“There was improvement of lung function, quality of life, and symptoms in exacerbations with low eosinophil count independent of whether placebo or prednisolone was prescribed,” the authors wrote in their discussion.

SOURCE:

The lead author on the study was Sanjay Ramakrishnan, MBBS, University of Oxford, United Kingdom. The study was published online in Lancet Respiratory Medicine .

LIMITATIONS:

A key limitation was an error in the randomization code that prevented the trial’s completion as a superiority study; other limitations included the relatively low number of exacerbations associated with low eosinophil counts and reduction in the recommended length of treatment with prednisolone during the study period.

DISCLOSURES:

The study was supported by the National Institute for Health and Care Research. Dr. Ramakrishnan disclosed personal salary support from the National Institute for Health and Care Research, an unrestricted research grant from AstraZeneca to his institution, and speaker fees and conference travel support from AstraZeneca, all unrelated to the current study.

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

TOPLINE:

Both blood eosinophil-directed treatment (BET) and standard care treatment (ST) similarly reduced treatment failure following acute exacerbations in chronic obstructive pulmonary disease (COPD).

METHODOLOGY:

• The researchers randomized 152 adults with a mean age of 70 years to BET or a placebo (if eosinophil counts were less than 2%) or to standard care treatment regardless of baseline eosinophil counts; the final population available for analysis included 47 patients in the blood eosinophil group and 46 in the primary care group, with 73 and 71 exacerbations, respectively.
• Participants were assessed at baseline and at day 14, day 30, and day 90 after exacerbation; the primary outcome was the rate of treatment failure at 30 days post exacerbation, defined as any need for retreatment with antibiotics or steroids, hospitalization, or death; secondary outcomes included health-related quality of life, forced expiratory volume in 1 second, and visual analogue score respiratory symptoms.
• Participants were recruited from 14 general practices between November 6, 2017, and April 30, 2020; the study was terminated on April 30, 2023, because of the COVID-19 pandemic.

TAKEAWAY:

• BET was noninferior to ST in a noninferiority analysis.
• At 30 days post exacerbation, 14 treatment failures had occurred in the BET group and 23 in the ST group; the relative risk was 0.60 (P = .070).
• The frequency of adverse events was similar between the groups; the most common adverse events were glycosuria and hospital admission for COPD exacerbation (2% in the BET group and 1% in the ST group for both event types), and no deaths occurred during the study period.
• Subgroup analysis showed the greatest benefit in both groups was to patients with higher eosinophil counts who received prednisolone.

IN PRACTICE: 

“There was improvement of lung function, quality of life, and symptoms in exacerbations with low eosinophil count independent of whether placebo or prednisolone was prescribed,” the authors wrote in their discussion.

SOURCE:

The lead author on the study was Sanjay Ramakrishnan, MBBS, University of Oxford, United Kingdom. The study was published online in Lancet Respiratory Medicine .

LIMITATIONS:

A key limitation was an error in the randomization code that prevented the trial’s completion as a superiority study; other limitations included the relatively low number of exacerbations associated with low eosinophil counts and reduction in the recommended length of treatment with prednisolone during the study period.

DISCLOSURES:

The study was supported by the National Institute for Health and Care Research. Dr. Ramakrishnan disclosed personal salary support from the National Institute for Health and Care Research, an unrestricted research grant from AstraZeneca to his institution, and speaker fees and conference travel support from AstraZeneca, all unrelated to the current study.

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

Use of pharmacomechanical catheter-directory thrombolysis significantly reduced the number of pulmonary artery branches with total or subtotal occlusions in patients with acute pulmonary embolism, based on data from more than 100 individuals.

Reduced distal vascular volume is a significant predictor of 30-day and 90-day mortality in acute pulmonary embolism (PE) patients, and pulmonary obstruction is often the cause, wrote Riyaz Bashir, MD, of Temple University, Philadelphia, Pennsylvania, and colleagues.

Some studies of catheter-based treatments have shown a reduction in pulmonary artery (PA) obstruction in PE patients, but the impact has been modest, the researchers said.

“The recently published RESCUE (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden) trial showed a 35.9% reduction in PA obstruction using the Refined Modified Miller Index (RMMI), the largest reduction of all published catheter studies with core lab measurement, with similar doses of tissue plasminogen activator (tPA),” the researchers wrote.

The Bashir endovascular catheter was designed to maximize thrombus reduction via a pharmacomechanical infusion. The catheter features an expandable basket of 6 nitinol-reinforced infusion limbs.

“There are three crucial goals that we want to accomplish in patients who have a severe pulmonary embolism,” Dr. Bashir said in an interview. “Those include, in the order of importance, survival, recovery of right ventricular function, and resolution of blocked pulmonary arteries; both segmental and proximal pulmonary arteries,” he said.

Most previous studies have focused on the first two goals, but they still need to evaluate the resolution of PA blockages carefully, said Dr. Bashir. “In our clinical practice, we have seen a large number of patients who develop debilitating shortness of breath from these blockages. We decided to carefully evaluate these blockages before and after pharmacomechanical catheter-directed thrombolysis with the Bashir endovascular catheter using the core lab data from the RESCUE study,” he said.

In the current study published in JACC: Advances), the researchers used baseline and 48-hour posttreatment contrast-enhanced chest computed tomography angiography of adult PE patients with right ventricular dilatation.

The study population included 107 adults with acute intermediate-risk PE who were treated with pharmacomechanical catheter-directory thrombolysis (PM-CDT) at 18 sites in the United States. Of these, 98 had intermediate high-risk PE with elevated troponin and/or brain-type natriuretic peptide (BNP) levels and 102 had bilateral PE.

The primary endpoint was the change in the number of segmental and proximal PA branches with total or subtotal occlusions (defined as > 65%) after 48 hours compared to baseline. Occlusions were assessed using McNemar’s test.

