Federal Practitioner

Lupin Pharmaceuticals is recalling all batches of irbesartan tablets USP 75 mg, 150 mg, and 300 mg and irbesartan and hydrochlorothiazide (HCTZ) tablets USP 150 mg/12.5 mg and 300 mg/12.5 mg because of the potential presence of the N-nitrosoirbesartan impurity.

“As part of Lupin’s ongoing assessment, analysis revealed that certain tested active pharmaceutical ingredient (API) batches (but not finished product batches) were above the specification limit for the impurity, N-nitrosoirbesartan,” the company said in a news release posted on the U.S. Food and Drug Administration’s website. It notes that the impurity is a “probable human carcinogen.”

Lupin discontinued the marketing of irbesartan and irbesartan/HCTZ tablets on Jan. 7, 2021. It says it “has received no reports of illness that appear to relate to this issue” and is issuing the recall out of “an abundance of caution.”

The company, however, goes on to note that from Oct. 8, 2018 (the earliest date of shipment from the manufacturing site of any of the affected batches) to September 30 of this year, Lupin received four reports of illness from irbesartan and 0 reports from irbesartan/HCTZ.

Irbesartan is an angiotensin II receptor blocker indicated for treatment of hypertension in patients with type 2 diabetes, elevated serum creatinine, and proteinuria.

Irbesartan/HCTZ tablets include irbesartan and hydrochlorothiazide, a thiazide diuretic, indicated for hypertension in patients not adequately controlled with monotherapy or as an initial therapy in patients likely to need multiple drugs to achieve blood pressure goals.

Lupin is notifying wholesalers, distributors, and retail outlets to immediately discontinue sales of the affected product lots and return them to the company. Specific lot numbers can be found here.

The company is advising patients to continue taking their medication and to contact their pharmacist, physician, or health care professional for advice regarding an alternative treatment.

Patients and physicians are also advised to report any adverse events or side effects related to the affected products to MedWatch, the U.S. Food and Drug Administration’s Safety Information and Adverse Event Reporting program.

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

Lupin Pharmaceuticals is recalling all batches of irbesartan tablets USP 75 mg, 150 mg, and 300 mg and irbesartan and hydrochlorothiazide (HCTZ) tablets USP 150 mg/12.5 mg and 300 mg/12.5 mg because of the potential presence of the N-nitrosoirbesartan impurity.

“As part of Lupin’s ongoing assessment, analysis revealed that certain tested active pharmaceutical ingredient (API) batches (but not finished product batches) were above the specification limit for the impurity, N-nitrosoirbesartan,” the company said in a news release posted on the U.S. Food and Drug Administration’s website. It notes that the impurity is a “probable human carcinogen.”

Lupin discontinued the marketing of irbesartan and irbesartan/HCTZ tablets on Jan. 7, 2021. It says it “has received no reports of illness that appear to relate to this issue” and is issuing the recall out of “an abundance of caution.”

The company, however, goes on to note that from Oct. 8, 2018 (the earliest date of shipment from the manufacturing site of any of the affected batches) to September 30 of this year, Lupin received four reports of illness from irbesartan and 0 reports from irbesartan/HCTZ.

Irbesartan is an angiotensin II receptor blocker indicated for treatment of hypertension in patients with type 2 diabetes, elevated serum creatinine, and proteinuria.

Irbesartan/HCTZ tablets include irbesartan and hydrochlorothiazide, a thiazide diuretic, indicated for hypertension in patients not adequately controlled with monotherapy or as an initial therapy in patients likely to need multiple drugs to achieve blood pressure goals.

Lupin is notifying wholesalers, distributors, and retail outlets to immediately discontinue sales of the affected product lots and return them to the company. Specific lot numbers can be found here.

The company is advising patients to continue taking their medication and to contact their pharmacist, physician, or health care professional for advice regarding an alternative treatment.

Patients and physicians are also advised to report any adverse events or side effects related to the affected products to MedWatch, the U.S. Food and Drug Administration’s Safety Information and Adverse Event Reporting program.

