Pulmonology

PHILADELPHIA – In the first controlled clinical trial to compare the two drugs, rituximab and cyclophosphamide were similarly effective in improving lung function in patients with interstitial lung disease (ILD) associated with idiopathic inflammatory myositis and mixed connective tissue disease (CTD). The findings also revealed some nuanced findings that could help clarify which drug to use in specific patients.

“We feel that rituximab is a reasonable alternative to cyclophosphamide as a treatment in patients with these diseases,” said Toby Maher, MD, of the University of Southern California, Los Angeles, who presented results of an analysis of three disease subgroups from the RECITAL (Rituximab versus Cyclophosphamide for the Treatment of Connective Tissue Disease Associated Interstitial Lung Disease) study at the annual meeting of the American College of Rheumatology.

“We didn’t show it to be better, so I think you can reasonably choose between the two, but rituximab almost certainly has the advantage of being safer and better tolerated than cyclophosphamide,” Dr. Maher said in an interview. The findings were published simultaneously in The Lancet Respiratory Medicine.
 

Double-blind, double-dummy

RECITAL is a phase 2b, randomized, controlled trial to test the hypothesis that intravenous rituximab would be superior to cyclophosphamide for ILD-associated CTD.

The study included adults with three separate diagnoses: myositis (n = 44), mixed CTD (n = 16), and systemic sclerosis (SSc, n = 37). The study was done in the United Kingdom when Dr. Maher was with Imperial College London.

Patients in the rituximab group received 1,000 mg of IV treatment at baseline and 2 weeks, then placebo treatment every 4 weeks to week 20. Cyclophosphamide patients received 600 mg/m² of body surface area intravenously every 4 weeks for six doses.

“When we designed this study there was limited evidence for any treatment for any disease associated with ILD,” Dr. Maher said. “But cyclophosphamide brings with it many challenges. It can be poorly tolerated and carries issues like infertility and risk of bladder cancer.”
 

Improved lung function

While the study failed to meet its primary endpoint – superiority of rituximab versus cyclophosphamide – it did show that both drugs led to improvement in lung function, measured by the rate of change in forced vital capacity (FVC), as well as quality of life measures, Dr. Maher said.

“Overall by week 48, we saw about a 5% improvement in FVC in the cyclophosphamide group and approximately a 4% improvement in FVC from baseline in the rituximab group, suggesting that both drugs almost certainly had a positive benefit in this patient group,” he said.

But secondary outcomes varied somewhat across the different disease groups. Patients with SSc saw a slight deterioration with cyclophosphamide in the modified Rodnan skin score at 24 weeks (1.6 ± 5.7 units) but an improvement with rituximab (–3.4 ± 8.1 units).

“One area where we did see a difference was in the number of adverse events,” Dr. Maher said. “They were fewer in the rituximab arm – namely gastrointestinal disorders [and] nausea, which we saw quite frequently following cyclophosphamide. Also, they had fewer headaches, which we saw quite frequently following cyclophosphamide.”

Rituximab patients also had fewer infusion reactions, but the number of infections was similar between the two treatment groups, he said.

“The patient group that responded best to treatment was the myositis group,” Dr. Maher said in his presentation. “Cyclophosphamide actually appears to be more effective than rituximab in improving their disease. By the end of 48 weeks, the cyclophosphamide group actually gained about 400 mL in FVC, so a close to 20% improvement.”

The rituximab group had “a little bit of a drop-off” in efficacy from weeks 24 to 48, although the trial didn’t repeat dosing at 6 months, “which is what perhaps one might do in clinical practice,” he said.

Oliver Distler, MD, chair of rheumatology at the University Hospital Zürich, raised questions about concurrent corticosteroid use in study patients that may have caused a “spillover” in the study’s efficacy analysis. But Dr. Maher noted that steroid use was balanced in all treatment arms. Patients in the cyclophosphamide arm averaged 42.9 mg of hydrocortisone daily versus 37.6 mg daily in the rituximab arm. That represents a 12.3% reduction in steroid exposure for the latter.

Dr. Distler noted that the myositis population represented the bulk of those study patients on steroids. “So in the myositis subanalysis we do see a combination of high-dose steroid plus cyclophosphamide and rituximab.”

Dr. Maher disclosed relationships with Boehringer Ingelheim, Genentech, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Trevi, CSL Behring, Pliant and Veracyte. Dr. Distler disclosed relationships with numerous pharmaceutical companies.






 

PHILADELPHIA – In the first controlled clinical trial to compare the two drugs, rituximab and cyclophosphamide were similarly effective in improving lung function in patients with interstitial lung disease (ILD) associated with idiopathic inflammatory myositis and mixed connective tissue disease (CTD). The findings also revealed some nuanced findings that could help clarify which drug to use in specific patients.

“We feel that rituximab is a reasonable alternative to cyclophosphamide as a treatment in patients with these diseases,” said Toby Maher, MD, of the University of Southern California, Los Angeles, who presented results of an analysis of three disease subgroups from the RECITAL (Rituximab versus Cyclophosphamide for the Treatment of Connective Tissue Disease Associated Interstitial Lung Disease) study at the annual meeting of the American College of Rheumatology.

“We didn’t show it to be better, so I think you can reasonably choose between the two, but rituximab almost certainly has the advantage of being safer and better tolerated than cyclophosphamide,” Dr. Maher said in an interview. The findings were published simultaneously in The Lancet Respiratory Medicine.
 

Double-blind, double-dummy

RECITAL is a phase 2b, randomized, controlled trial to test the hypothesis that intravenous rituximab would be superior to cyclophosphamide for ILD-associated CTD.

The study included adults with three separate diagnoses: myositis (n = 44), mixed CTD (n = 16), and systemic sclerosis (SSc, n = 37). The study was done in the United Kingdom when Dr. Maher was with Imperial College London.

Patients in the rituximab group received 1,000 mg of IV treatment at baseline and 2 weeks, then placebo treatment every 4 weeks to week 20. Cyclophosphamide patients received 600 mg/m² of body surface area intravenously every 4 weeks for six doses.

“When we designed this study there was limited evidence for any treatment for any disease associated with ILD,” Dr. Maher said. “But cyclophosphamide brings with it many challenges. It can be poorly tolerated and carries issues like infertility and risk of bladder cancer.”
 

Improved lung function

While the study failed to meet its primary endpoint – superiority of rituximab versus cyclophosphamide – it did show that both drugs led to improvement in lung function, measured by the rate of change in forced vital capacity (FVC), as well as quality of life measures, Dr. Maher said.

“Overall by week 48, we saw about a 5% improvement in FVC in the cyclophosphamide group and approximately a 4% improvement in FVC from baseline in the rituximab group, suggesting that both drugs almost certainly had a positive benefit in this patient group,” he said.

But secondary outcomes varied somewhat across the different disease groups. Patients with SSc saw a slight deterioration with cyclophosphamide in the modified Rodnan skin score at 24 weeks (1.6 ± 5.7 units) but an improvement with rituximab (–3.4 ± 8.1 units).

“One area where we did see a difference was in the number of adverse events,” Dr. Maher said. “They were fewer in the rituximab arm – namely gastrointestinal disorders [and] nausea, which we saw quite frequently following cyclophosphamide. Also, they had fewer headaches, which we saw quite frequently following cyclophosphamide.”

Rituximab patients also had fewer infusion reactions, but the number of infections was similar between the two treatment groups, he said.

“The patient group that responded best to treatment was the myositis group,” Dr. Maher said in his presentation. “Cyclophosphamide actually appears to be more effective than rituximab in improving their disease. By the end of 48 weeks, the cyclophosphamide group actually gained about 400 mL in FVC, so a close to 20% improvement.”

The rituximab group had “a little bit of a drop-off” in efficacy from weeks 24 to 48, although the trial didn’t repeat dosing at 6 months, “which is what perhaps one might do in clinical practice,” he said.

Oliver Distler, MD, chair of rheumatology at the University Hospital Zürich, raised questions about concurrent corticosteroid use in study patients that may have caused a “spillover” in the study’s efficacy analysis. But Dr. Maher noted that steroid use was balanced in all treatment arms. Patients in the cyclophosphamide arm averaged 42.9 mg of hydrocortisone daily versus 37.6 mg daily in the rituximab arm. That represents a 12.3% reduction in steroid exposure for the latter.

Dr. Distler noted that the myositis population represented the bulk of those study patients on steroids. “So in the myositis subanalysis we do see a combination of high-dose steroid plus cyclophosphamide and rituximab.”

Dr. Maher disclosed relationships with Boehringer Ingelheim, Genentech, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Trevi, CSL Behring, Pliant and Veracyte. Dr. Distler disclosed relationships with numerous pharmaceutical companies.






 

PHILADELPHIA – In the first controlled clinical trial to compare the two drugs, rituximab and cyclophosphamide were similarly effective in improving lung function in patients with interstitial lung disease (ILD) associated with idiopathic inflammatory myositis and mixed connective tissue disease (CTD). The findings also revealed some nuanced findings that could help clarify which drug to use in specific patients.

“We feel that rituximab is a reasonable alternative to cyclophosphamide as a treatment in patients with these diseases,” said Toby Maher, MD, of the University of Southern California, Los Angeles, who presented results of an analysis of three disease subgroups from the RECITAL (Rituximab versus Cyclophosphamide for the Treatment of Connective Tissue Disease Associated Interstitial Lung Disease) study at the annual meeting of the American College of Rheumatology.

“We didn’t show it to be better, so I think you can reasonably choose between the two, but rituximab almost certainly has the advantage of being safer and better tolerated than cyclophosphamide,” Dr. Maher said in an interview. The findings were published simultaneously in The Lancet Respiratory Medicine.
 

Double-blind, double-dummy

RECITAL is a phase 2b, randomized, controlled trial to test the hypothesis that intravenous rituximab would be superior to cyclophosphamide for ILD-associated CTD.

The study included adults with three separate diagnoses: myositis (n = 44), mixed CTD (n = 16), and systemic sclerosis (SSc, n = 37). The study was done in the United Kingdom when Dr. Maher was with Imperial College London.

Patients in the rituximab group received 1,000 mg of IV treatment at baseline and 2 weeks, then placebo treatment every 4 weeks to week 20. Cyclophosphamide patients received 600 mg/m² of body surface area intravenously every 4 weeks for six doses.

“When we designed this study there was limited evidence for any treatment for any disease associated with ILD,” Dr. Maher said. “But cyclophosphamide brings with it many challenges. It can be poorly tolerated and carries issues like infertility and risk of bladder cancer.”
 

Improved lung function

While the study failed to meet its primary endpoint – superiority of rituximab versus cyclophosphamide – it did show that both drugs led to improvement in lung function, measured by the rate of change in forced vital capacity (FVC), as well as quality of life measures, Dr. Maher said.