Patients with bilateral PE received two Bashir catheters; those with unilateral PE received one catheter each.

Each patient received a pulse spray of 2 mg of recombinant tPA (r-tPA) into each lung, followed by 5 mg of r-tPA over 5 hours; the total dose was 7 mg of r-tPA for patients with unilateral PEs and 14 mg for those with bilateral PEs, the researchers said. The median times for catheter placement and total procedure were 15 minutes and 54 minutes, respectively.

The number of segmental PA branches with total or subtotal occlusions decreased significantly, from 40.5% at baseline to 11.7% at 48 hours, and proximal PA branch total or subtotal occlusions decreased significantly, from 28.7% at baseline to 11.0% at 48 hours (P < 0.0001 for both).

The magnitude of the reductions in both total and subtotal occlusions of segmental arteries was significantly correlated with the extent of right ventricle recovery (measured by the reduction in right ventricular/left ventricular ratio) with a correlation coefficient of 0.287 (P = .0026); however, this correlation was not observed in the proximal PA arteries (correlation coefficient 0.132, P = .173).

One major bleeding event occurred within 72 hours in a patient who also experienced a device-related left common iliac vein thrombosis while not taking anticoagulation medication, and one death unrelated to PE occurred within 30 days.

“The two findings that surprised me include, first, a more than 70% reduction in total and subtotal occlusions in the segmental arteries with such a low dose of r-tPA and, second, the resolution of the blockages was seen not only in the arteries where the device was placed but also at remote sites away from the location of the catheter,” Dr. Bashir told this news organization.

The findings were limited by several factors including the lack of long-term clinical follow-up outcomes data and lack of comparison groups who underwent other treatments.

However, “This study implies that we now have a safe therapy for these patients that improves survival and right ventricular recovery in addition to dramatically improving blocked pulmonary arteries,” Dr. Bashir said.

As for additional research, “we need all the current and future prospective pulmonary embolism studies to include an assessment of pulmonary artery blockage resolution as an essential endpoint,” he said.
 

Catheter Expands Treatment Options

The current study, a subgroup analysis of the RESCUE trial, was one of the first to examine the impact of catheter-directed lysis on distal occlusions, study coauthor Parth M. Rali, MD, said in an interview.

To this point, literature has been limited to evaluation for proximal disease, said Dr. Rali, director of thoracic surgery and medicine and part of the Pulmonary Embolism Response Team at Temple University Hospital, Philadelphia.

Dr. Rali said he was encouraged to see confirmation that the BEC catheter, because of its design, works in patients with proximal or distal occlusive disease.

In clinical practice, “the catheter provides an additional option for care in patients with multiple distal occlusive disease when a systemic tissue plasminogen activator (tPA), may put patient at high bleeding risk,” Dr. Rali said.

Looking ahead, a prospective, observational multicenter study would be useful to validate the findings from the post hoc analysis of the current study, he noted.

The study was sponsored by the National Heart, Lung, and Blood Institute, Commonwealth of Pennsylvania, and Thrombolex Inc., a medical device company developing interventional catheter-based therapies for the rapid and effective treatment of acute venous thromboembolic disorders. Dr. Bashir is a cofounder and has an equity interest in Thrombolex Inc. Dr. Rali disclosed serving as a consultant for Thrombolex, Inari Medical, Viz AI, and ThinkSono.

Use of pharmacomechanical catheter-directory thrombolysis significantly reduced the number of pulmonary artery branches with total or subtotal occlusions in patients with acute pulmonary embolism, based on data from more than 100 individuals.

Reduced distal vascular volume is a significant predictor of 30-day and 90-day mortality in acute pulmonary embolism (PE) patients, and pulmonary obstruction is often the cause, wrote Riyaz Bashir, MD, of Temple University, Philadelphia, Pennsylvania, and colleagues.

Some studies of catheter-based treatments have shown a reduction in pulmonary artery (PA) obstruction in PE patients, but the impact has been modest, the researchers said.

“The recently published RESCUE (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden) trial showed a 35.9% reduction in PA obstruction using the Refined Modified Miller Index (RMMI), the largest reduction of all published catheter studies with core lab measurement, with similar doses of tissue plasminogen activator (tPA),” the researchers wrote.

The Bashir endovascular catheter was designed to maximize thrombus reduction via a pharmacomechanical infusion. The catheter features an expandable basket of 6 nitinol-reinforced infusion limbs.

“There are three crucial goals that we want to accomplish in patients who have a severe pulmonary embolism,” Dr. Bashir said in an interview. “Those include, in the order of importance, survival, recovery of right ventricular function, and resolution of blocked pulmonary arteries; both segmental and proximal pulmonary arteries,” he said.

Most previous studies have focused on the first two goals, but they still need to evaluate the resolution of PA blockages carefully, said Dr. Bashir. “In our clinical practice, we have seen a large number of patients who develop debilitating shortness of breath from these blockages. We decided to carefully evaluate these blockages before and after pharmacomechanical catheter-directed thrombolysis with the Bashir endovascular catheter using the core lab data from the RESCUE study,” he said.

In the current study published in JACC: Advances), the researchers used baseline and 48-hour posttreatment contrast-enhanced chest computed tomography angiography of adult PE patients with right ventricular dilatation.

The study population included 107 adults with acute intermediate-risk PE who were treated with pharmacomechanical catheter-directory thrombolysis (PM-CDT) at 18 sites in the United States. Of these, 98 had intermediate high-risk PE with elevated troponin and/or brain-type natriuretic peptide (BNP) levels and 102 had bilateral PE.

The primary endpoint was the change in the number of segmental and proximal PA branches with total or subtotal occlusions (defined as > 65%) after 48 hours compared to baseline. Occlusions were assessed using McNemar’s test.

