MDedge Emergency Medicine

Medical therapy for heart failure guided by an implanted pulmonary artery pressure (PAP) sensor didn’t improve survival or risk for HF events like hospitalization over a year in a major randomized trial that entered a broad range of patients with mild to moderate disease.

But medical therapy adjustments based on PAP readings from the miniature CardioMEMS (Abbott) implant might well have surpassed conventional HF management for outcomes had the world not been turned upside down by SARS-CoV-2 and the pandemic lockdowns, assert researchers from the GUIDE-HF trial.

Something about the crisis, they concluded – although not without some pushback – led to better outcomes in the standard-care control group, apparently muddling any potential differences from those on PAP-guided management.

Working with regulators, the team conducted a “pre–COVID-19 impact analysis” that compared outcomes before the March 2020 national COVID-19 emergency declaration that forced much of the United States with shelter in place.

By that time, all of the trial’s patients had been followed for at least 3 months, and about three-fourths of its endpoints had already been counted, JoAnn Lindenfeld, MD, Vanderbilt University Medical Center, Nashville, Tenn., said at a media briefing prior to unveiling GUIDE-HF at the all-virtual European Society of Cardiology Congress 2021.

The pre–COVID-19 analysis, approved several months before the end of the trial – while the data were still blinded – had been “suggested by both regulatory agencies and professional societies in Europe and in the United States,” Dr. Lindenfeld said.

It pointed to a possible benefit for the CardioMEMS-guided strategy, a barely significant 19% drop in risk (P = .049) for the primary endpoint of death, HF hospitalization, or urgent HF hospital visit. The effect was driven by a 24% decline in HF events (P = .014), with no significant contribution from mortality.

“The benefits of hemodynamic monitoring and management in reducing heart failure hospitalizations extended to patients with less severe heart failure”; that is, those in New York Heart Association class 2 and any in NYHA class 3 with “elevated natriuretic peptides but no previous hospitalization,” said Dr. Lindenfeld, who is also lead author on the GUIDE-HF report published in the Lancet.

Such benefits would suggest that CardioMEMS-guided management can improve outcomes in an HF population much broader than the device’s current indication.

But as it happens, the trial’s prospectively defined 12-month primary outcomes were less impressive. A 12% decline in risk for the composite endpoint among patients managed by CardioMEMS failed to reach significance compared with standard management (P = .16).

“Several factors could explain the considerable loss of benefit of hemodynamic-guided management during the COVID-19 pandemic,” the Lancet report explained. They include “improved patient compliance with medical and dietary regimens, reduced respiratory infections, altered health-care provider behavior, changes in disease progression due to COVID-19, or other as yet unknown effects of a major pandemic.”
 

Expanded population

Importantly, GUIDE-HF had entered 1,000 patients in NYHA class 2-4 and either an HF hospitalization in the previous year or elevated natriuretic peptide levels. About 44% of the entrants in NYHA class 3 did not have a 1-year history of HF hospitalization.

That’s a more heterogeneous and potentially lower-risk cohort than patients in the randomized CHAMPION study of 11 years ago, which led to the implant’s approval on both sides of the Atlantic.

In that trial, CardioMEMS-guided management was followed by 30% drop in risk for HF hospitalization over 6 months (P < .001). But CHAMPION was limited to patients in NYHA class 3 with a history of HF hospitalization, the device’s current indication in both the United States and Europe.

The GUIDE-HF findings “reinforce that patients with class 3 heart failure and prior heart failure hospitalization are those in whom there is the clearest benefit, based on the prior CHAMPION trial. These are the patients where this monitoring strategy may be best targeted,” Gregg C. Fonarow, MD, University of California Los Angeles Medical Center, said in an interview.

Although GUIDE-HF didn’t show a significant benefit for NYHA class 2 patients with elevated biomarkers, who aren’t covered by the device’s current labeling, that group showed “some suggestions of potential benefit,” noted Dr. Fonarow, who isn’t a coauthor on the Lancet report. So, “there may be select patients with class 2 heart failure where monitoring could be considered on a case-by-case basis.”

In an interview, Larry A. Allen, MD, MHS, said that, “while the technology is pretty amazing, the real question is whether it tells us something that we didn’t already know that leads to improved care. Unfortunately, as tested here, it doesn’t, or at least not enough to make a big difference.”

The pre–COVID-19 impact analysis “should be interpreted with caution, and not as the primary finding,” Dr. Allen, from the University of Colorado at Denver, Aurora, who is not a GUIDE-HF coauthor, said in an interview.

One might hypothesize, he said, “that, in the setting of limited in-person visits with loss of physical examination, perhaps CardioMEMS would be more – not less – helpful during the pandemic. And yet the opposite was seen.”

The pandemic has “markedly altered all kinds of aspects of patient care and trial conduct, but that doesn’t make the data derived during that period uninformative,” Dr. Allen said. “And as we are increasingly reminded, the future will be a new normal, not a prepandemic normal.”

A third group

The GUIDE-HF trial includes, in addition to the 1,000 randomized patients, a single-group observational cohort of 2,600 patients, whose outcomes will be reported at another time, noted the published report.

But in the randomized comparison, conducted at 118 centers in North America, all patients were implanted with the CardioMEMS device and blinded as to their assigned strategy. Enrollment took place between March 2018 and Dec. 20, 2019.

Of the 1,000 successfully implanted patients, 497 were assigned to the pressure-guided strategy, in which “titration of diuretics was recommended if pulmonary artery pressure provided evidence of excess intravascular volume, and titration of vasodilators was recommended if elevated vascular resistance was evident,” the report stated.

The remaining 503 patients assigned to standard care served as control subjects, for whom “investigators were aware of treatment assignment but did not have access to PAP data.”

The hazard ratio for the primary endpoint in the pressure-guided group, compared with the control group, was 0.88 (95% confidence interval, 0.74-1.05; P = .16) over a median follow-up of 11.7 months.

But in the sensitivity analysis comparing outcomes before and after the COVID-19 lockdowns, using established methodology, the report stated, the primary-endpoint HR was 0.81 (95% CI, 0.66-1.00; P = .049).

The difference is owed to improved outcomes in the control group under pandemic conditions, the researchers concluded. Patients assigned to conventional management –whatever that meant during shelter-in-place – experienced 21% fewer primary-endpoint events than their own rate before the pandemic. After the COVID-19 emergency was declared, there was no significant difference in event rates between the two randomization groups.

In the primary 12-month analysis, the HR for HF events in the guided-therapy was not significant reduced, at 0.85 (95% CI, 0.70-1.03; P = .096). But in the pre-COVID-19 analysis, that risk fell significantly with CardioMEMS-guided management, for an HR of 0.76 (95% CI, 0.61-0.95; P = .014).

An editorial accompanying the GUIDE-HF publication (Lancet. 2021 Aug 27. doi: 10.1016/S0140-6736[21]01914-0) asserts that the trial “did not enroll an ideal group of patients for showing the efficacy of pulmonary artery pressure monitoring, since many had baseline pressures in the target range with little possibility of short-term gain.”

Also, wrote John G. F. Cleland, MD, PhD, University of Glasgow, and Pierpaolo Pellicori, MD, Imperial College London, “follow-up was too short, and interventions did not substantially change pulmonary artery pressure.”

They continue: “Monitoring alone cannot improve outcome, but consequent actions might. The GUIDE-HF results are encouraging but inconclusive, and should inform further research, possibly a large, simple, open-label trial to investigate a system of care rather than a single technology.”

GUIDE-HF was funded by Abbott. Dr. Lindenfeld disclosed receiving research grants from AstraZeneca, Sensible Medical, and Volumetrix; and consulting for Abbott, Alleviant Medical, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards, Impulse Dynamics, and VWave. Dr. Fonarow reported consulting for Abbott and that his institution has participated in the GUIDE-HF trial; he has elsewhere disclosed consulting for Amgen, AstraZeneca, CHF Solutions Lifesciences, Janssen, Medtronic, and Novartis. Dr. Allen had elsewhere reported consulting for Abbott, Amgen, Boston Scientific, and Novartis. Dr. Cleland disclosed receiving personal fees from Abbott for serving on an advisory board for the MitraClip device, unrelated to the CardioMEMS device. Dr. Pellicori reported no relevant conflicts.

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

Medical therapy for heart failure guided by an implanted pulmonary artery pressure (PAP) sensor didn’t improve survival or risk for HF events like hospitalization over a year in a major randomized trial that entered a broad range of patients with mild to moderate disease.

But medical therapy adjustments based on PAP readings from the miniature CardioMEMS (Abbott) implant might well have surpassed conventional HF management for outcomes had the world not been turned upside down by SARS-CoV-2 and the pandemic lockdowns, assert researchers from the GUIDE-HF trial.

Something about the crisis, they concluded – although not without some pushback – led to better outcomes in the standard-care control group, apparently muddling any potential differences from those on PAP-guided management.

Working with regulators, the team conducted a “pre–COVID-19 impact analysis” that compared outcomes before the March 2020 national COVID-19 emergency declaration that forced much of the United States with shelter in place.

By that time, all of the trial’s patients had been followed for at least 3 months, and about three-fourths of its endpoints had already been counted, JoAnn Lindenfeld, MD, Vanderbilt University Medical Center, Nashville, Tenn., said at a media briefing prior to unveiling GUIDE-HF at the all-virtual European Society of Cardiology Congress 2021.

The pre–COVID-19 analysis, approved several months before the end of the trial – while the data were still blinded – had been “suggested by both regulatory agencies and professional societies in Europe and in the United States,” Dr. Lindenfeld said.

It pointed to a possible benefit for the CardioMEMS-guided strategy, a barely significant 19% drop in risk (P = .049) for the primary endpoint of death, HF hospitalization, or urgent HF hospital visit. The effect was driven by a 24% decline in HF events (P = .014), with no significant contribution from mortality.

“The benefits of hemodynamic monitoring and management in reducing heart failure hospitalizations extended to patients with less severe heart failure”; that is, those in New York Heart Association class 2 and any in NYHA class 3 with “elevated natriuretic peptides but no previous hospitalization,” said Dr. Lindenfeld, who is also lead author on the GUIDE-HF report published in the Lancet.

Such benefits would suggest that CardioMEMS-guided management can improve outcomes in an HF population much broader than the device’s current indication.

But as it happens, the trial’s prospectively defined 12-month primary outcomes were less impressive. A 12% decline in risk for the composite endpoint among patients managed by CardioMEMS failed to reach significance compared with standard management (P = .16).

“Several factors could explain the considerable loss of benefit of hemodynamic-guided management during the COVID-19 pandemic,” the Lancet report explained. They include “improved patient compliance with medical and dietary regimens, reduced respiratory infections, altered health-care provider behavior, changes in disease progression due to COVID-19, or other as yet unknown effects of a major pandemic.”
 

Expanded population

Importantly, GUIDE-HF had entered 1,000 patients in NYHA class 2-4 and either an HF hospitalization in the previous year or elevated natriuretic peptide levels. About 44% of the entrants in NYHA class 3 did not have a 1-year history of HF hospitalization.

That’s a more heterogeneous and potentially lower-risk cohort than patients in the randomized CHAMPION study of 11 years ago, which led to the implant’s approval on both sides of the Atlantic.

In that trial, CardioMEMS-guided management was followed by 30% drop in risk for HF hospitalization over 6 months (P < .001). But CHAMPION was limited to patients in NYHA class 3 with a history of HF hospitalization, the device’s current indication in both the United States and Europe.

The GUIDE-HF findings “reinforce that patients with class 3 heart failure and prior heart failure hospitalization are those in whom there is the clearest benefit, based on the prior CHAMPION trial. These are the patients where this monitoring strategy may be best targeted,” Gregg C. Fonarow, MD, University of California Los Angeles Medical Center, said in an interview.

Although GUIDE-HF didn’t show a significant benefit for NYHA class 2 patients with elevated biomarkers, who aren’t covered by the device’s current labeling, that group showed “some suggestions of potential benefit,” noted Dr. Fonarow, who isn’t a coauthor on the Lancet report. So, “there may be select patients with class 2 heart failure where monitoring could be considered on a case-by-case basis.”

In an interview, Larry A. Allen, MD, MHS, said that, “while the technology is pretty amazing, the real question is whether it tells us something that we didn’t already know that leads to improved care. Unfortunately, as tested here, it doesn’t, or at least not enough to make a big difference.”

The pre–COVID-19 impact analysis “should be interpreted with caution, and not as the primary finding,” Dr. Allen, from the University of Colorado at Denver, Aurora, who is not a GUIDE-HF coauthor, said in an interview.

One might hypothesize, he said, “that, in the setting of limited in-person visits with loss of physical examination, perhaps CardioMEMS would be more – not less – helpful during the pandemic. And yet the opposite was seen.”

The pandemic has “markedly altered all kinds of aspects of patient care and trial conduct, but that doesn’t make the data derived during that period uninformative,” Dr. Allen said. “And as we are increasingly reminded, the future will be a new normal, not a prepandemic normal.”

A third group

The GUIDE-HF trial includes, in addition to the 1,000 randomized patients, a single-group observational cohort of 2,600 patients, whose outcomes will be reported at another time, noted the published report.

But in the randomized comparison, conducted at 118 centers in North America, all patients were implanted with the CardioMEMS device and blinded as to their assigned strategy. Enrollment took place between March 2018 and Dec. 20, 2019.

Of the 1,000 successfully implanted patients, 497 were assigned to the pressure-guided strategy, in which “titration of diuretics was recommended if pulmonary artery pressure provided evidence of excess intravascular volume, and titration of vasodilators was recommended if elevated vascular resistance was evident,” the report stated.

The remaining 503 patients assigned to standard care served as control subjects, for whom “investigators were aware of treatment assignment but did not have access to PAP data.”

The hazard ratio for the primary endpoint in the pressure-guided group, compared with the control group, was 0.88 (95% confidence interval, 0.74-1.05; P = .16) over a median follow-up of 11.7 months.

But in the sensitivity analysis comparing outcomes before and after the COVID-19 lockdowns, using established methodology, the report stated, the primary-endpoint HR was 0.81 (95% CI, 0.66-1.00; P = .049).

The difference is owed to improved outcomes in the control group under pandemic conditions, the researchers concluded. Patients assigned to conventional management –whatever that meant during shelter-in-place – experienced 21% fewer primary-endpoint events than their own rate before the pandemic. After the COVID-19 emergency was declared, there was no significant difference in event rates between the two randomization groups.

In the primary 12-month analysis, the HR for HF events in the guided-therapy was not significant reduced, at 0.85 (95% CI, 0.70-1.03; P = .096). But in the pre-COVID-19 analysis, that risk fell significantly with CardioMEMS-guided management, for an HR of 0.76 (95% CI, 0.61-0.95; P = .014).

An editorial accompanying the GUIDE-HF publication (Lancet. 2021 Aug 27. doi: 10.1016/S0140-6736[21]01914-0) asserts that the trial “did not enroll an ideal group of patients for showing the efficacy of pulmonary artery pressure monitoring, since many had baseline pressures in the target range with little possibility of short-term gain.”

Also, wrote John G. F. Cleland, MD, PhD, University of Glasgow, and Pierpaolo Pellicori, MD, Imperial College London, “follow-up was too short, and interventions did not substantially change pulmonary artery pressure.”

They continue: “Monitoring alone cannot improve outcome, but consequent actions might. The GUIDE-HF results are encouraging but inconclusive, and should inform further research, possibly a large, simple, open-label trial to investigate a system of care rather than a single technology.”

GUIDE-HF was funded by Abbott. Dr. Lindenfeld disclosed receiving research grants from AstraZeneca, Sensible Medical, and Volumetrix; and consulting for Abbott, Alleviant Medical, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards, Impulse Dynamics, and VWave. Dr. Fonarow reported consulting for Abbott and that his institution has participated in the GUIDE-HF trial; he has elsewhere disclosed consulting for Amgen, AstraZeneca, CHF Solutions Lifesciences, Janssen, Medtronic, and Novartis. Dr. Allen had elsewhere reported consulting for Abbott, Amgen, Boston Scientific, and Novartis. Dr. Cleland disclosed receiving personal fees from Abbott for serving on an advisory board for the MitraClip device, unrelated to the CardioMEMS device. Dr. Pellicori reported no relevant conflicts.

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

Medical therapy for heart failure guided by an implanted pulmonary artery pressure (PAP) sensor didn’t improve survival or risk for HF events like hospitalization over a year in a major randomized trial that entered a broad range of patients with mild to moderate disease.

But medical therapy adjustments based on PAP readings from the miniature CardioMEMS (Abbott) implant might well have surpassed conventional HF management for outcomes had the world not been turned upside down by SARS-CoV-2 and the pandemic lockdowns, assert researchers from the GUIDE-HF trial.

Something about the crisis, they concluded – although not without some pushback – led to better outcomes in the standard-care control group, apparently muddling any potential differences from those on PAP-guided management.

Working with regulators, the team conducted a “pre–COVID-19 impact analysis” that compared outcomes before the March 2020 national COVID-19 emergency declaration that forced much of the United States with shelter in place.

By that time, all of the trial’s patients had been followed for at least 3 months, and about three-fourths of its endpoints had already been counted, JoAnn Lindenfeld, MD, Vanderbilt University Medical Center, Nashville, Tenn., said at a media briefing prior to unveiling GUIDE-HF at the all-virtual European Society of Cardiology Congress 2021.

The pre–COVID-19 analysis, approved several months before the end of the trial – while the data were still blinded – had been “suggested by both regulatory agencies and professional societies in Europe and in the United States,” Dr. Lindenfeld said.

It pointed to a possible benefit for the CardioMEMS-guided strategy, a barely significant 19% drop in risk (P = .049) for the primary endpoint of death, HF hospitalization, or urgent HF hospital visit. The effect was driven by a 24% decline in HF events (P = .014), with no significant contribution from mortality.

“The benefits of hemodynamic monitoring and management in reducing heart failure hospitalizations extended to patients with less severe heart failure”; that is, those in New York Heart Association class 2 and any in NYHA class 3 with “elevated natriuretic peptides but no previous hospitalization,” said Dr. Lindenfeld, who is also lead author on the GUIDE-HF report published in the Lancet.

Such benefits would suggest that CardioMEMS-guided management can improve outcomes in an HF population much broader than the device’s current indication.

But as it happens, the trial’s prospectively defined 12-month primary outcomes were less impressive. A 12% decline in risk for the composite endpoint among patients managed by CardioMEMS failed to reach significance compared with standard management (P = .16).

“Several factors could explain the considerable loss of benefit of hemodynamic-guided management during the COVID-19 pandemic,” the Lancet report explained. They include “improved patient compliance with medical and dietary regimens, reduced respiratory infections, altered health-care provider behavior, changes in disease progression due to COVID-19, or other as yet unknown effects of a major pandemic.”
 

Expanded population

Importantly, GUIDE-HF had entered 1,000 patients in NYHA class 2-4 and either an HF hospitalization in the previous year or elevated natriuretic peptide levels. About 44% of the entrants in NYHA class 3 did not have a 1-year history of HF hospitalization.

That’s a more heterogeneous and potentially lower-risk cohort than patients in the randomized CHAMPION study of 11 years ago, which led to the implant’s approval on both sides of the Atlantic.

In that trial, CardioMEMS-guided management was followed by 30% drop in risk for HF hospitalization over 6 months (P < .001). But CHAMPION was limited to patients in NYHA class 3 with a history of HF hospitalization, the device’s current indication in both the United States and Europe.

The GUIDE-HF findings “reinforce that patients with class 3 heart failure and prior heart failure hospitalization are those in whom there is the clearest benefit, based on the prior CHAMPION trial. These are the patients where this monitoring strategy may be best targeted,” Gregg C. Fonarow, MD, University of California Los Angeles Medical Center, said in an interview.

Although GUIDE-HF didn’t show a significant benefit for NYHA class 2 patients with elevated biomarkers, who aren’t covered by the device’s current labeling, that group showed “some suggestions of potential benefit,” noted Dr. Fonarow, who isn’t a coauthor on the Lancet report. So, “there may be select patients with class 2 heart failure where monitoring could be considered on a case-by-case basis.”