“Overall by week 48, we saw about a 5% improvement in FVC in the cyclophosphamide group and approximately a 4% improvement in FVC from baseline in the rituximab group, suggesting that both drugs almost certainly had a positive benefit in this patient group,” he said.

But secondary outcomes varied somewhat across the different disease groups. Patients with SSc saw a slight deterioration with cyclophosphamide in the modified Rodnan skin score at 24 weeks (1.6 ± 5.7 units) but an improvement with rituximab (–3.4 ± 8.1 units).

“One area where we did see a difference was in the number of adverse events,” Dr. Maher said. “They were fewer in the rituximab arm – namely gastrointestinal disorders [and] nausea, which we saw quite frequently following cyclophosphamide. Also, they had fewer headaches, which we saw quite frequently following cyclophosphamide.”

Rituximab patients also had fewer infusion reactions, but the number of infections was similar between the two treatment groups, he said.

“The patient group that responded best to treatment was the myositis group,” Dr. Maher said in his presentation. “Cyclophosphamide actually appears to be more effective than rituximab in improving their disease. By the end of 48 weeks, the cyclophosphamide group actually gained about 400 mL in FVC, so a close to 20% improvement.”

The rituximab group had “a little bit of a drop-off” in efficacy from weeks 24 to 48, although the trial didn’t repeat dosing at 6 months, “which is what perhaps one might do in clinical practice,” he said.

Oliver Distler, MD, chair of rheumatology at the University Hospital Zürich, raised questions about concurrent corticosteroid use in study patients that may have caused a “spillover” in the study’s efficacy analysis. But Dr. Maher noted that steroid use was balanced in all treatment arms. Patients in the cyclophosphamide arm averaged 42.9 mg of hydrocortisone daily versus 37.6 mg daily in the rituximab arm. That represents a 12.3% reduction in steroid exposure for the latter.

Dr. Distler noted that the myositis population represented the bulk of those study patients on steroids. “So in the myositis subanalysis we do see a combination of high-dose steroid plus cyclophosphamide and rituximab.”

Dr. Maher disclosed relationships with Boehringer Ingelheim, Genentech, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Trevi, CSL Behring, Pliant and Veracyte. Dr. Distler disclosed relationships with numerous pharmaceutical companies.






 

This Veterans Day we honor the passing of the largest expansion of veterans benefits and services in history. On August 10, 2022, President Biden signed the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act. This act was named for a combat medic who died of a rare form of lung cancer believed to be the result of a toxic military exposure. His widow was present during the President's State of the Union address that urged Congress to pass the legislation.² 

Like all other congressional bills and government regulations, the PACT Act is complex in its details and still a work in progress. Simply put, the PACT Act expands and/or extends enrollment for a group of previously ineligible veterans. Eligibility will no longer require that veterans demonstrate a service-connected disability due to toxic exposure, including those from burn pits. This has long been a barrier for many veterans seeking benefits and not just related to toxic exposures. Logistical barriers and documentary losses have prevented many service members from establishing a clean chain of evidence for the injuries or illnesses they sustained while in uniform.
 
The new process is a massive step forward by the US Department of Veterans Affairs (VA) to establish high standards of procedural justice for settling beneficiary claims. The PACT Act removes the burden from the shoulders of the veteran and places it squarely on the VA to demonstrate that > 20 different medical conditions--primarily cancers and respiratory illnesses--are linked to toxic exposure. The VA must establish that exposure occurred to cohorts of service members in specific theaters and time frames. A veteran who served in that area and period and has one of the indexed illnesses is presumed to have been exposed in the line of duty.^3,4

As a result, the VA instituted a new screening process to determine that toxic military exposures (a) led to illness; and (b) both exposure and illness are connected to service. According to the VA, the new process is evidence based, transparent, and allows the VA to fast-track policy decisions related to exposures. The PACT Act includes a provision intended to promote sustained implementation and prevent the program from succumbing as so many new initiatives have to inadequate adoption. VA is required to deploy its considerable internal research capacity to collaborate with external partners in and outside government to study military members with toxic exposures.⁴ 

Congress had initially proposed that the provisions of the PACT ACT would take effect in 2026, providing time to ramp up the process. The White House and VA telescoped that time line so veterans can begin now to apply for benefits that they could foreseeably receive in 2023. However, a long-standing problem for the VA has been unfunded agency or congressional mandates. These have often end in undermining the legislative intention or policy purpose of the program undermining their legislative intention or policy purpose through staffing shortages, leading to lack of or delayed access. The PACT Act promises to eschew the infamous Phoenix problem by providing increased personnel, training infrastructure, and technology resources for both the Veterans Benefit Administration and the Veterans Health Administration. Ironically, many seasoned VA observers expect the PACT expansion will lead to even larger backlogs of claims as hundreds of newly eligible veterans are added to the extant rolls of those seeking benefits.⁵ 

An estimated 1 in 5 veterans may be entitled to PACT benefits. The PACT Act is the latest of a long uneven movement toward distributive justice for veteran benefits and services. It is fitting in the month of Veterans Day 2022 to trace that trajectory. Congress first passed veteran benefits legislation in 1917, focused on soldiers with disabilities. This resulted in a massive investment in building hospitals. Ironically, part of the impetus for VA health care was an earlier toxic military exposure. World War I service members suffered from the detrimental effects of mustard gas among other chemical byproducts. In 1924, VA benefits and services underwent a momentous opening to include individuals with non-service-connected disabilities. Four years later, the VA tent became even bigger, welcoming women, National Guard, and militia members to receive care under its auspices.⁶ 

The PACT Act is a fitting memorial for Veterans Day as an increasingly divided country presents a unified response to veterans and their survivors exposed to a variety of toxins across multiple wars. The PACT Act was hard won with veterans and their advocates having to fight years of political bickering, government abdication of accountability, and scientific sparring before this bipartisan legislation passed.⁷ It covers Vietnam War veterans with several conditions due to Agent Orange exposure; Gulf War and post-9/11 veterans with cancer and respiratory conditions; and the service members deployed to Afghanistan and Iraq afflicted with illnesses due to the smoke of burn pits and other toxins. 

As many areas of the country roll back LGBTQ+ rights to health care and social services, the VA has emerged as a leader in the movement for diversity and inclusion. VA Secretary McDonough provided a pathway to VA eligibility for other than honorably discharged veterans, including those LGBTQ+ persons discharged under Don't Ask, Don't Tell.⁸ Lest we take this new inclusivity for granted, we should never forget that this journey toward equity for the military and VA has been long, slow, and uneven. There are many difficult miles yet to travel if we are to achieve liberty and justice for veteran members of racial minorities, women, and other marginalized populations. Even the PACT Act does not cover all putative exposures to toxins.⁹ Yet it is a significant step closer to fulfilling the motto of the VA LGBTQ+ program: to serve all who served.¹⁰ 

This Veterans Day we honor the passing of the largest expansion of veterans benefits and services in history. On August 10, 2022, President Biden signed the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act. This act was named for a combat medic who died of a rare form of lung cancer believed to be the result of a toxic military exposure. His widow was present during the President's State of the Union address that urged Congress to pass the legislation.² 

Like all other congressional bills and government regulations, the PACT Act is complex in its details and still a work in progress. Simply put, the PACT Act expands and/or extends enrollment for a group of previously ineligible veterans. Eligibility will no longer require that veterans demonstrate a service-connected disability due to toxic exposure, including those from burn pits. This has long been a barrier for many veterans seeking benefits and not just related to toxic exposures. Logistical barriers and documentary losses have prevented many service members from establishing a clean chain of evidence for the injuries or illnesses they sustained while in uniform.
 
The new process is a massive step forward by the US Department of Veterans Affairs (VA) to establish high standards of procedural justice for settling beneficiary claims. The PACT Act removes the burden from the shoulders of the veteran and places it squarely on the VA to demonstrate that > 20 different medical conditions--primarily cancers and respiratory illnesses--are linked to toxic exposure. The VA must establish that exposure occurred to cohorts of service members in specific theaters and time frames. A veteran who served in that area and period and has one of the indexed illnesses is presumed to have been exposed in the line of duty.^3,4

As a result, the VA instituted a new screening process to determine that toxic military exposures (a) led to illness; and (b) both exposure and illness are connected to service. According to the VA, the new process is evidence based, transparent, and allows the VA to fast-track policy decisions related to exposures. The PACT Act includes a provision intended to promote sustained implementation and prevent the program from succumbing as so many new initiatives have to inadequate adoption. VA is required to deploy its considerable internal research capacity to collaborate with external partners in and outside government to study military members with toxic exposures.⁴ 

Congress had initially proposed that the provisions of the PACT ACT would take effect in 2026, providing time to ramp up the process. The White House and VA telescoped that time line so veterans can begin now to apply for benefits that they could foreseeably receive in 2023. However, a long-standing problem for the VA has been unfunded agency or congressional mandates. These have often end in undermining the legislative intention or policy purpose of the program undermining their legislative intention or policy purpose through staffing shortages, leading to lack of or delayed access. The PACT Act promises to eschew the infamous Phoenix problem by providing increased personnel, training infrastructure, and technology resources for both the Veterans Benefit Administration and the Veterans Health Administration. Ironically, many seasoned VA observers expect the PACT expansion will lead to even larger backlogs of claims as hundreds of newly eligible veterans are added to the extant rolls of those seeking benefits.⁵ 

An estimated 1 in 5 veterans may be entitled to PACT benefits. The PACT Act is the latest of a long uneven movement toward distributive justice for veteran benefits and services. It is fitting in the month of Veterans Day 2022 to trace that trajectory. Congress first passed veteran benefits legislation in 1917, focused on soldiers with disabilities. This resulted in a massive investment in building hospitals. Ironically, part of the impetus for VA health care was an earlier toxic military exposure. World War I service members suffered from the detrimental effects of mustard gas among other chemical byproducts. In 1924, VA benefits and services underwent a momentous opening to include individuals with non-service-connected disabilities. Four years later, the VA tent became even bigger, welcoming women, National Guard, and militia members to receive care under its auspices.⁶ 

The PACT Act is a fitting memorial for Veterans Day as an increasingly divided country presents a unified response to veterans and their survivors exposed to a variety of toxins across multiple wars. The PACT Act was hard won with veterans and their advocates having to fight years of political bickering, government abdication of accountability, and scientific sparring before this bipartisan legislation passed.⁷ It covers Vietnam War veterans with several conditions due to Agent Orange exposure; Gulf War and post-9/11 veterans with cancer and respiratory conditions; and the service members deployed to Afghanistan and Iraq afflicted with illnesses due to the smoke of burn pits and other toxins. 