Patients with bilateral PE received two Bashir catheters; those with unilateral PE received one catheter each.

Each patient received a pulse spray of 2 mg of recombinant tPA (r-tPA) into each lung, followed by 5 mg of r-tPA over 5 hours; the total dose was 7 mg of r-tPA for patients with unilateral PEs and 14 mg for those with bilateral PEs, the researchers said. The median times for catheter placement and total procedure were 15 minutes and 54 minutes, respectively.

The number of segmental PA branches with total or subtotal occlusions decreased significantly, from 40.5% at baseline to 11.7% at 48 hours, and proximal PA branch total or subtotal occlusions decreased significantly, from 28.7% at baseline to 11.0% at 48 hours (P < 0.0001 for both).

The magnitude of the reductions in both total and subtotal occlusions of segmental arteries was significantly correlated with the extent of right ventricle recovery (measured by the reduction in right ventricular/left ventricular ratio) with a correlation coefficient of 0.287 (P = .0026); however, this correlation was not observed in the proximal PA arteries (correlation coefficient 0.132, P = .173).

One major bleeding event occurred within 72 hours in a patient who also experienced a device-related left common iliac vein thrombosis while not taking anticoagulation medication, and one death unrelated to PE occurred within 30 days.

“The two findings that surprised me include, first, a more than 70% reduction in total and subtotal occlusions in the segmental arteries with such a low dose of r-tPA and, second, the resolution of the blockages was seen not only in the arteries where the device was placed but also at remote sites away from the location of the catheter,” Dr. Bashir told this news organization.

The findings were limited by several factors including the lack of long-term clinical follow-up outcomes data and lack of comparison groups who underwent other treatments.

However, “This study implies that we now have a safe therapy for these patients that improves survival and right ventricular recovery in addition to dramatically improving blocked pulmonary arteries,” Dr. Bashir said.

As for additional research, “we need all the current and future prospective pulmonary embolism studies to include an assessment of pulmonary artery blockage resolution as an essential endpoint,” he said.
 

Catheter Expands Treatment Options

The current study, a subgroup analysis of the RESCUE trial, was one of the first to examine the impact of catheter-directed lysis on distal occlusions, study coauthor Parth M. Rali, MD, said in an interview.

To this point, literature has been limited to evaluation for proximal disease, said Dr. Rali, director of thoracic surgery and medicine and part of the Pulmonary Embolism Response Team at Temple University Hospital, Philadelphia.

Dr. Rali said he was encouraged to see confirmation that the BEC catheter, because of its design, works in patients with proximal or distal occlusive disease.

In clinical practice, “the catheter provides an additional option for care in patients with multiple distal occlusive disease when a systemic tissue plasminogen activator (tPA), may put patient at high bleeding risk,” Dr. Rali said.

Looking ahead, a prospective, observational multicenter study would be useful to validate the findings from the post hoc analysis of the current study, he noted.

The study was sponsored by the National Heart, Lung, and Blood Institute, Commonwealth of Pennsylvania, and Thrombolex Inc., a medical device company developing interventional catheter-based therapies for the rapid and effective treatment of acute venous thromboembolic disorders. Dr. Bashir is a cofounder and has an equity interest in Thrombolex Inc. Dr. Rali disclosed serving as a consultant for Thrombolex, Inari Medical, Viz AI, and ThinkSono.

Use of pharmacomechanical catheter-directory thrombolysis significantly reduced the number of pulmonary artery branches with total or subtotal occlusions in patients with acute pulmonary embolism, based on data from more than 100 individuals.

Reduced distal vascular volume is a significant predictor of 30-day and 90-day mortality in acute pulmonary embolism (PE) patients, and pulmonary obstruction is often the cause, wrote Riyaz Bashir, MD, of Temple University, Philadelphia, Pennsylvania, and colleagues.

Some studies of catheter-based treatments have shown a reduction in pulmonary artery (PA) obstruction in PE patients, but the impact has been modest, the researchers said.

“The recently published RESCUE (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden) trial showed a 35.9% reduction in PA obstruction using the Refined Modified Miller Index (RMMI), the largest reduction of all published catheter studies with core lab measurement, with similar doses of tissue plasminogen activator (tPA),” the researchers wrote.

The Bashir endovascular catheter was designed to maximize thrombus reduction via a pharmacomechanical infusion. The catheter features an expandable basket of 6 nitinol-reinforced infusion limbs.

“There are three crucial goals that we want to accomplish in patients who have a severe pulmonary embolism,” Dr. Bashir said in an interview. “Those include, in the order of importance, survival, recovery of right ventricular function, and resolution of blocked pulmonary arteries; both segmental and proximal pulmonary arteries,” he said.

Most previous studies have focused on the first two goals, but they still need to evaluate the resolution of PA blockages carefully, said Dr. Bashir. “In our clinical practice, we have seen a large number of patients who develop debilitating shortness of breath from these blockages. We decided to carefully evaluate these blockages before and after pharmacomechanical catheter-directed thrombolysis with the Bashir endovascular catheter using the core lab data from the RESCUE study,” he said.

In the current study published in JACC: Advances), the researchers used baseline and 48-hour posttreatment contrast-enhanced chest computed tomography angiography of adult PE patients with right ventricular dilatation.

The study population included 107 adults with acute intermediate-risk PE who were treated with pharmacomechanical catheter-directory thrombolysis (PM-CDT) at 18 sites in the United States. Of these, 98 had intermediate high-risk PE with elevated troponin and/or brain-type natriuretic peptide (BNP) levels and 102 had bilateral PE.

The primary endpoint was the change in the number of segmental and proximal PA branches with total or subtotal occlusions (defined as > 65%) after 48 hours compared to baseline. Occlusions were assessed using McNemar’s test.

Patients with bilateral PE received two Bashir catheters; those with unilateral PE received one catheter each.

