Federal Practitioner

The risk of arterial and venous thrombosis in patients with COVID-19 has been a major issue throughout the pandemic, and how best to manage this risk is the subject of a new review article.

The article, by Gregory Dr. Piazza, MD, and David A. Morrow, MD, Brigham and Women’s Hospital, Boston, was published online in JAMA on Nov. 23.

“Basically we’re saying: ‘Be proactive about prevention,’” Dr. Piazza told this news organization.

There is growing recognition among those on the frontline that there is an increased risk of thrombosis in COVID-19 patients, Dr. Piazza said. The risk is highest in patients in the intensive care unit, but the risk is also increased in patients hospitalized with COVID-19, even those not in ICU.

“We don’t really know what the risk is in nonhospitalized COVID-19 patients, but we think it’s much lower than in those who are hospitalized,” he said. “We are waiting for data on the optimal way of managing this increased risk of thrombosis in COVID patients, but for the time being, we believe a systematic way of addressing this risk is best, with every patient hospitalized with COVID-19 receiving some type of thromboprophylaxis. This would mainly be with anticoagulation, but in patients in whom anticoagulation is contraindicated, then mechanical methods could be used, such as pneumatic compression boots or compression stockings.”

The authors report thrombotic complication rates of 2.6% in noncritically ill hospitalized patients with COVID-19 and 35.3% in critically ill patients from a recent U.S. registry study.

Autopsy findings of microthrombi in multiple organ systems, including the lungs, heart, and kidneys, suggest that thrombosis may contribute to multisystem organ dysfunction in severe COVID-19, they note. Although the pathophysiology is not fully defined, prothrombotic abnormalities have been identified in patients with COVID-19, including elevated levels of D-dimer, fibrinogen, and factor VIII, they add.

“There are several major questions about which COVID-19 patients to treat with thromboprophylaxis, how to treat them in term of levels of anticoagulation, and there are many ongoing clinical trials to try and answer these questions,” Dr. Piazza commented. “We need results from these randomized trials to provide a better compass for COVID-19 patients at risk of clotting.”

At present, clinicians can follow two different sets of guidelines on the issue, one from the American College of Chest Physicians and the other from the International Society on Thrombosis and Hemostasis, the authors note.

“The ACCP guidelines are very conservative and basically follow the evidence base for medical patients, while the ISTH guidelines are more aggressive and recommend increased levels of anticoagulation in both ICU and hospitalized non-ICU patients and also extend prophylaxis after discharge,” Dr. Piazza said.

“There is quite a difference between the two sets of guidelines, which can be a point of confusion,” he added.

Dr. Piazza notes that at his center every hospitalized COVID patient who does not have a contraindication to anticoagulation receives a standard prophylactic dose of a once-daily low-molecular-weight heparin (for example, enoxaparin 40 mg). A once-daily product is used to minimize infection risk to staff.

While all COVID patients in the ICU should automatically receive some anticoagulation, the optimal dose is an area of active investigation, he explained. “There were several early reports of ICU patients developing blood clots despite receiving standard thromboprophylaxis so perhaps we need to use higher doses. There are trials underway looking at this, and we would advise enrolling patients into these trials.”

If patients can’t be enrolled into trials, and clinicians feel higher anticoagulation levels are needed, Dr. Piazza advises following the ISTH guidance, which allows an intermediate dose of low-molecular-weight heparin (up to 1 mg/kg enoxaparin).

“Some experts are suggesting even higher doses may be needed in some ICU patients, such as the full therapeutic dose, but I worry about the risk of bleeding with such a strategy,” he said.

Dr. Piazza says they do not routinely give anticoagulation after discharge, but if this is desired then patients could be switched to an oral agent, and some of the direct-acting oral anticoagulants are approved for prophylactic use in medically ill patients.

Dr. Piazza points out that whether thromboprophylaxis should be used for nonhospitalized COVID patients who have risk factors for clotting such as a prior history of thrombosis or obesity is a pressing question, and he encourages clinicians to enroll these patients in clinical trials evaluating this issue, such as the PREVENT-HD trial.

“If they can’t enroll patents in a trial, then they have to make a decision whether the patient is high-enough risk to justify off-label use of anticoagulant. There is a case to be made for this, but there is no evidence for or against such action at present,” he noted.

At this time, neither the ISTH nor ACCP recommend measuring D-dimer to screen for venous thromboembolism or to determine intensity of prophylaxis or treatment, the authors note.

“Ongoing investigation will determine optimal preventive regimens in COVID-19 in the intensive care unit, at hospital discharge, and in nonhospitalized patients at high risk for thrombosis,” they conclude.

Dr. Piazza reported grants from Bayer, Bristol Myers Squibb, Boston Scientific, Janssen, and Portola, and personal fees from Agile, Amgen, Pfizer, and the Prairie Education and Research Cooperative outside the submitted work. Dr. Morrow reported grants from Abbott Laboratories, Amgen, Anthos Therapeutics, Esai, GlaxoSmithKline, Takeda, and The Medicines Company; grants and personal fees from AstraZeneca, Merck, Novartis, and Roche Diagnostics; and personal fees from Bayer Pharma and InCarda outside the submitted work.

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

The risk of arterial and venous thrombosis in patients with COVID-19 has been a major issue throughout the pandemic, and how best to manage this risk is the subject of a new review article.

The article, by Gregory Dr. Piazza, MD, and David A. Morrow, MD, Brigham and Women’s Hospital, Boston, was published online in JAMA on Nov. 23.

“Basically we’re saying: ‘Be proactive about prevention,’” Dr. Piazza told this news organization.

There is growing recognition among those on the frontline that there is an increased risk of thrombosis in COVID-19 patients, Dr. Piazza said. The risk is highest in patients in the intensive care unit, but the risk is also increased in patients hospitalized with COVID-19, even those not in ICU.

“We don’t really know what the risk is in nonhospitalized COVID-19 patients, but we think it’s much lower than in those who are hospitalized,” he said. “We are waiting for data on the optimal way of managing this increased risk of thrombosis in COVID patients, but for the time being, we believe a systematic way of addressing this risk is best, with every patient hospitalized with COVID-19 receiving some type of thromboprophylaxis. This would mainly be with anticoagulation, but in patients in whom anticoagulation is contraindicated, then mechanical methods could be used, such as pneumatic compression boots or compression stockings.”

The authors report thrombotic complication rates of 2.6% in noncritically ill hospitalized patients with COVID-19 and 35.3% in critically ill patients from a recent U.S. registry study.

Autopsy findings of microthrombi in multiple organ systems, including the lungs, heart, and kidneys, suggest that thrombosis may contribute to multisystem organ dysfunction in severe COVID-19, they note. Although the pathophysiology is not fully defined, prothrombotic abnormalities have been identified in patients with COVID-19, including elevated levels of D-dimer, fibrinogen, and factor VIII, they add.

“There are several major questions about which COVID-19 patients to treat with thromboprophylaxis, how to treat them in term of levels of anticoagulation, and there are many ongoing clinical trials to try and answer these questions,” Dr. Piazza commented. “We need results from these randomized trials to provide a better compass for COVID-19 patients at risk of clotting.”

At present, clinicians can follow two different sets of guidelines on the issue, one from the American College of Chest Physicians and the other from the International Society on Thrombosis and Hemostasis, the authors note.

“The ACCP guidelines are very conservative and basically follow the evidence base for medical patients, while the ISTH guidelines are more aggressive and recommend increased levels of anticoagulation in both ICU and hospitalized non-ICU patients and also extend prophylaxis after discharge,” Dr. Piazza said.

“There is quite a difference between the two sets of guidelines, which can be a point of confusion,” he added.

Dr. Piazza notes that at his center every hospitalized COVID patient who does not have a contraindication to anticoagulation receives a standard prophylactic dose of a once-daily low-molecular-weight heparin (for example, enoxaparin 40 mg). A once-daily product is used to minimize infection risk to staff.

While all COVID patients in the ICU should automatically receive some anticoagulation, the optimal dose is an area of active investigation, he explained. “There were several early reports of ICU patients developing blood clots despite receiving standard thromboprophylaxis so perhaps we need to use higher doses. There are trials underway looking at this, and we would advise enrolling patients into these trials.”

If patients can’t be enrolled into trials, and clinicians feel higher anticoagulation levels are needed, Dr. Piazza advises following the ISTH guidance, which allows an intermediate dose of low-molecular-weight heparin (up to 1 mg/kg enoxaparin).

“Some experts are suggesting even higher doses may be needed in some ICU patients, such as the full therapeutic dose, but I worry about the risk of bleeding with such a strategy,” he said.

Dr. Piazza says they do not routinely give anticoagulation after discharge, but if this is desired then patients could be switched to an oral agent, and some of the direct-acting oral anticoagulants are approved for prophylactic use in medically ill patients.

Dr. Piazza points out that whether thromboprophylaxis should be used for nonhospitalized COVID patients who have risk factors for clotting such as a prior history of thrombosis or obesity is a pressing question, and he encourages clinicians to enroll these patients in clinical trials evaluating this issue, such as the PREVENT-HD trial.

“If they can’t enroll patents in a trial, then they have to make a decision whether the patient is high-enough risk to justify off-label use of anticoagulant. There is a case to be made for this, but there is no evidence for or against such action at present,” he noted.

At this time, neither the ISTH nor ACCP recommend measuring D-dimer to screen for venous thromboembolism or to determine intensity of prophylaxis or treatment, the authors note.

“Ongoing investigation will determine optimal preventive regimens in COVID-19 in the intensive care unit, at hospital discharge, and in nonhospitalized patients at high risk for thrombosis,” they conclude.

Dr. Piazza reported grants from Bayer, Bristol Myers Squibb, Boston Scientific, Janssen, and Portola, and personal fees from Agile, Amgen, Pfizer, and the Prairie Education and Research Cooperative outside the submitted work. Dr. Morrow reported grants from Abbott Laboratories, Amgen, Anthos Therapeutics, Esai, GlaxoSmithKline, Takeda, and The Medicines Company; grants and personal fees from AstraZeneca, Merck, Novartis, and Roche Diagnostics; and personal fees from Bayer Pharma and InCarda outside the submitted work.

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

The risk of arterial and venous thrombosis in patients with COVID-19 has been a major issue throughout the pandemic, and how best to manage this risk is the subject of a new review article.

The article, by Gregory Dr. Piazza, MD, and David A. Morrow, MD, Brigham and Women’s Hospital, Boston, was published online in JAMA on Nov. 23.

“Basically we’re saying: ‘Be proactive about prevention,’” Dr. Piazza told this news organization.

There is growing recognition among those on the frontline that there is an increased risk of thrombosis in COVID-19 patients, Dr. Piazza said. The risk is highest in patients in the intensive care unit, but the risk is also increased in patients hospitalized with COVID-19, even those not in ICU.

“We don’t really know what the risk is in nonhospitalized COVID-19 patients, but we think it’s much lower than in those who are hospitalized,” he said. “We are waiting for data on the optimal way of managing this increased risk of thrombosis in COVID patients, but for the time being, we believe a systematic way of addressing this risk is best, with every patient hospitalized with COVID-19 receiving some type of thromboprophylaxis. This would mainly be with anticoagulation, but in patients in whom anticoagulation is contraindicated, then mechanical methods could be used, such as pneumatic compression boots or compression stockings.”

The authors report thrombotic complication rates of 2.6% in noncritically ill hospitalized patients with COVID-19 and 35.3% in critically ill patients from a recent U.S. registry study.

Autopsy findings of microthrombi in multiple organ systems, including the lungs, heart, and kidneys, suggest that thrombosis may contribute to multisystem organ dysfunction in severe COVID-19, they note. Although the pathophysiology is not fully defined, prothrombotic abnormalities have been identified in patients with COVID-19, including elevated levels of D-dimer, fibrinogen, and factor VIII, they add.

“There are several major questions about which COVID-19 patients to treat with thromboprophylaxis, how to treat them in term of levels of anticoagulation, and there are many ongoing clinical trials to try and answer these questions,” Dr. Piazza commented. “We need results from these randomized trials to provide a better compass for COVID-19 patients at risk of clotting.”

At present, clinicians can follow two different sets of guidelines on the issue, one from the American College of Chest Physicians and the other from the International Society on Thrombosis and Hemostasis, the authors note.