In an interview, Larry A. Allen, MD, MHS, said that, “while the technology is pretty amazing, the real question is whether it tells us something that we didn’t already know that leads to improved care. Unfortunately, as tested here, it doesn’t, or at least not enough to make a big difference.”

The pre–COVID-19 impact analysis “should be interpreted with caution, and not as the primary finding,” Dr. Allen, from the University of Colorado at Denver, Aurora, who is not a GUIDE-HF coauthor, said in an interview.

One might hypothesize, he said, “that, in the setting of limited in-person visits with loss of physical examination, perhaps CardioMEMS would be more – not less – helpful during the pandemic. And yet the opposite was seen.”

The pandemic has “markedly altered all kinds of aspects of patient care and trial conduct, but that doesn’t make the data derived during that period uninformative,” Dr. Allen said. “And as we are increasingly reminded, the future will be a new normal, not a prepandemic normal.”

A third group

The GUIDE-HF trial includes, in addition to the 1,000 randomized patients, a single-group observational cohort of 2,600 patients, whose outcomes will be reported at another time, noted the published report.

But in the randomized comparison, conducted at 118 centers in North America, all patients were implanted with the CardioMEMS device and blinded as to their assigned strategy. Enrollment took place between March 2018 and Dec. 20, 2019.

Of the 1,000 successfully implanted patients, 497 were assigned to the pressure-guided strategy, in which “titration of diuretics was recommended if pulmonary artery pressure provided evidence of excess intravascular volume, and titration of vasodilators was recommended if elevated vascular resistance was evident,” the report stated.

The remaining 503 patients assigned to standard care served as control subjects, for whom “investigators were aware of treatment assignment but did not have access to PAP data.”

The hazard ratio for the primary endpoint in the pressure-guided group, compared with the control group, was 0.88 (95% confidence interval, 0.74-1.05; P = .16) over a median follow-up of 11.7 months.

But in the sensitivity analysis comparing outcomes before and after the COVID-19 lockdowns, using established methodology, the report stated, the primary-endpoint HR was 0.81 (95% CI, 0.66-1.00; P = .049).

The difference is owed to improved outcomes in the control group under pandemic conditions, the researchers concluded. Patients assigned to conventional management –whatever that meant during shelter-in-place – experienced 21% fewer primary-endpoint events than their own rate before the pandemic. After the COVID-19 emergency was declared, there was no significant difference in event rates between the two randomization groups.

In the primary 12-month analysis, the HR for HF events in the guided-therapy was not significant reduced, at 0.85 (95% CI, 0.70-1.03; P = .096). But in the pre-COVID-19 analysis, that risk fell significantly with CardioMEMS-guided management, for an HR of 0.76 (95% CI, 0.61-0.95; P = .014).

An editorial accompanying the GUIDE-HF publication (Lancet. 2021 Aug 27. doi: 10.1016/S0140-6736[21]01914-0) asserts that the trial “did not enroll an ideal group of patients for showing the efficacy of pulmonary artery pressure monitoring, since many had baseline pressures in the target range with little possibility of short-term gain.”

Also, wrote John G. F. Cleland, MD, PhD, University of Glasgow, and Pierpaolo Pellicori, MD, Imperial College London, “follow-up was too short, and interventions did not substantially change pulmonary artery pressure.”

They continue: “Monitoring alone cannot improve outcome, but consequent actions might. The GUIDE-HF results are encouraging but inconclusive, and should inform further research, possibly a large, simple, open-label trial to investigate a system of care rather than a single technology.”

GUIDE-HF was funded by Abbott. Dr. Lindenfeld disclosed receiving research grants from AstraZeneca, Sensible Medical, and Volumetrix; and consulting for Abbott, Alleviant Medical, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards, Impulse Dynamics, and VWave. Dr. Fonarow reported consulting for Abbott and that his institution has participated in the GUIDE-HF trial; he has elsewhere disclosed consulting for Amgen, AstraZeneca, CHF Solutions Lifesciences, Janssen, Medtronic, and Novartis. Dr. Allen had elsewhere reported consulting for Abbott, Amgen, Boston Scientific, and Novartis. Dr. Cleland disclosed receiving personal fees from Abbott for serving on an advisory board for the MitraClip device, unrelated to the CardioMEMS device. Dr. Pellicori reported no relevant conflicts.

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

Patients with atrial fibrillation (AFib) gained significant benefits from a 6-month program of supervised and unsupervised moderate exercise versus usual care, new randomized trial results show.  

Among 120 AFib patients in the ACTIVE-AF trial, those randomized to the exercise arm had significantly less frequent AFib recurrence and less severe symptoms over a 1-year period, said Adrian Elliott, PhD, who will present this late-breaking research at the European Society of Cardiology (ESC) Congress 2021.

The trial “demonstrates that some patients can control their arrhythmia through physical activity, without the need for complex interventions such as ablation or medications to keep their heart in normal rhythm,” Dr. Elliott, from the University of Adelaide, Australia, said in a statement from the ESC.

This is “the largest randomized controlled trial investigating the value of an exercise prescription in patients with symptomatic paroxysmal or persistent [AFib],” he told this news organization in an email.

The findings “really provide the evidence needed that recommending aerobic exercise in patients with symptomatic AFib can lower the severity of symptoms and prevent the recurrence of AFib for many patients,” he said. Aerobic exercise should be incorporated into patient treatment, he added, “alongside the use of medications, as guided by a cardiologist, and management of obesity, hypertension, and sleep apnea.”

Mina K. Chung, MD, lead author of a Scientific Statement from the American Heart Association on Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation, as previously reported, agrees.

The “findings support the AHA Scientific Statement that we should encourage our patients with AFib to include regular moderate exercise to help prevent AFib, reduce AFib burden, and improve AFib-related symptoms and quality of life,” Dr. Chung, a cardiologist at the Cleveland Clinic, summarized in an email.

“Our recommendation is to encourage AFib patients to aim for at least the AHA physical activity guidelines for the general population, which advise 150 minutes each week of moderate-intensity exercise,” Dr. Chung said.

This is a “reasonable” goal, but “some might argue that a slightly higher target of physical activity duration may be considered,” Dr. Elliott commented.

ACTIVE-AF, he noted, suggests that “as a general guide, patients [with AFib] should strive to build up to 3.5 hours per week of aerobic exercise and incorporate some higher intensity activities to improve cardiorespiratory fitness.”
 

Aim for 3.5 hours a week

A previous observational study showed that patients who improved their cardiorespiratory fitness over a 5-year period were significantly less likely to have AFib recurrences.

And in a randomized trial of 51 patients, 12 weeks of aerobic interval training reduced the time spent in AFib compared to usual care, during a 4-week follow-up.

ACTIVE-AF aimed to investigate the value of exercise in AFib in a larger, longer, randomized trial.

The researchers enrolled 120 patients with an average age of 65 years, of whom 43% were women.

Patients in the treatment group received individualized guided exercise from an exercise physiologist in the cardiology clinic once a week for 3 months, then every second week for the following 3 months along with a physical activity plan to follow at home for the other days – aiming to build up to 3.5 hours of physical activity a week.

The supervised sessions, Dr. Elliott explained, were typically higher intensity to raise cardiorespiratory fitness, while the home-based exercise was a moderate intensity aerobic activity of the patient’s choice, such as walking, indoor cycling, or swimming.

“We certainly cautioned against far exceeding this level,” he added.

Patients in the usual care group received exercise advice but no active intervention.

All patients received usual medical care from their cardiologist, who was blinded to the study group allocation.

The co-primary outcomes were AFib symptom severity score and the percentage of patients with recurrent AFib at 12 months, defined as having an AFib episode that lasted longer than 30 seconds or undergoing ablation or requiring ongoing anti-arrhythmic drug therapy.

At 12 months, the percentage of patients with AFib recurrence was significantly lower in the exercise group than in the control group (60% vs. 80%; hazard ratio, 0.50; 95% confidence interval, 0.33-0.78; P = .002).

This means that more patients in the exercise group had a normal heart rhythm without needing an invasive intervention (ablation) or continued use of drugs, Dr. Elliott stressed.

Patients in the exercise group also had significantly less severe symptoms – palpitations, shortness of breath, and fatigue – than patients in the control group.

“On average, patients were achieving close to 180 minutes [of physical activity] per week by 6 months of the intervention and attended 18 supervised sessions in the clinic,” Dr. Elliott said.

Cost was not a barrier since the sessions with an exercise physiologist were free.

Lack of time was the most common reason for missing the physical activity targets, especially for patients with work and family commitments.

Most patients liked the variety of physical activity options.

The researchers plan to determine any gender differences in ACTIVE-AF.

Further research is needed, Dr. Elliott added, to determine which type of exercise is best, whether exercise plus weight loss is synergistic, and whether exercise leads to better long-term freedom from arrhythmia, reduced hospitalization, and improved survival.

The study was partially supported by the National Heart Foundation of Australia through a postdoctoral fellowship to Dr. Elliott. The researchers and Dr. Chung have disclosed no relevant financial relationships.  

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

Patients with atrial fibrillation (AFib) gained significant benefits from a 6-month program of supervised and unsupervised moderate exercise versus usual care, new randomized trial results show.  

Among 120 AFib patients in the ACTIVE-AF trial, those randomized to the exercise arm had significantly less frequent AFib recurrence and less severe symptoms over a 1-year period, said Adrian Elliott, PhD, who will present this late-breaking research at the European Society of Cardiology (ESC) Congress 2021.

The trial “demonstrates that some patients can control their arrhythmia through physical activity, without the need for complex interventions such as ablation or medications to keep their heart in normal rhythm,” Dr. Elliott, from the University of Adelaide, Australia, said in a statement from the ESC.

This is “the largest randomized controlled trial investigating the value of an exercise prescription in patients with symptomatic paroxysmal or persistent [AFib],” he told this news organization in an email.

The findings “really provide the evidence needed that recommending aerobic exercise in patients with symptomatic AFib can lower the severity of symptoms and prevent the recurrence of AFib for many patients,” he said. Aerobic exercise should be incorporated into patient treatment, he added, “alongside the use of medications, as guided by a cardiologist, and management of obesity, hypertension, and sleep apnea.”

Mina K. Chung, MD, lead author of a Scientific Statement from the American Heart Association on Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation, as previously reported, agrees.

The “findings support the AHA Scientific Statement that we should encourage our patients with AFib to include regular moderate exercise to help prevent AFib, reduce AFib burden, and improve AFib-related symptoms and quality of life,” Dr. Chung, a cardiologist at the Cleveland Clinic, summarized in an email.

“Our recommendation is to encourage AFib patients to aim for at least the AHA physical activity guidelines for the general population, which advise 150 minutes each week of moderate-intensity exercise,” Dr. Chung said.

This is a “reasonable” goal, but “some might argue that a slightly higher target of physical activity duration may be considered,” Dr. Elliott commented.

ACTIVE-AF, he noted, suggests that “as a general guide, patients [with AFib] should strive to build up to 3.5 hours per week of aerobic exercise and incorporate some higher intensity activities to improve cardiorespiratory fitness.”
 

Aim for 3.5 hours a week

A previous observational study showed that patients who improved their cardiorespiratory fitness over a 5-year period were significantly less likely to have AFib recurrences.

And in a randomized trial of 51 patients, 12 weeks of aerobic interval training reduced the time spent in AFib compared to usual care, during a 4-week follow-up.

ACTIVE-AF aimed to investigate the value of exercise in AFib in a larger, longer, randomized trial.

The researchers enrolled 120 patients with an average age of 65 years, of whom 43% were women.

Patients in the treatment group received individualized guided exercise from an exercise physiologist in the cardiology clinic once a week for 3 months, then every second week for the following 3 months along with a physical activity plan to follow at home for the other days – aiming to build up to 3.5 hours of physical activity a week.

The supervised sessions, Dr. Elliott explained, were typically higher intensity to raise cardiorespiratory fitness, while the home-based exercise was a moderate intensity aerobic activity of the patient’s choice, such as walking, indoor cycling, or swimming.

“We certainly cautioned against far exceeding this level,” he added.

Patients in the usual care group received exercise advice but no active intervention.

All patients received usual medical care from their cardiologist, who was blinded to the study group allocation.

The co-primary outcomes were AFib symptom severity score and the percentage of patients with recurrent AFib at 12 months, defined as having an AFib episode that lasted longer than 30 seconds or undergoing ablation or requiring ongoing anti-arrhythmic drug therapy.

At 12 months, the percentage of patients with AFib recurrence was significantly lower in the exercise group than in the control group (60% vs. 80%; hazard ratio, 0.50; 95% confidence interval, 0.33-0.78; P = .002).

This means that more patients in the exercise group had a normal heart rhythm without needing an invasive intervention (ablation) or continued use of drugs, Dr. Elliott stressed.

Patients in the exercise group also had significantly less severe symptoms – palpitations, shortness of breath, and fatigue – than patients in the control group.

“On average, patients were achieving close to 180 minutes [of physical activity] per week by 6 months of the intervention and attended 18 supervised sessions in the clinic,” Dr. Elliott said.

Cost was not a barrier since the sessions with an exercise physiologist were free.

Lack of time was the most common reason for missing the physical activity targets, especially for patients with work and family commitments.

Most patients liked the variety of physical activity options.

The researchers plan to determine any gender differences in ACTIVE-AF.

Further research is needed, Dr. Elliott added, to determine which type of exercise is best, whether exercise plus weight loss is synergistic, and whether exercise leads to better long-term freedom from arrhythmia, reduced hospitalization, and improved survival.

The study was partially supported by the National Heart Foundation of Australia through a postdoctoral fellowship to Dr. Elliott. The researchers and Dr. Chung have disclosed no relevant financial relationships.  

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

Patients with atrial fibrillation (AFib) gained significant benefits from a 6-month program of supervised and unsupervised moderate exercise versus usual care, new randomized trial results show.  

Among 120 AFib patients in the ACTIVE-AF trial, those randomized to the exercise arm had significantly less frequent AFib recurrence and less severe symptoms over a 1-year period, said Adrian Elliott, PhD, who will present this late-breaking research at the European Society of Cardiology (ESC) Congress 2021.

The trial “demonstrates that some patients can control their arrhythmia through physical activity, without the need for complex interventions such as ablation or medications to keep their heart in normal rhythm,” Dr. Elliott, from the University of Adelaide, Australia, said in a statement from the ESC.

This is “the largest randomized controlled trial investigating the value of an exercise prescription in patients with symptomatic paroxysmal or persistent [AFib],” he told this news organization in an email.

The findings “really provide the evidence needed that recommending aerobic exercise in patients with symptomatic AFib can lower the severity of symptoms and prevent the recurrence of AFib for many patients,” he said. Aerobic exercise should be incorporated into patient treatment, he added, “alongside the use of medications, as guided by a cardiologist, and management of obesity, hypertension, and sleep apnea.”

Mina K. Chung, MD, lead author of a Scientific Statement from the American Heart Association on Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation, as previously reported, agrees.

The “findings support the AHA Scientific Statement that we should encourage our patients with AFib to include regular moderate exercise to help prevent AFib, reduce AFib burden, and improve AFib-related symptoms and quality of life,” Dr. Chung, a cardiologist at the Cleveland Clinic, summarized in an email.

“Our recommendation is to encourage AFib patients to aim for at least the AHA physical activity guidelines for the general population, which advise 150 minutes each week of moderate-intensity exercise,” Dr. Chung said.

This is a “reasonable” goal, but “some might argue that a slightly higher target of physical activity duration may be considered,” Dr. Elliott commented.

ACTIVE-AF, he noted, suggests that “as a general guide, patients [with AFib] should strive to build up to 3.5 hours per week of aerobic exercise and incorporate some higher intensity activities to improve cardiorespiratory fitness.”
 

Aim for 3.5 hours a week

A previous observational study showed that patients who improved their cardiorespiratory fitness over a 5-year period were significantly less likely to have AFib recurrences.

And in a randomized trial of 51 patients, 12 weeks of aerobic interval training reduced the time spent in AFib compared to usual care, during a 4-week follow-up.

ACTIVE-AF aimed to investigate the value of exercise in AFib in a larger, longer, randomized trial.

The researchers enrolled 120 patients with an average age of 65 years, of whom 43% were women.

Patients in the treatment group received individualized guided exercise from an exercise physiologist in the cardiology clinic once a week for 3 months, then every second week for the following 3 months along with a physical activity plan to follow at home for the other days – aiming to build up to 3.5 hours of physical activity a week.

The supervised sessions, Dr. Elliott explained, were typically higher intensity to raise cardiorespiratory fitness, while the home-based exercise was a moderate intensity aerobic activity of the patient’s choice, such as walking, indoor cycling, or swimming.

“We certainly cautioned against far exceeding this level,” he added.

Patients in the usual care group received exercise advice but no active intervention.

All patients received usual medical care from their cardiologist, who was blinded to the study group allocation.

The co-primary outcomes were AFib symptom severity score and the percentage of patients with recurrent AFib at 12 months, defined as having an AFib episode that lasted longer than 30 seconds or undergoing ablation or requiring ongoing anti-arrhythmic drug therapy.

At 12 months, the percentage of patients with AFib recurrence was significantly lower in the exercise group than in the control group (60% vs. 80%; hazard ratio, 0.50; 95% confidence interval, 0.33-0.78; P = .002).

This means that more patients in the exercise group had a normal heart rhythm without needing an invasive intervention (ablation) or continued use of drugs, Dr. Elliott stressed.

Patients in the exercise group also had significantly less severe symptoms – palpitations, shortness of breath, and fatigue – than patients in the control group.

“On average, patients were achieving close to 180 minutes [of physical activity] per week by 6 months of the intervention and attended 18 supervised sessions in the clinic,” Dr. Elliott said.

Cost was not a barrier since the sessions with an exercise physiologist were free.

Lack of time was the most common reason for missing the physical activity targets, especially for patients with work and family commitments.

Most patients liked the variety of physical activity options.

The researchers plan to determine any gender differences in ACTIVE-AF.

Further research is needed, Dr. Elliott added, to determine which type of exercise is best, whether exercise plus weight loss is synergistic, and whether exercise leads to better long-term freedom from arrhythmia, reduced hospitalization, and improved survival.

The study was partially supported by the National Heart Foundation of Australia through a postdoctoral fellowship to Dr. Elliott. The researchers and Dr. Chung have disclosed no relevant financial relationships.  

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

Urgent recommendations from a European Academy of Allergy and Clinical Immunology (EAACI) task force are aimed at reducing antibiotic overuse with allergic disease.

Top recommendations include limiting antibiotic therapy in pregnancy and early childhood to help reduce the allergy epidemic in children, and restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, especially asthma and atopic dermatitis.

The review, by lead author Gerdien Tramper-Stranders, MD, PhD, department of pediatrics, Franciscus Gasthuis & Vlietland Hospital, Rotterdam, the Netherlands, and colleagues, was published online Aug. 13 in the journal Allergy.

Several studies have shown that use of antibiotics in childhood and during pregnancy is associated with disturbing the intestinal and respiratory microbiome, which in turn leads to dysbiosis and an increased risk of acquiring allergic diseases, the authors noted.

In addition, patients with allergic diseases such as asthma have a higher risk of being prescribed antibiotics for infections compared with the general population, despite lack of clear clinical benefit.

“In fact, there are no clear data supporting antibiotic prescriptions for acute exacerbations; and clinical and/or laboratory criteria are lacking,” the authors wrote.

Despite that lack of data, antibiotics are often prescribed for exacerbations along with oral corticosteroids, Dr. Tramper-Stranders said in an interview. Some patients may benefit from antibiotics in a flare-up, she said, but more research is needed to determine which ones.

Dr. Tramper-Stranders said Franciscus has begun a large study that includes patients with asthma exacerbations to find biomarkers that might predict the type or origin of exacerbation to personalize treatment.
 

Recommendations have global relevance

She said although the recommendations are coming from the EAACI group, they apply worldwide.

“Especially in countries outside Northern Europe, antibiotic use is tremendous, leading to high rates of antibiotic resistance; but also increasing the risk for developing allergic diseases when prescribed in infancy,” she said.

She pointed out that in the United States, as many as one in six children receive unnecessary antibiotics for an asthma exacerbation. Overtreatment in adults with flare-ups is also prevalent, at rates from 40%-50%.