Each patient received a pulse spray of 2 mg of recombinant tPA (r-tPA) into each lung, followed by 5 mg of r-tPA over 5 hours; the total dose was 7 mg of r-tPA for patients with unilateral PEs and 14 mg for those with bilateral PEs, the researchers said. The median times for catheter placement and total procedure were 15 minutes and 54 minutes, respectively.

The number of segmental PA branches with total or subtotal occlusions decreased significantly, from 40.5% at baseline to 11.7% at 48 hours, and proximal PA branch total or subtotal occlusions decreased significantly, from 28.7% at baseline to 11.0% at 48 hours (P < 0.0001 for both).

The magnitude of the reductions in both total and subtotal occlusions of segmental arteries was significantly correlated with the extent of right ventricle recovery (measured by the reduction in right ventricular/left ventricular ratio) with a correlation coefficient of 0.287 (P = .0026); however, this correlation was not observed in the proximal PA arteries (correlation coefficient 0.132, P = .173).

One major bleeding event occurred within 72 hours in a patient who also experienced a device-related left common iliac vein thrombosis while not taking anticoagulation medication, and one death unrelated to PE occurred within 30 days.

“The two findings that surprised me include, first, a more than 70% reduction in total and subtotal occlusions in the segmental arteries with such a low dose of r-tPA and, second, the resolution of the blockages was seen not only in the arteries where the device was placed but also at remote sites away from the location of the catheter,” Dr. Bashir told this news organization.

The findings were limited by several factors including the lack of long-term clinical follow-up outcomes data and lack of comparison groups who underwent other treatments.

However, “This study implies that we now have a safe therapy for these patients that improves survival and right ventricular recovery in addition to dramatically improving blocked pulmonary arteries,” Dr. Bashir said.

As for additional research, “we need all the current and future prospective pulmonary embolism studies to include an assessment of pulmonary artery blockage resolution as an essential endpoint,” he said.
 

Catheter Expands Treatment Options

The current study, a subgroup analysis of the RESCUE trial, was one of the first to examine the impact of catheter-directed lysis on distal occlusions, study coauthor Parth M. Rali, MD, said in an interview.

To this point, literature has been limited to evaluation for proximal disease, said Dr. Rali, director of thoracic surgery and medicine and part of the Pulmonary Embolism Response Team at Temple University Hospital, Philadelphia.

Dr. Rali said he was encouraged to see confirmation that the BEC catheter, because of its design, works in patients with proximal or distal occlusive disease.

In clinical practice, “the catheter provides an additional option for care in patients with multiple distal occlusive disease when a systemic tissue plasminogen activator (tPA), may put patient at high bleeding risk,” Dr. Rali said.

Looking ahead, a prospective, observational multicenter study would be useful to validate the findings from the post hoc analysis of the current study, he noted.

The study was sponsored by the National Heart, Lung, and Blood Institute, Commonwealth of Pennsylvania, and Thrombolex Inc., a medical device company developing interventional catheter-based therapies for the rapid and effective treatment of acute venous thromboembolic disorders. Dr. Bashir is a cofounder and has an equity interest in Thrombolex Inc. Dr. Rali disclosed serving as a consultant for Thrombolex, Inari Medical, Viz AI, and ThinkSono.

Sabine Roman, MD, PhD, associate professor of gastroenterology and physiology at Lyon University Hospital in France, took the floor at the United European Gastroenterology Week to discuss the link between a chronic cough and gastroesophageal reflux disease (GERD). During a session on extraesophageal symptoms, Dr. Roman relayed two key messages: In patients with a chronic cough, reflux absolutely must be documented, and proton pump inhibitors (PPIs) must only be prescribed when a diagnosis of GERD has been made.
 

Overestimated Cause

Chronic cough is a widespread problem with a prevalence of between 9% and 33%, according to clinical studies. The root causes of this cough are varied; they’re mainly related to the respiratory system (eg, asthma, chronic obstructive pulmonary disease, respiratory infections, or smoking) and the ear, nose, and throat field (eg, postnasal drip). What’s more, taking certain medicines, notably angiotensin-converting enzyme inhibitors, can also be at the root of this condition.

GERD is also a possible cause of a chronic cough but one that is likely overestimated. A 2023 Spanish study provides evidence of this; GERD was suspected to be linked to cough in 46% of patients (compared with 32% for asthma and 15% for postnasal drip).

The treatments most commonly prescribed include PPIs (79.6%) and respiratory medicines (87.8%). Note that antibiotics are administered empirically to 28.6% of patients. For Roman, “the blame for a chronic cough is too often assigned to GERD, especially considering that in this study, only 43% of patients had seen a gastroenterologist, 27% had an endoscopy, and 24% had undergone esophageal pH monitoring.”

Added to this observation is the difficulty of establishing a causal link between a cough and GERD when the latter is present, even when the patient has had a diagnosis of GERD. Of course, a link between the two does not necessarily imply a cause–effect relationship, especially given that studies have shown that a cough itself can induce GERD. Studies using automatic cough detection to count cough events have shown that GERD certainly preceded a cough in 48% of patients, but in 56% of cases, it was the cough that came before the GERD. What’s more, both mechanisms were present in one third of patients.
 

Prescribing PPIs Effectively

PPIs are commonly prescribed as a test treatment. However, their efficacy is in no way proof of the existence of underlying GERD. In reality, all placebo-controlled studies have shown that in cases where no prior diagnosis of GERD has been made, PPIs have no superior efficacy.

If reflux has been proven, then the improvement provided by PPIs, compared with placebo, is between 12% and 35%. Therefore, it is essential that the presence of GERD be demonstrated, particularly if the patient has no characteristic symptoms of GERD, such as heartburn and acid reflux.