As many areas of the country roll back LGBTQ+ rights to health care and social services, the VA has emerged as a leader in the movement for diversity and inclusion. VA Secretary McDonough provided a pathway to VA eligibility for other than honorably discharged veterans, including those LGBTQ+ persons discharged under Don't Ask, Don't Tell.⁸ Lest we take this new inclusivity for granted, we should never forget that this journey toward equity for the military and VA has been long, slow, and uneven. There are many difficult miles yet to travel if we are to achieve liberty and justice for veteran members of racial minorities, women, and other marginalized populations. Even the PACT Act does not cover all putative exposures to toxins.⁹ Yet it is a significant step closer to fulfilling the motto of the VA LGBTQ+ program: to serve all who served.¹⁰ 

This Veterans Day we honor the passing of the largest expansion of veterans benefits and services in history. On August 10, 2022, President Biden signed the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act. This act was named for a combat medic who died of a rare form of lung cancer believed to be the result of a toxic military exposure. His widow was present during the President's State of the Union address that urged Congress to pass the legislation.² 

Like all other congressional bills and government regulations, the PACT Act is complex in its details and still a work in progress. Simply put, the PACT Act expands and/or extends enrollment for a group of previously ineligible veterans. Eligibility will no longer require that veterans demonstrate a service-connected disability due to toxic exposure, including those from burn pits. This has long been a barrier for many veterans seeking benefits and not just related to toxic exposures. Logistical barriers and documentary losses have prevented many service members from establishing a clean chain of evidence for the injuries or illnesses they sustained while in uniform.
 
The new process is a massive step forward by the US Department of Veterans Affairs (VA) to establish high standards of procedural justice for settling beneficiary claims. The PACT Act removes the burden from the shoulders of the veteran and places it squarely on the VA to demonstrate that > 20 different medical conditions--primarily cancers and respiratory illnesses--are linked to toxic exposure. The VA must establish that exposure occurred to cohorts of service members in specific theaters and time frames. A veteran who served in that area and period and has one of the indexed illnesses is presumed to have been exposed in the line of duty.^3,4

As a result, the VA instituted a new screening process to determine that toxic military exposures (a) led to illness; and (b) both exposure and illness are connected to service. According to the VA, the new process is evidence based, transparent, and allows the VA to fast-track policy decisions related to exposures. The PACT Act includes a provision intended to promote sustained implementation and prevent the program from succumbing as so many new initiatives have to inadequate adoption. VA is required to deploy its considerable internal research capacity to collaborate with external partners in and outside government to study military members with toxic exposures.⁴ 

Congress had initially proposed that the provisions of the PACT ACT would take effect in 2026, providing time to ramp up the process. The White House and VA telescoped that time line so veterans can begin now to apply for benefits that they could foreseeably receive in 2023. However, a long-standing problem for the VA has been unfunded agency or congressional mandates. These have often end in undermining the legislative intention or policy purpose of the program undermining their legislative intention or policy purpose through staffing shortages, leading to lack of or delayed access. The PACT Act promises to eschew the infamous Phoenix problem by providing increased personnel, training infrastructure, and technology resources for both the Veterans Benefit Administration and the Veterans Health Administration. Ironically, many seasoned VA observers expect the PACT expansion will lead to even larger backlogs of claims as hundreds of newly eligible veterans are added to the extant rolls of those seeking benefits.⁵ 

An estimated 1 in 5 veterans may be entitled to PACT benefits. The PACT Act is the latest of a long uneven movement toward distributive justice for veteran benefits and services. It is fitting in the month of Veterans Day 2022 to trace that trajectory. Congress first passed veteran benefits legislation in 1917, focused on soldiers with disabilities. This resulted in a massive investment in building hospitals. Ironically, part of the impetus for VA health care was an earlier toxic military exposure. World War I service members suffered from the detrimental effects of mustard gas among other chemical byproducts. In 1924, VA benefits and services underwent a momentous opening to include individuals with non-service-connected disabilities. Four years later, the VA tent became even bigger, welcoming women, National Guard, and militia members to receive care under its auspices.⁶ 

The PACT Act is a fitting memorial for Veterans Day as an increasingly divided country presents a unified response to veterans and their survivors exposed to a variety of toxins across multiple wars. The PACT Act was hard won with veterans and their advocates having to fight years of political bickering, government abdication of accountability, and scientific sparring before this bipartisan legislation passed.⁷ It covers Vietnam War veterans with several conditions due to Agent Orange exposure; Gulf War and post-9/11 veterans with cancer and respiratory conditions; and the service members deployed to Afghanistan and Iraq afflicted with illnesses due to the smoke of burn pits and other toxins. 

As many areas of the country roll back LGBTQ+ rights to health care and social services, the VA has emerged as a leader in the movement for diversity and inclusion. VA Secretary McDonough provided a pathway to VA eligibility for other than honorably discharged veterans, including those LGBTQ+ persons discharged under Don't Ask, Don't Tell.⁸ Lest we take this new inclusivity for granted, we should never forget that this journey toward equity for the military and VA has been long, slow, and uneven. There are many difficult miles yet to travel if we are to achieve liberty and justice for veteran members of racial minorities, women, and other marginalized populations. Even the PACT Act does not cover all putative exposures to toxins.⁹ Yet it is a significant step closer to fulfilling the motto of the VA LGBTQ+ program: to serve all who served.¹⁰ 

CHICAGO – A clinical decision-support tool designed to identify hospitalized patients who need thromboembolism prophylaxis and embedded in a hospital’s electronic health record led to significantly more appropriate prophylaxis, compared with usual care, and significantly cut the 30-day rate of thromboembolism in a randomized, multicenter trial with more than 10,000 patients.

“This is the first time that a clinical decision support tool not only changed [thromboprophylaxis prescribing] behavior but also affected hard outcomes. That’s remarkable,” lead investigator Alex C. Spyropoulos, MD, said in an interview.

Even so, outside experts expressed concerns about certain results and the trial design.

Mitchel L. Zoler/MDedge News

Use of the decision-support risk calculator for thromboembolism in the IMPROVE-DD VTE trial significantly boosted use of appropriate inpatient thromboprophylaxis starting at hospital admission by a relative 52%, and significantly increased outpatient thromboprophylaxis prescribed at discharge by a relative 93% in the study’s two primary endpoints, Dr. Spyropoulos reported at the American Heart Association scientific sessions.

This intervention led to a significant 29% relative reduction in the incidence of total thromboembolic events, both venous and arterial, during hospitalization and through 30 days post discharge.

The absolute thromboembolic event rates were 2.9% among 5,249 patients treated at either of two U.S. hospitals that used the EHR-based risk calculator and 4.0% in 5,450 patients seen at either of two other U.S. hospitals that served as controls and where usual care method identified patients who needed thromboprophylaxis, said Dr. Spyropoulos, professor and director of the anticoagulation and clinical thrombosis services for Northwell Health in New York. This included a 2.7% rate of venous thromboembolism and a 0.25% rate of arterial thromboembolism in the intervention patients, and a 3.3% rate of venous events and a 0.7% rate of arterial events in the controls.

Patients treated at the hospitals that used the EHR-embedded risk calculator also has a numerically lower rate of major bleeding events during hospitalization and 30-day postdischarge follow-up, a 0.15% rate compared with a 0.22% rate in the control patients, a difference that was not significant.
 

A ‘powerful message’

“It’s a powerful message to see an absolute 1.1% difference in the rate of thromboembolism and a trend to fewer major bleeds. I think this will change practice,” Dr. Spyropoulos added in the interview. “The next step is dissemination.”

But thromboprophylaxis experts cautioned that, while the results looked promising, the findings need more analysis and review, and the intervention may need further testing before it’s ready for widespread use.

For example, one unexpected result was an unexpected 2.1 percentage point increase in all-cause mortality linked with use of the decision-support tool. Total deaths from admission to 30 days after discharge occurred in 9.1% of the patients treated at the two hospitals that used the risk calculator and 7.0% among the control patients, a difference that Dr, Spyropoulos said was likely the result of unbalanced outcomes from COVID-19 infections that had no relevance to the tested intervention. The trial ran during December 2020–January 2022.
 

But wait – more detail and analysis needed

“I’d like to see more analysis of the data from this trial,” and “there is the issue of increased mortality,” commented Gregory Piazza, MD, director of vascular medicine at Brigham and Women’s Hospital in Boston, and a specialist in thromboembolism prevention and management. He also highlighted the need for greater detail on the arterial thromboembolic events tallied during the study.

With more details and analysis of these findings “we’ll learn more about the true impact” of this intervention, Dr. Piazza said in an interview.

Mitchel L. Zoler/MDedge News

“The increased mortality in the intervention group may have been due to differential treatment and decision-making and confounding and warrants further investigation,” commented Elaine M. Hylek, MD, a professor at Boston University and designated discussant for the report. Selection bias may have contributed to this possible confounding, Dr. Hylek noted.

Other limitations of the study cited by Dr. Hylek included its reliance on individual clinician decision-making to actually prescribe thromboprophylaxis, a lack of information on patient adherence to their thromboprophylaxis prescription, and an overall low rate of appropriate thromboprophylaxis prescribed to patients at discharge. The rates were 7.5% among the controls and 13.6% among patients in the intervention arm. For prescription at the time of hospitalization, the rates were 72.5% among control patients and 80.1% for patients seen at the two hospitals that used the decision-support tool.
 

The IMPROVE-DD VTE risk assessment tool

The clinical decision-support tool tested is called the IMPROVE-DD VTE risk assessment model, developed over several years by Dr. Spyropoulos and associates; they have also performed multiple validation studies. The model includes eight factors that score 1-3 points if positive that can add up to total scores of 0-14. A score of 0 or 1 is considered low risk, 2 or 3 intermediate risk, and 4 or more high risk. One of the scoring factors is the result of a D-dimer test, which explains the DD part of the name.

The eight factors and point assignments are prior venous thromboembolism: 3 points; known thrombophilia: 2 points; lower limb paralysis: 2 points; current cancer: 2 points; d-dimer level more than twofold the upper limit of normal: 2 points; immobilized for at least 7 days: 1 point; admitted to the ICU or coronary care unit: 1 point; and age greater than 60 years old: 1 point.

Development of the IMPROVE-DD VTE risk calculator received most of its funding from the U.S. Agency for Healthcare Research and Quality, and the risk tool will be available for hospitals and health systems to access at no charge through the agency’s website, Dr. Spyropoulos said. The researchers designed the calculator to operate in any EHR product.

IMPROVE-DD VTE “is a very valid, high-quality tool,” commented Dr. Piazza. “We’ve used some rather blunt tools in the past,” and especially praised inclusion of D-dimer results into the IMPROVE-DD VTE model.

“It’s nice to use a biomarker in addition to clinical factors,” he said. “A biomarker provides a more holistic picture; we can’t do genetic testing on every patient.”