Millie Kwan, MD, PhD, an allergy specialist at University of North Carolina in Chapel Hill, said in an interview that in the U.S. there’s been a culture change in the direction of antibiotic restraint – but there are still problems.

“It’s a lot easier for us to whip out our prescription pads and prescribe antibiotics for an asthma patient who’s having a flare-up or a patient who has atopic dermatitis before addressing the underlying mechanism directly,” Dr. Kwan said. She agreed that antibiotic overuse is prevalent in pregnancies in the U.S., and she said that starts with the high prevalence of cesarean births. Nearly one-third of all births in the U.S. are by C-section, twice the rate recommended by the World Health Organization.

“Just bypassing the birth canal actually changes what kind of microflora the infant is being exposed to,” Dr. Kwan said. “That’s the first huge problem.”

The second problem, she said, is the potential for overuse of antibiotics with the surgical procedure.

The researchers wrote that pre-, pro- or postbiotics might alter the course of allergic disease, but clear evidence is lacking.

Until now, Dr. Tramper-Stranders said, pre- or probiotic treatment in infancy, irrespective of previous antibiotic use, has not proved effective in preventing allergies.

Data describing the effect of pre- or probiotics after an antibiotic course are scarce, are limited to older children and adults, and are focused on short-term effects, such as diarrhea prevention, she explained.

Dr. Kwan says she agrees that current data are not strong enough to recommend one over another.

“We don’t even know what the normal amount of bacteria should be to constitute an environment where the immune system develops ‘normally,’ “ she said.

Antibiotics should be prescribed cautiously and by following current recommendations to use the narrowest spectrum available, the authors wrote. Future research in antibiotic stewardship should incorporate biomarker-guided therapy to determine which patients might benefit most from antibiotic therapy.

“Practicing antibiotic stewardship needs recurrent attention and we hope that with this initiative, we specifically reach allergy doctors who will rethink their next [antibiotic] prescription. Within our EAACI task force, we will next work on a guideline for rational antibiotic use in asthma,” Dr. Tramper-Stranders said.

The review’s authors and Dr. Kwan have disclosed no relevant financial relationships.

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

Urgent recommendations from a European Academy of Allergy and Clinical Immunology (EAACI) task force are aimed at reducing antibiotic overuse with allergic disease.

Top recommendations include limiting antibiotic therapy in pregnancy and early childhood to help reduce the allergy epidemic in children, and restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, especially asthma and atopic dermatitis.

The review, by lead author Gerdien Tramper-Stranders, MD, PhD, department of pediatrics, Franciscus Gasthuis & Vlietland Hospital, Rotterdam, the Netherlands, and colleagues, was published online Aug. 13 in the journal Allergy.

Several studies have shown that use of antibiotics in childhood and during pregnancy is associated with disturbing the intestinal and respiratory microbiome, which in turn leads to dysbiosis and an increased risk of acquiring allergic diseases, the authors noted.

In addition, patients with allergic diseases such as asthma have a higher risk of being prescribed antibiotics for infections compared with the general population, despite lack of clear clinical benefit.

“In fact, there are no clear data supporting antibiotic prescriptions for acute exacerbations; and clinical and/or laboratory criteria are lacking,” the authors wrote.

Despite that lack of data, antibiotics are often prescribed for exacerbations along with oral corticosteroids, Dr. Tramper-Stranders said in an interview. Some patients may benefit from antibiotics in a flare-up, she said, but more research is needed to determine which ones.

Dr. Tramper-Stranders said Franciscus has begun a large study that includes patients with asthma exacerbations to find biomarkers that might predict the type or origin of exacerbation to personalize treatment.
 

Recommendations have global relevance

She said although the recommendations are coming from the EAACI group, they apply worldwide.

“Especially in countries outside Northern Europe, antibiotic use is tremendous, leading to high rates of antibiotic resistance; but also increasing the risk for developing allergic diseases when prescribed in infancy,” she said.

She pointed out that in the United States, as many as one in six children receive unnecessary antibiotics for an asthma exacerbation. Overtreatment in adults with flare-ups is also prevalent, at rates from 40%-50%.

Millie Kwan, MD, PhD, an allergy specialist at University of North Carolina in Chapel Hill, said in an interview that in the U.S. there’s been a culture change in the direction of antibiotic restraint – but there are still problems.

“It’s a lot easier for us to whip out our prescription pads and prescribe antibiotics for an asthma patient who’s having a flare-up or a patient who has atopic dermatitis before addressing the underlying mechanism directly,” Dr. Kwan said. She agreed that antibiotic overuse is prevalent in pregnancies in the U.S., and she said that starts with the high prevalence of cesarean births. Nearly one-third of all births in the U.S. are by C-section, twice the rate recommended by the World Health Organization.

“Just bypassing the birth canal actually changes what kind of microflora the infant is being exposed to,” Dr. Kwan said. “That’s the first huge problem.”

The second problem, she said, is the potential for overuse of antibiotics with the surgical procedure.

The researchers wrote that pre-, pro- or postbiotics might alter the course of allergic disease, but clear evidence is lacking.

Until now, Dr. Tramper-Stranders said, pre- or probiotic treatment in infancy, irrespective of previous antibiotic use, has not proved effective in preventing allergies.

Data describing the effect of pre- or probiotics after an antibiotic course are scarce, are limited to older children and adults, and are focused on short-term effects, such as diarrhea prevention, she explained.

Dr. Kwan says she agrees that current data are not strong enough to recommend one over another.

“We don’t even know what the normal amount of bacteria should be to constitute an environment where the immune system develops ‘normally,’ “ she said.

Antibiotics should be prescribed cautiously and by following current recommendations to use the narrowest spectrum available, the authors wrote. Future research in antibiotic stewardship should incorporate biomarker-guided therapy to determine which patients might benefit most from antibiotic therapy.

“Practicing antibiotic stewardship needs recurrent attention and we hope that with this initiative, we specifically reach allergy doctors who will rethink their next [antibiotic] prescription. Within our EAACI task force, we will next work on a guideline for rational antibiotic use in asthma,” Dr. Tramper-Stranders said.

The review’s authors and Dr. Kwan have disclosed no relevant financial relationships.

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

Urgent recommendations from a European Academy of Allergy and Clinical Immunology (EAACI) task force are aimed at reducing antibiotic overuse with allergic disease.

Top recommendations include limiting antibiotic therapy in pregnancy and early childhood to help reduce the allergy epidemic in children, and restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, especially asthma and atopic dermatitis.

The review, by lead author Gerdien Tramper-Stranders, MD, PhD, department of pediatrics, Franciscus Gasthuis & Vlietland Hospital, Rotterdam, the Netherlands, and colleagues, was published online Aug. 13 in the journal Allergy.

Several studies have shown that use of antibiotics in childhood and during pregnancy is associated with disturbing the intestinal and respiratory microbiome, which in turn leads to dysbiosis and an increased risk of acquiring allergic diseases, the authors noted.

In addition, patients with allergic diseases such as asthma have a higher risk of being prescribed antibiotics for infections compared with the general population, despite lack of clear clinical benefit.

“In fact, there are no clear data supporting antibiotic prescriptions for acute exacerbations; and clinical and/or laboratory criteria are lacking,” the authors wrote.

Despite that lack of data, antibiotics are often prescribed for exacerbations along with oral corticosteroids, Dr. Tramper-Stranders said in an interview. Some patients may benefit from antibiotics in a flare-up, she said, but more research is needed to determine which ones.

Dr. Tramper-Stranders said Franciscus has begun a large study that includes patients with asthma exacerbations to find biomarkers that might predict the type or origin of exacerbation to personalize treatment.
 

Recommendations have global relevance

She said although the recommendations are coming from the EAACI group, they apply worldwide.

“Especially in countries outside Northern Europe, antibiotic use is tremendous, leading to high rates of antibiotic resistance; but also increasing the risk for developing allergic diseases when prescribed in infancy,” she said.

She pointed out that in the United States, as many as one in six children receive unnecessary antibiotics for an asthma exacerbation. Overtreatment in adults with flare-ups is also prevalent, at rates from 40%-50%.

Millie Kwan, MD, PhD, an allergy specialist at University of North Carolina in Chapel Hill, said in an interview that in the U.S. there’s been a culture change in the direction of antibiotic restraint – but there are still problems.

“It’s a lot easier for us to whip out our prescription pads and prescribe antibiotics for an asthma patient who’s having a flare-up or a patient who has atopic dermatitis before addressing the underlying mechanism directly,” Dr. Kwan said. She agreed that antibiotic overuse is prevalent in pregnancies in the U.S., and she said that starts with the high prevalence of cesarean births. Nearly one-third of all births in the U.S. are by C-section, twice the rate recommended by the World Health Organization.

“Just bypassing the birth canal actually changes what kind of microflora the infant is being exposed to,” Dr. Kwan said. “That’s the first huge problem.”

The second problem, she said, is the potential for overuse of antibiotics with the surgical procedure.

The researchers wrote that pre-, pro- or postbiotics might alter the course of allergic disease, but clear evidence is lacking.

Until now, Dr. Tramper-Stranders said, pre- or probiotic treatment in infancy, irrespective of previous antibiotic use, has not proved effective in preventing allergies.

Data describing the effect of pre- or probiotics after an antibiotic course are scarce, are limited to older children and adults, and are focused on short-term effects, such as diarrhea prevention, she explained.

Dr. Kwan says she agrees that current data are not strong enough to recommend one over another.

“We don’t even know what the normal amount of bacteria should be to constitute an environment where the immune system develops ‘normally,’ “ she said.

Antibiotics should be prescribed cautiously and by following current recommendations to use the narrowest spectrum available, the authors wrote. Future research in antibiotic stewardship should incorporate biomarker-guided therapy to determine which patients might benefit most from antibiotic therapy.

“Practicing antibiotic stewardship needs recurrent attention and we hope that with this initiative, we specifically reach allergy doctors who will rethink their next [antibiotic] prescription. Within our EAACI task force, we will next work on a guideline for rational antibiotic use in asthma,” Dr. Tramper-Stranders said.

The review’s authors and Dr. Kwan have disclosed no relevant financial relationships.

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

Updated August 30, 2021

The SGLT2 inhibitor empagliflozin achieved in EMPEROR-Preserved what no other agent could previously do: unequivocally cut the incidence of cardiovascular death or hospitalization in patients with heart failure and preserved ejection fraction (HFpEF).

MDedge News

Treatment with empagliflozin (Jardiance) led to a significant 21% relative reduction in the rate of cardiovascular death or hospitalization for heart failure (HHF), compared with placebo, among 5,988 randomized patients with HFpEF during a median 26 months of follow-up, proving that patients with HFpEF finally have a treatment that gives them clinically meaningful benefit, and paving the way to an abrupt change in management of these patients, experts said.

“This is the first trial to show unequivocal benefits of any drug on major heart failure outcomes in patients with HFpEF,” Stefan D. Anker, MD, PhD, declared at the virtual annual congress of the European Society of Cardiology.

The 21% relative reduction, which reflected a cut in the absolute rate of the trial’s primary composite endpoint of 3.3% compared with placebo, was driven mainly by a significant 27% relative reduction in the incidence of HHF (P < .001). Empagliflozin treatment, on top of standard therapy for patients with HFpEF, also resulted in a nonsignificant 9% relative risk reduction in the incidence of cardiovascular death, but it had no discernible impact on the rate of death from any cause, said Dr. Anker, professor of cardiology at Charité Medical University in Berlin.

Concurrently with his talk at the meeting, the results were published online in the New England Journal of Medicine.
 

Practice will change ‘quickly’

“This will definitely change our practice, and quite quickly,” said Carlos Aguiar, MD, chair of the Advanced Heart Failure and Heart Transplantation Unit at Hospital Santa Cruz in Carnaxide, Portugal, who was not involved in the study.

Transition to routine use of empagliflozin in patients with HFpEF should be swift because it has already become a mainstay of treatment for patients with heart failure with reduced ejection fraction (HFrEF) based on evidence for empagliflozin in EMPEROR-Reduced. A second sodium-glucose cotransporter 2 (SGLT2 ) inhibitor, dapagliflozin (Farxiga), is also an option for treating HFrEF based on results in the DAPA-HF trial, and the DELIVER trial, still in progress, is testing dapagliflozin as a HFpEF treatment in about 6,000 patients, with results expected in 2022.

About half of the patients in EMPEROR-Preserved had diabetes, and the treatment effects on HFpEF were similar regardless of patients’ diabetes status. Empagliflozin, like other members of the SGLT2 inhibitor class, boosts urinary excretion of glucose and received initial regulatory approval as an agent for glycemic control in patients with type 2 diabetes. Empagliflozin also has U.S.-approved marketing indications for treating patients with HFrEF whether or not they also have diabetes, and for reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease.

“We already use this drug class in cardiovascular medicine and to treat patients with type 2 diabetes, and we have been eager to find a treatment for patients with HFpEF. This is something that will be really significant,” said Dr. Aguiar.

Heart failure clinicians have “become familiar prescribing” SGLT2 inhibitors following approval of HFrEF indications for some of these agents, noted Mary Norine Walsh, MD, a heart failure specialist with Ascension Medical Group in Indianapolis. The new results “are good news because there have been so few options” for patients with HFpEF, she said in an interview.

EMPEROR-Preserved “is the first phase 3 clinical trial that exclusively enrolled patients with heart failure and an ejection fraction of more than 40% to meet its primary outcome,” and the results “represent a major win against a medical condition that had previously proven formidable,” Mark H. Drazner, MD, said in an editorial that accompanied the published results.

The trial’s findings “should contribute to a change in clinical practice given the paucity of therapeutic options available for patients with HFpEF,” wrote Dr. Drazner, a heart failure specialist who is professor and clinical chief of cardiology at UT Southwestern Medical Center in Dallas.

Theresa A, McDonagh, MD, MBChB, who chaired the panel that just released revised guidelines from the European Society of Cardiology for managing patients with heart failure, predicted that empagliflozin treatment for patients with HFpEF will soon show up in guidelines. It will likely receive a “should be considered” ranking despite being a single study because of the impressive size of the treatment effect and lack of well-supported alternative treatments, she commented as a discussant of the trial during its presentation at the congress. If the DELIVER trial with dapagliflozin shows a similar effect, the recommendation would likely become even stronger, added Dr. McDonagh, a heart failure specialist and professor of cardiology at King’s College, London.

More women enrolled than ever before

EMPEROR-Preserved enrolled adults with chronic HFpEF in New York Heart Association functional class II-IV and a left ventricular ejection fraction greater than 40% starting in 2017 at more than 600 sites in more than 20 countries worldwide including the United States. As background therapy, more than 80% of patients received treatment with either an ACE inhibitor or angiotensin receptor blocker (in some instances in the form of sacubitril/valsartan), more than 80% were on a beta-blocker, and about a third were taking a mineralocorticoid receptor antagonist, making them “very well treated HFpEF patients,” Dr. Anker said.

One of the most notable features of enrollment was that 45% of participants were women, giving this trial the highest inclusion of women compared with all prior studies in patients with HFpEF or with HFrEF, said Dr. Walsh. “HFpEF is very prevalent in woman,” she noted, and having this high participation rate of women in the study increases its relevance to these patients. “It’s important to be able to tell women that patients like you were in the study so we can more easily apply the lessons from the trial to you. That can’t be stressed enough,” she said.

The primary outcome occurred in 415 (13.8%) of the 2,997 patients in the empagliflozin group and in 511 (17.1%) of 2,991 patients who received placebo (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90; P < .001).

The study showed a safety profile consistent with prior experience with empagliflozin, Dr. Anker added.

Pooling EMPEROR-Preserved with EMPEROR-Reduced

The investigators who ran EMPEROR-Preserved designed the trial to closely parallel the EMPEROR-Reduced trial in patients with HFrEF, and they included a prespecified analysis (EMPEROR-Pooled) that combined the more than 9,700 patients in the two studies. This showed a consistent and robust benefit from empagliflozin for reducing HHF across a wide spectrum of patients with heart failure, ranging from patients with left ventricular ejection fractions of less than 25% to patients with ejection fractions as high as 64%. However, the analysis also showed that patients with ejection fractions of 65% or greater received no discernible benefit from empagliflozin, Milton Packer, MD, reported in a separate talk at the congress.

MDedge News

“The findings demonstrate the benefits of empagliflozin across a broad range of patients with heart failure who have ejection fractions of less than 60%-65%,” said Dr. Packer, a researcher at Baylor University Medical Center in Dallas.

This apparent attenuation of an effect at higher ejection fractions “has been observed in other HFpEF trials, most recently in the PARAGON-HF trial” of sacubitril/valsartan (Entresto), he noted. Additional analyses led by Dr. Packer showed that in patients with ejection fractions below 65% the HHF benefit from empagliflozin consistently surpassed the benefit seen with sacubitril/valsartan in PARAGON-HF. But he recommended using both drugs in patients with HFpEF and an ejection fraction up to about 60%.

“If I had a patient with HFpEF I would use both drugs as well as beta-blockers and mineralocorticoid receptor antagonists,” he said during a press briefing.

Another finding from analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials together was that patients with reduced ejection fractions showed a significant 49% relative reduction in the incidence of serious renal outcomes, but this effect was completely blunted in EMPEROR-Preserved.

“Ejection fraction influences the effects of empagliflozin on major renal outcomes,” concluded Dr. Packer in a report on this analysis published simultaneously with the main EMPEROR-Preserved findings (N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMc2112411). “These data from the EMPEROR trials are unique. We have no comparable data” from any of the other reported studies of SGLT2 inhibitors,” he said.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and by Eli Lilly, the two companies that jointly market empagliflozin (Jardiance). Dr. Anker has received personal fees from Boehringer Ingelheim and from several other companies, and he has received grants and personal fees from Abbott Vascular and Vifor. Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. McDonagh has has recent financial relationships with AstraZeneca, Cprpus, Novartis, Pfizer, and Vifor. Dr. Aguiar and Dr. Walsh had no disclosures.

mzoler@mdedge.com

Updated August 30, 2021

The SGLT2 inhibitor empagliflozin achieved in EMPEROR-Preserved what no other agent could previously do: unequivocally cut the incidence of cardiovascular death or hospitalization in patients with heart failure and preserved ejection fraction (HFpEF).

MDedge News

Treatment with empagliflozin (Jardiance) led to a significant 21% relative reduction in the rate of cardiovascular death or hospitalization for heart failure (HHF), compared with placebo, among 5,988 randomized patients with HFpEF during a median 26 months of follow-up, proving that patients with HFpEF finally have a treatment that gives them clinically meaningful benefit, and paving the way to an abrupt change in management of these patients, experts said.

“This is the first trial to show unequivocal benefits of any drug on major heart failure outcomes in patients with HFpEF,” Stefan D. Anker, MD, PhD, declared at the virtual annual congress of the European Society of Cardiology.

The 21% relative reduction, which reflected a cut in the absolute rate of the trial’s primary composite endpoint of 3.3% compared with placebo, was driven mainly by a significant 27% relative reduction in the incidence of HHF (P < .001). Empagliflozin treatment, on top of standard therapy for patients with HFpEF, also resulted in a nonsignificant 9% relative risk reduction in the incidence of cardiovascular death, but it had no discernible impact on the rate of death from any cause, said Dr. Anker, professor of cardiology at Charité Medical University in Berlin.

Concurrently with his talk at the meeting, the results were published online in the New England Journal of Medicine.
 

Practice will change ‘quickly’

“This will definitely change our practice, and quite quickly,” said Carlos Aguiar, MD, chair of the Advanced Heart Failure and Heart Transplantation Unit at Hospital Santa Cruz in Carnaxide, Portugal, who was not involved in the study.

Transition to routine use of empagliflozin in patients with HFpEF should be swift because it has already become a mainstay of treatment for patients with heart failure with reduced ejection fraction (HFrEF) based on evidence for empagliflozin in EMPEROR-Reduced. A second sodium-glucose cotransporter 2 (SGLT2 ) inhibitor, dapagliflozin (Farxiga), is also an option for treating HFrEF based on results in the DAPA-HF trial, and the DELIVER trial, still in progress, is testing dapagliflozin as a HFpEF treatment in about 6,000 patients, with results expected in 2022.