Response factors to PPIs were evaluated in 178 Italian patients with a chronic cough who presented with suspected GERD. Of those, 45% responded to treatment. It has been shown that typical symptoms, severe esophagitis (grade C/D), abnormal acid exposure, and low levels of nocturnal baseline impedance were independent factors of response to treatment.

In conclusion, patients with a chronic cough must be comprehensively tested for GERD before a long-term prescription of PPIs can be considered.
 

Cough Reflex Threshold

Various studies have also revealed that patients with GERD and presenting with a chronic cough have an increased sensitivity to the cough reflex. This hypersensitivity to the cough reflex has inspired several trials involving gabapentin and baclofen. A randomized controlled trial found the two treatments to be equally effective, achieving improvement of around 50%.

Lesogaberan, a new GABA(B) receptor agonist acting on the peripheral nervous system which is better tolerated than baclofen, a drug belonging to the same therapeutic class, showed a 26% benefit over placebo, but it was not statistically significant; lesogaberan has not been developed further.

Anti-reflux surgery is an option. A 2021 meta-analysis revealed that 84% of patients enrolled in these studies saw an improvement in their symptoms. However, these results must be regarded with caution because none of these studies were controlled, most of them were retrospective with very heterogeneous patient populations, and the data obtained on postoperative reflux control were often found to be lacking.

A retrospective study showed that among the factors for nonresponse or recurrence of symptoms after anti-reflux surgery, lack of response to medical treatment and extraesophageal symptoms such as a cough were significant factors. Consequently, potential candidates for surgery must be rigorously screened before being considered for such a procedure.

The recent recommendations for good practice published by the American Gastroenterological Association also insist that lack of response to medical treatment is a major factor for failure of surgical treatment.

In sum, patients with a chronic cough can be prescribed PPIs as first-line treatment if they have typical symptoms of GERD. In the event of treatment failure or isolated cough without typical symptoms, tests to confirm or rule out GERD are essential (such as endoscopy, esophageal pH monitoring, or impedance-pH monitoring).
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Sabine Roman, MD, PhD, associate professor of gastroenterology and physiology at Lyon University Hospital in France, took the floor at the United European Gastroenterology Week to discuss the link between a chronic cough and gastroesophageal reflux disease (GERD). During a session on extraesophageal symptoms, Dr. Roman relayed two key messages: In patients with a chronic cough, reflux absolutely must be documented, and proton pump inhibitors (PPIs) must only be prescribed when a diagnosis of GERD has been made.
 

Overestimated Cause

Chronic cough is a widespread problem with a prevalence of between 9% and 33%, according to clinical studies. The root causes of this cough are varied; they’re mainly related to the respiratory system (eg, asthma, chronic obstructive pulmonary disease, respiratory infections, or smoking) and the ear, nose, and throat field (eg, postnasal drip). What’s more, taking certain medicines, notably angiotensin-converting enzyme inhibitors, can also be at the root of this condition.

GERD is also a possible cause of a chronic cough but one that is likely overestimated. A 2023 Spanish study provides evidence of this; GERD was suspected to be linked to cough in 46% of patients (compared with 32% for asthma and 15% for postnasal drip).

The treatments most commonly prescribed include PPIs (79.6%) and respiratory medicines (87.8%). Note that antibiotics are administered empirically to 28.6% of patients. For Roman, “the blame for a chronic cough is too often assigned to GERD, especially considering that in this study, only 43% of patients had seen a gastroenterologist, 27% had an endoscopy, and 24% had undergone esophageal pH monitoring.”

Added to this observation is the difficulty of establishing a causal link between a cough and GERD when the latter is present, even when the patient has had a diagnosis of GERD. Of course, a link between the two does not necessarily imply a cause–effect relationship, especially given that studies have shown that a cough itself can induce GERD. Studies using automatic cough detection to count cough events have shown that GERD certainly preceded a cough in 48% of patients, but in 56% of cases, it was the cough that came before the GERD. What’s more, both mechanisms were present in one third of patients.
 

Prescribing PPIs Effectively

PPIs are commonly prescribed as a test treatment. However, their efficacy is in no way proof of the existence of underlying GERD. In reality, all placebo-controlled studies have shown that in cases where no prior diagnosis of GERD has been made, PPIs have no superior efficacy.

If reflux has been proven, then the improvement provided by PPIs, compared with placebo, is between 12% and 35%. Therefore, it is essential that the presence of GERD be demonstrated, particularly if the patient has no characteristic symptoms of GERD, such as heartburn and acid reflux.

Response factors to PPIs were evaluated in 178 Italian patients with a chronic cough who presented with suspected GERD. Of those, 45% responded to treatment. It has been shown that typical symptoms, severe esophagitis (grade C/D), abnormal acid exposure, and low levels of nocturnal baseline impedance were independent factors of response to treatment.

In conclusion, patients with a chronic cough must be comprehensively tested for GERD before a long-term prescription of PPIs can be considered.
 

Cough Reflex Threshold

Various studies have also revealed that patients with GERD and presenting with a chronic cough have an increased sensitivity to the cough reflex. This hypersensitivity to the cough reflex has inspired several trials involving gabapentin and baclofen. A randomized controlled trial found the two treatments to be equally effective, achieving improvement of around 50%.

Lesogaberan, a new GABA(B) receptor agonist acting on the peripheral nervous system which is better tolerated than baclofen, a drug belonging to the same therapeutic class, showed a 26% benefit over placebo, but it was not statistically significant; lesogaberan has not been developed further.

Anti-reflux surgery is an option. A 2021 meta-analysis revealed that 84% of patients enrolled in these studies saw an improvement in their symptoms. However, these results must be regarded with caution because none of these studies were controlled, most of them were retrospective with very heterogeneous patient populations, and the data obtained on postoperative reflux control were often found to be lacking.