“The ACCP guidelines are very conservative and basically follow the evidence base for medical patients, while the ISTH guidelines are more aggressive and recommend increased levels of anticoagulation in both ICU and hospitalized non-ICU patients and also extend prophylaxis after discharge,” Dr. Piazza said.

“There is quite a difference between the two sets of guidelines, which can be a point of confusion,” he added.

Dr. Piazza notes that at his center every hospitalized COVID patient who does not have a contraindication to anticoagulation receives a standard prophylactic dose of a once-daily low-molecular-weight heparin (for example, enoxaparin 40 mg). A once-daily product is used to minimize infection risk to staff.

While all COVID patients in the ICU should automatically receive some anticoagulation, the optimal dose is an area of active investigation, he explained. “There were several early reports of ICU patients developing blood clots despite receiving standard thromboprophylaxis so perhaps we need to use higher doses. There are trials underway looking at this, and we would advise enrolling patients into these trials.”

If patients can’t be enrolled into trials, and clinicians feel higher anticoagulation levels are needed, Dr. Piazza advises following the ISTH guidance, which allows an intermediate dose of low-molecular-weight heparin (up to 1 mg/kg enoxaparin).

“Some experts are suggesting even higher doses may be needed in some ICU patients, such as the full therapeutic dose, but I worry about the risk of bleeding with such a strategy,” he said.

Dr. Piazza says they do not routinely give anticoagulation after discharge, but if this is desired then patients could be switched to an oral agent, and some of the direct-acting oral anticoagulants are approved for prophylactic use in medically ill patients.

Dr. Piazza points out that whether thromboprophylaxis should be used for nonhospitalized COVID patients who have risk factors for clotting such as a prior history of thrombosis or obesity is a pressing question, and he encourages clinicians to enroll these patients in clinical trials evaluating this issue, such as the PREVENT-HD trial.

“If they can’t enroll patents in a trial, then they have to make a decision whether the patient is high-enough risk to justify off-label use of anticoagulant. There is a case to be made for this, but there is no evidence for or against such action at present,” he noted.

At this time, neither the ISTH nor ACCP recommend measuring D-dimer to screen for venous thromboembolism or to determine intensity of prophylaxis or treatment, the authors note.

“Ongoing investigation will determine optimal preventive regimens in COVID-19 in the intensive care unit, at hospital discharge, and in nonhospitalized patients at high risk for thrombosis,” they conclude.

Dr. Piazza reported grants from Bayer, Bristol Myers Squibb, Boston Scientific, Janssen, and Portola, and personal fees from Agile, Amgen, Pfizer, and the Prairie Education and Research Cooperative outside the submitted work. Dr. Morrow reported grants from Abbott Laboratories, Amgen, Anthos Therapeutics, Esai, GlaxoSmithKline, Takeda, and The Medicines Company; grants and personal fees from AstraZeneca, Merck, Novartis, and Roche Diagnostics; and personal fees from Bayer Pharma and InCarda outside the submitted work.

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

The 2020 Medical Specialties Matching Program (MSMP), a division of the National Resident Matching Program, matched a record number of applicants to subspecialty training programs for positions beginning in 2021, the NRMP reported.

“Specifically, the 2020 MSMP included 6,847 applicants submitting certified rank order lists (an 8.9% increase), 2042 programs submitting certified rank order lists (a 4.3% increase), 5,734 positions (a 2.8% increase), and 5,208 positions filled (a 6.1% increase),” according to a news release.

The MSMP now includes 14 internal medicine subspecialties and four sub-subspecialties. The MSMP offered 5,734 positions this year, and 5,208 (90.8%) were successfully filled. That represents an increase of almost 3 percentage points, compared with last year’s results.

Among those subspecialties that offered 30 positions or more, the most competitive were allergy and immunology, cardiovascular disease, clinical cardiac electrophysiology, gastroenterology, hematology and oncology, and pulmonary/critical care. Each of those filled at least 95% of available slots. More than half of the positions were filled by U.S. MDs.

By contrast, the least competitive subspecialties were geriatric medicine and nephrology. Programs in these two fields filled less than 75% of positions offered. Less than 45% were filled by U.S. MDs.

More than 76% of the 6,847 applicants who submitted rank order lists (5,208) matched into residency programs.

The number of U.S. MDs in this category increased nearly 7% over last year, with a total of 2,935. The number of DO graduates increased as well, with a total of 855, which was 9.6% more than the previous year.

More U.S. citizens who graduated from international medical schools matched this year as well; 1,087 placed into subspecialty residency, a 9% increase, compared with last year.

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

The 2020 Medical Specialties Matching Program (MSMP), a division of the National Resident Matching Program, matched a record number of applicants to subspecialty training programs for positions beginning in 2021, the NRMP reported.

“Specifically, the 2020 MSMP included 6,847 applicants submitting certified rank order lists (an 8.9% increase), 2042 programs submitting certified rank order lists (a 4.3% increase), 5,734 positions (a 2.8% increase), and 5,208 positions filled (a 6.1% increase),” according to a news release.

The MSMP now includes 14 internal medicine subspecialties and four sub-subspecialties. The MSMP offered 5,734 positions this year, and 5,208 (90.8%) were successfully filled. That represents an increase of almost 3 percentage points, compared with last year’s results.

Among those subspecialties that offered 30 positions or more, the most competitive were allergy and immunology, cardiovascular disease, clinical cardiac electrophysiology, gastroenterology, hematology and oncology, and pulmonary/critical care. Each of those filled at least 95% of available slots. More than half of the positions were filled by U.S. MDs.

By contrast, the least competitive subspecialties were geriatric medicine and nephrology. Programs in these two fields filled less than 75% of positions offered. Less than 45% were filled by U.S. MDs.

More than 76% of the 6,847 applicants who submitted rank order lists (5,208) matched into residency programs.

The number of U.S. MDs in this category increased nearly 7% over last year, with a total of 2,935. The number of DO graduates increased as well, with a total of 855, which was 9.6% more than the previous year.

More U.S. citizens who graduated from international medical schools matched this year as well; 1,087 placed into subspecialty residency, a 9% increase, compared with last year.

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

The 2020 Medical Specialties Matching Program (MSMP), a division of the National Resident Matching Program, matched a record number of applicants to subspecialty training programs for positions beginning in 2021, the NRMP reported.

“Specifically, the 2020 MSMP included 6,847 applicants submitting certified rank order lists (an 8.9% increase), 2042 programs submitting certified rank order lists (a 4.3% increase), 5,734 positions (a 2.8% increase), and 5,208 positions filled (a 6.1% increase),” according to a news release.

The MSMP now includes 14 internal medicine subspecialties and four sub-subspecialties. The MSMP offered 5,734 positions this year, and 5,208 (90.8%) were successfully filled. That represents an increase of almost 3 percentage points, compared with last year’s results.

Among those subspecialties that offered 30 positions or more, the most competitive were allergy and immunology, cardiovascular disease, clinical cardiac electrophysiology, gastroenterology, hematology and oncology, and pulmonary/critical care. Each of those filled at least 95% of available slots. More than half of the positions were filled by U.S. MDs.

By contrast, the least competitive subspecialties were geriatric medicine and nephrology. Programs in these two fields filled less than 75% of positions offered. Less than 45% were filled by U.S. MDs.

More than 76% of the 6,847 applicants who submitted rank order lists (5,208) matched into residency programs.

The number of U.S. MDs in this category increased nearly 7% over last year, with a total of 2,935. The number of DO graduates increased as well, with a total of 855, which was 9.6% more than the previous year.

More U.S. citizens who graduated from international medical schools matched this year as well; 1,087 placed into subspecialty residency, a 9% increase, compared with last year.

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

There has been a sharp increase in overdose-related cardiac arrests in the United States during the COVID-19 pandemic, a new analysis shows.

Overall rates in 2020 were elevated above the baseline from 2018 and 2019 by about 50%, the data show.

“Our results suggest that overdoses may be strongly on the rise in 2020, and efforts to combat the COVID-19 pandemic have not been effective at reducing overdoses,” Joseph Friedman, MPH, MD/PhD student, medical scientist training program, University of California, Los Angeles, said in an interview.

“We need to invest heavily in substance use treatment, harm reduction, and the structural drivers of overdose as core elements of the COVID-19 response,” said Mr. Friedman, who coauthored the study with UCLA colleague David Schriger, MD, MPH, and Leo Beletsky, JD, MPH, Northeastern University, Boston.

The study was published as a research letter Dec. 3 in JAMA Psychiatry.
 

Social isolation a key driver

Emergency medical services (EMS) data are available in near real time, providing a novel source of up-to-date information to monitor epidemiological shifts during the COVID-19 pandemic.

For the study, the researchers leveraged data from the National EMS Information System, a large registry of more than 10,000 EMS agencies in 47 states that represent over 80% of all EMS calls nationally in 2020. They used the data to track shifts in overdose-related cardiac arrests observed by EMS.

They found clear evidence of a large-scale uptick in overdose-related deaths during the COVID-19 pandemic.

The overall rate of overdose-related cardiac arrests in 2020 was about 50% higher than trends observed during 2018 and 2019, including a maximum peak of 123% above baseline reached in early May.

All overdose-related incidents (fatal and nonfatal) were elevated in 2020, by about 17% above baseline. However, there were larger increases in fatal overdose-related incidents, compared to all incidents, which may suggest a rising case fatality rate, the authors noted.

The observed trends line up in time with reductions in mobility (a metric of social interaction), as measured using cell phone data, they wrote.

“Many of the trends predicted by experts at the beginning of the pandemic could cause these shifts. Increases in social isolation likely play an important role, as people using [drugs] alone are less likely to receive help when they need it. Also shifts in the drug supply, and reduced access to healthcare and treatment,” said Mr. Friedman.

“We need to undertake short- and long-term strategies to combat the rising tide of overdose mortality in the United States,” he added.

In the short term, Mr. Friedman suggested reducing financial and logistical barriers for accessing a safe opioid supply. Such measures include allowing pharmacies to dispense methadone, allowing all physicians to prescribe buprenorphine without a special waiver, and releasing emergency funds to make these medications universally affordable.

“In the longer term, we should acknowledge that overdose is a symptom of structural problems in the U.S. We need to invest in making employment, housing, education, and health care accessible to all to address the upstream drivers of overdose,” he added.

The study had no commercial funding. The authors disclosed no relevant financial relationships.

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

There has been a sharp increase in overdose-related cardiac arrests in the United States during the COVID-19 pandemic, a new analysis shows.

Overall rates in 2020 were elevated above the baseline from 2018 and 2019 by about 50%, the data show.

“Our results suggest that overdoses may be strongly on the rise in 2020, and efforts to combat the COVID-19 pandemic have not been effective at reducing overdoses,” Joseph Friedman, MPH, MD/PhD student, medical scientist training program, University of California, Los Angeles, said in an interview.

“We need to invest heavily in substance use treatment, harm reduction, and the structural drivers of overdose as core elements of the COVID-19 response,” said Mr. Friedman, who coauthored the study with UCLA colleague David Schriger, MD, MPH, and Leo Beletsky, JD, MPH, Northeastern University, Boston.

The study was published as a research letter Dec. 3 in JAMA Psychiatry.
 

Social isolation a key driver

Emergency medical services (EMS) data are available in near real time, providing a novel source of up-to-date information to monitor epidemiological shifts during the COVID-19 pandemic.

For the study, the researchers leveraged data from the National EMS Information System, a large registry of more than 10,000 EMS agencies in 47 states that represent over 80% of all EMS calls nationally in 2020. They used the data to track shifts in overdose-related cardiac arrests observed by EMS.

They found clear evidence of a large-scale uptick in overdose-related deaths during the COVID-19 pandemic.

The overall rate of overdose-related cardiac arrests in 2020 was about 50% higher than trends observed during 2018 and 2019, including a maximum peak of 123% above baseline reached in early May.

All overdose-related incidents (fatal and nonfatal) were elevated in 2020, by about 17% above baseline. However, there were larger increases in fatal overdose-related incidents, compared to all incidents, which may suggest a rising case fatality rate, the authors noted.

The observed trends line up in time with reductions in mobility (a metric of social interaction), as measured using cell phone data, they wrote.