About half of the patients in EMPEROR-Preserved had diabetes, and the treatment effects on HFpEF were similar regardless of patients’ diabetes status. Empagliflozin, like other members of the SGLT2 inhibitor class, boosts urinary excretion of glucose and received initial regulatory approval as an agent for glycemic control in patients with type 2 diabetes. Empagliflozin also has U.S.-approved marketing indications for treating patients with HFrEF whether or not they also have diabetes, and for reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease.

“We already use this drug class in cardiovascular medicine and to treat patients with type 2 diabetes, and we have been eager to find a treatment for patients with HFpEF. This is something that will be really significant,” said Dr. Aguiar.

Heart failure clinicians have “become familiar prescribing” SGLT2 inhibitors following approval of HFrEF indications for some of these agents, noted Mary Norine Walsh, MD, a heart failure specialist with Ascension Medical Group in Indianapolis. The new results “are good news because there have been so few options” for patients with HFpEF, she said in an interview.

EMPEROR-Preserved “is the first phase 3 clinical trial that exclusively enrolled patients with heart failure and an ejection fraction of more than 40% to meet its primary outcome,” and the results “represent a major win against a medical condition that had previously proven formidable,” Mark H. Drazner, MD, said in an editorial that accompanied the published results.

The trial’s findings “should contribute to a change in clinical practice given the paucity of therapeutic options available for patients with HFpEF,” wrote Dr. Drazner, a heart failure specialist who is professor and clinical chief of cardiology at UT Southwestern Medical Center in Dallas.

Theresa A, McDonagh, MD, MBChB, who chaired the panel that just released revised guidelines from the European Society of Cardiology for managing patients with heart failure, predicted that empagliflozin treatment for patients with HFpEF will soon show up in guidelines. It will likely receive a “should be considered” ranking despite being a single study because of the impressive size of the treatment effect and lack of well-supported alternative treatments, she commented as a discussant of the trial during its presentation at the congress. If the DELIVER trial with dapagliflozin shows a similar effect, the recommendation would likely become even stronger, added Dr. McDonagh, a heart failure specialist and professor of cardiology at King’s College, London.

More women enrolled than ever before

EMPEROR-Preserved enrolled adults with chronic HFpEF in New York Heart Association functional class II-IV and a left ventricular ejection fraction greater than 40% starting in 2017 at more than 600 sites in more than 20 countries worldwide including the United States. As background therapy, more than 80% of patients received treatment with either an ACE inhibitor or angiotensin receptor blocker (in some instances in the form of sacubitril/valsartan), more than 80% were on a beta-blocker, and about a third were taking a mineralocorticoid receptor antagonist, making them “very well treated HFpEF patients,” Dr. Anker said.

One of the most notable features of enrollment was that 45% of participants were women, giving this trial the highest inclusion of women compared with all prior studies in patients with HFpEF or with HFrEF, said Dr. Walsh. “HFpEF is very prevalent in woman,” she noted, and having this high participation rate of women in the study increases its relevance to these patients. “It’s important to be able to tell women that patients like you were in the study so we can more easily apply the lessons from the trial to you. That can’t be stressed enough,” she said.

The primary outcome occurred in 415 (13.8%) of the 2,997 patients in the empagliflozin group and in 511 (17.1%) of 2,991 patients who received placebo (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90; P < .001).

The study showed a safety profile consistent with prior experience with empagliflozin, Dr. Anker added.

Pooling EMPEROR-Preserved with EMPEROR-Reduced

The investigators who ran EMPEROR-Preserved designed the trial to closely parallel the EMPEROR-Reduced trial in patients with HFrEF, and they included a prespecified analysis (EMPEROR-Pooled) that combined the more than 9,700 patients in the two studies. This showed a consistent and robust benefit from empagliflozin for reducing HHF across a wide spectrum of patients with heart failure, ranging from patients with left ventricular ejection fractions of less than 25% to patients with ejection fractions as high as 64%. However, the analysis also showed that patients with ejection fractions of 65% or greater received no discernible benefit from empagliflozin, Milton Packer, MD, reported in a separate talk at the congress.

MDedge News

“The findings demonstrate the benefits of empagliflozin across a broad range of patients with heart failure who have ejection fractions of less than 60%-65%,” said Dr. Packer, a researcher at Baylor University Medical Center in Dallas.

This apparent attenuation of an effect at higher ejection fractions “has been observed in other HFpEF trials, most recently in the PARAGON-HF trial” of sacubitril/valsartan (Entresto), he noted. Additional analyses led by Dr. Packer showed that in patients with ejection fractions below 65% the HHF benefit from empagliflozin consistently surpassed the benefit seen with sacubitril/valsartan in PARAGON-HF. But he recommended using both drugs in patients with HFpEF and an ejection fraction up to about 60%.

“If I had a patient with HFpEF I would use both drugs as well as beta-blockers and mineralocorticoid receptor antagonists,” he said during a press briefing.

Another finding from analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials together was that patients with reduced ejection fractions showed a significant 49% relative reduction in the incidence of serious renal outcomes, but this effect was completely blunted in EMPEROR-Preserved.

“Ejection fraction influences the effects of empagliflozin on major renal outcomes,” concluded Dr. Packer in a report on this analysis published simultaneously with the main EMPEROR-Preserved findings (N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMc2112411). “These data from the EMPEROR trials are unique. We have no comparable data” from any of the other reported studies of SGLT2 inhibitors,” he said.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and by Eli Lilly, the two companies that jointly market empagliflozin (Jardiance). Dr. Anker has received personal fees from Boehringer Ingelheim and from several other companies, and he has received grants and personal fees from Abbott Vascular and Vifor. Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. McDonagh has has recent financial relationships with AstraZeneca, Cprpus, Novartis, Pfizer, and Vifor. Dr. Aguiar and Dr. Walsh had no disclosures.

mzoler@mdedge.com

Updated August 30, 2021

The SGLT2 inhibitor empagliflozin achieved in EMPEROR-Preserved what no other agent could previously do: unequivocally cut the incidence of cardiovascular death or hospitalization in patients with heart failure and preserved ejection fraction (HFpEF).

MDedge News

Treatment with empagliflozin (Jardiance) led to a significant 21% relative reduction in the rate of cardiovascular death or hospitalization for heart failure (HHF), compared with placebo, among 5,988 randomized patients with HFpEF during a median 26 months of follow-up, proving that patients with HFpEF finally have a treatment that gives them clinically meaningful benefit, and paving the way to an abrupt change in management of these patients, experts said.

“This is the first trial to show unequivocal benefits of any drug on major heart failure outcomes in patients with HFpEF,” Stefan D. Anker, MD, PhD, declared at the virtual annual congress of the European Society of Cardiology.

The 21% relative reduction, which reflected a cut in the absolute rate of the trial’s primary composite endpoint of 3.3% compared with placebo, was driven mainly by a significant 27% relative reduction in the incidence of HHF (P < .001). Empagliflozin treatment, on top of standard therapy for patients with HFpEF, also resulted in a nonsignificant 9% relative risk reduction in the incidence of cardiovascular death, but it had no discernible impact on the rate of death from any cause, said Dr. Anker, professor of cardiology at Charité Medical University in Berlin.

Concurrently with his talk at the meeting, the results were published online in the New England Journal of Medicine.
 

Practice will change ‘quickly’

“This will definitely change our practice, and quite quickly,” said Carlos Aguiar, MD, chair of the Advanced Heart Failure and Heart Transplantation Unit at Hospital Santa Cruz in Carnaxide, Portugal, who was not involved in the study.

Transition to routine use of empagliflozin in patients with HFpEF should be swift because it has already become a mainstay of treatment for patients with heart failure with reduced ejection fraction (HFrEF) based on evidence for empagliflozin in EMPEROR-Reduced. A second sodium-glucose cotransporter 2 (SGLT2 ) inhibitor, dapagliflozin (Farxiga), is also an option for treating HFrEF based on results in the DAPA-HF trial, and the DELIVER trial, still in progress, is testing dapagliflozin as a HFpEF treatment in about 6,000 patients, with results expected in 2022.

About half of the patients in EMPEROR-Preserved had diabetes, and the treatment effects on HFpEF were similar regardless of patients’ diabetes status. Empagliflozin, like other members of the SGLT2 inhibitor class, boosts urinary excretion of glucose and received initial regulatory approval as an agent for glycemic control in patients with type 2 diabetes. Empagliflozin also has U.S.-approved marketing indications for treating patients with HFrEF whether or not they also have diabetes, and for reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease.

“We already use this drug class in cardiovascular medicine and to treat patients with type 2 diabetes, and we have been eager to find a treatment for patients with HFpEF. This is something that will be really significant,” said Dr. Aguiar.

Heart failure clinicians have “become familiar prescribing” SGLT2 inhibitors following approval of HFrEF indications for some of these agents, noted Mary Norine Walsh, MD, a heart failure specialist with Ascension Medical Group in Indianapolis. The new results “are good news because there have been so few options” for patients with HFpEF, she said in an interview.

EMPEROR-Preserved “is the first phase 3 clinical trial that exclusively enrolled patients with heart failure and an ejection fraction of more than 40% to meet its primary outcome,” and the results “represent a major win against a medical condition that had previously proven formidable,” Mark H. Drazner, MD, said in an editorial that accompanied the published results.

The trial’s findings “should contribute to a change in clinical practice given the paucity of therapeutic options available for patients with HFpEF,” wrote Dr. Drazner, a heart failure specialist who is professor and clinical chief of cardiology at UT Southwestern Medical Center in Dallas.

Theresa A, McDonagh, MD, MBChB, who chaired the panel that just released revised guidelines from the European Society of Cardiology for managing patients with heart failure, predicted that empagliflozin treatment for patients with HFpEF will soon show up in guidelines. It will likely receive a “should be considered” ranking despite being a single study because of the impressive size of the treatment effect and lack of well-supported alternative treatments, she commented as a discussant of the trial during its presentation at the congress. If the DELIVER trial with dapagliflozin shows a similar effect, the recommendation would likely become even stronger, added Dr. McDonagh, a heart failure specialist and professor of cardiology at King’s College, London.

More women enrolled than ever before

EMPEROR-Preserved enrolled adults with chronic HFpEF in New York Heart Association functional class II-IV and a left ventricular ejection fraction greater than 40% starting in 2017 at more than 600 sites in more than 20 countries worldwide including the United States. As background therapy, more than 80% of patients received treatment with either an ACE inhibitor or angiotensin receptor blocker (in some instances in the form of sacubitril/valsartan), more than 80% were on a beta-blocker, and about a third were taking a mineralocorticoid receptor antagonist, making them “very well treated HFpEF patients,” Dr. Anker said.

One of the most notable features of enrollment was that 45% of participants were women, giving this trial the highest inclusion of women compared with all prior studies in patients with HFpEF or with HFrEF, said Dr. Walsh. “HFpEF is very prevalent in woman,” she noted, and having this high participation rate of women in the study increases its relevance to these patients. “It’s important to be able to tell women that patients like you were in the study so we can more easily apply the lessons from the trial to you. That can’t be stressed enough,” she said.

The primary outcome occurred in 415 (13.8%) of the 2,997 patients in the empagliflozin group and in 511 (17.1%) of 2,991 patients who received placebo (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90; P < .001).

The study showed a safety profile consistent with prior experience with empagliflozin, Dr. Anker added.

Pooling EMPEROR-Preserved with EMPEROR-Reduced

The investigators who ran EMPEROR-Preserved designed the trial to closely parallel the EMPEROR-Reduced trial in patients with HFrEF, and they included a prespecified analysis (EMPEROR-Pooled) that combined the more than 9,700 patients in the two studies. This showed a consistent and robust benefit from empagliflozin for reducing HHF across a wide spectrum of patients with heart failure, ranging from patients with left ventricular ejection fractions of less than 25% to patients with ejection fractions as high as 64%. However, the analysis also showed that patients with ejection fractions of 65% or greater received no discernible benefit from empagliflozin, Milton Packer, MD, reported in a separate talk at the congress.

MDedge News

“The findings demonstrate the benefits of empagliflozin across a broad range of patients with heart failure who have ejection fractions of less than 60%-65%,” said Dr. Packer, a researcher at Baylor University Medical Center in Dallas.

This apparent attenuation of an effect at higher ejection fractions “has been observed in other HFpEF trials, most recently in the PARAGON-HF trial” of sacubitril/valsartan (Entresto), he noted. Additional analyses led by Dr. Packer showed that in patients with ejection fractions below 65% the HHF benefit from empagliflozin consistently surpassed the benefit seen with sacubitril/valsartan in PARAGON-HF. But he recommended using both drugs in patients with HFpEF and an ejection fraction up to about 60%.

“If I had a patient with HFpEF I would use both drugs as well as beta-blockers and mineralocorticoid receptor antagonists,” he said during a press briefing.

Another finding from analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials together was that patients with reduced ejection fractions showed a significant 49% relative reduction in the incidence of serious renal outcomes, but this effect was completely blunted in EMPEROR-Preserved.

“Ejection fraction influences the effects of empagliflozin on major renal outcomes,” concluded Dr. Packer in a report on this analysis published simultaneously with the main EMPEROR-Preserved findings (N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMc2112411). “These data from the EMPEROR trials are unique. We have no comparable data” from any of the other reported studies of SGLT2 inhibitors,” he said.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and by Eli Lilly, the two companies that jointly market empagliflozin (Jardiance). Dr. Anker has received personal fees from Boehringer Ingelheim and from several other companies, and he has received grants and personal fees from Abbott Vascular and Vifor. Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. McDonagh has has recent financial relationships with AstraZeneca, Cprpus, Novartis, Pfizer, and Vifor. Dr. Aguiar and Dr. Walsh had no disclosures.

mzoler@mdedge.com

Doctor sentenced for unlawful prescriptions leading to five patient deaths

Darrel R. Rinehart, MD, was sentenced to 3 years in prison in June 2021 for unlawfully distributing controlled substances, primarily opioids, out of his clinic in Columbia, Tenn. Five of his patients who received prescriptions died of fatal overdoses within a year, according to the Indianapolis Star. Dr. Rinehart agreed to leave Tennessee to avoid punishment in that state before setting up his Indiana clinic.

Dr. Rinehart, 66, admitted to distributing Schedule II controlled substances to four different patients without legitimate medical purpose on 18 occasions between December 2014 and December 2015. He also admitted to knowingly distributing hydrocodone, also a Schedule II controlled substance, in January 2016 to a patient who did not have any health issues justifying the prescription. His medical license has been revoked. 
 

Judge approves $15 million settlement in patient’s sexual assault

An incapacitated woman at Hacienda Healthcare, a long-term care center in Phoenix, Ariz., gave birth in late 2018 after being raped by one of the nursing staff, according to Insurance Journal. In June 2021, a judge approved a $15 million settlement in a lawsuit by the woman’s parents against Phillip E. Gear Jr., MD, the woman’s caregiver for 26 years at the center. The woman had been in a vegetative state at Hacienda Healthcare since childhood, and the judge ruled that she had been the victim of numerous sexual assaults prior to the birth. 

The pregnancy was discovered when an employee was changing the garments of the then 29-year-old victim and saw that she was delivering a child. Employees told police they had no idea the woman was pregnant. Police have said that DNA from Nathan Sutherland, a licensed practical nurse who worked at Hacienda and has since given up his nursing license, matched a genetic sample taken from the woman’s son.

The woman’s parents, who care for her son, also sued the state of Arizona and another doctor, Thanh Nguyen, MD, who cared for their daughter. Arizona, which contracts with companies like Hacienda to provide services to people with developmental disabilities, settled last year for $7.5 million. Both Hacienda and Dr. Nguyen, who cared for the woman in the months before the birth, settled for undisclosed amounts.

The insurer for Dr. Gear, who died in late 2020, said it has no obligation to pay the amount, arguing that the doctor’s policy didn’t cover claims arising from a sexual act. The insurer also argued that Dr. Gear wasn’t the woman’s primary care physician when she gave birth and couldn’t be held responsible for sexual assault. 

The judge declared the $15 million settlement reasonable, concluding that Dr. Gear’s treatment of the woman had fallen below the standard of care, which included failing to examine her regularly and to diagnose her pregnancy. Requests by the woman’s mother to have exclusively female employees tend to her were not followed, as shown by medical records.
 

Doctor fired for contributing to suffering and death of prisoners

Washington’s prison system will pay $3.25 million and has fired the medical director of one of its facilities, stemming from the death of an inmate. 

John Kleutsch, a 57-year-old prisoner, died in late 2018 of septic shock, acute pancreatitis, and a perforated intestine caused by an improperly treated abdominal wound, according to the Seattle Times. A lawsuit filed by his wife, Julia Kleutsch, said that the staff offered him only Tylenol for his pain and that Julia Barnett, MD, the former prison medical director, refused to take him to a hospital.

Dr. Barnett, whose medical license has been indefinitely suspended, was fired in 2019 after an internal investigation found that her medical care and supervision contributed to the suffering and deaths of several men in the prison, including Mr. Kleutsch. 

Mr. Kleutsch, imprisoned for child molestation, was recovering from outpatient cancer surgery and sent back to the prison infirmary to recover. The lawsuit says that Mr. Kleutsch asked staff for help when his abdominal wound became excruciatingly painful, puffy, and oozing, and that at least one nurse asked Dr. Barnett to transfer him to a hospital, but she refused. Dr. Kleutsch’s causes of death were conditions never diagnosed at the prison.

Plaintiff attorney Marta O’Brien called the case “one of the worst medical malpractice cases I have encountered” and said it showed “a systemic failure” by the Department of Corrections.
 

SNF pays $11 million to resolve Medicare fraud allegations

SavaSeniorCare (Sava) and related entities agreed to pay $11.2 million in May 2021 to resolve allegations that they violated the False Claims Act by making their skilled nursing facilities (SNFs) bill Medicare for rehabilitation therapy services that were not reasonable, necessary, or skilled. The payment was also to resolve allegations that Sava billed the Medicare and Medicaid programs for substandard skilled nursing services, according to the U.S. Department of Justice. Sava is based in Georgia but owns and operates SNFs across the country.

The government filed a complaint against Sava in 2015, alleging that between October 2008 and September 2012, Sava intentionally submitted false claims for rehabilitation therapy services as a result of a systematic effort to increase its Medicare and Medicaid billings. The claim alleged that Sava exerted significant pressure on its SNFs to meet unrealistic financial goals, resulting in the provision of medically unreasonable, unnecessary, or unskilled services to Medicare patients. Sava also allegedly sought to increase its Medicare payments by delaying the discharge of patients from its facilities, even though the patients were medically ready to be discharged. 

Additionally, the government alleged that some of Sava’s nursing services failed to meet federal standards of care, including failing to have sufficient staffing at certain facilities, failing to follow appropriate pressure ulcer and falls protocols, and failing to appropriately administer medications. 

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

Doctor sentenced for unlawful prescriptions leading to five patient deaths

Darrel R. Rinehart, MD, was sentenced to 3 years in prison in June 2021 for unlawfully distributing controlled substances, primarily opioids, out of his clinic in Columbia, Tenn. Five of his patients who received prescriptions died of fatal overdoses within a year, according to the Indianapolis Star. Dr. Rinehart agreed to leave Tennessee to avoid punishment in that state before setting up his Indiana clinic.

Dr. Rinehart, 66, admitted to distributing Schedule II controlled substances to four different patients without legitimate medical purpose on 18 occasions between December 2014 and December 2015. He also admitted to knowingly distributing hydrocodone, also a Schedule II controlled substance, in January 2016 to a patient who did not have any health issues justifying the prescription. His medical license has been revoked. 
 

Judge approves $15 million settlement in patient’s sexual assault

An incapacitated woman at Hacienda Healthcare, a long-term care center in Phoenix, Ariz., gave birth in late 2018 after being raped by one of the nursing staff, according to Insurance Journal. In June 2021, a judge approved a $15 million settlement in a lawsuit by the woman’s parents against Phillip E. Gear Jr., MD, the woman’s caregiver for 26 years at the center. The woman had been in a vegetative state at Hacienda Healthcare since childhood, and the judge ruled that she had been the victim of numerous sexual assaults prior to the birth. 