Enrollment focused on higher-risk patients

The study ran at four academic, tertiary-care hospitals in the Northwell Health network in the New York region. It enrolled patients aged more than 60 years who were hospitalized for any of five diagnoses: heart failure; acute respiratory insufficiency, including chronic obstructive lung disease or asthma; acute infectious disease, including COVID-19; acute inflammatory disease, including rheumatic disease; or acute stroke. The study excluded patients with a history of atrial fibrillation, those who used an anticoagulant at home, or those who had received therapeutic anticoagulation within 24 hours of their hospital admission.

The anticoagulant prophylaxis that patients received depended on their calculated risk level – intermediate or high – and whether they were inpatients or being discharged. The anticoagulants that clinicians could prescribe included unfractionated heparin, enoxaparin, fondaparinux, rivaroxaban, and apixaban.

“We’ve been looking for a long time for a tool for medically ill patients that’s like the CHA2DS2-VASc score” for patients with atrial fibrillation. “These powerful data say we now have this, and the EHR provides a vehicle to easily implement it,” Dr. Spyropoulos said.

The IMPROVE-DD VTE study received partial funding from Janssen. Dr. Spyropoulos has been a consultant to Nayer, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Pfizer, and Sanofi; adviser to the ATLAS Group; and has received research support from Janssen. Dr. Piazza has received research funding from Bayer, BIG/EKOS, BMS, Janssen, and Portola. Dr. Hylek had been a consultant to Bayer and Ionis, and has received honoraria from Boehringer Ingelheim and Pfizer.

CHICAGO – A clinical decision-support tool designed to identify hospitalized patients who need thromboembolism prophylaxis and embedded in a hospital’s electronic health record led to significantly more appropriate prophylaxis, compared with usual care, and significantly cut the 30-day rate of thromboembolism in a randomized, multicenter trial with more than 10,000 patients.

“This is the first time that a clinical decision support tool not only changed [thromboprophylaxis prescribing] behavior but also affected hard outcomes. That’s remarkable,” lead investigator Alex C. Spyropoulos, MD, said in an interview.

Even so, outside experts expressed concerns about certain results and the trial design.

Mitchel L. Zoler/MDedge News

Use of the decision-support risk calculator for thromboembolism in the IMPROVE-DD VTE trial significantly boosted use of appropriate inpatient thromboprophylaxis starting at hospital admission by a relative 52%, and significantly increased outpatient thromboprophylaxis prescribed at discharge by a relative 93% in the study’s two primary endpoints, Dr. Spyropoulos reported at the American Heart Association scientific sessions.

This intervention led to a significant 29% relative reduction in the incidence of total thromboembolic events, both venous and arterial, during hospitalization and through 30 days post discharge.

The absolute thromboembolic event rates were 2.9% among 5,249 patients treated at either of two U.S. hospitals that used the EHR-based risk calculator and 4.0% in 5,450 patients seen at either of two other U.S. hospitals that served as controls and where usual care method identified patients who needed thromboprophylaxis, said Dr. Spyropoulos, professor and director of the anticoagulation and clinical thrombosis services for Northwell Health in New York. This included a 2.7% rate of venous thromboembolism and a 0.25% rate of arterial thromboembolism in the intervention patients, and a 3.3% rate of venous events and a 0.7% rate of arterial events in the controls.

Patients treated at the hospitals that used the EHR-embedded risk calculator also has a numerically lower rate of major bleeding events during hospitalization and 30-day postdischarge follow-up, a 0.15% rate compared with a 0.22% rate in the control patients, a difference that was not significant.
 

A ‘powerful message’

“It’s a powerful message to see an absolute 1.1% difference in the rate of thromboembolism and a trend to fewer major bleeds. I think this will change practice,” Dr. Spyropoulos added in the interview. “The next step is dissemination.”

But thromboprophylaxis experts cautioned that, while the results looked promising, the findings need more analysis and review, and the intervention may need further testing before it’s ready for widespread use.

For example, one unexpected result was an unexpected 2.1 percentage point increase in all-cause mortality linked with use of the decision-support tool. Total deaths from admission to 30 days after discharge occurred in 9.1% of the patients treated at the two hospitals that used the risk calculator and 7.0% among the control patients, a difference that Dr, Spyropoulos said was likely the result of unbalanced outcomes from COVID-19 infections that had no relevance to the tested intervention. The trial ran during December 2020–January 2022.
 

But wait – more detail and analysis needed

“I’d like to see more analysis of the data from this trial,” and “there is the issue of increased mortality,” commented Gregory Piazza, MD, director of vascular medicine at Brigham and Women’s Hospital in Boston, and a specialist in thromboembolism prevention and management. He also highlighted the need for greater detail on the arterial thromboembolic events tallied during the study.

With more details and analysis of these findings “we’ll learn more about the true impact” of this intervention, Dr. Piazza said in an interview.

Mitchel L. Zoler/MDedge News

“The increased mortality in the intervention group may have been due to differential treatment and decision-making and confounding and warrants further investigation,” commented Elaine M. Hylek, MD, a professor at Boston University and designated discussant for the report. Selection bias may have contributed to this possible confounding, Dr. Hylek noted.

Other limitations of the study cited by Dr. Hylek included its reliance on individual clinician decision-making to actually prescribe thromboprophylaxis, a lack of information on patient adherence to their thromboprophylaxis prescription, and an overall low rate of appropriate thromboprophylaxis prescribed to patients at discharge. The rates were 7.5% among the controls and 13.6% among patients in the intervention arm. For prescription at the time of hospitalization, the rates were 72.5% among control patients and 80.1% for patients seen at the two hospitals that used the decision-support tool.
 

The IMPROVE-DD VTE risk assessment tool

The clinical decision-support tool tested is called the IMPROVE-DD VTE risk assessment model, developed over several years by Dr. Spyropoulos and associates; they have also performed multiple validation studies. The model includes eight factors that score 1-3 points if positive that can add up to total scores of 0-14. A score of 0 or 1 is considered low risk, 2 or 3 intermediate risk, and 4 or more high risk. One of the scoring factors is the result of a D-dimer test, which explains the DD part of the name.

The eight factors and point assignments are prior venous thromboembolism: 3 points; known thrombophilia: 2 points; lower limb paralysis: 2 points; current cancer: 2 points; d-dimer level more than twofold the upper limit of normal: 2 points; immobilized for at least 7 days: 1 point; admitted to the ICU or coronary care unit: 1 point; and age greater than 60 years old: 1 point.

Development of the IMPROVE-DD VTE risk calculator received most of its funding from the U.S. Agency for Healthcare Research and Quality, and the risk tool will be available for hospitals and health systems to access at no charge through the agency’s website, Dr. Spyropoulos said. The researchers designed the calculator to operate in any EHR product.

IMPROVE-DD VTE “is a very valid, high-quality tool,” commented Dr. Piazza. “We’ve used some rather blunt tools in the past,” and especially praised inclusion of D-dimer results into the IMPROVE-DD VTE model.

“It’s nice to use a biomarker in addition to clinical factors,” he said. “A biomarker provides a more holistic picture; we can’t do genetic testing on every patient.”

Enrollment focused on higher-risk patients

The study ran at four academic, tertiary-care hospitals in the Northwell Health network in the New York region. It enrolled patients aged more than 60 years who were hospitalized for any of five diagnoses: heart failure; acute respiratory insufficiency, including chronic obstructive lung disease or asthma; acute infectious disease, including COVID-19; acute inflammatory disease, including rheumatic disease; or acute stroke. The study excluded patients with a history of atrial fibrillation, those who used an anticoagulant at home, or those who had received therapeutic anticoagulation within 24 hours of their hospital admission.

The anticoagulant prophylaxis that patients received depended on their calculated risk level – intermediate or high – and whether they were inpatients or being discharged. The anticoagulants that clinicians could prescribe included unfractionated heparin, enoxaparin, fondaparinux, rivaroxaban, and apixaban.

“We’ve been looking for a long time for a tool for medically ill patients that’s like the CHA2DS2-VASc score” for patients with atrial fibrillation. “These powerful data say we now have this, and the EHR provides a vehicle to easily implement it,” Dr. Spyropoulos said.

The IMPROVE-DD VTE study received partial funding from Janssen. Dr. Spyropoulos has been a consultant to Nayer, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Pfizer, and Sanofi; adviser to the ATLAS Group; and has received research support from Janssen. Dr. Piazza has received research funding from Bayer, BIG/EKOS, BMS, Janssen, and Portola. Dr. Hylek had been a consultant to Bayer and Ionis, and has received honoraria from Boehringer Ingelheim and Pfizer.

CHICAGO – A clinical decision-support tool designed to identify hospitalized patients who need thromboembolism prophylaxis and embedded in a hospital’s electronic health record led to significantly more appropriate prophylaxis, compared with usual care, and significantly cut the 30-day rate of thromboembolism in a randomized, multicenter trial with more than 10,000 patients.

“This is the first time that a clinical decision support tool not only changed [thromboprophylaxis prescribing] behavior but also affected hard outcomes. That’s remarkable,” lead investigator Alex C. Spyropoulos, MD, said in an interview.

Even so, outside experts expressed concerns about certain results and the trial design.

Mitchel L. Zoler/MDedge News

Use of the decision-support risk calculator for thromboembolism in the IMPROVE-DD VTE trial significantly boosted use of appropriate inpatient thromboprophylaxis starting at hospital admission by a relative 52%, and significantly increased outpatient thromboprophylaxis prescribed at discharge by a relative 93% in the study’s two primary endpoints, Dr. Spyropoulos reported at the American Heart Association scientific sessions.

This intervention led to a significant 29% relative reduction in the incidence of total thromboembolic events, both venous and arterial, during hospitalization and through 30 days post discharge.

The absolute thromboembolic event rates were 2.9% among 5,249 patients treated at either of two U.S. hospitals that used the EHR-based risk calculator and 4.0% in 5,450 patients seen at either of two other U.S. hospitals that served as controls and where usual care method identified patients who needed thromboprophylaxis, said Dr. Spyropoulos, professor and director of the anticoagulation and clinical thrombosis services for Northwell Health in New York. This included a 2.7% rate of venous thromboembolism and a 0.25% rate of arterial thromboembolism in the intervention patients, and a 3.3% rate of venous events and a 0.7% rate of arterial events in the controls.

Patients treated at the hospitals that used the EHR-embedded risk calculator also has a numerically lower rate of major bleeding events during hospitalization and 30-day postdischarge follow-up, a 0.15% rate compared with a 0.22% rate in the control patients, a difference that was not significant.
 

A ‘powerful message’

“It’s a powerful message to see an absolute 1.1% difference in the rate of thromboembolism and a trend to fewer major bleeds. I think this will change practice,” Dr. Spyropoulos added in the interview. “The next step is dissemination.”