“Many of the trends predicted by experts at the beginning of the pandemic could cause these shifts. Increases in social isolation likely play an important role, as people using [drugs] alone are less likely to receive help when they need it. Also shifts in the drug supply, and reduced access to healthcare and treatment,” said Mr. Friedman.

“We need to undertake short- and long-term strategies to combat the rising tide of overdose mortality in the United States,” he added.

In the short term, Mr. Friedman suggested reducing financial and logistical barriers for accessing a safe opioid supply. Such measures include allowing pharmacies to dispense methadone, allowing all physicians to prescribe buprenorphine without a special waiver, and releasing emergency funds to make these medications universally affordable.

“In the longer term, we should acknowledge that overdose is a symptom of structural problems in the U.S. We need to invest in making employment, housing, education, and health care accessible to all to address the upstream drivers of overdose,” he added.

The study had no commercial funding. The authors disclosed no relevant financial relationships.

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

There has been a sharp increase in overdose-related cardiac arrests in the United States during the COVID-19 pandemic, a new analysis shows.

Overall rates in 2020 were elevated above the baseline from 2018 and 2019 by about 50%, the data show.

“Our results suggest that overdoses may be strongly on the rise in 2020, and efforts to combat the COVID-19 pandemic have not been effective at reducing overdoses,” Joseph Friedman, MPH, MD/PhD student, medical scientist training program, University of California, Los Angeles, said in an interview.

“We need to invest heavily in substance use treatment, harm reduction, and the structural drivers of overdose as core elements of the COVID-19 response,” said Mr. Friedman, who coauthored the study with UCLA colleague David Schriger, MD, MPH, and Leo Beletsky, JD, MPH, Northeastern University, Boston.

The study was published as a research letter Dec. 3 in JAMA Psychiatry.
 

Social isolation a key driver

Emergency medical services (EMS) data are available in near real time, providing a novel source of up-to-date information to monitor epidemiological shifts during the COVID-19 pandemic.

For the study, the researchers leveraged data from the National EMS Information System, a large registry of more than 10,000 EMS agencies in 47 states that represent over 80% of all EMS calls nationally in 2020. They used the data to track shifts in overdose-related cardiac arrests observed by EMS.

They found clear evidence of a large-scale uptick in overdose-related deaths during the COVID-19 pandemic.

The overall rate of overdose-related cardiac arrests in 2020 was about 50% higher than trends observed during 2018 and 2019, including a maximum peak of 123% above baseline reached in early May.

All overdose-related incidents (fatal and nonfatal) were elevated in 2020, by about 17% above baseline. However, there were larger increases in fatal overdose-related incidents, compared to all incidents, which may suggest a rising case fatality rate, the authors noted.

The observed trends line up in time with reductions in mobility (a metric of social interaction), as measured using cell phone data, they wrote.

“Many of the trends predicted by experts at the beginning of the pandemic could cause these shifts. Increases in social isolation likely play an important role, as people using [drugs] alone are less likely to receive help when they need it. Also shifts in the drug supply, and reduced access to healthcare and treatment,” said Mr. Friedman.

“We need to undertake short- and long-term strategies to combat the rising tide of overdose mortality in the United States,” he added.

In the short term, Mr. Friedman suggested reducing financial and logistical barriers for accessing a safe opioid supply. Such measures include allowing pharmacies to dispense methadone, allowing all physicians to prescribe buprenorphine without a special waiver, and releasing emergency funds to make these medications universally affordable.

“In the longer term, we should acknowledge that overdose is a symptom of structural problems in the U.S. We need to invest in making employment, housing, education, and health care accessible to all to address the upstream drivers of overdose,” he added.

The study had no commercial funding. The authors disclosed no relevant financial relationships.

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

There is “compelling” evidence of the harmful effects of alcohol on the brain. The greatest risk occurs during three periods of life that are marked by dynamic brain changes, say researchers from Australia and the United Kingdom.

alenkadr/Thinkstock

The three periods are:

• Gestation (conception to birth), which is characterized by extensive production, migration, and differentiation of neurons, as well as substantial apoptosis.
• Later adolescence (aged 15-19 years), a period marked by synaptic pruning and increased axonal myelination.
• Older adulthood (aged 65 and beyond), a period associated with brain atrophy. Changes accelerate after age 65, largely driven by decreases in neuron size and reductions in the number of dendritic spines and synapses.

These changes in neurocircuitry could increase sensitivity to the neurotoxic effects of alcohol, Louise Mewton, PhD, of the Center for Healthy Brain Aging, University of New South Wales, Sydney, and colleagues said.

“A life course perspective on brain health supports the formulation of policy and public health interventions to reduce alcohol use and misuse at all ages,” they wrote in an editorial published online Dec. 4 in The BMJ.
 

Worrisome trends

Research has shown that globally about 10% of pregnant women drink alcohol. In European countries, the rates are much higher than the global average.

Heavy drinking during gestation can cause fetal alcohol spectrum disorder, which is associated with widespread reductions in brain volume and cognitive impairment.

Even low or moderate alcohol consumption during pregnancy is significantly associated with poorer psychological and behavioral outcomes in children, the investigators noted.

In adolescence, more than 20% of 15- to 19-year-olds in European and other high-income countries report at least occasional binge drinking, which is linked to reduced brain volume, poorer white matter development, and deficits in a range of cognitive functions, they added.

In a recent study of older adults, alcohol use disorders emerged as one of the strongest modifiable risk factors for dementia (particularly early-onset dementia), compared with other established risk factors such as high blood pressure and smoking.

Alcohol use disorders are relatively rare in older adults, but even moderate drinking during midlife has been linked to “small but significant” brain volume loss, the authors said.

Dr. Mewton and colleagues said demographic trends may compound the effect of alcohol use on brain health.

They noted that women are now just as likely as men to drink alcohol and suffer alcohol-related problems. Global consumption is forecast to increase further in the next decade.

Although the effects of the COVID-19 pandemic on alcohol intake and related harms remain unclear, alcohol use has increased in the long term after other major public health crises, they added.

Given the data, Dr. Mewton and colleagues called for “an integrated approach” to reducing the harms of alcohol intake at all ages.

“Population-based interventions such as guidelines on low-risk drinking, alcohol pricing policies, and lower drink driving limits need to be accompanied by the development of training and care pathways that consider the human brain at risk throughout life,” they concluded.

The authors have disclosed no relevant financial relationships.
 

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

There is “compelling” evidence of the harmful effects of alcohol on the brain. The greatest risk occurs during three periods of life that are marked by dynamic brain changes, say researchers from Australia and the United Kingdom.

alenkadr/Thinkstock

The three periods are:

• Gestation (conception to birth), which is characterized by extensive production, migration, and differentiation of neurons, as well as substantial apoptosis.
• Later adolescence (aged 15-19 years), a period marked by synaptic pruning and increased axonal myelination.
• Older adulthood (aged 65 and beyond), a period associated with brain atrophy. Changes accelerate after age 65, largely driven by decreases in neuron size and reductions in the number of dendritic spines and synapses.

These changes in neurocircuitry could increase sensitivity to the neurotoxic effects of alcohol, Louise Mewton, PhD, of the Center for Healthy Brain Aging, University of New South Wales, Sydney, and colleagues said.

“A life course perspective on brain health supports the formulation of policy and public health interventions to reduce alcohol use and misuse at all ages,” they wrote in an editorial published online Dec. 4 in The BMJ.
 

Worrisome trends

Research has shown that globally about 10% of pregnant women drink alcohol. In European countries, the rates are much higher than the global average.

Heavy drinking during gestation can cause fetal alcohol spectrum disorder, which is associated with widespread reductions in brain volume and cognitive impairment.

Even low or moderate alcohol consumption during pregnancy is significantly associated with poorer psychological and behavioral outcomes in children, the investigators noted.

In adolescence, more than 20% of 15- to 19-year-olds in European and other high-income countries report at least occasional binge drinking, which is linked to reduced brain volume, poorer white matter development, and deficits in a range of cognitive functions, they added.

In a recent study of older adults, alcohol use disorders emerged as one of the strongest modifiable risk factors for dementia (particularly early-onset dementia), compared with other established risk factors such as high blood pressure and smoking.

Alcohol use disorders are relatively rare in older adults, but even moderate drinking during midlife has been linked to “small but significant” brain volume loss, the authors said.

Dr. Mewton and colleagues said demographic trends may compound the effect of alcohol use on brain health.

They noted that women are now just as likely as men to drink alcohol and suffer alcohol-related problems. Global consumption is forecast to increase further in the next decade.

Although the effects of the COVID-19 pandemic on alcohol intake and related harms remain unclear, alcohol use has increased in the long term after other major public health crises, they added.

Given the data, Dr. Mewton and colleagues called for “an integrated approach” to reducing the harms of alcohol intake at all ages.

“Population-based interventions such as guidelines on low-risk drinking, alcohol pricing policies, and lower drink driving limits need to be accompanied by the development of training and care pathways that consider the human brain at risk throughout life,” they concluded.

The authors have disclosed no relevant financial relationships.
 

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

There is “compelling” evidence of the harmful effects of alcohol on the brain. The greatest risk occurs during three periods of life that are marked by dynamic brain changes, say researchers from Australia and the United Kingdom.

alenkadr/Thinkstock

The three periods are:

• Gestation (conception to birth), which is characterized by extensive production, migration, and differentiation of neurons, as well as substantial apoptosis.
• Later adolescence (aged 15-19 years), a period marked by synaptic pruning and increased axonal myelination.
• Older adulthood (aged 65 and beyond), a period associated with brain atrophy. Changes accelerate after age 65, largely driven by decreases in neuron size and reductions in the number of dendritic spines and synapses.

These changes in neurocircuitry could increase sensitivity to the neurotoxic effects of alcohol, Louise Mewton, PhD, of the Center for Healthy Brain Aging, University of New South Wales, Sydney, and colleagues said.

“A life course perspective on brain health supports the formulation of policy and public health interventions to reduce alcohol use and misuse at all ages,” they wrote in an editorial published online Dec. 4 in The BMJ.
 

Worrisome trends

Research has shown that globally about 10% of pregnant women drink alcohol. In European countries, the rates are much higher than the global average.

Heavy drinking during gestation can cause fetal alcohol spectrum disorder, which is associated with widespread reductions in brain volume and cognitive impairment.

Even low or moderate alcohol consumption during pregnancy is significantly associated with poorer psychological and behavioral outcomes in children, the investigators noted.

In adolescence, more than 20% of 15- to 19-year-olds in European and other high-income countries report at least occasional binge drinking, which is linked to reduced brain volume, poorer white matter development, and deficits in a range of cognitive functions, they added.

In a recent study of older adults, alcohol use disorders emerged as one of the strongest modifiable risk factors for dementia (particularly early-onset dementia), compared with other established risk factors such as high blood pressure and smoking.

Alcohol use disorders are relatively rare in older adults, but even moderate drinking during midlife has been linked to “small but significant” brain volume loss, the authors said.

Dr. Mewton and colleagues said demographic trends may compound the effect of alcohol use on brain health.

They noted that women are now just as likely as men to drink alcohol and suffer alcohol-related problems. Global consumption is forecast to increase further in the next decade.

Although the effects of the COVID-19 pandemic on alcohol intake and related harms remain unclear, alcohol use has increased in the long term after other major public health crises, they added.

Given the data, Dr. Mewton and colleagues called for “an integrated approach” to reducing the harms of alcohol intake at all ages.

“Population-based interventions such as guidelines on low-risk drinking, alcohol pricing policies, and lower drink driving limits need to be accompanied by the development of training and care pathways that consider the human brain at risk throughout life,” they concluded.

The authors have disclosed no relevant financial relationships.
 

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

President-elect Joe Biden has nominated California Attorney General Xavier Becerra to run the US Department of Health & Human Services (HHS) under his new administration, according to a statement from the Biden-Harris transition team.

Rich Pedroncelli/AP

If confirmed by the US Senate, Becerra will face the challenge of overseeing the federal agency charged with protecting the health of all Americans in the midst of the COVID-19 pandemic. At the time of the announcement, nearly 15 million Americans had tested positive for COVID-19 and more than 280,000 had died.

Becerra served 12 terms in Congress, representing the Los Angeles area. Although his public health experience is limited, he served on the Congressional Ways and Means Committee overseeing health-related issues. Becerra is known as an advocate for the health and well-being of women in particular.