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

Lupin Pharmaceuticals is recalling all batches of irbesartan tablets USP 75 mg, 150 mg, and 300 mg and irbesartan and hydrochlorothiazide (HCTZ) tablets USP 150 mg/12.5 mg and 300 mg/12.5 mg because of the potential presence of the N-nitrosoirbesartan impurity.

“As part of Lupin’s ongoing assessment, analysis revealed that certain tested active pharmaceutical ingredient (API) batches (but not finished product batches) were above the specification limit for the impurity, N-nitrosoirbesartan,” the company said in a news release posted on the U.S. Food and Drug Administration’s website. It notes that the impurity is a “probable human carcinogen.”

Lupin discontinued the marketing of irbesartan and irbesartan/HCTZ tablets on Jan. 7, 2021. It says it “has received no reports of illness that appear to relate to this issue” and is issuing the recall out of “an abundance of caution.”

The company, however, goes on to note that from Oct. 8, 2018 (the earliest date of shipment from the manufacturing site of any of the affected batches) to September 30 of this year, Lupin received four reports of illness from irbesartan and 0 reports from irbesartan/HCTZ.

Irbesartan is an angiotensin II receptor blocker indicated for treatment of hypertension in patients with type 2 diabetes, elevated serum creatinine, and proteinuria.

Irbesartan/HCTZ tablets include irbesartan and hydrochlorothiazide, a thiazide diuretic, indicated for hypertension in patients not adequately controlled with monotherapy or as an initial therapy in patients likely to need multiple drugs to achieve blood pressure goals.

Lupin is notifying wholesalers, distributors, and retail outlets to immediately discontinue sales of the affected product lots and return them to the company. Specific lot numbers can be found here.

The company is advising patients to continue taking their medication and to contact their pharmacist, physician, or health care professional for advice regarding an alternative treatment.

Patients and physicians are also advised to report any adverse events or side effects related to the affected products to MedWatch, the U.S. Food and Drug Administration’s Safety Information and Adverse Event Reporting program.

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

New classes of antimigraine drugs demonstrate efficacy and improved tolerability for patients with chronic migraine, a new systematic review and meta-analysis finds.

“[T]he lack of cardiovascular risks of these new classes of migraine-specific treatments may provide alternative treatment options for individuals for whom currently available acute treatments have failed or for those with cardiovascular contraindications,” write lead author Chun-Pai Yang, MD, PhD, of Taichung (Taiwan) Veterans General Hospital and colleagues, in the paper, published online in JAMA Network Open.
 

Methods

The new study compared the outcomes for acute migraine management using the ditan, lasmiditan (a 5-hydroxytryptamine [5HT]1F–receptor agonist), and the two gepants, rimegepant, and ubrogepant (calcitonin gene–related peptide [CGRP] antagonists), with standard triptan (selective 5-HT1B/1D–receptor agonist) therapy.

The researchers evaluated 64 double-blind randomized clinical trials which included 46,442 patients, the majority of whom (74%-87%) were women with an age range of 36-43 years.

The primary outcome evaluated was the odds ratio for freedom from pain at 2 hours after a single dose and secondary outcomes were the OR for pain relief at 2 hours following a dose, as well as any adverse events.
 

Results

Dr. Yang and colleagues found that virtually all medications with widespread clinical use, regardless of class, were associated with higher ORs for pain freedom when compared with placebo.

Compared to ditan and gepant agents, however, triptans were associated with significantly higher ORs for pain freedom. The odds ratio ranges were 1.72-3.40 for lasmiditan, 1.58-3.13 for rimegepant, and 1.54-3.05 for ubrogepant.

With respect to pain relief at 2 hours, while all medications were more effective than placebo, triptans were associated with higher ORs when compared with the other drug classes: lasmiditan (range: OR, 1.46; 95% confidence interval, 1.09-1.96 to OR, 3.31; 95% CI, 2.41-4.55), rimegepant (range: OR, 1.33; 95% CI, 1.01-1.76 to OR, 3.01; 95% CI, 2.33-3.88), and ubrogepant (range: OR, 1.38; 95% CI, 1.02-1.88 to OR, 3.13; 95% CI, 2.35-4.15)

When assessing tolerability, the researchers found that overall, triptans were associated with the higher ORs for any adverse events (AE) with a trend of dose-response relationship. Lasmiditan (in the ditan class) was associated with the highest risk for AEs among all treatments. Most of the AEs were mild to moderate and included chest pain, tightness, heaviness, and pressure.