But thromboprophylaxis experts cautioned that, while the results looked promising, the findings need more analysis and review, and the intervention may need further testing before it’s ready for widespread use.

For example, one unexpected result was an unexpected 2.1 percentage point increase in all-cause mortality linked with use of the decision-support tool. Total deaths from admission to 30 days after discharge occurred in 9.1% of the patients treated at the two hospitals that used the risk calculator and 7.0% among the control patients, a difference that Dr, Spyropoulos said was likely the result of unbalanced outcomes from COVID-19 infections that had no relevance to the tested intervention. The trial ran during December 2020–January 2022.
 

But wait – more detail and analysis needed

“I’d like to see more analysis of the data from this trial,” and “there is the issue of increased mortality,” commented Gregory Piazza, MD, director of vascular medicine at Brigham and Women’s Hospital in Boston, and a specialist in thromboembolism prevention and management. He also highlighted the need for greater detail on the arterial thromboembolic events tallied during the study.

With more details and analysis of these findings “we’ll learn more about the true impact” of this intervention, Dr. Piazza said in an interview.

Mitchel L. Zoler/MDedge News

“The increased mortality in the intervention group may have been due to differential treatment and decision-making and confounding and warrants further investigation,” commented Elaine M. Hylek, MD, a professor at Boston University and designated discussant for the report. Selection bias may have contributed to this possible confounding, Dr. Hylek noted.

Other limitations of the study cited by Dr. Hylek included its reliance on individual clinician decision-making to actually prescribe thromboprophylaxis, a lack of information on patient adherence to their thromboprophylaxis prescription, and an overall low rate of appropriate thromboprophylaxis prescribed to patients at discharge. The rates were 7.5% among the controls and 13.6% among patients in the intervention arm. For prescription at the time of hospitalization, the rates were 72.5% among control patients and 80.1% for patients seen at the two hospitals that used the decision-support tool.
 

The IMPROVE-DD VTE risk assessment tool

The clinical decision-support tool tested is called the IMPROVE-DD VTE risk assessment model, developed over several years by Dr. Spyropoulos and associates; they have also performed multiple validation studies. The model includes eight factors that score 1-3 points if positive that can add up to total scores of 0-14. A score of 0 or 1 is considered low risk, 2 or 3 intermediate risk, and 4 or more high risk. One of the scoring factors is the result of a D-dimer test, which explains the DD part of the name.

The eight factors and point assignments are prior venous thromboembolism: 3 points; known thrombophilia: 2 points; lower limb paralysis: 2 points; current cancer: 2 points; d-dimer level more than twofold the upper limit of normal: 2 points; immobilized for at least 7 days: 1 point; admitted to the ICU or coronary care unit: 1 point; and age greater than 60 years old: 1 point.

Development of the IMPROVE-DD VTE risk calculator received most of its funding from the U.S. Agency for Healthcare Research and Quality, and the risk tool will be available for hospitals and health systems to access at no charge through the agency’s website, Dr. Spyropoulos said. The researchers designed the calculator to operate in any EHR product.

IMPROVE-DD VTE “is a very valid, high-quality tool,” commented Dr. Piazza. “We’ve used some rather blunt tools in the past,” and especially praised inclusion of D-dimer results into the IMPROVE-DD VTE model.

“It’s nice to use a biomarker in addition to clinical factors,” he said. “A biomarker provides a more holistic picture; we can’t do genetic testing on every patient.”

Enrollment focused on higher-risk patients

The study ran at four academic, tertiary-care hospitals in the Northwell Health network in the New York region. It enrolled patients aged more than 60 years who were hospitalized for any of five diagnoses: heart failure; acute respiratory insufficiency, including chronic obstructive lung disease or asthma; acute infectious disease, including COVID-19; acute inflammatory disease, including rheumatic disease; or acute stroke. The study excluded patients with a history of atrial fibrillation, those who used an anticoagulant at home, or those who had received therapeutic anticoagulation within 24 hours of their hospital admission.

The anticoagulant prophylaxis that patients received depended on their calculated risk level – intermediate or high – and whether they were inpatients or being discharged. The anticoagulants that clinicians could prescribe included unfractionated heparin, enoxaparin, fondaparinux, rivaroxaban, and apixaban.

“We’ve been looking for a long time for a tool for medically ill patients that’s like the CHA2DS2-VASc score” for patients with atrial fibrillation. “These powerful data say we now have this, and the EHR provides a vehicle to easily implement it,” Dr. Spyropoulos said.

The IMPROVE-DD VTE study received partial funding from Janssen. Dr. Spyropoulos has been a consultant to Nayer, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Pfizer, and Sanofi; adviser to the ATLAS Group; and has received research support from Janssen. Dr. Piazza has received research funding from Bayer, BIG/EKOS, BMS, Janssen, and Portola. Dr. Hylek had been a consultant to Bayer and Ionis, and has received honoraria from Boehringer Ingelheim and Pfizer.

The Centers for Disease Control and Prevention is warning of an early surge in respiratory disease caused by multiple viruses. As influenza viruses, respiratory syncytial virus (RSV), SARS-CoV-2, and rhinovirus/enterovirus simultaneously circulate, the agency cautioned that this confluence of viral activity could strain the health care system, according to a CDC Health Network Alert advisory issued Nov. 4.

“This early increase in disease incidence highlights the importance of optimizing respiratory virus prevention and treatment measures, including prompt vaccination and antiviral treatment,” the alert stated.

The CDC reports that RSV activity is increasing nationally, but in some areas – such as the South and Mountain West – cases appear to be trending downward.

Influenza cases continue to climb, with the virus activity being the highest in the South, Mid-Atlantic, and the south-central West Coast, according to CDC data. “In fact, we’re seeing the highest influenza hospitalization rates going back a decade,” said José Romero, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, during a press briefing. The agency estimates that there have been 1.6 million illnesses, 13,000 hospitalizations, and 730 deaths from the flu so far this season. As of Nov. 4, there have been two pediatric deaths.

COVID-19 cases appear to have plateaued in the past three weeks, Dr. Romero said; however, the CDC expects that there will be “high-level circulation of SARS-CoV-2 this fall and winter,” the health alert stated.

The CDC advised that all eligible individuals aged 6-months or older should be vaccinated against COVID-19 and influenza. To protect against RSV-hospitalization, high-risk children should receive the monoclonal antibody drug palivizumab (Synagis). High-risk children include infants born before 29 weeks, children younger than age 2 with chronic lung disease or hemodynamically significant congenital heart disease, and children with suppressed immune systems or neuromuscular disorders.

Any patient with confirmed or suspected flu who is hospitalized, at higher risk for influenza complications, or who has a severe or progressive illness should be treated as early as possible with antivirals, such as oral oseltamivir (Tamiflu).

Patients with confirmed SARS-CoV-2 infection with increased risk of complications should also be treated with antivirals, such as nirmatrelvir and ritonavir (Paxlovid) or remdesivir (Veklury).

Patients should also be reminded to wash their hands frequently, cover coughs and sneezes, stay home when sick, and avoid close contact with people who are sick, the CDC advised.

“There’s no doubt that we will face some challenges this winter,” said Dawn O’Connell, HHS Assistant Secretary for Preparedness and Response, “but it’s important to remember that RSV and flu are not new, and we have safe and effective vaccines for COVID-19 and the flu.”

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

The Centers for Disease Control and Prevention is warning of an early surge in respiratory disease caused by multiple viruses. As influenza viruses, respiratory syncytial virus (RSV), SARS-CoV-2, and rhinovirus/enterovirus simultaneously circulate, the agency cautioned that this confluence of viral activity could strain the health care system, according to a CDC Health Network Alert advisory issued Nov. 4.

“This early increase in disease incidence highlights the importance of optimizing respiratory virus prevention and treatment measures, including prompt vaccination and antiviral treatment,” the alert stated.

The CDC reports that RSV activity is increasing nationally, but in some areas – such as the South and Mountain West – cases appear to be trending downward.

Influenza cases continue to climb, with the virus activity being the highest in the South, Mid-Atlantic, and the south-central West Coast, according to CDC data. “In fact, we’re seeing the highest influenza hospitalization rates going back a decade,” said José Romero, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, during a press briefing. The agency estimates that there have been 1.6 million illnesses, 13,000 hospitalizations, and 730 deaths from the flu so far this season. As of Nov. 4, there have been two pediatric deaths.

COVID-19 cases appear to have plateaued in the past three weeks, Dr. Romero said; however, the CDC expects that there will be “high-level circulation of SARS-CoV-2 this fall and winter,” the health alert stated.

The CDC advised that all eligible individuals aged 6-months or older should be vaccinated against COVID-19 and influenza. To protect against RSV-hospitalization, high-risk children should receive the monoclonal antibody drug palivizumab (Synagis). High-risk children include infants born before 29 weeks, children younger than age 2 with chronic lung disease or hemodynamically significant congenital heart disease, and children with suppressed immune systems or neuromuscular disorders.

Any patient with confirmed or suspected flu who is hospitalized, at higher risk for influenza complications, or who has a severe or progressive illness should be treated as early as possible with antivirals, such as oral oseltamivir (Tamiflu).

Patients with confirmed SARS-CoV-2 infection with increased risk of complications should also be treated with antivirals, such as nirmatrelvir and ritonavir (Paxlovid) or remdesivir (Veklury).

Patients should also be reminded to wash their hands frequently, cover coughs and sneezes, stay home when sick, and avoid close contact with people who are sick, the CDC advised.

“There’s no doubt that we will face some challenges this winter,” said Dawn O’Connell, HHS Assistant Secretary for Preparedness and Response, “but it’s important to remember that RSV and flu are not new, and we have safe and effective vaccines for COVID-19 and the flu.”

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

The Centers for Disease Control and Prevention is warning of an early surge in respiratory disease caused by multiple viruses. As influenza viruses, respiratory syncytial virus (RSV), SARS-CoV-2, and rhinovirus/enterovirus simultaneously circulate, the agency cautioned that this confluence of viral activity could strain the health care system, according to a CDC Health Network Alert advisory issued Nov. 4.

“This early increase in disease incidence highlights the importance of optimizing respiratory virus prevention and treatment measures, including prompt vaccination and antiviral treatment,” the alert stated.

The CDC reports that RSV activity is increasing nationally, but in some areas – such as the South and Mountain West – cases appear to be trending downward.

Influenza cases continue to climb, with the virus activity being the highest in the South, Mid-Atlantic, and the south-central West Coast, according to CDC data. “In fact, we’re seeing the highest influenza hospitalization rates going back a decade,” said José Romero, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, during a press briefing. The agency estimates that there have been 1.6 million illnesses, 13,000 hospitalizations, and 730 deaths from the flu so far this season. As of Nov. 4, there have been two pediatric deaths.