The American College of Physicians, American Academy of Pediatrics, American College of Obstetricians & Gynecologists, American Academy of Family Physicians, and the American Psychiatric Association wrote a letter to Biden on December 3 urging him to select leaders with medical and healthcare expertise, in particular physicians.

“We believe that your administration and the country would be well-served by the appointment of qualified physicians to serve in key positions critical to advancing the health of our nation,” they wrote. “Therefore, our organizations, which represent more than 400,000 front-line physicians practicing in the United States, write to request that you identify and appoint physicians to healthcare leadership positions within your administration.”
 

Recent advocacy

Becerra has worked with Republican attorneys general to lobby HHS to increase access to remdesivir to treat people with COVID-19.

As attorney general, Becerra filed more than 100 lawsuits against the Trump administration. In November, he also represented more than 20 states in arguments supporting the Affordable Care Act before the Supreme Court.

On December 4, Becerra joined with attorneys general from 23 states and the District of Columbia opposing a proposed rule from the outgoing Trump administration. The rule would deregulate HHS and “sunset”many agency provisions before Trump leaves office next month.

Becerra will be the first Latino appointed as HHS secretary, which furthers Biden’s goal to create a diverse cabinet. Becerra has been attorney general of California since 2017, replacing Vice President-elect Kamala Harris when she became senator.

Biden’s choice of Becerra was unexpected, according to The New York Times, and he was not the only candidate. Speculation was that Biden initially considered Vivek Murthy, MD, later chosen as the next US surgeon general, as well New Mexico Gov. Michelle Lujan Grisham and Rhode Island Gov. Gina Raimondo.
 

A huge undertaking

As HHS secretary, Becerra would oversee a wide range of federal agencies, including the US Food and Drug Administration, the Centers for Disease Control and Prevention, the National Institutes of Health, and the Centers for Medicare & Medicaid Services.

The fiscal year 2021 budget proposed for HHS includes $94.5 billion in discretionary budget authority and $1.3 trillion in mandatory funding. Overall, HHS controls nearly one quarter of all federal expenditures and provides more grant money than all other federal agencies combined.

Becerra, 62, grew up in Sacramento, California. He was the first in his family to graduate from college. He received his undergraduate and law degrees from Stanford University.

This article first appeared on Medscape.com.

President-elect Joe Biden has nominated California Attorney General Xavier Becerra to run the US Department of Health & Human Services (HHS) under his new administration, according to a statement from the Biden-Harris transition team.

Rich Pedroncelli/AP

If confirmed by the US Senate, Becerra will face the challenge of overseeing the federal agency charged with protecting the health of all Americans in the midst of the COVID-19 pandemic. At the time of the announcement, nearly 15 million Americans had tested positive for COVID-19 and more than 280,000 had died.

Becerra served 12 terms in Congress, representing the Los Angeles area. Although his public health experience is limited, he served on the Congressional Ways and Means Committee overseeing health-related issues. Becerra is known as an advocate for the health and well-being of women in particular.

The American College of Physicians, American Academy of Pediatrics, American College of Obstetricians & Gynecologists, American Academy of Family Physicians, and the American Psychiatric Association wrote a letter to Biden on December 3 urging him to select leaders with medical and healthcare expertise, in particular physicians.

“We believe that your administration and the country would be well-served by the appointment of qualified physicians to serve in key positions critical to advancing the health of our nation,” they wrote. “Therefore, our organizations, which represent more than 400,000 front-line physicians practicing in the United States, write to request that you identify and appoint physicians to healthcare leadership positions within your administration.”
 

Recent advocacy

Becerra has worked with Republican attorneys general to lobby HHS to increase access to remdesivir to treat people with COVID-19.

As attorney general, Becerra filed more than 100 lawsuits against the Trump administration. In November, he also represented more than 20 states in arguments supporting the Affordable Care Act before the Supreme Court.

On December 4, Becerra joined with attorneys general from 23 states and the District of Columbia opposing a proposed rule from the outgoing Trump administration. The rule would deregulate HHS and “sunset”many agency provisions before Trump leaves office next month.

Becerra will be the first Latino appointed as HHS secretary, which furthers Biden’s goal to create a diverse cabinet. Becerra has been attorney general of California since 2017, replacing Vice President-elect Kamala Harris when she became senator.

Biden’s choice of Becerra was unexpected, according to The New York Times, and he was not the only candidate. Speculation was that Biden initially considered Vivek Murthy, MD, later chosen as the next US surgeon general, as well New Mexico Gov. Michelle Lujan Grisham and Rhode Island Gov. Gina Raimondo.
 

A huge undertaking

As HHS secretary, Becerra would oversee a wide range of federal agencies, including the US Food and Drug Administration, the Centers for Disease Control and Prevention, the National Institutes of Health, and the Centers for Medicare & Medicaid Services.

The fiscal year 2021 budget proposed for HHS includes $94.5 billion in discretionary budget authority and $1.3 trillion in mandatory funding. Overall, HHS controls nearly one quarter of all federal expenditures and provides more grant money than all other federal agencies combined.

Becerra, 62, grew up in Sacramento, California. He was the first in his family to graduate from college. He received his undergraduate and law degrees from Stanford University.

This article first appeared on Medscape.com.

President-elect Joe Biden has nominated California Attorney General Xavier Becerra to run the US Department of Health & Human Services (HHS) under his new administration, according to a statement from the Biden-Harris transition team.

Rich Pedroncelli/AP

If confirmed by the US Senate, Becerra will face the challenge of overseeing the federal agency charged with protecting the health of all Americans in the midst of the COVID-19 pandemic. At the time of the announcement, nearly 15 million Americans had tested positive for COVID-19 and more than 280,000 had died.

Becerra served 12 terms in Congress, representing the Los Angeles area. Although his public health experience is limited, he served on the Congressional Ways and Means Committee overseeing health-related issues. Becerra is known as an advocate for the health and well-being of women in particular.

The American College of Physicians, American Academy of Pediatrics, American College of Obstetricians & Gynecologists, American Academy of Family Physicians, and the American Psychiatric Association wrote a letter to Biden on December 3 urging him to select leaders with medical and healthcare expertise, in particular physicians.

“We believe that your administration and the country would be well-served by the appointment of qualified physicians to serve in key positions critical to advancing the health of our nation,” they wrote. “Therefore, our organizations, which represent more than 400,000 front-line physicians practicing in the United States, write to request that you identify and appoint physicians to healthcare leadership positions within your administration.”
 

Recent advocacy

Becerra has worked with Republican attorneys general to lobby HHS to increase access to remdesivir to treat people with COVID-19.

As attorney general, Becerra filed more than 100 lawsuits against the Trump administration. In November, he also represented more than 20 states in arguments supporting the Affordable Care Act before the Supreme Court.

On December 4, Becerra joined with attorneys general from 23 states and the District of Columbia opposing a proposed rule from the outgoing Trump administration. The rule would deregulate HHS and “sunset”many agency provisions before Trump leaves office next month.

Becerra will be the first Latino appointed as HHS secretary, which furthers Biden’s goal to create a diverse cabinet. Becerra has been attorney general of California since 2017, replacing Vice President-elect Kamala Harris when she became senator.

Biden’s choice of Becerra was unexpected, according to The New York Times, and he was not the only candidate. Speculation was that Biden initially considered Vivek Murthy, MD, later chosen as the next US surgeon general, as well New Mexico Gov. Michelle Lujan Grisham and Rhode Island Gov. Gina Raimondo.
 

A huge undertaking

As HHS secretary, Becerra would oversee a wide range of federal agencies, including the US Food and Drug Administration, the Centers for Disease Control and Prevention, the National Institutes of Health, and the Centers for Medicare & Medicaid Services.

The fiscal year 2021 budget proposed for HHS includes $94.5 billion in discretionary budget authority and $1.3 trillion in mandatory funding. Overall, HHS controls nearly one quarter of all federal expenditures and provides more grant money than all other federal agencies combined.

Becerra, 62, grew up in Sacramento, California. He was the first in his family to graduate from college. He received his undergraduate and law degrees from Stanford University.

This article first appeared on Medscape.com.

Duvelisib is demonstrating encouraging activity and manageable toxicities among patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) in a phase 2 trial, an investigator said.

The overall response rate in the dose-optimization phase of the PRIMO trial was more than 60% among patients receiving 75 mg of duvelisib twice daily, with a median duration of response exceeding 12 months, said investigator Barbara Pro, MD, of Northwestern University, Chicago.

In the ongoing dose-expansion phase, in which patients start on 75 mg twice daily and then transition to a lower dose, the ORR is over 50%, including complete responses (CRs) in about one-third of patients, Dr. Pro reported at the annual meeting of the American Society of Hematology.

Most previously approved treatments for relapsed/refractory PTCL are associated with ORRs of less than 30%, low rates of CR, and median progression-free survival of less than 4 months, Dr. Pro said in her presentation.

There have been no unexpected toxicities in the dose-expansion phase, and the adverse event profile is consistent with what has been observed previously for this oral phosphatidylinositol 3-kinase (PI3K) inhibitor, according to Dr. Pro.

Based on results to date, Dr. Pro said she and coinvestigators are hopeful that duvelisib will have a place in the treatment armamentarium for relapsed/refractory PTCL in the future.

“This is one of the most effective agents in T-cell lymphoma, and hopefully will be approved and available for treatment soon,” she said in remarks following her presentation of PRIMO study data.

“The next question would be how to try to move this agent up front,” she added. “We’ll have to try to see what could be the possible combinations and evaluate the possible overlapping toxicity with alternative treatments.”

The PRIMO trial provides “very exciting numbers” that include roughly half of relapsed/refractory PTCL patients are responding to the oral therapy, said Andrei R. Shustov, MD, professor of medicine in the division of hematology at the University of Washington, Seattle.

Perhaps more importantly, at least half of those responses have been CRs, Dr. Shustov noted in an interview: “We haven’t seen this yet in T-cell lymphomas, short of brentuximab vedotin targeting CD30,” he said, referring to the 2018 Food and Drug Administration approval of brentuximab vedotin for previously untreated CD30-expressing PTCL.

If duvelisib is approved, it would be the first oral agent with an indication for relapsed/refractory PTCL, which could have important implications for patient quality of life, Dr. Shustov added.

“The fact that you can take a pill at home, and don’t have to be in clinic once a week, or have the port device, or be infused every week would be an incredible change in quality of life,” he said, “and this is really amplified in the older population where quality of life is so important.”

Duvelisib was FDA approved in 2018, at a dose of 25 mg orally twice daily, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma, and follicular lymphoma, following at least two previous treatments.

In relapsed/refractory PTCL, results of a phase 1 study previously published in Blood showed that duvelisib demonstrated an ORR of 50%, or 8 out of 16 patients treated with 25 or 75 mg twice daily continuously.

The phase 2 study described by Dr. Pro at this year’s ASH meeting included 33 patients with relapsed/refractory PTCL treated with duvelisib 25 mg or 75 mg twice daily as part of a dose-optimization phase, and 25 patients treated in an expansion phase at 75 mg twice daily for two 28-day cycles, followed by treatment at 25 mg twice daily.

Starting at the higher dose of 75 mg twice daily is intended to achieve rapid tumor control, while switching to the lower 25-mg twice-daily dose is to maintain long-term control of the disease while mitigating potential for later toxicities, according to the published abstract for the PRIMO trial.

Results of the dose-optimization phase included an ORR by independent review committee of 62% for patients treated at the 75-mg twice-daily dose, and 40% for those treated at 25 mg twice daily. The median duration of response in the 75-mg twice-daily group was 12.2 months, which Dr. Pro said was significantly higher than what was observed for the lower dose.

In the ongoing dose-expansion phase, the ORR by investigator was 52% (13 of 25 patients), with a CR rate of 36% (9 of 25 patients). The reported data show that with a median duration of follow-up of 3.78 months, the median duration of response thus far is 4.1 months.

The most common grade 3 or higher adverse events were increases in ALT and AST, seen in 24% and 20% of patients, respectively. The most common grade 3 or greater hematologic toxicity was decreased lymphocyte count, seen in 16%.

Three serious treatment-emergent adverse events thought to be related to duvelisib occurred in two patients, including grade 5 pneumonitis in one patient, and skin lesion plus posttransplant lymphoproliferative disorder in the other patient, according to Dr. Pro. Serious treatment-emergent adverse events leading to duvelisib discontinuation included increased ALT/AST in 2 patients and pneumonitis in one patient.