The pregnancy was discovered when an employee was changing the garments of the then 29-year-old victim and saw that she was delivering a child. Employees told police they had no idea the woman was pregnant. Police have said that DNA from Nathan Sutherland, a licensed practical nurse who worked at Hacienda and has since given up his nursing license, matched a genetic sample taken from the woman’s son.

The woman’s parents, who care for her son, also sued the state of Arizona and another doctor, Thanh Nguyen, MD, who cared for their daughter. Arizona, which contracts with companies like Hacienda to provide services to people with developmental disabilities, settled last year for $7.5 million. Both Hacienda and Dr. Nguyen, who cared for the woman in the months before the birth, settled for undisclosed amounts.

The insurer for Dr. Gear, who died in late 2020, said it has no obligation to pay the amount, arguing that the doctor’s policy didn’t cover claims arising from a sexual act. The insurer also argued that Dr. Gear wasn’t the woman’s primary care physician when she gave birth and couldn’t be held responsible for sexual assault. 

The judge declared the $15 million settlement reasonable, concluding that Dr. Gear’s treatment of the woman had fallen below the standard of care, which included failing to examine her regularly and to diagnose her pregnancy. Requests by the woman’s mother to have exclusively female employees tend to her were not followed, as shown by medical records.
 

Doctor fired for contributing to suffering and death of prisoners

Washington’s prison system will pay $3.25 million and has fired the medical director of one of its facilities, stemming from the death of an inmate. 

John Kleutsch, a 57-year-old prisoner, died in late 2018 of septic shock, acute pancreatitis, and a perforated intestine caused by an improperly treated abdominal wound, according to the Seattle Times. A lawsuit filed by his wife, Julia Kleutsch, said that the staff offered him only Tylenol for his pain and that Julia Barnett, MD, the former prison medical director, refused to take him to a hospital.

Dr. Barnett, whose medical license has been indefinitely suspended, was fired in 2019 after an internal investigation found that her medical care and supervision contributed to the suffering and deaths of several men in the prison, including Mr. Kleutsch. 

Mr. Kleutsch, imprisoned for child molestation, was recovering from outpatient cancer surgery and sent back to the prison infirmary to recover. The lawsuit says that Mr. Kleutsch asked staff for help when his abdominal wound became excruciatingly painful, puffy, and oozing, and that at least one nurse asked Dr. Barnett to transfer him to a hospital, but she refused. Dr. Kleutsch’s causes of death were conditions never diagnosed at the prison.

Plaintiff attorney Marta O’Brien called the case “one of the worst medical malpractice cases I have encountered” and said it showed “a systemic failure” by the Department of Corrections.
 

SNF pays $11 million to resolve Medicare fraud allegations

SavaSeniorCare (Sava) and related entities agreed to pay $11.2 million in May 2021 to resolve allegations that they violated the False Claims Act by making their skilled nursing facilities (SNFs) bill Medicare for rehabilitation therapy services that were not reasonable, necessary, or skilled. The payment was also to resolve allegations that Sava billed the Medicare and Medicaid programs for substandard skilled nursing services, according to the U.S. Department of Justice. Sava is based in Georgia but owns and operates SNFs across the country.

The government filed a complaint against Sava in 2015, alleging that between October 2008 and September 2012, Sava intentionally submitted false claims for rehabilitation therapy services as a result of a systematic effort to increase its Medicare and Medicaid billings. The claim alleged that Sava exerted significant pressure on its SNFs to meet unrealistic financial goals, resulting in the provision of medically unreasonable, unnecessary, or unskilled services to Medicare patients. Sava also allegedly sought to increase its Medicare payments by delaying the discharge of patients from its facilities, even though the patients were medically ready to be discharged. 

Additionally, the government alleged that some of Sava’s nursing services failed to meet federal standards of care, including failing to have sufficient staffing at certain facilities, failing to follow appropriate pressure ulcer and falls protocols, and failing to appropriately administer medications. 

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

Doctor sentenced for unlawful prescriptions leading to five patient deaths

Darrel R. Rinehart, MD, was sentenced to 3 years in prison in June 2021 for unlawfully distributing controlled substances, primarily opioids, out of his clinic in Columbia, Tenn. Five of his patients who received prescriptions died of fatal overdoses within a year, according to the Indianapolis Star. Dr. Rinehart agreed to leave Tennessee to avoid punishment in that state before setting up his Indiana clinic.

Dr. Rinehart, 66, admitted to distributing Schedule II controlled substances to four different patients without legitimate medical purpose on 18 occasions between December 2014 and December 2015. He also admitted to knowingly distributing hydrocodone, also a Schedule II controlled substance, in January 2016 to a patient who did not have any health issues justifying the prescription. His medical license has been revoked. 
 

Judge approves $15 million settlement in patient’s sexual assault

An incapacitated woman at Hacienda Healthcare, a long-term care center in Phoenix, Ariz., gave birth in late 2018 after being raped by one of the nursing staff, according to Insurance Journal. In June 2021, a judge approved a $15 million settlement in a lawsuit by the woman’s parents against Phillip E. Gear Jr., MD, the woman’s caregiver for 26 years at the center. The woman had been in a vegetative state at Hacienda Healthcare since childhood, and the judge ruled that she had been the victim of numerous sexual assaults prior to the birth. 

The pregnancy was discovered when an employee was changing the garments of the then 29-year-old victim and saw that she was delivering a child. Employees told police they had no idea the woman was pregnant. Police have said that DNA from Nathan Sutherland, a licensed practical nurse who worked at Hacienda and has since given up his nursing license, matched a genetic sample taken from the woman’s son.

The woman’s parents, who care for her son, also sued the state of Arizona and another doctor, Thanh Nguyen, MD, who cared for their daughter. Arizona, which contracts with companies like Hacienda to provide services to people with developmental disabilities, settled last year for $7.5 million. Both Hacienda and Dr. Nguyen, who cared for the woman in the months before the birth, settled for undisclosed amounts.

The insurer for Dr. Gear, who died in late 2020, said it has no obligation to pay the amount, arguing that the doctor’s policy didn’t cover claims arising from a sexual act. The insurer also argued that Dr. Gear wasn’t the woman’s primary care physician when she gave birth and couldn’t be held responsible for sexual assault. 

The judge declared the $15 million settlement reasonable, concluding that Dr. Gear’s treatment of the woman had fallen below the standard of care, which included failing to examine her regularly and to diagnose her pregnancy. Requests by the woman’s mother to have exclusively female employees tend to her were not followed, as shown by medical records.
 

Doctor fired for contributing to suffering and death of prisoners

Washington’s prison system will pay $3.25 million and has fired the medical director of one of its facilities, stemming from the death of an inmate. 

John Kleutsch, a 57-year-old prisoner, died in late 2018 of septic shock, acute pancreatitis, and a perforated intestine caused by an improperly treated abdominal wound, according to the Seattle Times. A lawsuit filed by his wife, Julia Kleutsch, said that the staff offered him only Tylenol for his pain and that Julia Barnett, MD, the former prison medical director, refused to take him to a hospital.

Dr. Barnett, whose medical license has been indefinitely suspended, was fired in 2019 after an internal investigation found that her medical care and supervision contributed to the suffering and deaths of several men in the prison, including Mr. Kleutsch. 

Mr. Kleutsch, imprisoned for child molestation, was recovering from outpatient cancer surgery and sent back to the prison infirmary to recover. The lawsuit says that Mr. Kleutsch asked staff for help when his abdominal wound became excruciatingly painful, puffy, and oozing, and that at least one nurse asked Dr. Barnett to transfer him to a hospital, but she refused. Dr. Kleutsch’s causes of death were conditions never diagnosed at the prison.

Plaintiff attorney Marta O’Brien called the case “one of the worst medical malpractice cases I have encountered” and said it showed “a systemic failure” by the Department of Corrections.
 

SNF pays $11 million to resolve Medicare fraud allegations

SavaSeniorCare (Sava) and related entities agreed to pay $11.2 million in May 2021 to resolve allegations that they violated the False Claims Act by making their skilled nursing facilities (SNFs) bill Medicare for rehabilitation therapy services that were not reasonable, necessary, or skilled. The payment was also to resolve allegations that Sava billed the Medicare and Medicaid programs for substandard skilled nursing services, according to the U.S. Department of Justice. Sava is based in Georgia but owns and operates SNFs across the country.

The government filed a complaint against Sava in 2015, alleging that between October 2008 and September 2012, Sava intentionally submitted false claims for rehabilitation therapy services as a result of a systematic effort to increase its Medicare and Medicaid billings. The claim alleged that Sava exerted significant pressure on its SNFs to meet unrealistic financial goals, resulting in the provision of medically unreasonable, unnecessary, or unskilled services to Medicare patients. Sava also allegedly sought to increase its Medicare payments by delaying the discharge of patients from its facilities, even though the patients were medically ready to be discharged. 

Additionally, the government alleged that some of Sava’s nursing services failed to meet federal standards of care, including failing to have sufficient staffing at certain facilities, failing to follow appropriate pressure ulcer and falls protocols, and failing to appropriately administer medications. 

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

The same genetic variations may boost susceptibility to both severe COVID-19 and cannabis use disorder (CUD), a new study suggests. The research does not confirm a genetic link, but the lead author said the signs of an association are still “troubling.”

“Reducing cannabis use among heavy users may potentially provide protection against severe COVID-19 presentations,” Alexander S. Hatoum, PhD, a postdoctoral scholar at Washington University, St. Louis, said in an interview. “Outside of individual risk, these data also have important implications for policy regarding vaccination as well as treatment prioritization in an overly taxed medical system.”

The study was published in the journal Biological Psychiatry Global Open Science.

Dr. Hatoum and colleagues launched the study to gain insight into whether CUD might be a risk factor for severe COVID-19 presentations.

As defined by the DSM-5, people with CUD suffer from impairment or distress because of their cannabis use and meet at least 2 of 11 criteria over a 12-month period, such as cravings, cannabis tolerance, and withdrawal symptoms. According to a 2020 study that examined 2008-2016 data, 2.72% of children aged 12-17 showed signs of CUD, as did 1.23% of those aged over 26.

The primary reasons for hospitalization and death related to COVID-19 are respiratory symptoms. “And we have observed that genetic vulnerability to CUD is shared with respiratory disease, even after tobacco use is considered,” Dr. Hatoum said.

He and his colleagues examined data from genomewide association studies and searched for genetic correlations between CUD (14,080 cases, 343,726 controls) and COVID-19 hospitalization (9,373 cases, 1,197,256 controls). “Genetic vulnerability to COVID-19 was correlated with genetic liability to CUD (P = 1.33e^–6),” the researchers wrote. “This association remained when accounting for genetic liability to related risk factors and covariates (P = .012-.049).”

According to Dr. Hatoum, the researchers found inconclusive evidence that CUD might worsen COVID-19 cases. “We applied statistical causal models, which found an effect consistent with causality, but it was nonsignificant,” he said.

Despite the absence of causality, the study findings could prove useful for clinicians and policy makers.

“Those struggling with CUD may be prioritized for vaccination and vaccination boosters to mitigate their higher likelihood of a severe COVID-19 presentation,” Dr. Hatoum said. “When testing positive for COVID-19, they may also be prioritized for earlier treatment.”

The study authors also added that the findings “urge caution” in regard to the wave of U.S. states legalizing cannabis. “Our data suggest that heavy cannabis use, but not lifetime cannabis use, represents a risk factor for severe COVID-19 presentations,” Dr. Hatoum said.

In an interview, Danielle Dick, PhD, who was not involved with the study, said it applies “cutting-edge methods to an important research question” and offers a “hint” of a genetic risk factor that makes some people more likely to be hospitalized for COVID-19. However, “the study does not tell us what those underlying genetically influenced processes might be,” added Dr. Dick, professor of psychology, and human and molecular genetics at Virginia Commonwealth University, Richmond. “And it’s an important caveat to point out that the results from this study are limited in that they are based on data from people from European descent – so they can’t necessarily be applied to address the harm experienced by so many people of color from the COVID pandemic. That’s an unfortunate limitation.”

As for the idea that the study findings should prompt caution about marijuana legalization, Dr. Dick said it’s true that increased acceptability of drug use “increases the likelihood that individuals who are genetically vulnerable will develop problems. There is robust evidence of this.”

However, Dr. Dick said, “the legalization of marijuana is a complex topic because the health consequences aren’t the only consideration when it comes to legalization. The other side of the coin is the huge harm that has been caused to communities of color through marijuana criminalization. Legalization will hopefully lead to decreased harm on that front. So it’s a double-edged sword.”

Dr. Hatoum, his colleagues, and Dr. Dick reported no relevant disclosures.

The same genetic variations may boost susceptibility to both severe COVID-19 and cannabis use disorder (CUD), a new study suggests. The research does not confirm a genetic link, but the lead author said the signs of an association are still “troubling.”

“Reducing cannabis use among heavy users may potentially provide protection against severe COVID-19 presentations,” Alexander S. Hatoum, PhD, a postdoctoral scholar at Washington University, St. Louis, said in an interview. “Outside of individual risk, these data also have important implications for policy regarding vaccination as well as treatment prioritization in an overly taxed medical system.”

The study was published in the journal Biological Psychiatry Global Open Science.

Dr. Hatoum and colleagues launched the study to gain insight into whether CUD might be a risk factor for severe COVID-19 presentations.

As defined by the DSM-5, people with CUD suffer from impairment or distress because of their cannabis use and meet at least 2 of 11 criteria over a 12-month period, such as cravings, cannabis tolerance, and withdrawal symptoms. According to a 2020 study that examined 2008-2016 data, 2.72% of children aged 12-17 showed signs of CUD, as did 1.23% of those aged over 26.

The primary reasons for hospitalization and death related to COVID-19 are respiratory symptoms. “And we have observed that genetic vulnerability to CUD is shared with respiratory disease, even after tobacco use is considered,” Dr. Hatoum said.

He and his colleagues examined data from genomewide association studies and searched for genetic correlations between CUD (14,080 cases, 343,726 controls) and COVID-19 hospitalization (9,373 cases, 1,197,256 controls). “Genetic vulnerability to COVID-19 was correlated with genetic liability to CUD (P = 1.33e^–6),” the researchers wrote. “This association remained when accounting for genetic liability to related risk factors and covariates (P = .012-.049).”

According to Dr. Hatoum, the researchers found inconclusive evidence that CUD might worsen COVID-19 cases. “We applied statistical causal models, which found an effect consistent with causality, but it was nonsignificant,” he said.

Despite the absence of causality, the study findings could prove useful for clinicians and policy makers.

“Those struggling with CUD may be prioritized for vaccination and vaccination boosters to mitigate their higher likelihood of a severe COVID-19 presentation,” Dr. Hatoum said. “When testing positive for COVID-19, they may also be prioritized for earlier treatment.”

The study authors also added that the findings “urge caution” in regard to the wave of U.S. states legalizing cannabis. “Our data suggest that heavy cannabis use, but not lifetime cannabis use, represents a risk factor for severe COVID-19 presentations,” Dr. Hatoum said.

In an interview, Danielle Dick, PhD, who was not involved with the study, said it applies “cutting-edge methods to an important research question” and offers a “hint” of a genetic risk factor that makes some people more likely to be hospitalized for COVID-19. However, “the study does not tell us what those underlying genetically influenced processes might be,” added Dr. Dick, professor of psychology, and human and molecular genetics at Virginia Commonwealth University, Richmond. “And it’s an important caveat to point out that the results from this study are limited in that they are based on data from people from European descent – so they can’t necessarily be applied to address the harm experienced by so many people of color from the COVID pandemic. That’s an unfortunate limitation.”

As for the idea that the study findings should prompt caution about marijuana legalization, Dr. Dick said it’s true that increased acceptability of drug use “increases the likelihood that individuals who are genetically vulnerable will develop problems. There is robust evidence of this.”

However, Dr. Dick said, “the legalization of marijuana is a complex topic because the health consequences aren’t the only consideration when it comes to legalization. The other side of the coin is the huge harm that has been caused to communities of color through marijuana criminalization. Legalization will hopefully lead to decreased harm on that front. So it’s a double-edged sword.”

Dr. Hatoum, his colleagues, and Dr. Dick reported no relevant disclosures.

The same genetic variations may boost susceptibility to both severe COVID-19 and cannabis use disorder (CUD), a new study suggests. The research does not confirm a genetic link, but the lead author said the signs of an association are still “troubling.”

“Reducing cannabis use among heavy users may potentially provide protection against severe COVID-19 presentations,” Alexander S. Hatoum, PhD, a postdoctoral scholar at Washington University, St. Louis, said in an interview. “Outside of individual risk, these data also have important implications for policy regarding vaccination as well as treatment prioritization in an overly taxed medical system.”

The study was published in the journal Biological Psychiatry Global Open Science.

Dr. Hatoum and colleagues launched the study to gain insight into whether CUD might be a risk factor for severe COVID-19 presentations.

As defined by the DSM-5, people with CUD suffer from impairment or distress because of their cannabis use and meet at least 2 of 11 criteria over a 12-month period, such as cravings, cannabis tolerance, and withdrawal symptoms. According to a 2020 study that examined 2008-2016 data, 2.72% of children aged 12-17 showed signs of CUD, as did 1.23% of those aged over 26.

The primary reasons for hospitalization and death related to COVID-19 are respiratory symptoms. “And we have observed that genetic vulnerability to CUD is shared with respiratory disease, even after tobacco use is considered,” Dr. Hatoum said.

He and his colleagues examined data from genomewide association studies and searched for genetic correlations between CUD (14,080 cases, 343,726 controls) and COVID-19 hospitalization (9,373 cases, 1,197,256 controls). “Genetic vulnerability to COVID-19 was correlated with genetic liability to CUD (P = 1.33e^–6),” the researchers wrote. “This association remained when accounting for genetic liability to related risk factors and covariates (P = .012-.049).”

According to Dr. Hatoum, the researchers found inconclusive evidence that CUD might worsen COVID-19 cases. “We applied statistical causal models, which found an effect consistent with causality, but it was nonsignificant,” he said.

Despite the absence of causality, the study findings could prove useful for clinicians and policy makers.

“Those struggling with CUD may be prioritized for vaccination and vaccination boosters to mitigate their higher likelihood of a severe COVID-19 presentation,” Dr. Hatoum said. “When testing positive for COVID-19, they may also be prioritized for earlier treatment.”

The study authors also added that the findings “urge caution” in regard to the wave of U.S. states legalizing cannabis. “Our data suggest that heavy cannabis use, but not lifetime cannabis use, represents a risk factor for severe COVID-19 presentations,” Dr. Hatoum said.

In an interview, Danielle Dick, PhD, who was not involved with the study, said it applies “cutting-edge methods to an important research question” and offers a “hint” of a genetic risk factor that makes some people more likely to be hospitalized for COVID-19. However, “the study does not tell us what those underlying genetically influenced processes might be,” added Dr. Dick, professor of psychology, and human and molecular genetics at Virginia Commonwealth University, Richmond. “And it’s an important caveat to point out that the results from this study are limited in that they are based on data from people from European descent – so they can’t necessarily be applied to address the harm experienced by so many people of color from the COVID pandemic. That’s an unfortunate limitation.”

As for the idea that the study findings should prompt caution about marijuana legalization, Dr. Dick said it’s true that increased acceptability of drug use “increases the likelihood that individuals who are genetically vulnerable will develop problems. There is robust evidence of this.”

However, Dr. Dick said, “the legalization of marijuana is a complex topic because the health consequences aren’t the only consideration when it comes to legalization. The other side of the coin is the huge harm that has been caused to communities of color through marijuana criminalization. Legalization will hopefully lead to decreased harm on that front. So it’s a double-edged sword.”

Dr. Hatoum, his colleagues, and Dr. Dick reported no relevant disclosures.

A previously healthy infant who survived sudden cardiac arrest at home was later found to have a de novo likely pathogenic genetic mutation in the SOS1 gene, which might be an unrecognized cause of sudden infant death, report clinicians from Missouri.