COVID-19 cases appear to have plateaued in the past three weeks, Dr. Romero said; however, the CDC expects that there will be “high-level circulation of SARS-CoV-2 this fall and winter,” the health alert stated.

The CDC advised that all eligible individuals aged 6-months or older should be vaccinated against COVID-19 and influenza. To protect against RSV-hospitalization, high-risk children should receive the monoclonal antibody drug palivizumab (Synagis). High-risk children include infants born before 29 weeks, children younger than age 2 with chronic lung disease or hemodynamically significant congenital heart disease, and children with suppressed immune systems or neuromuscular disorders.

Any patient with confirmed or suspected flu who is hospitalized, at higher risk for influenza complications, or who has a severe or progressive illness should be treated as early as possible with antivirals, such as oral oseltamivir (Tamiflu).

Patients with confirmed SARS-CoV-2 infection with increased risk of complications should also be treated with antivirals, such as nirmatrelvir and ritonavir (Paxlovid) or remdesivir (Veklury).

Patients should also be reminded to wash their hands frequently, cover coughs and sneezes, stay home when sick, and avoid close contact with people who are sick, the CDC advised.

“There’s no doubt that we will face some challenges this winter,” said Dawn O’Connell, HHS Assistant Secretary for Preparedness and Response, “but it’s important to remember that RSV and flu are not new, and we have safe and effective vaccines for COVID-19 and the flu.”

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

A man in England who was infected with an early strain of COVID-19 was finally cleared 411 days after first testing positive, according to experts in the United Kingdom. 

The man was treated with a mixture of neutralizing monoclonal antibodies, King’s College London said in a news release.

The man, 59, tested positive in December 2020 and tested negative in January 2022. He had a weakened immune system because of a previous kidney transplant. He received three doses of vaccine and his symptoms lessened, but he kept testing positive for COVID.

To find out if the man had a persistent infection or had been infected several times, doctors did a genetic analysis of the virus.

“This revealed that the patient’s infection was a persistent infection with an early COVID variant – a variation of the original Wuhan variant that was dominant in the United Kingdom in the later months of 2020. Analysis found the patient’s virus had multiple mutations since he was first infected,” King’s College said.

The doctors treated him with a Regeneron treatment that is no longer widely used because it’s not effective against newer COVID variants.

“Some new variants of the virus are resistant to all the antibody treatments available in the United Kingdom and Europe. Some people with weakened immune systems are still at risk of severe illness and becoming persistently infected. We are still working to understand the best way to protect and treat them,” Luke Snell, MD, from the King’s College School of Immunology & Microbial Sciences, said in the news release.

This is one of the longest known cases of COVID infection. Another man in England was infected with COVID for 505 days before his death, which King’s College said was the longest known COVID infection.

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

A man in England who was infected with an early strain of COVID-19 was finally cleared 411 days after first testing positive, according to experts in the United Kingdom. 

The man was treated with a mixture of neutralizing monoclonal antibodies, King’s College London said in a news release.

The man, 59, tested positive in December 2020 and tested negative in January 2022. He had a weakened immune system because of a previous kidney transplant. He received three doses of vaccine and his symptoms lessened, but he kept testing positive for COVID.

To find out if the man had a persistent infection or had been infected several times, doctors did a genetic analysis of the virus.

“This revealed that the patient’s infection was a persistent infection with an early COVID variant – a variation of the original Wuhan variant that was dominant in the United Kingdom in the later months of 2020. Analysis found the patient’s virus had multiple mutations since he was first infected,” King’s College said.

The doctors treated him with a Regeneron treatment that is no longer widely used because it’s not effective against newer COVID variants.

“Some new variants of the virus are resistant to all the antibody treatments available in the United Kingdom and Europe. Some people with weakened immune systems are still at risk of severe illness and becoming persistently infected. We are still working to understand the best way to protect and treat them,” Luke Snell, MD, from the King’s College School of Immunology & Microbial Sciences, said in the news release.

This is one of the longest known cases of COVID infection. Another man in England was infected with COVID for 505 days before his death, which King’s College said was the longest known COVID infection.

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

A man in England who was infected with an early strain of COVID-19 was finally cleared 411 days after first testing positive, according to experts in the United Kingdom. 

The man was treated with a mixture of neutralizing monoclonal antibodies, King’s College London said in a news release.

The man, 59, tested positive in December 2020 and tested negative in January 2022. He had a weakened immune system because of a previous kidney transplant. He received three doses of vaccine and his symptoms lessened, but he kept testing positive for COVID.

To find out if the man had a persistent infection or had been infected several times, doctors did a genetic analysis of the virus.

“This revealed that the patient’s infection was a persistent infection with an early COVID variant – a variation of the original Wuhan variant that was dominant in the United Kingdom in the later months of 2020. Analysis found the patient’s virus had multiple mutations since he was first infected,” King’s College said.

The doctors treated him with a Regeneron treatment that is no longer widely used because it’s not effective against newer COVID variants.

“Some new variants of the virus are resistant to all the antibody treatments available in the United Kingdom and Europe. Some people with weakened immune systems are still at risk of severe illness and becoming persistently infected. We are still working to understand the best way to protect and treat them,” Luke Snell, MD, from the King’s College School of Immunology & Microbial Sciences, said in the news release.

This is one of the longest known cases of COVID infection. Another man in England was infected with COVID for 505 days before his death, which King’s College said was the longest known COVID infection.

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

The COVID-19 bivalent Pfizer/BioNTech vaccine triggers a stronger immune response than a fourth dose of the original vaccine, the company reported on Nov. 4, supporting calls by public health officials for eligible people to get this booster before a potential COVID-19 surge this winter.

The company’s ongoing phase 2/3 study of their Omicron BA.4 and BA.5 bivalent – which targets both the virus’ original strain and the two subvariants – shows that the vaccine offered the strongest protection in people older than 55 years.

One month after receiving a 30-mcg booster with the bivalent vaccine, those older than 55 had four times more neutralizing antibodies against these Omicron subvariants, compared with people who received the original monovalent vaccine as a booster in the study.

Researchers compared the geometric mean titer (GMT) levels of these antibodies in three groups before and 1 month after boosting. The 36 people older than 55 years in the released study findings had an GMT level of 896 with the bivalent booster, a level 13 times higher than before this immunization.

For the 38 adults ages 18-55 in the study, the GMT level increased to 606 at 1 month after the bivalent booster, an increase of almost 10-fold, compared with baseline. In a comparator group of 40 people receiving the original vaccine as a fourth dose, the GMT level was 236, or threefold higher than before their booster shot.

The newly released data is “very encouraging and consistent now with three studies all showing a substantial 3-4 fold increased level of neutralizing antibodies versus BA.5 as compared with the original booster,” said Eric Topol, MD, director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape Medical News.

Pfizer and BioNTech announced the updated findings in a Nov. 4 press release.

A booster dose of the BA.4/BA.5-adapted bivalent vaccine is authorized for emergency use by the Food and Drug Administration for ages 5 years and older. The safety and tolerability profile of the Pfizer/BioNTech bivalent booster remains favorable and similar to the original COVID-19 vaccine, the company reported.

Until recently, the BA.5 Omicron variant was the dominant strain in the United States, but is now getting elbowed out by the subvariants BQ.1.1, BQ.1, and BA.4.6, which together make up almost 45% of the circulating virus.
 

Some skepticism

“It is important to note that these data are press-release level, which does not allow a view of the data totality,” Hana El Sahly, MD, professor of molecular virology and microbiology, Baylor College of Medicine, Houston, said in an interview.

“For example, there may be significant differences between the groups, and the release mentions at least one difference that is of importance: the interval since the last vaccination which often affects the response to subsequent boosting,” she said.

Dr. El Sahly added that the findings are not surprising. “In the short term, a variant-specific vaccine produces a higher level of antibody against the variant in the vaccine than the vaccines based on the ancestral strains.”

More researcher results are warranted. “These data do not indicate that these differences between the two vaccines translate into a meaningful clinical benefit at a population level,” Dr. El Sahly said.
 

An uncertain winter ahead

“As we head into the holiday season, we hope these updated data will encourage people to seek out a COVID-19 bivalent booster as soon as they are eligible in order to maintain high levels of protection against the widely circulating Omicron BA.4 and BA.5 sublineages,” Albert Bourla, Pfizer chairman and CEO, stated in the release.

The updated data from the Pfizer/BioNTech study are “all the more reason to get a booster, with added protection also versus BQ.1.1, which will soon become dominant in the U.S.,” Dr. Topol predicted.

It is unclear when the next surge will happen, as COVID-19 does not always follow a seasonal pattern, at least not yet, Dr. El Sahly said. “Regardless, it is reasonable to recommend additional vaccine doses to immunocompromised and frail or older persons. More importantly, influenza vaccination and being up to date on pneumococcal vaccines are highly recommended as soon as feasible, given the early and intense flu season.”

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

The COVID-19 bivalent Pfizer/BioNTech vaccine triggers a stronger immune response than a fourth dose of the original vaccine, the company reported on Nov. 4, supporting calls by public health officials for eligible people to get this booster before a potential COVID-19 surge this winter.

The company’s ongoing phase 2/3 study of their Omicron BA.4 and BA.5 bivalent – which targets both the virus’ original strain and the two subvariants – shows that the vaccine offered the strongest protection in people older than 55 years.

One month after receiving a 30-mcg booster with the bivalent vaccine, those older than 55 had four times more neutralizing antibodies against these Omicron subvariants, compared with people who received the original monovalent vaccine as a booster in the study.

Researchers compared the geometric mean titer (GMT) levels of these antibodies in three groups before and 1 month after boosting. The 36 people older than 55 years in the released study findings had an GMT level of 896 with the bivalent booster, a level 13 times higher than before this immunization.

For the 38 adults ages 18-55 in the study, the GMT level increased to 606 at 1 month after the bivalent booster, an increase of almost 10-fold, compared with baseline. In a comparator group of 40 people receiving the original vaccine as a fourth dose, the GMT level was 236, or threefold higher than before their booster shot.

The newly released data is “very encouraging and consistent now with three studies all showing a substantial 3-4 fold increased level of neutralizing antibodies versus BA.5 as compared with the original booster,” said Eric Topol, MD, director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape Medical News.

Pfizer and BioNTech announced the updated findings in a Nov. 4 press release.

A booster dose of the BA.4/BA.5-adapted bivalent vaccine is authorized for emergency use by the Food and Drug Administration for ages 5 years and older. The safety and tolerability profile of the Pfizer/BioNTech bivalent booster remains favorable and similar to the original COVID-19 vaccine, the company reported.