Grade 1-2 adverse events reported at ASH included hypertension, nausea, anemia, fatigue, diarrhea, constipation and pyrexia, among others.

Enrollment in the dose-expansion phase of PRIMO is ongoing and should be complete in February, according to Dr. Pro.

Support for the study came from Verastem Oncology and Secura Bio. Dr. Pro reported research funding from Verastem Oncology, Takeda, and other pharmaceutical companies and honoraria from Takeda and Seattle Genetics.

SOURCE: Pro B et al. ASH 2020, Abstract 44.

Duvelisib is demonstrating encouraging activity and manageable toxicities among patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) in a phase 2 trial, an investigator said.

The overall response rate in the dose-optimization phase of the PRIMO trial was more than 60% among patients receiving 75 mg of duvelisib twice daily, with a median duration of response exceeding 12 months, said investigator Barbara Pro, MD, of Northwestern University, Chicago.

In the ongoing dose-expansion phase, in which patients start on 75 mg twice daily and then transition to a lower dose, the ORR is over 50%, including complete responses (CRs) in about one-third of patients, Dr. Pro reported at the annual meeting of the American Society of Hematology.

Most previously approved treatments for relapsed/refractory PTCL are associated with ORRs of less than 30%, low rates of CR, and median progression-free survival of less than 4 months, Dr. Pro said in her presentation.

There have been no unexpected toxicities in the dose-expansion phase, and the adverse event profile is consistent with what has been observed previously for this oral phosphatidylinositol 3-kinase (PI3K) inhibitor, according to Dr. Pro.

Based on results to date, Dr. Pro said she and coinvestigators are hopeful that duvelisib will have a place in the treatment armamentarium for relapsed/refractory PTCL in the future.

“This is one of the most effective agents in T-cell lymphoma, and hopefully will be approved and available for treatment soon,” she said in remarks following her presentation of PRIMO study data.

“The next question would be how to try to move this agent up front,” she added. “We’ll have to try to see what could be the possible combinations and evaluate the possible overlapping toxicity with alternative treatments.”

The PRIMO trial provides “very exciting numbers” that include roughly half of relapsed/refractory PTCL patients are responding to the oral therapy, said Andrei R. Shustov, MD, professor of medicine in the division of hematology at the University of Washington, Seattle.

Perhaps more importantly, at least half of those responses have been CRs, Dr. Shustov noted in an interview: “We haven’t seen this yet in T-cell lymphomas, short of brentuximab vedotin targeting CD30,” he said, referring to the 2018 Food and Drug Administration approval of brentuximab vedotin for previously untreated CD30-expressing PTCL.

If duvelisib is approved, it would be the first oral agent with an indication for relapsed/refractory PTCL, which could have important implications for patient quality of life, Dr. Shustov added.

“The fact that you can take a pill at home, and don’t have to be in clinic once a week, or have the port device, or be infused every week would be an incredible change in quality of life,” he said, “and this is really amplified in the older population where quality of life is so important.”

Duvelisib was FDA approved in 2018, at a dose of 25 mg orally twice daily, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma, and follicular lymphoma, following at least two previous treatments.

In relapsed/refractory PTCL, results of a phase 1 study previously published in Blood showed that duvelisib demonstrated an ORR of 50%, or 8 out of 16 patients treated with 25 or 75 mg twice daily continuously.

The phase 2 study described by Dr. Pro at this year’s ASH meeting included 33 patients with relapsed/refractory PTCL treated with duvelisib 25 mg or 75 mg twice daily as part of a dose-optimization phase, and 25 patients treated in an expansion phase at 75 mg twice daily for two 28-day cycles, followed by treatment at 25 mg twice daily.

Starting at the higher dose of 75 mg twice daily is intended to achieve rapid tumor control, while switching to the lower 25-mg twice-daily dose is to maintain long-term control of the disease while mitigating potential for later toxicities, according to the published abstract for the PRIMO trial.

Results of the dose-optimization phase included an ORR by independent review committee of 62% for patients treated at the 75-mg twice-daily dose, and 40% for those treated at 25 mg twice daily. The median duration of response in the 75-mg twice-daily group was 12.2 months, which Dr. Pro said was significantly higher than what was observed for the lower dose.

In the ongoing dose-expansion phase, the ORR by investigator was 52% (13 of 25 patients), with a CR rate of 36% (9 of 25 patients). The reported data show that with a median duration of follow-up of 3.78 months, the median duration of response thus far is 4.1 months.

The most common grade 3 or higher adverse events were increases in ALT and AST, seen in 24% and 20% of patients, respectively. The most common grade 3 or greater hematologic toxicity was decreased lymphocyte count, seen in 16%.

Three serious treatment-emergent adverse events thought to be related to duvelisib occurred in two patients, including grade 5 pneumonitis in one patient, and skin lesion plus posttransplant lymphoproliferative disorder in the other patient, according to Dr. Pro. Serious treatment-emergent adverse events leading to duvelisib discontinuation included increased ALT/AST in 2 patients and pneumonitis in one patient.

Grade 1-2 adverse events reported at ASH included hypertension, nausea, anemia, fatigue, diarrhea, constipation and pyrexia, among others.

Enrollment in the dose-expansion phase of PRIMO is ongoing and should be complete in February, according to Dr. Pro.

Support for the study came from Verastem Oncology and Secura Bio. Dr. Pro reported research funding from Verastem Oncology, Takeda, and other pharmaceutical companies and honoraria from Takeda and Seattle Genetics.

SOURCE: Pro B et al. ASH 2020, Abstract 44.

Duvelisib is demonstrating encouraging activity and manageable toxicities among patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) in a phase 2 trial, an investigator said.

The overall response rate in the dose-optimization phase of the PRIMO trial was more than 60% among patients receiving 75 mg of duvelisib twice daily, with a median duration of response exceeding 12 months, said investigator Barbara Pro, MD, of Northwestern University, Chicago.

In the ongoing dose-expansion phase, in which patients start on 75 mg twice daily and then transition to a lower dose, the ORR is over 50%, including complete responses (CRs) in about one-third of patients, Dr. Pro reported at the annual meeting of the American Society of Hematology.

Most previously approved treatments for relapsed/refractory PTCL are associated with ORRs of less than 30%, low rates of CR, and median progression-free survival of less than 4 months, Dr. Pro said in her presentation.

There have been no unexpected toxicities in the dose-expansion phase, and the adverse event profile is consistent with what has been observed previously for this oral phosphatidylinositol 3-kinase (PI3K) inhibitor, according to Dr. Pro.

Based on results to date, Dr. Pro said she and coinvestigators are hopeful that duvelisib will have a place in the treatment armamentarium for relapsed/refractory PTCL in the future.

“This is one of the most effective agents in T-cell lymphoma, and hopefully will be approved and available for treatment soon,” she said in remarks following her presentation of PRIMO study data.

“The next question would be how to try to move this agent up front,” she added. “We’ll have to try to see what could be the possible combinations and evaluate the possible overlapping toxicity with alternative treatments.”

The PRIMO trial provides “very exciting numbers” that include roughly half of relapsed/refractory PTCL patients are responding to the oral therapy, said Andrei R. Shustov, MD, professor of medicine in the division of hematology at the University of Washington, Seattle.

Perhaps more importantly, at least half of those responses have been CRs, Dr. Shustov noted in an interview: “We haven’t seen this yet in T-cell lymphomas, short of brentuximab vedotin targeting CD30,” he said, referring to the 2018 Food and Drug Administration approval of brentuximab vedotin for previously untreated CD30-expressing PTCL.

If duvelisib is approved, it would be the first oral agent with an indication for relapsed/refractory PTCL, which could have important implications for patient quality of life, Dr. Shustov added.

“The fact that you can take a pill at home, and don’t have to be in clinic once a week, or have the port device, or be infused every week would be an incredible change in quality of life,” he said, “and this is really amplified in the older population where quality of life is so important.”

Duvelisib was FDA approved in 2018, at a dose of 25 mg orally twice daily, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma, and follicular lymphoma, following at least two previous treatments.

In relapsed/refractory PTCL, results of a phase 1 study previously published in Blood showed that duvelisib demonstrated an ORR of 50%, or 8 out of 16 patients treated with 25 or 75 mg twice daily continuously.

The phase 2 study described by Dr. Pro at this year’s ASH meeting included 33 patients with relapsed/refractory PTCL treated with duvelisib 25 mg or 75 mg twice daily as part of a dose-optimization phase, and 25 patients treated in an expansion phase at 75 mg twice daily for two 28-day cycles, followed by treatment at 25 mg twice daily.

Starting at the higher dose of 75 mg twice daily is intended to achieve rapid tumor control, while switching to the lower 25-mg twice-daily dose is to maintain long-term control of the disease while mitigating potential for later toxicities, according to the published abstract for the PRIMO trial.

Results of the dose-optimization phase included an ORR by independent review committee of 62% for patients treated at the 75-mg twice-daily dose, and 40% for those treated at 25 mg twice daily. The median duration of response in the 75-mg twice-daily group was 12.2 months, which Dr. Pro said was significantly higher than what was observed for the lower dose.

In the ongoing dose-expansion phase, the ORR by investigator was 52% (13 of 25 patients), with a CR rate of 36% (9 of 25 patients). The reported data show that with a median duration of follow-up of 3.78 months, the median duration of response thus far is 4.1 months.

The most common grade 3 or higher adverse events were increases in ALT and AST, seen in 24% and 20% of patients, respectively. The most common grade 3 or greater hematologic toxicity was decreased lymphocyte count, seen in 16%.

Three serious treatment-emergent adverse events thought to be related to duvelisib occurred in two patients, including grade 5 pneumonitis in one patient, and skin lesion plus posttransplant lymphoproliferative disorder in the other patient, according to Dr. Pro. Serious treatment-emergent adverse events leading to duvelisib discontinuation included increased ALT/AST in 2 patients and pneumonitis in one patient.

Grade 1-2 adverse events reported at ASH included hypertension, nausea, anemia, fatigue, diarrhea, constipation and pyrexia, among others.

Enrollment in the dose-expansion phase of PRIMO is ongoing and should be complete in February, according to Dr. Pro.

Support for the study came from Verastem Oncology and Secura Bio. Dr. Pro reported research funding from Verastem Oncology, Takeda, and other pharmaceutical companies and honoraria from Takeda and Seattle Genetics.

SOURCE: Pro B et al. ASH 2020, Abstract 44.

The U.S. Surgeon General and Department of Health & Human Services are calling on health care professionals, hospitals, employers, insurers, women, and the nation to work together to reduce maternal morbidity and mortality – and the disparities that make the risks higher for women of color.

The maternal mortality rate in the United States is the highest among developed countries of the world and continues to rise. In 2018, for every 100,000 live births, approximately 17 women died while pregnant or within 42 days of the end of pregnancy from causes related to pregnancy or delivery – that’s a substantial increase from 7 deaths per 100,000 live births in 1987, according to the surgeon general’s new call to action.

“Our mothers had much lower rates of dying related to pregnancy, compared to women today,” Dorothy Fink, MD, HHS deputy assistant secretary for women’s health, said at a briefing held Dec. 3 to mark the call to action.

Cardiovascular conditions were the most common cause of pregnancy-related deaths between 2011 and 2015, accounting for more than one in three of the deaths. HHS’s related action plan sets a target of achieving blood pressure control in 80% of women of reproductive age with hypertension by 2025.

The plan also seeks to reduce the maternal mortality rate by 50% and decrease low-risk cesarean deliveries by 25% within 5 years.

“A woman dies every 12 hours in this country from pregnancy-related complications,” Surgeon General Jerome Adams, MD, said at the briefing. “This is not just unacceptable, it is just something that we need to understand is not inevitable,” he said, adding that the Centers for Disease Control and Prevention has determined that two thirds of the deaths are preventable.

Dr. Adams also noted that it was important to address maternal health now, especially with COVID-19 raging. “Without attention and action, maternal health could actually worsen because of this pandemic,” he said.

“We cannot discuss maternal health, much less improve it, unless we acknowledge women of color are at a much greater risk of harm related to childbirth,” Dr. Adams said. “Black women are two to three times more likely to die of pregnancy-related causes compared to many other racial and ethnic groups.” The disparity increases with age, according to the CDC.