SOS1 gene variants are associated with Noonan syndrome, a genetic disorder that affects the RAS/MAPK signaling pathway. However, on presentation, the infant had none of the usual structural cardiac findings typical of Noonan syndrome, such as valvular disease or hypertrophic cardiomyopathy.

“To date, this is the first case reported of a ventricular fibrillation arrest in a patient with a RASopathy-related variant prior to development of the typically associated structural cardiac phenotype and may represent a previously unrecognized etiology of sudden death during infancy,” write Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO, from the Ward Family Heart Center, Children’s Mercy Kansas City, and the University of Missouri School of Medicine.

“Genetic testing in cases of unexplained aborted or sudden cardiac deaths, even in previously healthy children, can be valuable in establishing a diagnosis, determining the prognosis, and assessing risk to family members,” they add in a news release.

Dr. Follansbee and Dr. Malloy-Walton describe the case in a report published in the August issue of HeartRhythm Case Reports.
 

Case details

The case involved a 2-month-old girl who did not wake up as usual for her morning feeding. Her mother found her limp, pale, and having difficulty breathing.

When emergency medical services arrived, the infant had no pulse. Cardiopulmonary resuscitation was initiated and an external defibrillator revealed coarse ventricular fibrillation. An initial shock of 10 J was given with conversion to an atrial rhythm with aberrant ventricular conduction.

The infant developed increasing frequency of ectopy before degenerating to ventricular fibrillation. A second shock with 20 J was unsuccessful, but a third shock of 20 J successfully converted the rhythm to sinus with aberrant ventricular conduction and atrial ectopy with return of spontaneous circulation.

In the ICU, the infant displayed incessant, nonsustained ectopic atrial tachycardia, with rapid episodes of ectopic atrial tachycardia with ventricular rates up to 300 beats per minute in the setting of seizure activity, they report. 

With intravenous lorazepam, seizure activity resolved and treatment with amiodarone boluses led to transient establishment of sinus rhythm.

The QTc was noted to be above 500 ms and Brugada positioning of leads was unrevealing, the authors note.

Transthoracic echocardiogram showed a structurally normal heart with normal valve morphology and a patent foramen ovale with left-to-right flow. The initial ejection fraction was 49%. There was no evidence of ventricular hypertrophy, dilation, or noncompaction.

The infant was started on an esmolol infusion titrated to 225 μg/kg per min with frequent, nonsustained breakthrough of ectopic atrial tachycardia. Over the next 24 hours, the QTc interval normalized with normal T-wave morphology.

A procainamide challenge was negative. Cardiac MRI revealed normalization of ventricular function.

The genetics team was called in and a standard three-generation family history was obtained. An older sibling, 2 years of age, had no known medical conditions. The child’s paternal grandfather had died of a presumed myocardial infarction in his 50s, but no autopsy had been performed.

There was no family history of congenital heart disease, arrhythmia, sudden death, cardiomyopathy, recurrent syncope, congenital deafness, seizure, miscarriage, or developmental delay. Electrocardiograms obtained on the parents were normal.

Genetic testing using a comprehensive arrhythmia and cardiomyopathy next-generation sequencing panel revealed a de novo likely pathogenetic variant of the SOS1 gene associated with Noonan syndrome.

Given the aborted sudden cardiac death, the patient underwent dual-chamber epicardial implantable cardioverter-defibrillator implantation prior to discharge.

Dr. Follansbee and Dr. Malloy-Walton say a limitation to the case report is the lack of definitive association of the SOS1 variant with the presentation.

However, knowing the infant has the SOS1 variant and a history of aborted sudden death will allow for “monitoring and early intervention on typical manifestations of Noonan syndrome as the patient grows,” they say.

This research had no specific funding. Dr. Follansbee and Dr. Malloy-Walton have disclosed no relevant conflicts of interest.

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

A previously healthy infant who survived sudden cardiac arrest at home was later found to have a de novo likely pathogenic genetic mutation in the SOS1 gene, which might be an unrecognized cause of sudden infant death, report clinicians from Missouri.

SOS1 gene variants are associated with Noonan syndrome, a genetic disorder that affects the RAS/MAPK signaling pathway. However, on presentation, the infant had none of the usual structural cardiac findings typical of Noonan syndrome, such as valvular disease or hypertrophic cardiomyopathy.

“To date, this is the first case reported of a ventricular fibrillation arrest in a patient with a RASopathy-related variant prior to development of the typically associated structural cardiac phenotype and may represent a previously unrecognized etiology of sudden death during infancy,” write Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO, from the Ward Family Heart Center, Children’s Mercy Kansas City, and the University of Missouri School of Medicine.

“Genetic testing in cases of unexplained aborted or sudden cardiac deaths, even in previously healthy children, can be valuable in establishing a diagnosis, determining the prognosis, and assessing risk to family members,” they add in a news release.

Dr. Follansbee and Dr. Malloy-Walton describe the case in a report published in the August issue of HeartRhythm Case Reports.
 

Case details

The case involved a 2-month-old girl who did not wake up as usual for her morning feeding. Her mother found her limp, pale, and having difficulty breathing.

When emergency medical services arrived, the infant had no pulse. Cardiopulmonary resuscitation was initiated and an external defibrillator revealed coarse ventricular fibrillation. An initial shock of 10 J was given with conversion to an atrial rhythm with aberrant ventricular conduction.

The infant developed increasing frequency of ectopy before degenerating to ventricular fibrillation. A second shock with 20 J was unsuccessful, but a third shock of 20 J successfully converted the rhythm to sinus with aberrant ventricular conduction and atrial ectopy with return of spontaneous circulation.

In the ICU, the infant displayed incessant, nonsustained ectopic atrial tachycardia, with rapid episodes of ectopic atrial tachycardia with ventricular rates up to 300 beats per minute in the setting of seizure activity, they report. 

With intravenous lorazepam, seizure activity resolved and treatment with amiodarone boluses led to transient establishment of sinus rhythm.

The QTc was noted to be above 500 ms and Brugada positioning of leads was unrevealing, the authors note.

Transthoracic echocardiogram showed a structurally normal heart with normal valve morphology and a patent foramen ovale with left-to-right flow. The initial ejection fraction was 49%. There was no evidence of ventricular hypertrophy, dilation, or noncompaction.

The infant was started on an esmolol infusion titrated to 225 μg/kg per min with frequent, nonsustained breakthrough of ectopic atrial tachycardia. Over the next 24 hours, the QTc interval normalized with normal T-wave morphology.

A procainamide challenge was negative. Cardiac MRI revealed normalization of ventricular function.

The genetics team was called in and a standard three-generation family history was obtained. An older sibling, 2 years of age, had no known medical conditions. The child’s paternal grandfather had died of a presumed myocardial infarction in his 50s, but no autopsy had been performed.

There was no family history of congenital heart disease, arrhythmia, sudden death, cardiomyopathy, recurrent syncope, congenital deafness, seizure, miscarriage, or developmental delay. Electrocardiograms obtained on the parents were normal.

Genetic testing using a comprehensive arrhythmia and cardiomyopathy next-generation sequencing panel revealed a de novo likely pathogenetic variant of the SOS1 gene associated with Noonan syndrome.

Given the aborted sudden cardiac death, the patient underwent dual-chamber epicardial implantable cardioverter-defibrillator implantation prior to discharge.

Dr. Follansbee and Dr. Malloy-Walton say a limitation to the case report is the lack of definitive association of the SOS1 variant with the presentation.

However, knowing the infant has the SOS1 variant and a history of aborted sudden death will allow for “monitoring and early intervention on typical manifestations of Noonan syndrome as the patient grows,” they say.

This research had no specific funding. Dr. Follansbee and Dr. Malloy-Walton have disclosed no relevant conflicts of interest.

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

A previously healthy infant who survived sudden cardiac arrest at home was later found to have a de novo likely pathogenic genetic mutation in the SOS1 gene, which might be an unrecognized cause of sudden infant death, report clinicians from Missouri.

SOS1 gene variants are associated with Noonan syndrome, a genetic disorder that affects the RAS/MAPK signaling pathway. However, on presentation, the infant had none of the usual structural cardiac findings typical of Noonan syndrome, such as valvular disease or hypertrophic cardiomyopathy.

“To date, this is the first case reported of a ventricular fibrillation arrest in a patient with a RASopathy-related variant prior to development of the typically associated structural cardiac phenotype and may represent a previously unrecognized etiology of sudden death during infancy,” write Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO, from the Ward Family Heart Center, Children’s Mercy Kansas City, and the University of Missouri School of Medicine.

“Genetic testing in cases of unexplained aborted or sudden cardiac deaths, even in previously healthy children, can be valuable in establishing a diagnosis, determining the prognosis, and assessing risk to family members,” they add in a news release.

Dr. Follansbee and Dr. Malloy-Walton describe the case in a report published in the August issue of HeartRhythm Case Reports.
 

Case details

The case involved a 2-month-old girl who did not wake up as usual for her morning feeding. Her mother found her limp, pale, and having difficulty breathing.

When emergency medical services arrived, the infant had no pulse. Cardiopulmonary resuscitation was initiated and an external defibrillator revealed coarse ventricular fibrillation. An initial shock of 10 J was given with conversion to an atrial rhythm with aberrant ventricular conduction.

The infant developed increasing frequency of ectopy before degenerating to ventricular fibrillation. A second shock with 20 J was unsuccessful, but a third shock of 20 J successfully converted the rhythm to sinus with aberrant ventricular conduction and atrial ectopy with return of spontaneous circulation.

In the ICU, the infant displayed incessant, nonsustained ectopic atrial tachycardia, with rapid episodes of ectopic atrial tachycardia with ventricular rates up to 300 beats per minute in the setting of seizure activity, they report. 

With intravenous lorazepam, seizure activity resolved and treatment with amiodarone boluses led to transient establishment of sinus rhythm.

The QTc was noted to be above 500 ms and Brugada positioning of leads was unrevealing, the authors note.

Transthoracic echocardiogram showed a structurally normal heart with normal valve morphology and a patent foramen ovale with left-to-right flow. The initial ejection fraction was 49%. There was no evidence of ventricular hypertrophy, dilation, or noncompaction.

The infant was started on an esmolol infusion titrated to 225 μg/kg per min with frequent, nonsustained breakthrough of ectopic atrial tachycardia. Over the next 24 hours, the QTc interval normalized with normal T-wave morphology.

A procainamide challenge was negative. Cardiac MRI revealed normalization of ventricular function.

The genetics team was called in and a standard three-generation family history was obtained. An older sibling, 2 years of age, had no known medical conditions. The child’s paternal grandfather had died of a presumed myocardial infarction in his 50s, but no autopsy had been performed.

There was no family history of congenital heart disease, arrhythmia, sudden death, cardiomyopathy, recurrent syncope, congenital deafness, seizure, miscarriage, or developmental delay. Electrocardiograms obtained on the parents were normal.

Genetic testing using a comprehensive arrhythmia and cardiomyopathy next-generation sequencing panel revealed a de novo likely pathogenetic variant of the SOS1 gene associated with Noonan syndrome.

Given the aborted sudden cardiac death, the patient underwent dual-chamber epicardial implantable cardioverter-defibrillator implantation prior to discharge.

Dr. Follansbee and Dr. Malloy-Walton say a limitation to the case report is the lack of definitive association of the SOS1 variant with the presentation.

However, knowing the infant has the SOS1 variant and a history of aborted sudden death will allow for “monitoring and early intervention on typical manifestations of Noonan syndrome as the patient grows,” they say.

This research had no specific funding. Dr. Follansbee and Dr. Malloy-Walton have disclosed no relevant conflicts of interest.

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

About one-third of the U.S. population had been infected with SARS-CoV-2 by the end of 2020, according to a modeling study published Aug. 26 online in Nature.

Jeffrey Shaman, PhD, professor in the department of environmental health sciences and director of the climate and health program at the Columbia University Mailman School of Public Health, New York City, and colleagues developed a model to simulate how SARS-CoV-2 was transmitted within and between all 3,142 counties in the United States.

In their model, the researchers considered migration data between counties, the observed case numbers, and estimates of infections based on the number of people who test positive for SARS-CoV-2 antibodies.

The United States had the highest number of confirmed COVID-19 cases and deaths in the world during 2020. More than 19.6 million cases were reported by the end of the year.

But the authors point out that “69% of the population remained susceptible to viral infection.”

The researchers also studied the ascertainment rate, or the ratio of detected cases to the number of confirmed cases. Nationally, that value increased from 11.3% in March 2020 to 24.5% in December 2020.

That’s one of the biggest pandemic lessons from the data, Dr. Shaman said: “It is vitally important when there is an outbreak and you’re counting cases that there are many more people infected in your community who are contagious than reported cases. Each individual is infectious for multiple days, and there are many more unreported cases.”

That applies now with the Delta variant, he said.

“Vaccinated people who get infected with the Delta variant are part of the transmission chain,” he said.
 

Fatality rates dropped

Some of the data were very positive, Dr. Shaman told this news organization. The infection fatality rate fell from 0.77% in April to 0.31% in December. The authors suggest that that may be because of improvements in diagnosis and treatment, patient care, and reduced disease severity.

However, the fatality rate was still nearly four times as high as the estimated fatality rate for seasonal influenza (0.08%) and the 2009 influenza pandemic (0.0076%), the authors point out.

Joe K. Gerald, MD, PhD, associate professor and program director of public health policy and management at the University of Arizona, Tucson, told this news organization that this article helps confirm that COVID is much deadlier than the flu and that the intensity of the response has been appropriate.

“We should be willing to invest a lot more in mitigating COVID-19 than seasonal influenza because it has much greater consequences,” he said.

The numbers emphasize that testing must improve.

“We didn’t have enough tests available, and they weren’t easily accessible. For much of the year we were flying in the dark,” Dr. Gerald said.

The number of tests has increased this year, he acknowledged, but testing still lags. “We just can’t miss this many infections or diagnoses and hope to gain control,” he said.

The study also points out the huge variation by state and by county in infections and deaths, and that variation continues. Gerald noted that the varied numbers make it difficult for some regions to accept broader mandates, because the threat from COVID-19 appears very different where they are.

“We have to think about regions, how many people are susceptible, and what the testing capacity is,” he said. “States and even counties should have some leeway to make some important public health decisions, because local conditions are going to differ at different points in time.”
 

‘We have not turned the corner’

Jill Foster, MD, a pediatric infectious disease physician at the University of Minnesota Medical School, Minneapolis, said in an interview that the study adds evidence: “We have not turned the corner on COVID-19 and are nowhere near herd immunity – if it exists for SARS-CoV-2.”

She said the numbers presented are particularly concerning in regard to how many people were susceptible and were actively able to infect others: “Much higher than most people imagined and very much higher than their comparison, influenza.

“There are still more people susceptible than we had believed,” Dr. Foster added. “If the pattern continues where the Delta variant infects a significant portion of those vaccinated, the number of people susceptible rises even higher than was predicted.”

She said that it is reassuring that the analysis shows a decrease in case fatality and said the finding supports the common opinion that medicine is better able to fight the disease.

“However,” she said, “the optimism is tempered by acknowledging that in order to benefit from these advances, we must not overwhelm the facilities where patients are cared for so that optimal care can be delivered.”

Dr. Foster said these numbers represent a warning that COVID should be treated as a continuing threat.

“We need to acknowledge that there is COVID-19 infection simmering and periodically erupting throughout the country,” she said. “It is not monolithic and varies by geography and seasons in ways that are difficult to predict other than at any given time there is likely more infection present than we are identifying and more people susceptible to infection than we have calculated.”

The authors and Dr. Gerald have disclosed no relevant financial relationships. Dr. Foster has received clinical trials funding from Moderna.

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

About one-third of the U.S. population had been infected with SARS-CoV-2 by the end of 2020, according to a modeling study published Aug. 26 online in Nature.

Jeffrey Shaman, PhD, professor in the department of environmental health sciences and director of the climate and health program at the Columbia University Mailman School of Public Health, New York City, and colleagues developed a model to simulate how SARS-CoV-2 was transmitted within and between all 3,142 counties in the United States.

In their model, the researchers considered migration data between counties, the observed case numbers, and estimates of infections based on the number of people who test positive for SARS-CoV-2 antibodies.

The United States had the highest number of confirmed COVID-19 cases and deaths in the world during 2020. More than 19.6 million cases were reported by the end of the year.

But the authors point out that “69% of the population remained susceptible to viral infection.”

The researchers also studied the ascertainment rate, or the ratio of detected cases to the number of confirmed cases. Nationally, that value increased from 11.3% in March 2020 to 24.5% in December 2020.

That’s one of the biggest pandemic lessons from the data, Dr. Shaman said: “It is vitally important when there is an outbreak and you’re counting cases that there are many more people infected in your community who are contagious than reported cases. Each individual is infectious for multiple days, and there are many more unreported cases.”

That applies now with the Delta variant, he said.

“Vaccinated people who get infected with the Delta variant are part of the transmission chain,” he said.
 

Fatality rates dropped

Some of the data were very positive, Dr. Shaman told this news organization. The infection fatality rate fell from 0.77% in April to 0.31% in December. The authors suggest that that may be because of improvements in diagnosis and treatment, patient care, and reduced disease severity.

However, the fatality rate was still nearly four times as high as the estimated fatality rate for seasonal influenza (0.08%) and the 2009 influenza pandemic (0.0076%), the authors point out.

Joe K. Gerald, MD, PhD, associate professor and program director of public health policy and management at the University of Arizona, Tucson, told this news organization that this article helps confirm that COVID is much deadlier than the flu and that the intensity of the response has been appropriate.

“We should be willing to invest a lot more in mitigating COVID-19 than seasonal influenza because it has much greater consequences,” he said.

The numbers emphasize that testing must improve.

“We didn’t have enough tests available, and they weren’t easily accessible. For much of the year we were flying in the dark,” Dr. Gerald said.

The number of tests has increased this year, he acknowledged, but testing still lags. “We just can’t miss this many infections or diagnoses and hope to gain control,” he said.

The study also points out the huge variation by state and by county in infections and deaths, and that variation continues. Gerald noted that the varied numbers make it difficult for some regions to accept broader mandates, because the threat from COVID-19 appears very different where they are.

“We have to think about regions, how many people are susceptible, and what the testing capacity is,” he said. “States and even counties should have some leeway to make some important public health decisions, because local conditions are going to differ at different points in time.”
 

‘We have not turned the corner’

Jill Foster, MD, a pediatric infectious disease physician at the University of Minnesota Medical School, Minneapolis, said in an interview that the study adds evidence: “We have not turned the corner on COVID-19 and are nowhere near herd immunity – if it exists for SARS-CoV-2.”

She said the numbers presented are particularly concerning in regard to how many people were susceptible and were actively able to infect others: “Much higher than most people imagined and very much higher than their comparison, influenza.

“There are still more people susceptible than we had believed,” Dr. Foster added. “If the pattern continues where the Delta variant infects a significant portion of those vaccinated, the number of people susceptible rises even higher than was predicted.”

She said that it is reassuring that the analysis shows a decrease in case fatality and said the finding supports the common opinion that medicine is better able to fight the disease.

“However,” she said, “the optimism is tempered by acknowledging that in order to benefit from these advances, we must not overwhelm the facilities where patients are cared for so that optimal care can be delivered.”

Dr. Foster said these numbers represent a warning that COVID should be treated as a continuing threat.

“We need to acknowledge that there is COVID-19 infection simmering and periodically erupting throughout the country,” she said. “It is not monolithic and varies by geography and seasons in ways that are difficult to predict other than at any given time there is likely more infection present than we are identifying and more people susceptible to infection than we have calculated.”

The authors and Dr. Gerald have disclosed no relevant financial relationships. Dr. Foster has received clinical trials funding from Moderna.

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

About one-third of the U.S. population had been infected with SARS-CoV-2 by the end of 2020, according to a modeling study published Aug. 26 online in Nature.

Jeffrey Shaman, PhD, professor in the department of environmental health sciences and director of the climate and health program at the Columbia University Mailman School of Public Health, New York City, and colleagues developed a model to simulate how SARS-CoV-2 was transmitted within and between all 3,142 counties in the United States.

In their model, the researchers considered migration data between counties, the observed case numbers, and estimates of infections based on the number of people who test positive for SARS-CoV-2 antibodies.