A retrospective study showed that among the factors for nonresponse or recurrence of symptoms after anti-reflux surgery, lack of response to medical treatment and extraesophageal symptoms such as a cough were significant factors. Consequently, potential candidates for surgery must be rigorously screened before being considered for such a procedure.

The recent recommendations for good practice published by the American Gastroenterological Association also insist that lack of response to medical treatment is a major factor for failure of surgical treatment.

In sum, patients with a chronic cough can be prescribed PPIs as first-line treatment if they have typical symptoms of GERD. In the event of treatment failure or isolated cough without typical symptoms, tests to confirm or rule out GERD are essential (such as endoscopy, esophageal pH monitoring, or impedance-pH monitoring).
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Sabine Roman, MD, PhD, associate professor of gastroenterology and physiology at Lyon University Hospital in France, took the floor at the United European Gastroenterology Week to discuss the link between a chronic cough and gastroesophageal reflux disease (GERD). During a session on extraesophageal symptoms, Dr. Roman relayed two key messages: In patients with a chronic cough, reflux absolutely must be documented, and proton pump inhibitors (PPIs) must only be prescribed when a diagnosis of GERD has been made.
 

Overestimated Cause

Chronic cough is a widespread problem with a prevalence of between 9% and 33%, according to clinical studies. The root causes of this cough are varied; they’re mainly related to the respiratory system (eg, asthma, chronic obstructive pulmonary disease, respiratory infections, or smoking) and the ear, nose, and throat field (eg, postnasal drip). What’s more, taking certain medicines, notably angiotensin-converting enzyme inhibitors, can also be at the root of this condition.

GERD is also a possible cause of a chronic cough but one that is likely overestimated. A 2023 Spanish study provides evidence of this; GERD was suspected to be linked to cough in 46% of patients (compared with 32% for asthma and 15% for postnasal drip).

The treatments most commonly prescribed include PPIs (79.6%) and respiratory medicines (87.8%). Note that antibiotics are administered empirically to 28.6% of patients. For Roman, “the blame for a chronic cough is too often assigned to GERD, especially considering that in this study, only 43% of patients had seen a gastroenterologist, 27% had an endoscopy, and 24% had undergone esophageal pH monitoring.”

Added to this observation is the difficulty of establishing a causal link between a cough and GERD when the latter is present, even when the patient has had a diagnosis of GERD. Of course, a link between the two does not necessarily imply a cause–effect relationship, especially given that studies have shown that a cough itself can induce GERD. Studies using automatic cough detection to count cough events have shown that GERD certainly preceded a cough in 48% of patients, but in 56% of cases, it was the cough that came before the GERD. What’s more, both mechanisms were present in one third of patients.
 

Prescribing PPIs Effectively

PPIs are commonly prescribed as a test treatment. However, their efficacy is in no way proof of the existence of underlying GERD. In reality, all placebo-controlled studies have shown that in cases where no prior diagnosis of GERD has been made, PPIs have no superior efficacy.

If reflux has been proven, then the improvement provided by PPIs, compared with placebo, is between 12% and 35%. Therefore, it is essential that the presence of GERD be demonstrated, particularly if the patient has no characteristic symptoms of GERD, such as heartburn and acid reflux.

Response factors to PPIs were evaluated in 178 Italian patients with a chronic cough who presented with suspected GERD. Of those, 45% responded to treatment. It has been shown that typical symptoms, severe esophagitis (grade C/D), abnormal acid exposure, and low levels of nocturnal baseline impedance were independent factors of response to treatment.

In conclusion, patients with a chronic cough must be comprehensively tested for GERD before a long-term prescription of PPIs can be considered.
 

Cough Reflex Threshold

Various studies have also revealed that patients with GERD and presenting with a chronic cough have an increased sensitivity to the cough reflex. This hypersensitivity to the cough reflex has inspired several trials involving gabapentin and baclofen. A randomized controlled trial found the two treatments to be equally effective, achieving improvement of around 50%.

Lesogaberan, a new GABA(B) receptor agonist acting on the peripheral nervous system which is better tolerated than baclofen, a drug belonging to the same therapeutic class, showed a 26% benefit over placebo, but it was not statistically significant; lesogaberan has not been developed further.

Anti-reflux surgery is an option. A 2021 meta-analysis revealed that 84% of patients enrolled in these studies saw an improvement in their symptoms. However, these results must be regarded with caution because none of these studies were controlled, most of them were retrospective with very heterogeneous patient populations, and the data obtained on postoperative reflux control were often found to be lacking.

A retrospective study showed that among the factors for nonresponse or recurrence of symptoms after anti-reflux surgery, lack of response to medical treatment and extraesophageal symptoms such as a cough were significant factors. Consequently, potential candidates for surgery must be rigorously screened before being considered for such a procedure.

The recent recommendations for good practice published by the American Gastroenterological Association also insist that lack of response to medical treatment is a major factor for failure of surgical treatment.

In sum, patients with a chronic cough can be prescribed PPIs as first-line treatment if they have typical symptoms of GERD. In the event of treatment failure or isolated cough without typical symptoms, tests to confirm or rule out GERD are essential (such as endoscopy, esophageal pH monitoring, or impedance-pH monitoring).
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

UnitedHealth Group, the parent company of the nation’s largest private insurer, UnitedHealthcare (UHC), is now affiliated with or employs approximately 10% of the US physician workforce, raising anti-trust and noncompete concerns as more payers and private equity firms pursue medical practice acquisitions.

The company added 20,000 physicians in the last year alone, including a previously physician-owned multispecialty group practice of 400 doctors in New York. They join the growing web of doctors — about 90,000 of the 950,000 active US physicians — working for the UnitedHealth Group subsidiary, Optum Health, providing primary, specialty, urgent, and surgical care. Amar Desai, MD, chief executive officer of Optum Health, shared the updated workforce numbers during the health care conglomerate’s annual investor conference.