Until recently, the BA.5 Omicron variant was the dominant strain in the United States, but is now getting elbowed out by the subvariants BQ.1.1, BQ.1, and BA.4.6, which together make up almost 45% of the circulating virus.
 

Some skepticism

“It is important to note that these data are press-release level, which does not allow a view of the data totality,” Hana El Sahly, MD, professor of molecular virology and microbiology, Baylor College of Medicine, Houston, said in an interview.

“For example, there may be significant differences between the groups, and the release mentions at least one difference that is of importance: the interval since the last vaccination which often affects the response to subsequent boosting,” she said.

Dr. El Sahly added that the findings are not surprising. “In the short term, a variant-specific vaccine produces a higher level of antibody against the variant in the vaccine than the vaccines based on the ancestral strains.”

More researcher results are warranted. “These data do not indicate that these differences between the two vaccines translate into a meaningful clinical benefit at a population level,” Dr. El Sahly said.
 

An uncertain winter ahead

“As we head into the holiday season, we hope these updated data will encourage people to seek out a COVID-19 bivalent booster as soon as they are eligible in order to maintain high levels of protection against the widely circulating Omicron BA.4 and BA.5 sublineages,” Albert Bourla, Pfizer chairman and CEO, stated in the release.

The updated data from the Pfizer/BioNTech study are “all the more reason to get a booster, with added protection also versus BQ.1.1, which will soon become dominant in the U.S.,” Dr. Topol predicted.

It is unclear when the next surge will happen, as COVID-19 does not always follow a seasonal pattern, at least not yet, Dr. El Sahly said. “Regardless, it is reasonable to recommend additional vaccine doses to immunocompromised and frail or older persons. More importantly, influenza vaccination and being up to date on pneumococcal vaccines are highly recommended as soon as feasible, given the early and intense flu season.”

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

The COVID-19 bivalent Pfizer/BioNTech vaccine triggers a stronger immune response than a fourth dose of the original vaccine, the company reported on Nov. 4, supporting calls by public health officials for eligible people to get this booster before a potential COVID-19 surge this winter.

The company’s ongoing phase 2/3 study of their Omicron BA.4 and BA.5 bivalent – which targets both the virus’ original strain and the two subvariants – shows that the vaccine offered the strongest protection in people older than 55 years.

One month after receiving a 30-mcg booster with the bivalent vaccine, those older than 55 had four times more neutralizing antibodies against these Omicron subvariants, compared with people who received the original monovalent vaccine as a booster in the study.

Researchers compared the geometric mean titer (GMT) levels of these antibodies in three groups before and 1 month after boosting. The 36 people older than 55 years in the released study findings had an GMT level of 896 with the bivalent booster, a level 13 times higher than before this immunization.

For the 38 adults ages 18-55 in the study, the GMT level increased to 606 at 1 month after the bivalent booster, an increase of almost 10-fold, compared with baseline. In a comparator group of 40 people receiving the original vaccine as a fourth dose, the GMT level was 236, or threefold higher than before their booster shot.

The newly released data is “very encouraging and consistent now with three studies all showing a substantial 3-4 fold increased level of neutralizing antibodies versus BA.5 as compared with the original booster,” said Eric Topol, MD, director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape Medical News.

Pfizer and BioNTech announced the updated findings in a Nov. 4 press release.

A booster dose of the BA.4/BA.5-adapted bivalent vaccine is authorized for emergency use by the Food and Drug Administration for ages 5 years and older. The safety and tolerability profile of the Pfizer/BioNTech bivalent booster remains favorable and similar to the original COVID-19 vaccine, the company reported.

Until recently, the BA.5 Omicron variant was the dominant strain in the United States, but is now getting elbowed out by the subvariants BQ.1.1, BQ.1, and BA.4.6, which together make up almost 45% of the circulating virus.
 

Some skepticism

“It is important to note that these data are press-release level, which does not allow a view of the data totality,” Hana El Sahly, MD, professor of molecular virology and microbiology, Baylor College of Medicine, Houston, said in an interview.

“For example, there may be significant differences between the groups, and the release mentions at least one difference that is of importance: the interval since the last vaccination which often affects the response to subsequent boosting,” she said.

Dr. El Sahly added that the findings are not surprising. “In the short term, a variant-specific vaccine produces a higher level of antibody against the variant in the vaccine than the vaccines based on the ancestral strains.”

More researcher results are warranted. “These data do not indicate that these differences between the two vaccines translate into a meaningful clinical benefit at a population level,” Dr. El Sahly said.
 

An uncertain winter ahead

“As we head into the holiday season, we hope these updated data will encourage people to seek out a COVID-19 bivalent booster as soon as they are eligible in order to maintain high levels of protection against the widely circulating Omicron BA.4 and BA.5 sublineages,” Albert Bourla, Pfizer chairman and CEO, stated in the release.

The updated data from the Pfizer/BioNTech study are “all the more reason to get a booster, with added protection also versus BQ.1.1, which will soon become dominant in the U.S.,” Dr. Topol predicted.

It is unclear when the next surge will happen, as COVID-19 does not always follow a seasonal pattern, at least not yet, Dr. El Sahly said. “Regardless, it is reasonable to recommend additional vaccine doses to immunocompromised and frail or older persons. More importantly, influenza vaccination and being up to date on pneumococcal vaccines are highly recommended as soon as feasible, given the early and intense flu season.”

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

CHICAGO – Routine early, expeditious use of extracorporeal membrane oxygenation (ECMO) is a common strategy in patients with severe cardiogenic shock, but a less aggressive initial approach may be just as effective, a randomized trial suggests.

In the study that assigned patients with “rapidly deteriorating or severe” cardiogenic shock to one or the other approach, clinical outcomes were no better for those who received immediate ECMO than for those initially managed with inotropes and vasopressors, researchers said.

The conservative strategy, importantly, allowed for downstream ECMO in the event of hemodynamic deterioration, which occurred in a substantial 39% of cases, observed Petr Ostadal, MD, PhD, when presenting the results at the American Heart Association scientific sessions.

Dr. Ostadal of Na Homolce Hospital, Prague, is also first author on the published report of the study, called Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock (ECMO-CS), which was published the same day in Circulation.

The trial makes a firm case for preferring the conservative initial approach over routine early ECMO in the kind of patients it entered, Larry A. Allen, MD, MHS, University of Coloradoat Denver, Aurora, told this news organization.

More than 60% of the trial’s 117 patients had shock secondary to an acute coronary syndrome; another 23% were in heart failure decompensation.

A preference for the conservative initial approach would be welcome, he said. The early aggressive ECMO approach is resource intensive and carries some important risks, such as stroke or coagulopathy, said Dr. Allen, who is not connected with ECMO-CS. Yet it is increasingly the go-to approach in such patients, based primarily on observational data.

Although early ECMO apparently didn’t benefit patients in this study in their specific stage of cardiogenic shock, Dr. Allen observed, it would presumably help some, but identifying them in practice presents challenges. “Defining where people are in the spectrum of early versus middle versus late cardiogenic shock is actually very tricky.”

It will therefore be important, he said, to identify ways to predict which conservatively managed patients do well with the strategy, and which are most at risk for hemodynamic deterioration and for whom ECMO should be readily available.

“I think part of what ECMO-CS tells us is that, if a patient is stable on intravenous inotropic and vasopressor support, you can defer ECMO while you’re thinking about the patient – about their larger context and the right medical decision-making for them.”

The trial randomly assigned 122 patients with rapidly deteriorating or severe cardiogenic shock to the immediate-ECMO or the conservative strategy at four centers in the Czech Republic. The 117 patients for whom informed consent could be obtained were included in the analysis, 58 and 59 patients, respectively. Their mean age was about 65 years and three-fourths were male.

The primary endpoint, the only endpoint for which the study was powered, consisted of death from any cause, resuscitated circulatory arrest, or use of a different form of mechanical circulatory support (MCS) by 30 days.

It occurred in 63.8% of patients assigned to immediate ECMO and 71.2% of those in the conservative strategy group, for a hazard ratio of 0.72 (95% confidence interval, 0.46-1.12; P = .21).

As individual endpoints, rates of death from any cause and resuscitated arrest did not significantly differ between the groups, but conservatively managed patients more often used another form of MCS. The HRs were 1.11 (95% CI, 0.66-1.87) for death from any cause, 0.79 (95% CI, 0.27-2.28) for resuscitated cardiac arrest, and 0.38 (95% CI, 0.18-0.79) for use of another MCS device.

The rates for serious adverse events – including bleeding, ischemia, stroke, pneumonia, or sepsis – were similar at 60.3% in the early-ECMO group and 61% in group with conservative initial management, Dr. Ostadal reported.

Other than the 23 patients in the conservative initial strategy group who went on to receive ECMO (1.9 days after randomization, on average), 1 went on to undergo implantation with a HeartMate (Abbott) ventricular assist device and 3 received an Impella pump (Abiomed).

Six patients in the early-ECMO group were already receiving intra-aortic balloon pump (IABP) support at randomization, two underwent temporary implantation with a Centrimag device (Abbott), and three went on to receive a HeartMate device, the published report notes.

ECMO is the optimal first choice for MCS in such patients with cardiogenic shock who need a circulatory support device, especially because it also oxygenates the blood, Dr. Ostadal told this news organization.

But ECMO doesn’t help with ventricular unloading. Indeed, it can sometimes reduce ventricular preload, especially if right-heart pressures are low. So MCS devices that unload the ventricle, typically an IABP, can complement ECMO.

Dr. Ostadal speculates, however, that there may be a better pairing option. “Impella plus ECMO, I think, is the combination which has a future,” he said, for patients in cardiogenic shock who need a short-term percutaneous hemodynamic support device. Impella “supports the whole circulation” and unloads the left ventricle.

“A balloon pump in combination with ECMO is still not a bad choice. It’s very cheap in comparison with Impella.” But in his opinion, Dr. Ostadal said, “The combination of Impella plus ECMO is more efficient from a hemodynamic point of view.”

As the published report notes, ongoing randomized trials looking at ECMO plus other MCS devices in cardiogenic shock include ECLS-SHOCK, with a projected enrollment of 420 patients, and EURO-SHOCK, aiming for a similar number of patients; both compare routine ECMO to conservative management.

In addition, ANCHOR, in which ECMO is combined with IABP, and DanShock, which looks at early use of Impella rather than ECMO, are enrolling patients with shock secondary to acute coronary syndromes.

Dr. Ostadal disclosed consulting for Getinge, Edwards, Medtronic, Biomedica, and Xenios/Fresenius, and receiving research support from Xenios/Fresenius. Dr. Allen disclosed modest or significant relationships with ACI Clinical, Novartis, UpToDate, Boston Scientific, and Cytokinetics.