The United States had the highest number of confirmed COVID-19 cases and deaths in the world during 2020. More than 19.6 million cases were reported by the end of the year.

But the authors point out that “69% of the population remained susceptible to viral infection.”

The researchers also studied the ascertainment rate, or the ratio of detected cases to the number of confirmed cases. Nationally, that value increased from 11.3% in March 2020 to 24.5% in December 2020.

That’s one of the biggest pandemic lessons from the data, Dr. Shaman said: “It is vitally important when there is an outbreak and you’re counting cases that there are many more people infected in your community who are contagious than reported cases. Each individual is infectious for multiple days, and there are many more unreported cases.”

That applies now with the Delta variant, he said.

“Vaccinated people who get infected with the Delta variant are part of the transmission chain,” he said.
 

Fatality rates dropped

Some of the data were very positive, Dr. Shaman told this news organization. The infection fatality rate fell from 0.77% in April to 0.31% in December. The authors suggest that that may be because of improvements in diagnosis and treatment, patient care, and reduced disease severity.

However, the fatality rate was still nearly four times as high as the estimated fatality rate for seasonal influenza (0.08%) and the 2009 influenza pandemic (0.0076%), the authors point out.

Joe K. Gerald, MD, PhD, associate professor and program director of public health policy and management at the University of Arizona, Tucson, told this news organization that this article helps confirm that COVID is much deadlier than the flu and that the intensity of the response has been appropriate.

“We should be willing to invest a lot more in mitigating COVID-19 than seasonal influenza because it has much greater consequences,” he said.

The numbers emphasize that testing must improve.

“We didn’t have enough tests available, and they weren’t easily accessible. For much of the year we were flying in the dark,” Dr. Gerald said.

The number of tests has increased this year, he acknowledged, but testing still lags. “We just can’t miss this many infections or diagnoses and hope to gain control,” he said.

The study also points out the huge variation by state and by county in infections and deaths, and that variation continues. Gerald noted that the varied numbers make it difficult for some regions to accept broader mandates, because the threat from COVID-19 appears very different where they are.

“We have to think about regions, how many people are susceptible, and what the testing capacity is,” he said. “States and even counties should have some leeway to make some important public health decisions, because local conditions are going to differ at different points in time.”
 

‘We have not turned the corner’

Jill Foster, MD, a pediatric infectious disease physician at the University of Minnesota Medical School, Minneapolis, said in an interview that the study adds evidence: “We have not turned the corner on COVID-19 and are nowhere near herd immunity – if it exists for SARS-CoV-2.”

She said the numbers presented are particularly concerning in regard to how many people were susceptible and were actively able to infect others: “Much higher than most people imagined and very much higher than their comparison, influenza.

“There are still more people susceptible than we had believed,” Dr. Foster added. “If the pattern continues where the Delta variant infects a significant portion of those vaccinated, the number of people susceptible rises even higher than was predicted.”

She said that it is reassuring that the analysis shows a decrease in case fatality and said the finding supports the common opinion that medicine is better able to fight the disease.

“However,” she said, “the optimism is tempered by acknowledging that in order to benefit from these advances, we must not overwhelm the facilities where patients are cared for so that optimal care can be delivered.”

Dr. Foster said these numbers represent a warning that COVID should be treated as a continuing threat.

“We need to acknowledge that there is COVID-19 infection simmering and periodically erupting throughout the country,” she said. “It is not monolithic and varies by geography and seasons in ways that are difficult to predict other than at any given time there is likely more infection present than we are identifying and more people susceptible to infection than we have calculated.”

The authors and Dr. Gerald have disclosed no relevant financial relationships. Dr. Foster has received clinical trials funding from Moderna.

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

The Food and Drug Administration has approved difelikefalin for treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis, the first agent approved from a novel class of kappa opioid receptor agonists.

Olivier Le Moal/Getty Images

Some nephrologists welcomed the Aug. 23 approval of this new option for treating pruritus, a relatively common and often hard-to-resolve complication of dialysis in patients with chronic kidney disease (CKD) that can substantially impinge on quality of life for some patients, but also voiced uncertainty about the role of a new agent with a modest trial track record that may be expensive and face insurance-coverage hurdles.

“Uptake of difelikefalin will depend on awareness of itch among patients dependent on hemodialysis, and on payment policies,” predicted Daniel E. Weiner, MD, a nephrologist at Tufts Medical Center in Boston. “Pruritus is underdiagnosed among people with kidney failure, and in some patients ongoing pruritus can be highly impactful on sleep and quality of life. The clinical trial results were very encouraging that difelikefalin is effective and safe,” which makes recognition of pruritus as a significant issue for patients a key factor in uptake of the new drug, Dr. Weiner, an investigator in a difelikefalin clinical study, said in an interview.

Other nephrologists acknowledged the substantial problem that itch can pose for many patients with CKD on dialysis but questioned the weight of evidence behind difelikefalin’s approval.
 

Two pivotal trials with fewer than 900 total randomized patients

The data considered by the FDA primarily featured results from two pivotal trials, KALM-1 and KALM-2. KALM-1 randomized 378 patients with CKD and on hemodialysis and with moderate to severe pruritus to intravenous treatment with difelikefalin or placebo three times a week for 12 weeks with a primary endpoint of an improvement (decrease) of at least 3 points from baseline in their Worst Itching Intensity Numerical Rating Scale (WI-NRS) score, which averaged just over 7 points at baseline. After 12 weeks on treatment, 52% of patients who received difelikefalin had at least a 3-point drop, compared with 31% of patients who received placebo, a significant difference. The results appeared in a 2020 report in the New England Journal of Medicine.

Confirmatory results came in the second pivotal trial, KALM-2, a similarly designed, 12-week study that randomized 473 patients, with 54% of those in the active arm achieving at least a 3-point cut in their baseline WI-NRS score, compared with 42% of patients who received placebo, a significant difference. A report at the Kidney Week meeting sponsored by the National Kidney Foundation in October 2020 presented the KALM-2 results, but the findings have not yet appeared in a published article.

In sum, the data suggest that treatment with difelikefalin will, on average, produce a clinically meaningful effect on itch compared with placebo in about 20% of patients, with nearly half the patients who receive the active drug having a less robust response and many patients who receive no active treatment also show a meaningful cut in their pruritus severity in a trial setting, noted Paul Palevsky, MD, professor of medicine at the University of Pittsburgh and chief of the renal section at the Veterans Affairs Pittsburgh Healthcare System.

The upshot is that questions linger over which patients are the best candidates for this drug and how it might perform in real-world practice given difelikefalin’s limited track record, Dr. Palevsky said in an interview.

In addition, the labeling specifies the indication is for patients with moderate to severe pruritus, but itching severity is not routinely quantified in these patients in current practice, added Dr. Palevsky, who is also president of the National Kidney Foundation.

Dr. Weiner noted that another unknown is the appropriate duration of treatment in real-world use.
 

What will it cost, and will it be covered?

The drug’s price and insurance coverage will likely be a major factor in uptake of the new drug, agreed both Dr. Weiner and Dr. Palevsky, especially the coverage decision for Medicare patients by the Centers for Medicare & Medicaid Services. A corollary is whether or not coverage for difelikefalin, which patients receive as an intravenous infusion during each of their usual three-times-a-week dialysis sessions, will lie outside of the bundled dialysis reimbursement payment. If is no mechanism exists to pay for difelikefalin separately beyond the current bundled dialysis rate, “I suspect it will not get used very much unless it is very inexpensive,” predicted Dr. Weiner.

Another issue is where difelikefalin fits within the lineup of standard treatment options. “A lot of people receiving hemodialysis suffer from pruritus and have not been successfully treated. For these individuals difelikefalin could be a game changer,” Dr. Weiner said.

Other nephrologists have a more positive take on the existing treatment options.

“Start systemic therapy for patients with itch that is significantly affecting quality of life; stepping up from topical therapy just delays effective treatment,” advised Hugh C. Rayner, MD, a nephrologist affiliated with Birmingham (England) Heartland’s Hospital who was lead author on a review of pruritus treatments for patients with CKD on hemodialysis.

“Standard systemic therapy is gabapentin or pregabalin,” an approach “supported by robust evidence confirmed in a Cochrane review,” he said in an interview. The impact of difelikefalin “will be limited as its effectiveness in reducing itch is modest at best and far inferior to gabapentin and pregabalin,” Dr. Rayner added. Difelikefalin’s “main downsides will be its cost, compared with gabapentin, and its gastrointestinal side effects.”
 

Adverse-event profiles

In KALM-1, the most frequent adverse effects from difelikefalin treatment was diarrhea, in 10% of patients, compared with a 4% rate among patients who received placebo. Vomiting occurred at a 5% incidence on difelikefalin and in 3% of patients on placebo. All serious adverse events occurred in 26% of patients on difelikefalin and in 22% of those who received placebo. Discontinuations because of an adverse event occurred in 8% of patients on difelikefalin and in 5% of the placebo patients.

An editorial that accompanied the published KALM-1 report in 2020 said “the findings are compelling, although diarrhea, dizziness, and vomiting were frequent side effects.”

Both Dr. Weiner and Dr. Palevsky were more reserved than Dr. Rayner in their appraisal of gabapentin and pregabalin, although Dr. Palevsky admitted that he has prescribed one or the other of these two drugs to “lots of patients,” especially gabapentin. “But they are not completely benign drugs,” he cautioned, a concern echoed by Dr. Weiner.

“Antihistamines, gabapentin, and pregabalin have a high side-effect burden in patients on hemodialysis and limited efficacy, and are poor options for chronic pruritus management,” explained Dr. Weiner. “I would favor difelikefalin to chronic prescription of these other agents” because difelikefalin “appears effective and has a very low side effect burden. Very few effective treatments for pruritus do not have side effects.”

Difelikefalin is a peripherally restricted, selective kappa opioid receptor agonist that exerts antipruritic effects by activating kappa opioid receptors on peripheral neurons and immune cells. The drug’s hydrophilic, small-peptide structure restricts passive diffusion across membranes, which limits the drug’s access to kappa opioid receptors in the central nervous system and hence reduces potential adverse effects.

The FDA made this approval decision without consulting an advisory committee. The companies that will market difelikefalin (Korsuva), Cara Therapeutics and Vifor Pharma, announced that their U.S. promotional launch of the drug starts early in 2022.

The KALM-1 and KALM-2 studies were sponsored by Cara Therapeutics and Vifor Pharma, the two companies that have been jointly developing difelikefalin. Dr. Pavelsky and Dr. Rayner had no relevant disclosures. Dr. Weiner was previously an adviser to Cara and Vifor and participated as an investigator in a difelikefalin clinical study, but more recently has had no relationships with the companies.

mzoler@mdedge.com

The Food and Drug Administration has approved difelikefalin for treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis, the first agent approved from a novel class of kappa opioid receptor agonists.

Olivier Le Moal/Getty Images

Some nephrologists welcomed the Aug. 23 approval of this new option for treating pruritus, a relatively common and often hard-to-resolve complication of dialysis in patients with chronic kidney disease (CKD) that can substantially impinge on quality of life for some patients, but also voiced uncertainty about the role of a new agent with a modest trial track record that may be expensive and face insurance-coverage hurdles.

“Uptake of difelikefalin will depend on awareness of itch among patients dependent on hemodialysis, and on payment policies,” predicted Daniel E. Weiner, MD, a nephrologist at Tufts Medical Center in Boston. “Pruritus is underdiagnosed among people with kidney failure, and in some patients ongoing pruritus can be highly impactful on sleep and quality of life. The clinical trial results were very encouraging that difelikefalin is effective and safe,” which makes recognition of pruritus as a significant issue for patients a key factor in uptake of the new drug, Dr. Weiner, an investigator in a difelikefalin clinical study, said in an interview.

Other nephrologists acknowledged the substantial problem that itch can pose for many patients with CKD on dialysis but questioned the weight of evidence behind difelikefalin’s approval.
 

Two pivotal trials with fewer than 900 total randomized patients

The data considered by the FDA primarily featured results from two pivotal trials, KALM-1 and KALM-2. KALM-1 randomized 378 patients with CKD and on hemodialysis and with moderate to severe pruritus to intravenous treatment with difelikefalin or placebo three times a week for 12 weeks with a primary endpoint of an improvement (decrease) of at least 3 points from baseline in their Worst Itching Intensity Numerical Rating Scale (WI-NRS) score, which averaged just over 7 points at baseline. After 12 weeks on treatment, 52% of patients who received difelikefalin had at least a 3-point drop, compared with 31% of patients who received placebo, a significant difference. The results appeared in a 2020 report in the New England Journal of Medicine.

Confirmatory results came in the second pivotal trial, KALM-2, a similarly designed, 12-week study that randomized 473 patients, with 54% of those in the active arm achieving at least a 3-point cut in their baseline WI-NRS score, compared with 42% of patients who received placebo, a significant difference. A report at the Kidney Week meeting sponsored by the National Kidney Foundation in October 2020 presented the KALM-2 results, but the findings have not yet appeared in a published article.

In sum, the data suggest that treatment with difelikefalin will, on average, produce a clinically meaningful effect on itch compared with placebo in about 20% of patients, with nearly half the patients who receive the active drug having a less robust response and many patients who receive no active treatment also show a meaningful cut in their pruritus severity in a trial setting, noted Paul Palevsky, MD, professor of medicine at the University of Pittsburgh and chief of the renal section at the Veterans Affairs Pittsburgh Healthcare System.

The upshot is that questions linger over which patients are the best candidates for this drug and how it might perform in real-world practice given difelikefalin’s limited track record, Dr. Palevsky said in an interview.

In addition, the labeling specifies the indication is for patients with moderate to severe pruritus, but itching severity is not routinely quantified in these patients in current practice, added Dr. Palevsky, who is also president of the National Kidney Foundation.

Dr. Weiner noted that another unknown is the appropriate duration of treatment in real-world use.
 

What will it cost, and will it be covered?

The drug’s price and insurance coverage will likely be a major factor in uptake of the new drug, agreed both Dr. Weiner and Dr. Palevsky, especially the coverage decision for Medicare patients by the Centers for Medicare & Medicaid Services. A corollary is whether or not coverage for difelikefalin, which patients receive as an intravenous infusion during each of their usual three-times-a-week dialysis sessions, will lie outside of the bundled dialysis reimbursement payment. If is no mechanism exists to pay for difelikefalin separately beyond the current bundled dialysis rate, “I suspect it will not get used very much unless it is very inexpensive,” predicted Dr. Weiner.

Another issue is where difelikefalin fits within the lineup of standard treatment options. “A lot of people receiving hemodialysis suffer from pruritus and have not been successfully treated. For these individuals difelikefalin could be a game changer,” Dr. Weiner said.

Other nephrologists have a more positive take on the existing treatment options.

“Start systemic therapy for patients with itch that is significantly affecting quality of life; stepping up from topical therapy just delays effective treatment,” advised Hugh C. Rayner, MD, a nephrologist affiliated with Birmingham (England) Heartland’s Hospital who was lead author on a review of pruritus treatments for patients with CKD on hemodialysis.

“Standard systemic therapy is gabapentin or pregabalin,” an approach “supported by robust evidence confirmed in a Cochrane review,” he said in an interview. The impact of difelikefalin “will be limited as its effectiveness in reducing itch is modest at best and far inferior to gabapentin and pregabalin,” Dr. Rayner added. Difelikefalin’s “main downsides will be its cost, compared with gabapentin, and its gastrointestinal side effects.”
 

Adverse-event profiles

In KALM-1, the most frequent adverse effects from difelikefalin treatment was diarrhea, in 10% of patients, compared with a 4% rate among patients who received placebo. Vomiting occurred at a 5% incidence on difelikefalin and in 3% of patients on placebo. All serious adverse events occurred in 26% of patients on difelikefalin and in 22% of those who received placebo. Discontinuations because of an adverse event occurred in 8% of patients on difelikefalin and in 5% of the placebo patients.

An editorial that accompanied the published KALM-1 report in 2020 said “the findings are compelling, although diarrhea, dizziness, and vomiting were frequent side effects.”

Both Dr. Weiner and Dr. Palevsky were more reserved than Dr. Rayner in their appraisal of gabapentin and pregabalin, although Dr. Palevsky admitted that he has prescribed one or the other of these two drugs to “lots of patients,” especially gabapentin. “But they are not completely benign drugs,” he cautioned, a concern echoed by Dr. Weiner.

“Antihistamines, gabapentin, and pregabalin have a high side-effect burden in patients on hemodialysis and limited efficacy, and are poor options for chronic pruritus management,” explained Dr. Weiner. “I would favor difelikefalin to chronic prescription of these other agents” because difelikefalin “appears effective and has a very low side effect burden. Very few effective treatments for pruritus do not have side effects.”

Difelikefalin is a peripherally restricted, selective kappa opioid receptor agonist that exerts antipruritic effects by activating kappa opioid receptors on peripheral neurons and immune cells. The drug’s hydrophilic, small-peptide structure restricts passive diffusion across membranes, which limits the drug’s access to kappa opioid receptors in the central nervous system and hence reduces potential adverse effects.

The FDA made this approval decision without consulting an advisory committee. The companies that will market difelikefalin (Korsuva), Cara Therapeutics and Vifor Pharma, announced that their U.S. promotional launch of the drug starts early in 2022.

The KALM-1 and KALM-2 studies were sponsored by Cara Therapeutics and Vifor Pharma, the two companies that have been jointly developing difelikefalin. Dr. Pavelsky and Dr. Rayner had no relevant disclosures. Dr. Weiner was previously an adviser to Cara and Vifor and participated as an investigator in a difelikefalin clinical study, but more recently has had no relationships with the companies.

mzoler@mdedge.com

The Food and Drug Administration has approved difelikefalin for treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis, the first agent approved from a novel class of kappa opioid receptor agonists.

Olivier Le Moal/Getty Images

Some nephrologists welcomed the Aug. 23 approval of this new option for treating pruritus, a relatively common and often hard-to-resolve complication of dialysis in patients with chronic kidney disease (CKD) that can substantially impinge on quality of life for some patients, but also voiced uncertainty about the role of a new agent with a modest trial track record that may be expensive and face insurance-coverage hurdles.

“Uptake of difelikefalin will depend on awareness of itch among patients dependent on hemodialysis, and on payment policies,” predicted Daniel E. Weiner, MD, a nephrologist at Tufts Medical Center in Boston. “Pruritus is underdiagnosed among people with kidney failure, and in some patients ongoing pruritus can be highly impactful on sleep and quality of life. The clinical trial results were very encouraging that difelikefalin is effective and safe,” which makes recognition of pruritus as a significant issue for patients a key factor in uptake of the new drug, Dr. Weiner, an investigator in a difelikefalin clinical study, said in an interview.

Other nephrologists acknowledged the substantial problem that itch can pose for many patients with CKD on dialysis but questioned the weight of evidence behind difelikefalin’s approval.
 

Two pivotal trials with fewer than 900 total randomized patients

The data considered by the FDA primarily featured results from two pivotal trials, KALM-1 and KALM-2. KALM-1 randomized 378 patients with CKD and on hemodialysis and with moderate to severe pruritus to intravenous treatment with difelikefalin or placebo three times a week for 12 weeks with a primary endpoint of an improvement (decrease) of at least 3 points from baseline in their Worst Itching Intensity Numerical Rating Scale (WI-NRS) score, which averaged just over 7 points at baseline. After 12 weeks on treatment, 52% of patients who received difelikefalin had at least a 3-point drop, compared with 31% of patients who received placebo, a significant difference. The results appeared in a 2020 report in the New England Journal of Medicine.

Confirmatory results came in the second pivotal trial, KALM-2, a similarly designed, 12-week study that randomized 473 patients, with 54% of those in the active arm achieving at least a 3-point cut in their baseline WI-NRS score, compared with 42% of patients who received placebo, a significant difference. A report at the Kidney Week meeting sponsored by the National Kidney Foundation in October 2020 presented the KALM-2 results, but the findings have not yet appeared in a published article.

In sum, the data suggest that treatment with difelikefalin will, on average, produce a clinically meaningful effect on itch compared with placebo in about 20% of patients, with nearly half the patients who receive the active drug having a less robust response and many patients who receive no active treatment also show a meaningful cut in their pruritus severity in a trial setting, noted Paul Palevsky, MD, professor of medicine at the University of Pittsburgh and chief of the renal section at the Veterans Affairs Pittsburgh Healthcare System.