Studies have shown that education does not eliminate those disparities. Black women with a college degree are twice as likely to die as White or Asian American women who did not finish high school, Dr. Adams said.

He held up a photo of a colleague, Shalone Irving, who he said was a PhD-educated epidemiologist who “died not long ago from pregnancy-related complications.”

Income is also not a factor, said Dr. Adams, noting that pop singer Beyonce had a near-death experience with preeclampsia. He also noted that Serena Williams, a top athlete, also struggled with pregnancy complications.
 

Recommendations not all funded

The HHS action plan is not explicitly funded, although Dr. Fink and Dr. Adams said that President Donald J. Trump’s fiscal 2021 budget includes some specific requests for improving maternal health. It will be up to Congress to grant the requests.

The budget seeks $80 million for the Health Resources and Services Administration to improve access to and quality of care. It also includes money to expand Medicaid coverage for 1 year after birth for women with substance use disorders. The American Medical Association in 2019 adopted a policy urging Medicaid coverage to be expanded to include all women for a year after childbirth. The American College of Obstetricians and Gynecologists has also encouraged this extension.

“We are encouraged that the HHS action plan includes support for policies to close coverage and care gaps for all postpartum women after pregnancy-related Medicaid coverage expires,” Maureen G. Phipps, MD, MPH, CEO of the American College of Obstetricians and Gynecologists, said in an interview.

The HHS could act immediately by approving Medicaid waivers to extend such coverage, Dr. Phipps said.

The budget also requests $24 million to expand maternal mortality review programs to every state, said Dr. Fink. Currently, 43 states and the District of Columbia, have such committees, which are charged with reviewing deaths of women within a year of pregnancy or birth.

The HHS will also join with the March of Dimes to address the disparities in Black women by implementing evidence-based best practices to improve quality in hospital settings.

It is not the first time the Trump administration has taken aim at reducing maternal morbidity and mortality. In 2018, the president signed the Preventing Maternal Deaths Act, which authorized the CDC to award $50 million over 5 years so that every state could form maternal mortality review committees.

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

The U.S. Surgeon General and Department of Health & Human Services are calling on health care professionals, hospitals, employers, insurers, women, and the nation to work together to reduce maternal morbidity and mortality – and the disparities that make the risks higher for women of color.

The maternal mortality rate in the United States is the highest among developed countries of the world and continues to rise. In 2018, for every 100,000 live births, approximately 17 women died while pregnant or within 42 days of the end of pregnancy from causes related to pregnancy or delivery – that’s a substantial increase from 7 deaths per 100,000 live births in 1987, according to the surgeon general’s new call to action.

“Our mothers had much lower rates of dying related to pregnancy, compared to women today,” Dorothy Fink, MD, HHS deputy assistant secretary for women’s health, said at a briefing held Dec. 3 to mark the call to action.

Cardiovascular conditions were the most common cause of pregnancy-related deaths between 2011 and 2015, accounting for more than one in three of the deaths. HHS’s related action plan sets a target of achieving blood pressure control in 80% of women of reproductive age with hypertension by 2025.

The plan also seeks to reduce the maternal mortality rate by 50% and decrease low-risk cesarean deliveries by 25% within 5 years.

“A woman dies every 12 hours in this country from pregnancy-related complications,” Surgeon General Jerome Adams, MD, said at the briefing. “This is not just unacceptable, it is just something that we need to understand is not inevitable,” he said, adding that the Centers for Disease Control and Prevention has determined that two thirds of the deaths are preventable.

Dr. Adams also noted that it was important to address maternal health now, especially with COVID-19 raging. “Without attention and action, maternal health could actually worsen because of this pandemic,” he said.

“We cannot discuss maternal health, much less improve it, unless we acknowledge women of color are at a much greater risk of harm related to childbirth,” Dr. Adams said. “Black women are two to three times more likely to die of pregnancy-related causes compared to many other racial and ethnic groups.” The disparity increases with age, according to the CDC.

Studies have shown that education does not eliminate those disparities. Black women with a college degree are twice as likely to die as White or Asian American women who did not finish high school, Dr. Adams said.

He held up a photo of a colleague, Shalone Irving, who he said was a PhD-educated epidemiologist who “died not long ago from pregnancy-related complications.”

Income is also not a factor, said Dr. Adams, noting that pop singer Beyonce had a near-death experience with preeclampsia. He also noted that Serena Williams, a top athlete, also struggled with pregnancy complications.
 

Recommendations not all funded

The HHS action plan is not explicitly funded, although Dr. Fink and Dr. Adams said that President Donald J. Trump’s fiscal 2021 budget includes some specific requests for improving maternal health. It will be up to Congress to grant the requests.

The budget seeks $80 million for the Health Resources and Services Administration to improve access to and quality of care. It also includes money to expand Medicaid coverage for 1 year after birth for women with substance use disorders. The American Medical Association in 2019 adopted a policy urging Medicaid coverage to be expanded to include all women for a year after childbirth. The American College of Obstetricians and Gynecologists has also encouraged this extension.

“We are encouraged that the HHS action plan includes support for policies to close coverage and care gaps for all postpartum women after pregnancy-related Medicaid coverage expires,” Maureen G. Phipps, MD, MPH, CEO of the American College of Obstetricians and Gynecologists, said in an interview.

The HHS could act immediately by approving Medicaid waivers to extend such coverage, Dr. Phipps said.

The budget also requests $24 million to expand maternal mortality review programs to every state, said Dr. Fink. Currently, 43 states and the District of Columbia, have such committees, which are charged with reviewing deaths of women within a year of pregnancy or birth.

The HHS will also join with the March of Dimes to address the disparities in Black women by implementing evidence-based best practices to improve quality in hospital settings.

It is not the first time the Trump administration has taken aim at reducing maternal morbidity and mortality. In 2018, the president signed the Preventing Maternal Deaths Act, which authorized the CDC to award $50 million over 5 years so that every state could form maternal mortality review committees.

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

The U.S. Surgeon General and Department of Health & Human Services are calling on health care professionals, hospitals, employers, insurers, women, and the nation to work together to reduce maternal morbidity and mortality – and the disparities that make the risks higher for women of color.

The maternal mortality rate in the United States is the highest among developed countries of the world and continues to rise. In 2018, for every 100,000 live births, approximately 17 women died while pregnant or within 42 days of the end of pregnancy from causes related to pregnancy or delivery – that’s a substantial increase from 7 deaths per 100,000 live births in 1987, according to the surgeon general’s new call to action.

“Our mothers had much lower rates of dying related to pregnancy, compared to women today,” Dorothy Fink, MD, HHS deputy assistant secretary for women’s health, said at a briefing held Dec. 3 to mark the call to action.

Cardiovascular conditions were the most common cause of pregnancy-related deaths between 2011 and 2015, accounting for more than one in three of the deaths. HHS’s related action plan sets a target of achieving blood pressure control in 80% of women of reproductive age with hypertension by 2025.

The plan also seeks to reduce the maternal mortality rate by 50% and decrease low-risk cesarean deliveries by 25% within 5 years.

“A woman dies every 12 hours in this country from pregnancy-related complications,” Surgeon General Jerome Adams, MD, said at the briefing. “This is not just unacceptable, it is just something that we need to understand is not inevitable,” he said, adding that the Centers for Disease Control and Prevention has determined that two thirds of the deaths are preventable.

Dr. Adams also noted that it was important to address maternal health now, especially with COVID-19 raging. “Without attention and action, maternal health could actually worsen because of this pandemic,” he said.

“We cannot discuss maternal health, much less improve it, unless we acknowledge women of color are at a much greater risk of harm related to childbirth,” Dr. Adams said. “Black women are two to three times more likely to die of pregnancy-related causes compared to many other racial and ethnic groups.” The disparity increases with age, according to the CDC.

Studies have shown that education does not eliminate those disparities. Black women with a college degree are twice as likely to die as White or Asian American women who did not finish high school, Dr. Adams said.

He held up a photo of a colleague, Shalone Irving, who he said was a PhD-educated epidemiologist who “died not long ago from pregnancy-related complications.”

Income is also not a factor, said Dr. Adams, noting that pop singer Beyonce had a near-death experience with preeclampsia. He also noted that Serena Williams, a top athlete, also struggled with pregnancy complications.
 

Recommendations not all funded

The HHS action plan is not explicitly funded, although Dr. Fink and Dr. Adams said that President Donald J. Trump’s fiscal 2021 budget includes some specific requests for improving maternal health. It will be up to Congress to grant the requests.

The budget seeks $80 million for the Health Resources and Services Administration to improve access to and quality of care. It also includes money to expand Medicaid coverage for 1 year after birth for women with substance use disorders. The American Medical Association in 2019 adopted a policy urging Medicaid coverage to be expanded to include all women for a year after childbirth. The American College of Obstetricians and Gynecologists has also encouraged this extension.

“We are encouraged that the HHS action plan includes support for policies to close coverage and care gaps for all postpartum women after pregnancy-related Medicaid coverage expires,” Maureen G. Phipps, MD, MPH, CEO of the American College of Obstetricians and Gynecologists, said in an interview.

The HHS could act immediately by approving Medicaid waivers to extend such coverage, Dr. Phipps said.

The budget also requests $24 million to expand maternal mortality review programs to every state, said Dr. Fink. Currently, 43 states and the District of Columbia, have such committees, which are charged with reviewing deaths of women within a year of pregnancy or birth.

The HHS will also join with the March of Dimes to address the disparities in Black women by implementing evidence-based best practices to improve quality in hospital settings.

It is not the first time the Trump administration has taken aim at reducing maternal morbidity and mortality. In 2018, the president signed the Preventing Maternal Deaths Act, which authorized the CDC to award $50 million over 5 years so that every state could form maternal mortality review committees.

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

Despite being routinely used in clinical settings, prophylactic use of tranexamic acid, an antifibrinolytic agent administered with platelet transfusions, did not reduce bleeding among patients with blood cancers and severe thrombocytopenia, according to a new study.

The study compared tranexamic acid to placebo and found no significant differences in terms of the number of bleeding events, the number of red blood cell transfusions, or the number of platelet transfusions that were required.

However, the rate of occlusions in the central venous line was significantly higher for patients in the tranexamic acid group, although there was no difference between groups for other types of thrombotic events.

The findings were presented at the annual meeting of the American Society of Hematology, which was held online.

The study was highlighted as potentially practice changing at a press preview webinar by ASH Secretary Robert Brodsky, MD.

“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”

Senior author Terry B. Gernsheimer, MD, of the University of Washington, Seattle, noted that tranexamic acid has been found to be effective in the treatment of bleeding related to childbirth, surgery, and inherited blood disorders.

It is also used for patients with blood cancers and severe thrombocytopenia. There is little evidence to support this use, which is why the researchers decided to investigate.

“Clearly patients with low platelet counts and blood cancers have a different kind of bleeding than the bleeding experienced by patients who have suffered some kind of trauma or surgery,” Dr. Gernsheimer said in a statement.

“Their bleeding likely is due to endothelial damage – damage to the lining of blood vessels – that tranexamic acid would not treat,” she added.

“To prevent bleeding in these patients, we may need to look at ways to speed the healing of the endothelium that occurs with chemotherapy, radiation, and graft-vs-host disease in patients receiving a transplant,” Dr. Gernsheimer commented.
 

Temper enthusiasm

“Overall, I think these results will temper enthusiasm for using tranexamic acid in this setting,” said Mitul Gandhi, MD, a medical oncologist with Virginia Cancer Specialists, who was approached for comment.

These data do not support the routine use of prophylactic tranexamic acid in chemotherapy-induced thrombocytopenia for patients with platelet counts lower than 30,000/μL, he added.

“The primary objective was not met, and there was an observed increased rate of catheter-associated thrombosis,” he said. “Continued use of judicious transfusion support and correction of a concomitant coagulopathy remains the main clinical approach to these patients.”

Dr. Gandhi commented that tranexamic acid “remains a potentially useful adjunct agent in certain cases of recalcitrant bleeding related to thrombocytopenia or coagulopathy.

“While there is no uniform scenario, it is typically reserved on a case-by-case basis after addressing vascular defects, utilization of platelet, fresh frozen plasma, cryoprecipitate transfusions, vitamin K repletion, and of course excluding any antiplatelet or anticoagulant therapy,» he told this news organization. “For persistent bleeding in spite of all corrective measures or hemorrhage into noncompressible vascular beds, such as with intracranial bleeds, antifibrinolytic therapy may assist in mitigating further blood loss.”