Health care mergers and consolidations have become more common as physician groups struggle to stay afloat amid dwindling payer reimbursements. Although private equity and health systems often acquire practices, payers like UHC are increasingly doing so as part of their model to advance value-based care. 

Yashaswini Singh, PhD, health care economist and assistant professor of health services, policy, and practice at Brown University, says such moves mirror the broader trend in corporate consolidation of physician practices. She said in an interview that the integrated models could possibly enhance care coordination and improve outcomes, but the impact of payer-led consolidation has not been extensively studied. 

Meanwhile, evidence considering private equity ownership is just emerging. In a 2022 study published in JAMA Health Forum, with Dr. Singh as lead author, findings showed that private equity involvement increased healthcare spending through higher prices and utilization. 

Consolidation can also raise anti-trust concerns. “If payers incentivize referral patterns of their employed physicians to favor other physicians employed by the payer, it can reduce competition by restricting consumer choice,” said Dr. Singh. 

A potential merger between Cigna and Humana that could happen by the end of the year will likely face intense scrutiny as it would create a company that rivals the size of UnitedHealth Group or CVS Health. If it goes through, the duo could streamline its insurance offerings and leverage each other’s care delivery platforms, clinics, and provider workforce. 

The Biden Administration has sought to strengthen anti-trust statutes to prevent industry monopolies and consumer harm, and the US Department of Justice and Federal Trade Commission have proposed new merger guidelines that have yet to be finalized. 

According to Dr. Singh, some of Optum’s medical practice purchases may bypass anti-trust statutes since most prospective mergers and acquisitions are reviewed only if they exceed a specific value ($101 million for 2023). Limited transparency in ownership structures further complicates matters. Plus, Dr. Singh said instances where physicians are hired instead of acquired through mergers would not be subject to current anti-trust laws. 

The ‘corporatization’ of health care is not good for patients or physicians, said Robert McNamara, MD, chief medical officer of the American Academy of Emergency Medicine Physician Group and cofounder of Take Medicine Back, a physician group advocating to remove corporate interests from health care. 

“If you ask a physician what causes them the most moral conflict, they’ll tell you it’s the insurance companies denying something they want to do for their patients,” he said. “To have the doctors now working for the insurance industry conflicts with a physician’s duty to put the patient first.” 

Dr. McNamara, chair of emergency medicine at Temple University’s Katz School of Medicine, said in an interview that more than half the states in the United States have laws or court rulings that support protecting physician autonomy from corporate interests. Still, he hopes a federal prohibition on private equity’s involvement in healthcare can soon gain traction. In November, Take Medicine Back raised a resolution at the American Medical Association’s interim House of Delegates meeting, which he said was subsequently referred to a committee. 

Emergency medicine was among the first specialties to succumb to private equity firms, but Dr. McNamara said that all types of health care providers and entities — from cardiology and urology to addiction treatment centers and nursing homes — are being swallowed up by larger organizations, including payers. 

UHC was named in a class action suit recently for allegedly shirking doctors’ orders and relying on a flawed algorithm to determine the length of skilled nursing facility stays for Medicare Advantage policyholders. 

At the investor meeting, Dr. Desai reiterated Optum’s desire to continue expanding care delivery options, especially in its pharmacy and behavioral health business lines, and focus on adopting value-based care. He credited the rapid growth to developing strong relationships with providers and standardizing technology and clinical systems.

A version of this article appeared on Medscape.com.

UnitedHealth Group, the parent company of the nation’s largest private insurer, UnitedHealthcare (UHC), is now affiliated with or employs approximately 10% of the US physician workforce, raising anti-trust and noncompete concerns as more payers and private equity firms pursue medical practice acquisitions.

The company added 20,000 physicians in the last year alone, including a previously physician-owned multispecialty group practice of 400 doctors in New York. They join the growing web of doctors — about 90,000 of the 950,000 active US physicians — working for the UnitedHealth Group subsidiary, Optum Health, providing primary, specialty, urgent, and surgical care. Amar Desai, MD, chief executive officer of Optum Health, shared the updated workforce numbers during the health care conglomerate’s annual investor conference.

Health care mergers and consolidations have become more common as physician groups struggle to stay afloat amid dwindling payer reimbursements. Although private equity and health systems often acquire practices, payers like UHC are increasingly doing so as part of their model to advance value-based care. 

Yashaswini Singh, PhD, health care economist and assistant professor of health services, policy, and practice at Brown University, says such moves mirror the broader trend in corporate consolidation of physician practices. She said in an interview that the integrated models could possibly enhance care coordination and improve outcomes, but the impact of payer-led consolidation has not been extensively studied. 

Meanwhile, evidence considering private equity ownership is just emerging. In a 2022 study published in JAMA Health Forum, with Dr. Singh as lead author, findings showed that private equity involvement increased healthcare spending through higher prices and utilization. 

Consolidation can also raise anti-trust concerns. “If payers incentivize referral patterns of their employed physicians to favor other physicians employed by the payer, it can reduce competition by restricting consumer choice,” said Dr. Singh. 

A potential merger between Cigna and Humana that could happen by the end of the year will likely face intense scrutiny as it would create a company that rivals the size of UnitedHealth Group or CVS Health. If it goes through, the duo could streamline its insurance offerings and leverage each other’s care delivery platforms, clinics, and provider workforce. 

The Biden Administration has sought to strengthen anti-trust statutes to prevent industry monopolies and consumer harm, and the US Department of Justice and Federal Trade Commission have proposed new merger guidelines that have yet to be finalized. 

According to Dr. Singh, some of Optum’s medical practice purchases may bypass anti-trust statutes since most prospective mergers and acquisitions are reviewed only if they exceed a specific value ($101 million for 2023). Limited transparency in ownership structures further complicates matters. Plus, Dr. Singh said instances where physicians are hired instead of acquired through mergers would not be subject to current anti-trust laws. 