The upshot is that questions linger over which patients are the best candidates for this drug and how it might perform in real-world practice given difelikefalin’s limited track record, Dr. Palevsky said in an interview.

In addition, the labeling specifies the indication is for patients with moderate to severe pruritus, but itching severity is not routinely quantified in these patients in current practice, added Dr. Palevsky, who is also president of the National Kidney Foundation.

Dr. Weiner noted that another unknown is the appropriate duration of treatment in real-world use.
 

What will it cost, and will it be covered?

The drug’s price and insurance coverage will likely be a major factor in uptake of the new drug, agreed both Dr. Weiner and Dr. Palevsky, especially the coverage decision for Medicare patients by the Centers for Medicare & Medicaid Services. A corollary is whether or not coverage for difelikefalin, which patients receive as an intravenous infusion during each of their usual three-times-a-week dialysis sessions, will lie outside of the bundled dialysis reimbursement payment. If is no mechanism exists to pay for difelikefalin separately beyond the current bundled dialysis rate, “I suspect it will not get used very much unless it is very inexpensive,” predicted Dr. Weiner.

Another issue is where difelikefalin fits within the lineup of standard treatment options. “A lot of people receiving hemodialysis suffer from pruritus and have not been successfully treated. For these individuals difelikefalin could be a game changer,” Dr. Weiner said.

Other nephrologists have a more positive take on the existing treatment options.

“Start systemic therapy for patients with itch that is significantly affecting quality of life; stepping up from topical therapy just delays effective treatment,” advised Hugh C. Rayner, MD, a nephrologist affiliated with Birmingham (England) Heartland’s Hospital who was lead author on a review of pruritus treatments for patients with CKD on hemodialysis.

“Standard systemic therapy is gabapentin or pregabalin,” an approach “supported by robust evidence confirmed in a Cochrane review,” he said in an interview. The impact of difelikefalin “will be limited as its effectiveness in reducing itch is modest at best and far inferior to gabapentin and pregabalin,” Dr. Rayner added. Difelikefalin’s “main downsides will be its cost, compared with gabapentin, and its gastrointestinal side effects.”
 

Adverse-event profiles

In KALM-1, the most frequent adverse effects from difelikefalin treatment was diarrhea, in 10% of patients, compared with a 4% rate among patients who received placebo. Vomiting occurred at a 5% incidence on difelikefalin and in 3% of patients on placebo. All serious adverse events occurred in 26% of patients on difelikefalin and in 22% of those who received placebo. Discontinuations because of an adverse event occurred in 8% of patients on difelikefalin and in 5% of the placebo patients.

An editorial that accompanied the published KALM-1 report in 2020 said “the findings are compelling, although diarrhea, dizziness, and vomiting were frequent side effects.”

Both Dr. Weiner and Dr. Palevsky were more reserved than Dr. Rayner in their appraisal of gabapentin and pregabalin, although Dr. Palevsky admitted that he has prescribed one or the other of these two drugs to “lots of patients,” especially gabapentin. “But they are not completely benign drugs,” he cautioned, a concern echoed by Dr. Weiner.

“Antihistamines, gabapentin, and pregabalin have a high side-effect burden in patients on hemodialysis and limited efficacy, and are poor options for chronic pruritus management,” explained Dr. Weiner. “I would favor difelikefalin to chronic prescription of these other agents” because difelikefalin “appears effective and has a very low side effect burden. Very few effective treatments for pruritus do not have side effects.”

Difelikefalin is a peripherally restricted, selective kappa opioid receptor agonist that exerts antipruritic effects by activating kappa opioid receptors on peripheral neurons and immune cells. The drug’s hydrophilic, small-peptide structure restricts passive diffusion across membranes, which limits the drug’s access to kappa opioid receptors in the central nervous system and hence reduces potential adverse effects.

The FDA made this approval decision without consulting an advisory committee. The companies that will market difelikefalin (Korsuva), Cara Therapeutics and Vifor Pharma, announced that their U.S. promotional launch of the drug starts early in 2022.

The KALM-1 and KALM-2 studies were sponsored by Cara Therapeutics and Vifor Pharma, the two companies that have been jointly developing difelikefalin. Dr. Pavelsky and Dr. Rayner had no relevant disclosures. Dr. Weiner was previously an adviser to Cara and Vifor and participated as an investigator in a difelikefalin clinical study, but more recently has had no relationships with the companies.

mzoler@mdedge.com

The death ‘dog’

Imagine you’re out in your backyard managing the grill for a big family barbecue. You’ve got a dazzling assortment of meat assorted on your fancy new propane grill, all charring nicely. Naturally, the hot dogs finish first, and as you pull them off, you figure you’ll help yourself to one now. After all, you are the chef, you deserve a reward. But, as you bite into your smoking hot sandwich, a cold, bony finger taps you on the shoulder. You turn and come face to face with the Grim Reaper. “YOU JUST LOST 36 MINUTES,” Death says. “ALSO, MAY I HAVE ONE OF THOSE? THEY LOOK DELICIOUS.”

PxHere

Nonplussed and moving automatically, you scoop up another hot dog and place it in a bun. “WITH KETCHUP PLEASE,” Death says. “I NEVER CARED FOR MUSTARD.”

“I don’t understand,” you say. “Surely I won’t die at a family barbecue.”

“DO NOT CALL ME SHIRLEY,” Death says. “AND YOU WILL NOT. IT’S PART OF MY NEW CONTRACT.”

A new study, published in Nature Food, found that a person may lose up to 36 minutes for every hot dog consumed. Researchers from the University of Michigan analyzed nearly 6,000 different foods using a new nutritional index to quantify their health effects in minutes of healthy life lost or gained. Eating a serving of nuts adds an extra 26 minutes of life. The researchers determined that replacing just 10% of daily caloric intake from beef and processed foods with fruits, vegetables, and nuts can add 48 minutes per day. It would also reduce the daily carbon footprint by 33%.

“So you go around to everyone eating bad food and tell them how much life they’ve lost?” you ask when the Grim Reaper finishes his story. “Sounds like a drag.”

“IT IS. WE’VE HAD TO HIRE NEW BLOOD.” Death chuckles at its own bad pun. “NOW IF YOU’LL EXCUSE ME, I MUST CHASTISE A MAN IN FLORIDA FOR EATING A WELL-DONE STEAK.”
 

More stress, less sex

As the world becomes a more stressful place, the human population could face a 50% drop by the end of the century.

John Hain/Pixabay

Think of stress as a one-two punch to the libido and human fertility. The more people are stressed out, the less likely they are to have quality interactions with others. Many of us would rather be alone with our wine and cheese to watch our favorite show.

Researchers have found that high stress levels have been known to drop sperm count, ovulation, and sexual activity. Guess what? There has been a 50% decrease in sperm counts over the last 50 years. That’s the second punch. But let’s not forget, the times are changing.

“Changes in reproductive behavior that contribute to the population drop include more young couples choosing to be ‘child-free,’ people having fewer children, and couples waiting longer to start families,” said Alexander Suvorov, PhD, of the University of Massachusetts, the paper’s author.

Let’s summarize: The more stress we’re dealing with, the less people want to deal with each other.

Who would have thought the future would be less fun?
 

‘You are not a horse. You are not a cow. Seriously, y’all. Stop it.’

WARNING: The following descriptions of COVID-19–related insanity may be offensive to some readers.

Greetings, ladies and gentlemen! Welcome to the first round of Pandemic Pandemonium. Let’s get right to the action.

South_agency/Getty Images

This week’s preshow match-off involves face mask woes. The first comes to us from Alabama, where a woman wore a space helmet to a school board meeting to protest mask mandates. The second comes from Australia, in the form of mischievous magpies. We will explain.

It is not uncommon for magpies to attack those who come too close to their nests in the spring, or “swooping season,” as it’s affectionately called. The magpies are smart enough to recognize the faces of people they see regularly and not attack; however, it’s feared that mask wearing will change this.

While you’re chewing on that exciting appetizer, let’s take a look at our main course, which has a distinct governmental flavor. Jeff Landry is the attorney general of Louisiana, and, like our space-helmet wearer, he’s not a fan of mask mandates. According to Business Insider, Mr. Landry “drafted and distributed sample letters intended to help parents evade mask-wearing ordinances and COVID-19 vaccination requirements for their children in schools.”

Up against him is the Food and Drug Administration’s Twitter account. In an unrelated matter, the agency tweeted, “You are not a horse. You are not a cow. Seriously, y’all. Stop it.” This was in response to people using the nonhuman forms of ivermectin to treat very human COVID-19.

Well, there you have it. Who will win tonight’s exciting edition of Pandemic Pandemonium? The first reader to contact us gets to decide the fate of these worthy contestants.
 

From venomous poison to heart drug

It’s not likely that anyone who sees a giant, venomous spider is thinking, “Hey! That thing could save my life!” It’s usually quite the opposite. Honestly, we would run away from just about any spider. But what if one of the deadliest spiders in the world could also save you from dying of a heart attack?

PxHere

You probably don’t believe us, right? That’s fair, but the deadly Fraser Island (K’gari) funnel web spider, might also be the most helpful. Investigators from the University of Queensland in Australia have found a way to extract a molecule from the spider’s venom that might help stop damage from heart attacks and may even preserve hearts being used for transplants. “The Hi1a protein from spider venom blocks acid-sensing ion channels in the heart, so the death message is blocked, cell death is reduced, and we see improved heart cell survival,” Nathan Palpant, PhD, of the university, noted in a written statement.

No one has ever developed a drug to stop the “death signal,” so maybe it’s time to befriend spiders instead of running away from them in horror. Just leave the venom extraction to the professionals.

The death ‘dog’

Imagine you’re out in your backyard managing the grill for a big family barbecue. You’ve got a dazzling assortment of meat assorted on your fancy new propane grill, all charring nicely. Naturally, the hot dogs finish first, and as you pull them off, you figure you’ll help yourself to one now. After all, you are the chef, you deserve a reward. But, as you bite into your smoking hot sandwich, a cold, bony finger taps you on the shoulder. You turn and come face to face with the Grim Reaper. “YOU JUST LOST 36 MINUTES,” Death says. “ALSO, MAY I HAVE ONE OF THOSE? THEY LOOK DELICIOUS.”

PxHere

Nonplussed and moving automatically, you scoop up another hot dog and place it in a bun. “WITH KETCHUP PLEASE,” Death says. “I NEVER CARED FOR MUSTARD.”

“I don’t understand,” you say. “Surely I won’t die at a family barbecue.”

“DO NOT CALL ME SHIRLEY,” Death says. “AND YOU WILL NOT. IT’S PART OF MY NEW CONTRACT.”

A new study, published in Nature Food, found that a person may lose up to 36 minutes for every hot dog consumed. Researchers from the University of Michigan analyzed nearly 6,000 different foods using a new nutritional index to quantify their health effects in minutes of healthy life lost or gained. Eating a serving of nuts adds an extra 26 minutes of life. The researchers determined that replacing just 10% of daily caloric intake from beef and processed foods with fruits, vegetables, and nuts can add 48 minutes per day. It would also reduce the daily carbon footprint by 33%.

“So you go around to everyone eating bad food and tell them how much life they’ve lost?” you ask when the Grim Reaper finishes his story. “Sounds like a drag.”

“IT IS. WE’VE HAD TO HIRE NEW BLOOD.” Death chuckles at its own bad pun. “NOW IF YOU’LL EXCUSE ME, I MUST CHASTISE A MAN IN FLORIDA FOR EATING A WELL-DONE STEAK.”
 

More stress, less sex

As the world becomes a more stressful place, the human population could face a 50% drop by the end of the century.

John Hain/Pixabay

Think of stress as a one-two punch to the libido and human fertility. The more people are stressed out, the less likely they are to have quality interactions with others. Many of us would rather be alone with our wine and cheese to watch our favorite show.

Researchers have found that high stress levels have been known to drop sperm count, ovulation, and sexual activity. Guess what? There has been a 50% decrease in sperm counts over the last 50 years. That’s the second punch. But let’s not forget, the times are changing.

“Changes in reproductive behavior that contribute to the population drop include more young couples choosing to be ‘child-free,’ people having fewer children, and couples waiting longer to start families,” said Alexander Suvorov, PhD, of the University of Massachusetts, the paper’s author.

Let’s summarize: The more stress we’re dealing with, the less people want to deal with each other.

Who would have thought the future would be less fun?
 

‘You are not a horse. You are not a cow. Seriously, y’all. Stop it.’

WARNING: The following descriptions of COVID-19–related insanity may be offensive to some readers.

Greetings, ladies and gentlemen! Welcome to the first round of Pandemic Pandemonium. Let’s get right to the action.

South_agency/Getty Images

This week’s preshow match-off involves face mask woes. The first comes to us from Alabama, where a woman wore a space helmet to a school board meeting to protest mask mandates. The second comes from Australia, in the form of mischievous magpies. We will explain.

It is not uncommon for magpies to attack those who come too close to their nests in the spring, or “swooping season,” as it’s affectionately called. The magpies are smart enough to recognize the faces of people they see regularly and not attack; however, it’s feared that mask wearing will change this.

While you’re chewing on that exciting appetizer, let’s take a look at our main course, which has a distinct governmental flavor. Jeff Landry is the attorney general of Louisiana, and, like our space-helmet wearer, he’s not a fan of mask mandates. According to Business Insider, Mr. Landry “drafted and distributed sample letters intended to help parents evade mask-wearing ordinances and COVID-19 vaccination requirements for their children in schools.”

Up against him is the Food and Drug Administration’s Twitter account. In an unrelated matter, the agency tweeted, “You are not a horse. You are not a cow. Seriously, y’all. Stop it.” This was in response to people using the nonhuman forms of ivermectin to treat very human COVID-19.

Well, there you have it. Who will win tonight’s exciting edition of Pandemic Pandemonium? The first reader to contact us gets to decide the fate of these worthy contestants.
 

From venomous poison to heart drug

It’s not likely that anyone who sees a giant, venomous spider is thinking, “Hey! That thing could save my life!” It’s usually quite the opposite. Honestly, we would run away from just about any spider. But what if one of the deadliest spiders in the world could also save you from dying of a heart attack?

PxHere

You probably don’t believe us, right? That’s fair, but the deadly Fraser Island (K’gari) funnel web spider, might also be the most helpful. Investigators from the University of Queensland in Australia have found a way to extract a molecule from the spider’s venom that might help stop damage from heart attacks and may even preserve hearts being used for transplants. “The Hi1a protein from spider venom blocks acid-sensing ion channels in the heart, so the death message is blocked, cell death is reduced, and we see improved heart cell survival,” Nathan Palpant, PhD, of the university, noted in a written statement.

No one has ever developed a drug to stop the “death signal,” so maybe it’s time to befriend spiders instead of running away from them in horror. Just leave the venom extraction to the professionals.

The death ‘dog’

Imagine you’re out in your backyard managing the grill for a big family barbecue. You’ve got a dazzling assortment of meat assorted on your fancy new propane grill, all charring nicely. Naturally, the hot dogs finish first, and as you pull them off, you figure you’ll help yourself to one now. After all, you are the chef, you deserve a reward. But, as you bite into your smoking hot sandwich, a cold, bony finger taps you on the shoulder. You turn and come face to face with the Grim Reaper. “YOU JUST LOST 36 MINUTES,” Death says. “ALSO, MAY I HAVE ONE OF THOSE? THEY LOOK DELICIOUS.”

PxHere

Nonplussed and moving automatically, you scoop up another hot dog and place it in a bun. “WITH KETCHUP PLEASE,” Death says. “I NEVER CARED FOR MUSTARD.”

“I don’t understand,” you say. “Surely I won’t die at a family barbecue.”

“DO NOT CALL ME SHIRLEY,” Death says. “AND YOU WILL NOT. IT’S PART OF MY NEW CONTRACT.”

A new study, published in Nature Food, found that a person may lose up to 36 minutes for every hot dog consumed. Researchers from the University of Michigan analyzed nearly 6,000 different foods using a new nutritional index to quantify their health effects in minutes of healthy life lost or gained. Eating a serving of nuts adds an extra 26 minutes of life. The researchers determined that replacing just 10% of daily caloric intake from beef and processed foods with fruits, vegetables, and nuts can add 48 minutes per day. It would also reduce the daily carbon footprint by 33%.

“So you go around to everyone eating bad food and tell them how much life they’ve lost?” you ask when the Grim Reaper finishes his story. “Sounds like a drag.”

“IT IS. WE’VE HAD TO HIRE NEW BLOOD.” Death chuckles at its own bad pun. “NOW IF YOU’LL EXCUSE ME, I MUST CHASTISE A MAN IN FLORIDA FOR EATING A WELL-DONE STEAK.”
 

More stress, less sex

As the world becomes a more stressful place, the human population could face a 50% drop by the end of the century.

John Hain/Pixabay

Think of stress as a one-two punch to the libido and human fertility. The more people are stressed out, the less likely they are to have quality interactions with others. Many of us would rather be alone with our wine and cheese to watch our favorite show.

Researchers have found that high stress levels have been known to drop sperm count, ovulation, and sexual activity. Guess what? There has been a 50% decrease in sperm counts over the last 50 years. That’s the second punch. But let’s not forget, the times are changing.

“Changes in reproductive behavior that contribute to the population drop include more young couples choosing to be ‘child-free,’ people having fewer children, and couples waiting longer to start families,” said Alexander Suvorov, PhD, of the University of Massachusetts, the paper’s author.

Let’s summarize: The more stress we’re dealing with, the less people want to deal with each other.

Who would have thought the future would be less fun?
 

‘You are not a horse. You are not a cow. Seriously, y’all. Stop it.’

WARNING: The following descriptions of COVID-19–related insanity may be offensive to some readers.

Greetings, ladies and gentlemen! Welcome to the first round of Pandemic Pandemonium. Let’s get right to the action.

South_agency/Getty Images

This week’s preshow match-off involves face mask woes. The first comes to us from Alabama, where a woman wore a space helmet to a school board meeting to protest mask mandates. The second comes from Australia, in the form of mischievous magpies. We will explain.

It is not uncommon for magpies to attack those who come too close to their nests in the spring, or “swooping season,” as it’s affectionately called. The magpies are smart enough to recognize the faces of people they see regularly and not attack; however, it’s feared that mask wearing will change this.

While you’re chewing on that exciting appetizer, let’s take a look at our main course, which has a distinct governmental flavor. Jeff Landry is the attorney general of Louisiana, and, like our space-helmet wearer, he’s not a fan of mask mandates. According to Business Insider, Mr. Landry “drafted and distributed sample letters intended to help parents evade mask-wearing ordinances and COVID-19 vaccination requirements for their children in schools.”

Up against him is the Food and Drug Administration’s Twitter account. In an unrelated matter, the agency tweeted, “You are not a horse. You are not a cow. Seriously, y’all. Stop it.” This was in response to people using the nonhuman forms of ivermectin to treat very human COVID-19.

Well, there you have it. Who will win tonight’s exciting edition of Pandemic Pandemonium? The first reader to contact us gets to decide the fate of these worthy contestants.
 

From venomous poison to heart drug

It’s not likely that anyone who sees a giant, venomous spider is thinking, “Hey! That thing could save my life!” It’s usually quite the opposite. Honestly, we would run away from just about any spider. But what if one of the deadliest spiders in the world could also save you from dying of a heart attack?

PxHere

You probably don’t believe us, right? That’s fair, but the deadly Fraser Island (K’gari) funnel web spider, might also be the most helpful. Investigators from the University of Queensland in Australia have found a way to extract a molecule from the spider’s venom that might help stop damage from heart attacks and may even preserve hearts being used for transplants. “The Hi1a protein from spider venom blocks acid-sensing ion channels in the heart, so the death message is blocked, cell death is reduced, and we see improved heart cell survival,” Nathan Palpant, PhD, of the university, noted in a written statement.

No one has ever developed a drug to stop the “death signal,” so maybe it’s time to befriend spiders instead of running away from them in horror. Just leave the venom extraction to the professionals.