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

CHICAGO – Routine early, expeditious use of extracorporeal membrane oxygenation (ECMO) is a common strategy in patients with severe cardiogenic shock, but a less aggressive initial approach may be just as effective, a randomized trial suggests.

In the study that assigned patients with “rapidly deteriorating or severe” cardiogenic shock to one or the other approach, clinical outcomes were no better for those who received immediate ECMO than for those initially managed with inotropes and vasopressors, researchers said.

The conservative strategy, importantly, allowed for downstream ECMO in the event of hemodynamic deterioration, which occurred in a substantial 39% of cases, observed Petr Ostadal, MD, PhD, when presenting the results at the American Heart Association scientific sessions.

Dr. Ostadal of Na Homolce Hospital, Prague, is also first author on the published report of the study, called Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock (ECMO-CS), which was published the same day in Circulation.

The trial makes a firm case for preferring the conservative initial approach over routine early ECMO in the kind of patients it entered, Larry A. Allen, MD, MHS, University of Coloradoat Denver, Aurora, told this news organization.

More than 60% of the trial’s 117 patients had shock secondary to an acute coronary syndrome; another 23% were in heart failure decompensation.

A preference for the conservative initial approach would be welcome, he said. The early aggressive ECMO approach is resource intensive and carries some important risks, such as stroke or coagulopathy, said Dr. Allen, who is not connected with ECMO-CS. Yet it is increasingly the go-to approach in such patients, based primarily on observational data.

Although early ECMO apparently didn’t benefit patients in this study in their specific stage of cardiogenic shock, Dr. Allen observed, it would presumably help some, but identifying them in practice presents challenges. “Defining where people are in the spectrum of early versus middle versus late cardiogenic shock is actually very tricky.”

It will therefore be important, he said, to identify ways to predict which conservatively managed patients do well with the strategy, and which are most at risk for hemodynamic deterioration and for whom ECMO should be readily available.

“I think part of what ECMO-CS tells us is that, if a patient is stable on intravenous inotropic and vasopressor support, you can defer ECMO while you’re thinking about the patient – about their larger context and the right medical decision-making for them.”

The trial randomly assigned 122 patients with rapidly deteriorating or severe cardiogenic shock to the immediate-ECMO or the conservative strategy at four centers in the Czech Republic. The 117 patients for whom informed consent could be obtained were included in the analysis, 58 and 59 patients, respectively. Their mean age was about 65 years and three-fourths were male.

The primary endpoint, the only endpoint for which the study was powered, consisted of death from any cause, resuscitated circulatory arrest, or use of a different form of mechanical circulatory support (MCS) by 30 days.

It occurred in 63.8% of patients assigned to immediate ECMO and 71.2% of those in the conservative strategy group, for a hazard ratio of 0.72 (95% confidence interval, 0.46-1.12; P = .21).

As individual endpoints, rates of death from any cause and resuscitated arrest did not significantly differ between the groups, but conservatively managed patients more often used another form of MCS. The HRs were 1.11 (95% CI, 0.66-1.87) for death from any cause, 0.79 (95% CI, 0.27-2.28) for resuscitated cardiac arrest, and 0.38 (95% CI, 0.18-0.79) for use of another MCS device.

The rates for serious adverse events – including bleeding, ischemia, stroke, pneumonia, or sepsis – were similar at 60.3% in the early-ECMO group and 61% in group with conservative initial management, Dr. Ostadal reported.

Other than the 23 patients in the conservative initial strategy group who went on to receive ECMO (1.9 days after randomization, on average), 1 went on to undergo implantation with a HeartMate (Abbott) ventricular assist device and 3 received an Impella pump (Abiomed).

Six patients in the early-ECMO group were already receiving intra-aortic balloon pump (IABP) support at randomization, two underwent temporary implantation with a Centrimag device (Abbott), and three went on to receive a HeartMate device, the published report notes.

ECMO is the optimal first choice for MCS in such patients with cardiogenic shock who need a circulatory support device, especially because it also oxygenates the blood, Dr. Ostadal told this news organization.

But ECMO doesn’t help with ventricular unloading. Indeed, it can sometimes reduce ventricular preload, especially if right-heart pressures are low. So MCS devices that unload the ventricle, typically an IABP, can complement ECMO.

Dr. Ostadal speculates, however, that there may be a better pairing option. “Impella plus ECMO, I think, is the combination which has a future,” he said, for patients in cardiogenic shock who need a short-term percutaneous hemodynamic support device. Impella “supports the whole circulation” and unloads the left ventricle.

“A balloon pump in combination with ECMO is still not a bad choice. It’s very cheap in comparison with Impella.” But in his opinion, Dr. Ostadal said, “The combination of Impella plus ECMO is more efficient from a hemodynamic point of view.”

As the published report notes, ongoing randomized trials looking at ECMO plus other MCS devices in cardiogenic shock include ECLS-SHOCK, with a projected enrollment of 420 patients, and EURO-SHOCK, aiming for a similar number of patients; both compare routine ECMO to conservative management.

In addition, ANCHOR, in which ECMO is combined with IABP, and DanShock, which looks at early use of Impella rather than ECMO, are enrolling patients with shock secondary to acute coronary syndromes.

Dr. Ostadal disclosed consulting for Getinge, Edwards, Medtronic, Biomedica, and Xenios/Fresenius, and receiving research support from Xenios/Fresenius. Dr. Allen disclosed modest or significant relationships with ACI Clinical, Novartis, UpToDate, Boston Scientific, and Cytokinetics.

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

CHICAGO – Routine early, expeditious use of extracorporeal membrane oxygenation (ECMO) is a common strategy in patients with severe cardiogenic shock, but a less aggressive initial approach may be just as effective, a randomized trial suggests.

In the study that assigned patients with “rapidly deteriorating or severe” cardiogenic shock to one or the other approach, clinical outcomes were no better for those who received immediate ECMO than for those initially managed with inotropes and vasopressors, researchers said.

The conservative strategy, importantly, allowed for downstream ECMO in the event of hemodynamic deterioration, which occurred in a substantial 39% of cases, observed Petr Ostadal, MD, PhD, when presenting the results at the American Heart Association scientific sessions.

Dr. Ostadal of Na Homolce Hospital, Prague, is also first author on the published report of the study, called Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock (ECMO-CS), which was published the same day in Circulation.

The trial makes a firm case for preferring the conservative initial approach over routine early ECMO in the kind of patients it entered, Larry A. Allen, MD, MHS, University of Coloradoat Denver, Aurora, told this news organization.

More than 60% of the trial’s 117 patients had shock secondary to an acute coronary syndrome; another 23% were in heart failure decompensation.

A preference for the conservative initial approach would be welcome, he said. The early aggressive ECMO approach is resource intensive and carries some important risks, such as stroke or coagulopathy, said Dr. Allen, who is not connected with ECMO-CS. Yet it is increasingly the go-to approach in such patients, based primarily on observational data.

Although early ECMO apparently didn’t benefit patients in this study in their specific stage of cardiogenic shock, Dr. Allen observed, it would presumably help some, but identifying them in practice presents challenges. “Defining where people are in the spectrum of early versus middle versus late cardiogenic shock is actually very tricky.”

It will therefore be important, he said, to identify ways to predict which conservatively managed patients do well with the strategy, and which are most at risk for hemodynamic deterioration and for whom ECMO should be readily available.

“I think part of what ECMO-CS tells us is that, if a patient is stable on intravenous inotropic and vasopressor support, you can defer ECMO while you’re thinking about the patient – about their larger context and the right medical decision-making for them.”

The trial randomly assigned 122 patients with rapidly deteriorating or severe cardiogenic shock to the immediate-ECMO or the conservative strategy at four centers in the Czech Republic. The 117 patients for whom informed consent could be obtained were included in the analysis, 58 and 59 patients, respectively. Their mean age was about 65 years and three-fourths were male.

The primary endpoint, the only endpoint for which the study was powered, consisted of death from any cause, resuscitated circulatory arrest, or use of a different form of mechanical circulatory support (MCS) by 30 days.

It occurred in 63.8% of patients assigned to immediate ECMO and 71.2% of those in the conservative strategy group, for a hazard ratio of 0.72 (95% confidence interval, 0.46-1.12; P = .21).

As individual endpoints, rates of death from any cause and resuscitated arrest did not significantly differ between the groups, but conservatively managed patients more often used another form of MCS. The HRs were 1.11 (95% CI, 0.66-1.87) for death from any cause, 0.79 (95% CI, 0.27-2.28) for resuscitated cardiac arrest, and 0.38 (95% CI, 0.18-0.79) for use of another MCS device.

The rates for serious adverse events – including bleeding, ischemia, stroke, pneumonia, or sepsis – were similar at 60.3% in the early-ECMO group and 61% in group with conservative initial management, Dr. Ostadal reported.

Other than the 23 patients in the conservative initial strategy group who went on to receive ECMO (1.9 days after randomization, on average), 1 went on to undergo implantation with a HeartMate (Abbott) ventricular assist device and 3 received an Impella pump (Abiomed).

Six patients in the early-ECMO group were already receiving intra-aortic balloon pump (IABP) support at randomization, two underwent temporary implantation with a Centrimag device (Abbott), and three went on to receive a HeartMate device, the published report notes.

ECMO is the optimal first choice for MCS in such patients with cardiogenic shock who need a circulatory support device, especially because it also oxygenates the blood, Dr. Ostadal told this news organization.

But ECMO doesn’t help with ventricular unloading. Indeed, it can sometimes reduce ventricular preload, especially if right-heart pressures are low. So MCS devices that unload the ventricle, typically an IABP, can complement ECMO.

Dr. Ostadal speculates, however, that there may be a better pairing option. “Impella plus ECMO, I think, is the combination which has a future,” he said, for patients in cardiogenic shock who need a short-term percutaneous hemodynamic support device. Impella “supports the whole circulation” and unloads the left ventricle.

“A balloon pump in combination with ECMO is still not a bad choice. It’s very cheap in comparison with Impella.” But in his opinion, Dr. Ostadal said, “The combination of Impella plus ECMO is more efficient from a hemodynamic point of view.”

As the published report notes, ongoing randomized trials looking at ECMO plus other MCS devices in cardiogenic shock include ECLS-SHOCK, with a projected enrollment of 420 patients, and EURO-SHOCK, aiming for a similar number of patients; both compare routine ECMO to conservative management.

In addition, ANCHOR, in which ECMO is combined with IABP, and DanShock, which looks at early use of Impella rather than ECMO, are enrolling patients with shock secondary to acute coronary syndromes.

Dr. Ostadal disclosed consulting for Getinge, Edwards, Medtronic, Biomedica, and Xenios/Fresenius, and receiving research support from Xenios/Fresenius. Dr. Allen disclosed modest or significant relationships with ACI Clinical, Novartis, UpToDate, Boston Scientific, and Cytokinetics.

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