However, this has to be balanced with the potential increased risk for thrombosis after correction of the hemostatic insult.

At present, tranexamic acid “only has an FDA indication for uterine bleeding, but it is frequently used in trauma settings and obstetrical emergencies,” said Douglas Tremblay, MD, an internist at the Icahn School of Medicine at Mount Sinai, New York, who was also approached for comment.

“There is evidence from prior studies that were done 20 or 30 years ago that it may help in this setting, so it is used in some institutions, although we don’t give it prophylactically for patients with a hematologic malignancy.”

Although this was a negative study, Dr. Tremblay pointed out that one thing that may come out of it is that there may be subgroups who can benefit from the prophylactic use of tranexamic acid. “There is very wide inclusion criteria for the study – any type of hematologic malignancy in patients undergoing chemotherapy or stem cell transplant,” he said in an interview. “Even among chemotherapy and transplant patients, there are different risks for bleeding.”

For example, patients undergoing induction chemotherapy for acute myeloid leukemia are at an increased risk of bleeding in comparison with patients with other hematologic malignancies, and those undergoing allogeneic transplant are at an increased risk of bleeding in comparison with patients undergoing autologous transplant. “So while its unclear if a subgroup may benefit from this strategy, lumped together, it doesn’t appear it is of any benefit and potentially harmful, in terms of line occlusions,” he said. “While that may seem to be a nuisance, it can delay chemotherapy or supportive infusions, and that can be a big deal.”
 

No evidence of benefit

Dr. Gernsheimer and colleagues conducted the American Trial Using Tranexamic Acid in Thrombocytopenia (A-TREAT), which evaluated the effects of prophylactic tranexamic acid as an adjunct to routine transfusion therapy on bleeding and transfusion requirements.

A total of 330 patients were randomly assigned to receive either tranexamic acid 1,000 mg IV or 1,300 mg or placebo. Randomization was stratified by site and therapy: chemotherapy, allogeneic transplant, or autologous transplant. It was anticipated that all patients had hypoproliferative thrombocytopenia (expected platelet count, 10,000/µL for at least 5 days).

Treatment continued for 30 days or platelet count recovery (>30,000/µL), diagnosis of thrombosis or veno-occlusive disease, recurrent line occlusion, visible hematuria, or physician or patient request.

The primary endpoint of the study was the proportion of patients with bleeding of World Health Organization grade 2 or above over 30 days after beginning therapy. Secondary endpoints included the number of transfusions and the number of days alive without WHO grade 2+ bleeding during the first 30 days post activation of study drug.

The time to first WHO 2+ bleeding was “remarkably similar” between the tranexamic acid groups and the placebo group, said Dr. Gernsheimer.

In the cohort as a whole, 48.8% in the placebo group experienced a grade 2+ bleed vs. 45.4% in the tranexamic group (odds ratio, 0.86).

Similar results were observed across subgroups: allogeneic transplant, 57.3% vs. 58.8% (OR, 0.94); autologous transplant, 19.9% vs. 24.7% ( OR, 0.71); or chemotherapy, 48% vs. 52.1% (OR, 0.84).

There were no significant differences in mean number of transfusions (difference, 0.1; 95% confidence interval, –1.9 to 2) or days alive without grade 2 or higher bleeding (difference, 0.1; 95% CI, –1.4 to 1.5).

“A post hoc analysis of WHO 3+ bleeding showed these events to be rare and without any improvement with tranexamic acid,” she said.

A higher percentage of patients in the tranexamic acid group experienced thrombotic events (19.5% vs. 11%). “But importantly, in both groups, it was primarily due to central line occlusions without an associated thrombus,” said Dr. Gernsheimer. “This was statistically significant.”

Fewer non–catheter related thrombotic events occurred in the tranexamic acid group (3.7% vs. 5.5%), but the difference was not statistically significant.

There was also no significant difference between groups in veno-occlusive disease after 30 days (1.8% vs. 1.2%) or all-cause mortality at 30 days (2.4% vs. 3%) or 100 days (11.5% vs. 11.5%). No deaths associated with thrombosis had occurred in either group at 120 days.

The study was supported by the University of Washington and the National Heart, Lung, and Blood Institute. Dr. Gernsheimer has relationships with Amgen, Cellphire, Dova Pharmaceuticals, Novartis, Principia, Rigel, Sanofi, and Vertex. Dr. Tremblay and Dr. Gandhi have disclosed no relevant financial relationships.

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

Despite being routinely used in clinical settings, prophylactic use of tranexamic acid, an antifibrinolytic agent administered with platelet transfusions, did not reduce bleeding among patients with blood cancers and severe thrombocytopenia, according to a new study.

The study compared tranexamic acid to placebo and found no significant differences in terms of the number of bleeding events, the number of red blood cell transfusions, or the number of platelet transfusions that were required.

However, the rate of occlusions in the central venous line was significantly higher for patients in the tranexamic acid group, although there was no difference between groups for other types of thrombotic events.

The findings were presented at the annual meeting of the American Society of Hematology, which was held online.

The study was highlighted as potentially practice changing at a press preview webinar by ASH Secretary Robert Brodsky, MD.

“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”

Senior author Terry B. Gernsheimer, MD, of the University of Washington, Seattle, noted that tranexamic acid has been found to be effective in the treatment of bleeding related to childbirth, surgery, and inherited blood disorders.

It is also used for patients with blood cancers and severe thrombocytopenia. There is little evidence to support this use, which is why the researchers decided to investigate.

“Clearly patients with low platelet counts and blood cancers have a different kind of bleeding than the bleeding experienced by patients who have suffered some kind of trauma or surgery,” Dr. Gernsheimer said in a statement.

“Their bleeding likely is due to endothelial damage – damage to the lining of blood vessels – that tranexamic acid would not treat,” she added.

“To prevent bleeding in these patients, we may need to look at ways to speed the healing of the endothelium that occurs with chemotherapy, radiation, and graft-vs-host disease in patients receiving a transplant,” Dr. Gernsheimer commented.
 

Temper enthusiasm

“Overall, I think these results will temper enthusiasm for using tranexamic acid in this setting,” said Mitul Gandhi, MD, a medical oncologist with Virginia Cancer Specialists, who was approached for comment.

These data do not support the routine use of prophylactic tranexamic acid in chemotherapy-induced thrombocytopenia for patients with platelet counts lower than 30,000/μL, he added.

“The primary objective was not met, and there was an observed increased rate of catheter-associated thrombosis,” he said. “Continued use of judicious transfusion support and correction of a concomitant coagulopathy remains the main clinical approach to these patients.”

Dr. Gandhi commented that tranexamic acid “remains a potentially useful adjunct agent in certain cases of recalcitrant bleeding related to thrombocytopenia or coagulopathy.

“While there is no uniform scenario, it is typically reserved on a case-by-case basis after addressing vascular defects, utilization of platelet, fresh frozen plasma, cryoprecipitate transfusions, vitamin K repletion, and of course excluding any antiplatelet or anticoagulant therapy,» he told this news organization. “For persistent bleeding in spite of all corrective measures or hemorrhage into noncompressible vascular beds, such as with intracranial bleeds, antifibrinolytic therapy may assist in mitigating further blood loss.”

However, this has to be balanced with the potential increased risk for thrombosis after correction of the hemostatic insult.

At present, tranexamic acid “only has an FDA indication for uterine bleeding, but it is frequently used in trauma settings and obstetrical emergencies,” said Douglas Tremblay, MD, an internist at the Icahn School of Medicine at Mount Sinai, New York, who was also approached for comment.

“There is evidence from prior studies that were done 20 or 30 years ago that it may help in this setting, so it is used in some institutions, although we don’t give it prophylactically for patients with a hematologic malignancy.”

Although this was a negative study, Dr. Tremblay pointed out that one thing that may come out of it is that there may be subgroups who can benefit from the prophylactic use of tranexamic acid. “There is very wide inclusion criteria for the study – any type of hematologic malignancy in patients undergoing chemotherapy or stem cell transplant,” he said in an interview. “Even among chemotherapy and transplant patients, there are different risks for bleeding.”

For example, patients undergoing induction chemotherapy for acute myeloid leukemia are at an increased risk of bleeding in comparison with patients with other hematologic malignancies, and those undergoing allogeneic transplant are at an increased risk of bleeding in comparison with patients undergoing autologous transplant. “So while its unclear if a subgroup may benefit from this strategy, lumped together, it doesn’t appear it is of any benefit and potentially harmful, in terms of line occlusions,” he said. “While that may seem to be a nuisance, it can delay chemotherapy or supportive infusions, and that can be a big deal.”
 

No evidence of benefit

Dr. Gernsheimer and colleagues conducted the American Trial Using Tranexamic Acid in Thrombocytopenia (A-TREAT), which evaluated the effects of prophylactic tranexamic acid as an adjunct to routine transfusion therapy on bleeding and transfusion requirements.

A total of 330 patients were randomly assigned to receive either tranexamic acid 1,000 mg IV or 1,300 mg or placebo. Randomization was stratified by site and therapy: chemotherapy, allogeneic transplant, or autologous transplant. It was anticipated that all patients had hypoproliferative thrombocytopenia (expected platelet count, 10,000/µL for at least 5 days).

Treatment continued for 30 days or platelet count recovery (>30,000/µL), diagnosis of thrombosis or veno-occlusive disease, recurrent line occlusion, visible hematuria, or physician or patient request.

The primary endpoint of the study was the proportion of patients with bleeding of World Health Organization grade 2 or above over 30 days after beginning therapy. Secondary endpoints included the number of transfusions and the number of days alive without WHO grade 2+ bleeding during the first 30 days post activation of study drug.

The time to first WHO 2+ bleeding was “remarkably similar” between the tranexamic acid groups and the placebo group, said Dr. Gernsheimer.

In the cohort as a whole, 48.8% in the placebo group experienced a grade 2+ bleed vs. 45.4% in the tranexamic group (odds ratio, 0.86).

Similar results were observed across subgroups: allogeneic transplant, 57.3% vs. 58.8% (OR, 0.94); autologous transplant, 19.9% vs. 24.7% ( OR, 0.71); or chemotherapy, 48% vs. 52.1% (OR, 0.84).

There were no significant differences in mean number of transfusions (difference, 0.1; 95% confidence interval, –1.9 to 2) or days alive without grade 2 or higher bleeding (difference, 0.1; 95% CI, –1.4 to 1.5).

“A post hoc analysis of WHO 3+ bleeding showed these events to be rare and without any improvement with tranexamic acid,” she said.

A higher percentage of patients in the tranexamic acid group experienced thrombotic events (19.5% vs. 11%). “But importantly, in both groups, it was primarily due to central line occlusions without an associated thrombus,” said Dr. Gernsheimer. “This was statistically significant.”

Fewer non–catheter related thrombotic events occurred in the tranexamic acid group (3.7% vs. 5.5%), but the difference was not statistically significant.

There was also no significant difference between groups in veno-occlusive disease after 30 days (1.8% vs. 1.2%) or all-cause mortality at 30 days (2.4% vs. 3%) or 100 days (11.5% vs. 11.5%). No deaths associated with thrombosis had occurred in either group at 120 days.

The study was supported by the University of Washington and the National Heart, Lung, and Blood Institute. Dr. Gernsheimer has relationships with Amgen, Cellphire, Dova Pharmaceuticals, Novartis, Principia, Rigel, Sanofi, and Vertex. Dr. Tremblay and Dr. Gandhi have disclosed no relevant financial relationships.

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

Despite being routinely used in clinical settings, prophylactic use of tranexamic acid, an antifibrinolytic agent administered with platelet transfusions, did not reduce bleeding among patients with blood cancers and severe thrombocytopenia, according to a new study.

The study compared tranexamic acid to placebo and found no significant differences in terms of the number of bleeding events, the number of red blood cell transfusions, or the number of platelet transfusions that were required.

However, the rate of occlusions in the central venous line was significantly higher for patients in the tranexamic acid group, although there was no difference between groups for other types of thrombotic events.

The findings were presented at the annual meeting of the American Society of Hematology, which was held online.