The ‘corporatization’ of health care is not good for patients or physicians, said Robert McNamara, MD, chief medical officer of the American Academy of Emergency Medicine Physician Group and cofounder of Take Medicine Back, a physician group advocating to remove corporate interests from health care. 

“If you ask a physician what causes them the most moral conflict, they’ll tell you it’s the insurance companies denying something they want to do for their patients,” he said. “To have the doctors now working for the insurance industry conflicts with a physician’s duty to put the patient first.” 

Dr. McNamara, chair of emergency medicine at Temple University’s Katz School of Medicine, said in an interview that more than half the states in the United States have laws or court rulings that support protecting physician autonomy from corporate interests. Still, he hopes a federal prohibition on private equity’s involvement in healthcare can soon gain traction. In November, Take Medicine Back raised a resolution at the American Medical Association’s interim House of Delegates meeting, which he said was subsequently referred to a committee. 

Emergency medicine was among the first specialties to succumb to private equity firms, but Dr. McNamara said that all types of health care providers and entities — from cardiology and urology to addiction treatment centers and nursing homes — are being swallowed up by larger organizations, including payers. 

UHC was named in a class action suit recently for allegedly shirking doctors’ orders and relying on a flawed algorithm to determine the length of skilled nursing facility stays for Medicare Advantage policyholders. 

At the investor meeting, Dr. Desai reiterated Optum’s desire to continue expanding care delivery options, especially in its pharmacy and behavioral health business lines, and focus on adopting value-based care. He credited the rapid growth to developing strong relationships with providers and standardizing technology and clinical systems.

A version of this article appeared on Medscape.com.

UnitedHealth Group, the parent company of the nation’s largest private insurer, UnitedHealthcare (UHC), is now affiliated with or employs approximately 10% of the US physician workforce, raising anti-trust and noncompete concerns as more payers and private equity firms pursue medical practice acquisitions.

The company added 20,000 physicians in the last year alone, including a previously physician-owned multispecialty group practice of 400 doctors in New York. They join the growing web of doctors — about 90,000 of the 950,000 active US physicians — working for the UnitedHealth Group subsidiary, Optum Health, providing primary, specialty, urgent, and surgical care. Amar Desai, MD, chief executive officer of Optum Health, shared the updated workforce numbers during the health care conglomerate’s annual investor conference.

Health care mergers and consolidations have become more common as physician groups struggle to stay afloat amid dwindling payer reimbursements. Although private equity and health systems often acquire practices, payers like UHC are increasingly doing so as part of their model to advance value-based care. 

Yashaswini Singh, PhD, health care economist and assistant professor of health services, policy, and practice at Brown University, says such moves mirror the broader trend in corporate consolidation of physician practices. She said in an interview that the integrated models could possibly enhance care coordination and improve outcomes, but the impact of payer-led consolidation has not been extensively studied. 

Meanwhile, evidence considering private equity ownership is just emerging. In a 2022 study published in JAMA Health Forum, with Dr. Singh as lead author, findings showed that private equity involvement increased healthcare spending through higher prices and utilization. 

Consolidation can also raise anti-trust concerns. “If payers incentivize referral patterns of their employed physicians to favor other physicians employed by the payer, it can reduce competition by restricting consumer choice,” said Dr. Singh. 

A potential merger between Cigna and Humana that could happen by the end of the year will likely face intense scrutiny as it would create a company that rivals the size of UnitedHealth Group or CVS Health. If it goes through, the duo could streamline its insurance offerings and leverage each other’s care delivery platforms, clinics, and provider workforce. 

The Biden Administration has sought to strengthen anti-trust statutes to prevent industry monopolies and consumer harm, and the US Department of Justice and Federal Trade Commission have proposed new merger guidelines that have yet to be finalized. 

According to Dr. Singh, some of Optum’s medical practice purchases may bypass anti-trust statutes since most prospective mergers and acquisitions are reviewed only if they exceed a specific value ($101 million for 2023). Limited transparency in ownership structures further complicates matters. Plus, Dr. Singh said instances where physicians are hired instead of acquired through mergers would not be subject to current anti-trust laws. 

The ‘corporatization’ of health care is not good for patients or physicians, said Robert McNamara, MD, chief medical officer of the American Academy of Emergency Medicine Physician Group and cofounder of Take Medicine Back, a physician group advocating to remove corporate interests from health care. 

“If you ask a physician what causes them the most moral conflict, they’ll tell you it’s the insurance companies denying something they want to do for their patients,” he said. “To have the doctors now working for the insurance industry conflicts with a physician’s duty to put the patient first.” 

Dr. McNamara, chair of emergency medicine at Temple University’s Katz School of Medicine, said in an interview that more than half the states in the United States have laws or court rulings that support protecting physician autonomy from corporate interests. Still, he hopes a federal prohibition on private equity’s involvement in healthcare can soon gain traction. In November, Take Medicine Back raised a resolution at the American Medical Association’s interim House of Delegates meeting, which he said was subsequently referred to a committee. 

Emergency medicine was among the first specialties to succumb to private equity firms, but Dr. McNamara said that all types of health care providers and entities — from cardiology and urology to addiction treatment centers and nursing homes — are being swallowed up by larger organizations, including payers. 

UHC was named in a class action suit recently for allegedly shirking doctors’ orders and relying on a flawed algorithm to determine the length of skilled nursing facility stays for Medicare Advantage policyholders. 

At the investor meeting, Dr. Desai reiterated Optum’s desire to continue expanding care delivery options, especially in its pharmacy and behavioral health business lines, and focus on adopting value-based care. He credited the rapid growth to developing strong relationships with providers and standardizing technology and clinical systems.

A version of this article appeared on Medscape.com.