The study was highlighted as potentially practice changing at a press preview webinar by ASH Secretary Robert Brodsky, MD.

“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”

Senior author Terry B. Gernsheimer, MD, of the University of Washington, Seattle, noted that tranexamic acid has been found to be effective in the treatment of bleeding related to childbirth, surgery, and inherited blood disorders.

It is also used for patients with blood cancers and severe thrombocytopenia. There is little evidence to support this use, which is why the researchers decided to investigate.

“Clearly patients with low platelet counts and blood cancers have a different kind of bleeding than the bleeding experienced by patients who have suffered some kind of trauma or surgery,” Dr. Gernsheimer said in a statement.

“Their bleeding likely is due to endothelial damage – damage to the lining of blood vessels – that tranexamic acid would not treat,” she added.

“To prevent bleeding in these patients, we may need to look at ways to speed the healing of the endothelium that occurs with chemotherapy, radiation, and graft-vs-host disease in patients receiving a transplant,” Dr. Gernsheimer commented.
 

Temper enthusiasm

“Overall, I think these results will temper enthusiasm for using tranexamic acid in this setting,” said Mitul Gandhi, MD, a medical oncologist with Virginia Cancer Specialists, who was approached for comment.

These data do not support the routine use of prophylactic tranexamic acid in chemotherapy-induced thrombocytopenia for patients with platelet counts lower than 30,000/μL, he added.

“The primary objective was not met, and there was an observed increased rate of catheter-associated thrombosis,” he said. “Continued use of judicious transfusion support and correction of a concomitant coagulopathy remains the main clinical approach to these patients.”

Dr. Gandhi commented that tranexamic acid “remains a potentially useful adjunct agent in certain cases of recalcitrant bleeding related to thrombocytopenia or coagulopathy.

“While there is no uniform scenario, it is typically reserved on a case-by-case basis after addressing vascular defects, utilization of platelet, fresh frozen plasma, cryoprecipitate transfusions, vitamin K repletion, and of course excluding any antiplatelet or anticoagulant therapy,» he told this news organization. “For persistent bleeding in spite of all corrective measures or hemorrhage into noncompressible vascular beds, such as with intracranial bleeds, antifibrinolytic therapy may assist in mitigating further blood loss.”

However, this has to be balanced with the potential increased risk for thrombosis after correction of the hemostatic insult.

At present, tranexamic acid “only has an FDA indication for uterine bleeding, but it is frequently used in trauma settings and obstetrical emergencies,” said Douglas Tremblay, MD, an internist at the Icahn School of Medicine at Mount Sinai, New York, who was also approached for comment.

“There is evidence from prior studies that were done 20 or 30 years ago that it may help in this setting, so it is used in some institutions, although we don’t give it prophylactically for patients with a hematologic malignancy.”

Although this was a negative study, Dr. Tremblay pointed out that one thing that may come out of it is that there may be subgroups who can benefit from the prophylactic use of tranexamic acid. “There is very wide inclusion criteria for the study – any type of hematologic malignancy in patients undergoing chemotherapy or stem cell transplant,” he said in an interview. “Even among chemotherapy and transplant patients, there are different risks for bleeding.”

For example, patients undergoing induction chemotherapy for acute myeloid leukemia are at an increased risk of bleeding in comparison with patients with other hematologic malignancies, and those undergoing allogeneic transplant are at an increased risk of bleeding in comparison with patients undergoing autologous transplant. “So while its unclear if a subgroup may benefit from this strategy, lumped together, it doesn’t appear it is of any benefit and potentially harmful, in terms of line occlusions,” he said. “While that may seem to be a nuisance, it can delay chemotherapy or supportive infusions, and that can be a big deal.”
 

No evidence of benefit

Dr. Gernsheimer and colleagues conducted the American Trial Using Tranexamic Acid in Thrombocytopenia (A-TREAT), which evaluated the effects of prophylactic tranexamic acid as an adjunct to routine transfusion therapy on bleeding and transfusion requirements.

A total of 330 patients were randomly assigned to receive either tranexamic acid 1,000 mg IV or 1,300 mg or placebo. Randomization was stratified by site and therapy: chemotherapy, allogeneic transplant, or autologous transplant. It was anticipated that all patients had hypoproliferative thrombocytopenia (expected platelet count, 10,000/µL for at least 5 days).

Treatment continued for 30 days or platelet count recovery (>30,000/µL), diagnosis of thrombosis or veno-occlusive disease, recurrent line occlusion, visible hematuria, or physician or patient request.

The primary endpoint of the study was the proportion of patients with bleeding of World Health Organization grade 2 or above over 30 days after beginning therapy. Secondary endpoints included the number of transfusions and the number of days alive without WHO grade 2+ bleeding during the first 30 days post activation of study drug.

The time to first WHO 2+ bleeding was “remarkably similar” between the tranexamic acid groups and the placebo group, said Dr. Gernsheimer.

In the cohort as a whole, 48.8% in the placebo group experienced a grade 2+ bleed vs. 45.4% in the tranexamic group (odds ratio, 0.86).

Similar results were observed across subgroups: allogeneic transplant, 57.3% vs. 58.8% (OR, 0.94); autologous transplant, 19.9% vs. 24.7% ( OR, 0.71); or chemotherapy, 48% vs. 52.1% (OR, 0.84).

There were no significant differences in mean number of transfusions (difference, 0.1; 95% confidence interval, –1.9 to 2) or days alive without grade 2 or higher bleeding (difference, 0.1; 95% CI, –1.4 to 1.5).

“A post hoc analysis of WHO 3+ bleeding showed these events to be rare and without any improvement with tranexamic acid,” she said.

A higher percentage of patients in the tranexamic acid group experienced thrombotic events (19.5% vs. 11%). “But importantly, in both groups, it was primarily due to central line occlusions without an associated thrombus,” said Dr. Gernsheimer. “This was statistically significant.”

Fewer non–catheter related thrombotic events occurred in the tranexamic acid group (3.7% vs. 5.5%), but the difference was not statistically significant.

There was also no significant difference between groups in veno-occlusive disease after 30 days (1.8% vs. 1.2%) or all-cause mortality at 30 days (2.4% vs. 3%) or 100 days (11.5% vs. 11.5%). No deaths associated with thrombosis had occurred in either group at 120 days.

The study was supported by the University of Washington and the National Heart, Lung, and Blood Institute. Dr. Gernsheimer has relationships with Amgen, Cellphire, Dova Pharmaceuticals, Novartis, Principia, Rigel, Sanofi, and Vertex. Dr. Tremblay and Dr. Gandhi have disclosed no relevant financial relationships.

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

A majority of hospitals and health care facilities surveyed report operating according to “crisis standards of care” as they struggle to provide sufficient personal protective equipment (PPE).

For example, in a national survey, 73% of 1,083 infection prevention experts said respirator shortages related to care for patients with COVID-19 drove their facility to move beyond conventional standards of care. Furthermore, 69% of facilities are using crisis standards of care (CSC) to provide masks, and 76% are apportioning face shields or eye protection.

Almost 76% of respondents who report reusing respirators said their facility allows them to use each respirator either five times or as many times as possible before replacement; 74% allow similar reuse of masks.

Although the majority of institutions remain in this crisis mode, many health care providers have better access to PPE than they did in the spring 2020, the Association for Professionals in Infection Control and Epidemiology (APIC) noted in its latest national survey.

“It is disheartening to see our healthcare system strained and implementing PPE crisis standards of care more than eight months into the pandemic,” APIC President Connie Steed, MSN, RN, said in a December 3 news release.

The association surveyed experts online between Oct. 22 and Nov. 5. The survey was timed to gauge the extent of resource shortages as COVID-19 cases increase and the 2020-2021 flu season begins.

“Many of us on the front lines are waiting for the other shoe to drop. With the upcoming flu season, we implore people to do what they can to keep safe, protect our healthcare personnel, and lessen the strain on our health care system,” Ms. Steed said.
 

COVID-19 linked to more infections, too

APIC also asked infection prevention specialists about changes in health care–associated infection rates since the onset of the pandemic. The experts reported an almost 28% increase in central line–associated bloodstream infections and 21% more catheter-associated urinary tract infections. They also reported an 18% rise in ventilator-associated pneumonia or ventilator-associated events, compared with before the COVID-19 pandemic.

This is the second PPE survey the APIC has conducted during the pandemic. The organization first reported a dire situation in March. For example, the initial survey found that 48% of facilities were almost out or were out of respirators used to care for patients with COVID-19.

This article first appeared on Medscape.com.

A majority of hospitals and health care facilities surveyed report operating according to “crisis standards of care” as they struggle to provide sufficient personal protective equipment (PPE).

For example, in a national survey, 73% of 1,083 infection prevention experts said respirator shortages related to care for patients with COVID-19 drove their facility to move beyond conventional standards of care. Furthermore, 69% of facilities are using crisis standards of care (CSC) to provide masks, and 76% are apportioning face shields or eye protection.

Almost 76% of respondents who report reusing respirators said their facility allows them to use each respirator either five times or as many times as possible before replacement; 74% allow similar reuse of masks.

Although the majority of institutions remain in this crisis mode, many health care providers have better access to PPE than they did in the spring 2020, the Association for Professionals in Infection Control and Epidemiology (APIC) noted in its latest national survey.

“It is disheartening to see our healthcare system strained and implementing PPE crisis standards of care more than eight months into the pandemic,” APIC President Connie Steed, MSN, RN, said in a December 3 news release.

The association surveyed experts online between Oct. 22 and Nov. 5. The survey was timed to gauge the extent of resource shortages as COVID-19 cases increase and the 2020-2021 flu season begins.

“Many of us on the front lines are waiting for the other shoe to drop. With the upcoming flu season, we implore people to do what they can to keep safe, protect our healthcare personnel, and lessen the strain on our health care system,” Ms. Steed said.
 

COVID-19 linked to more infections, too

APIC also asked infection prevention specialists about changes in health care–associated infection rates since the onset of the pandemic. The experts reported an almost 28% increase in central line–associated bloodstream infections and 21% more catheter-associated urinary tract infections. They also reported an 18% rise in ventilator-associated pneumonia or ventilator-associated events, compared with before the COVID-19 pandemic.

This is the second PPE survey the APIC has conducted during the pandemic. The organization first reported a dire situation in March. For example, the initial survey found that 48% of facilities were almost out or were out of respirators used to care for patients with COVID-19.

This article first appeared on Medscape.com.

A majority of hospitals and health care facilities surveyed report operating according to “crisis standards of care” as they struggle to provide sufficient personal protective equipment (PPE).

For example, in a national survey, 73% of 1,083 infection prevention experts said respirator shortages related to care for patients with COVID-19 drove their facility to move beyond conventional standards of care. Furthermore, 69% of facilities are using crisis standards of care (CSC) to provide masks, and 76% are apportioning face shields or eye protection.

Almost 76% of respondents who report reusing respirators said their facility allows them to use each respirator either five times or as many times as possible before replacement; 74% allow similar reuse of masks.

Although the majority of institutions remain in this crisis mode, many health care providers have better access to PPE than they did in the spring 2020, the Association for Professionals in Infection Control and Epidemiology (APIC) noted in its latest national survey.

“It is disheartening to see our healthcare system strained and implementing PPE crisis standards of care more than eight months into the pandemic,” APIC President Connie Steed, MSN, RN, said in a December 3 news release.

The association surveyed experts online between Oct. 22 and Nov. 5. The survey was timed to gauge the extent of resource shortages as COVID-19 cases increase and the 2020-2021 flu season begins.

“Many of us on the front lines are waiting for the other shoe to drop. With the upcoming flu season, we implore people to do what they can to keep safe, protect our healthcare personnel, and lessen the strain on our health care system,” Ms. Steed said.
 

COVID-19 linked to more infections, too

APIC also asked infection prevention specialists about changes in health care–associated infection rates since the onset of the pandemic. The experts reported an almost 28% increase in central line–associated bloodstream infections and 21% more catheter-associated urinary tract infections. They also reported an 18% rise in ventilator-associated pneumonia or ventilator-associated events, compared with before the COVID-19 pandemic.

This is the second PPE survey the APIC has conducted during the pandemic. The organization first reported a dire situation in March. For example, the initial survey found that 48% of facilities were almost out or were out of respirators used to care for patients with COVID-19.

This article first appeared on Medscape.com.