Dr. Yang and colleagues note that, “although these two new classes of antimigraine drugs may not be as efficacious as triptans, these novel abortive agents without cardiovascular risks might offer an alternative to current specific migraine treatments for patients at risk of cardiovascular disease.”
 

Balancing efficacy and tolerability

“When choosing an acute medication for a patient there is always a balance between efficacy and tolerability,” headache specialist and associate director of North Shore Headache and Spine Lauren Natbony, MD, said in an interview.

“A medication can only be effective if a patient is able to tolerate it and will actually use it,” Dr. Natbony said.

With respect to the current review, Dr. Natbony pointed out, “response to acute therapy can differ between migraine attacks and may be based on variables not controlled for, such as how early in an attack the medication was taken, associated symptoms such as nausea that may make oral medications less efficacious, etc.”

The authors acknowledge that the focus on short-term responses and AEs after a single dose is a limitation of the study. They also pointed out what they considered to be a strength of the study, which was its network meta-analysis design. According to the authors, this design allowed for “multiple direct and indirect comparisons, ranking the efficacy and safety of individual pharmacologic interventions and providing more precise estimates than those of RCTs and traditional meta-analysis.”

Funding for this study was provided through grants from the Ministry of Science and Technology, Taiwan; the Brain Research Center; and National Yang Ming Chiao Tung University.

Dr. Yang has received personal fees and grants from various pharmaceutical companies. He has also received grants from the Taiwan Ministry of Technology and Science, the Brain Research Center, National Yang Ming Chiao Tung University, and Taipei Veterans General Hospital outside the submitted work. The other authors and Dr. Natbony disclosed no relevant financial relationships.

New classes of antimigraine drugs demonstrate efficacy and improved tolerability for patients with chronic migraine, a new systematic review and meta-analysis finds.

“[T]he lack of cardiovascular risks of these new classes of migraine-specific treatments may provide alternative treatment options for individuals for whom currently available acute treatments have failed or for those with cardiovascular contraindications,” write lead author Chun-Pai Yang, MD, PhD, of Taichung (Taiwan) Veterans General Hospital and colleagues, in the paper, published online in JAMA Network Open.
 

Methods

The new study compared the outcomes for acute migraine management using the ditan, lasmiditan (a 5-hydroxytryptamine [5HT]1F–receptor agonist), and the two gepants, rimegepant, and ubrogepant (calcitonin gene–related peptide [CGRP] antagonists), with standard triptan (selective 5-HT1B/1D–receptor agonist) therapy.

The researchers evaluated 64 double-blind randomized clinical trials which included 46,442 patients, the majority of whom (74%-87%) were women with an age range of 36-43 years.

The primary outcome evaluated was the odds ratio for freedom from pain at 2 hours after a single dose and secondary outcomes were the OR for pain relief at 2 hours following a dose, as well as any adverse events.
 

Results

Dr. Yang and colleagues found that virtually all medications with widespread clinical use, regardless of class, were associated with higher ORs for pain freedom when compared with placebo.

Compared to ditan and gepant agents, however, triptans were associated with significantly higher ORs for pain freedom. The odds ratio ranges were 1.72-3.40 for lasmiditan, 1.58-3.13 for rimegepant, and 1.54-3.05 for ubrogepant.

With respect to pain relief at 2 hours, while all medications were more effective than placebo, triptans were associated with higher ORs when compared with the other drug classes: lasmiditan (range: OR, 1.46; 95% confidence interval, 1.09-1.96 to OR, 3.31; 95% CI, 2.41-4.55), rimegepant (range: OR, 1.33; 95% CI, 1.01-1.76 to OR, 3.01; 95% CI, 2.33-3.88), and ubrogepant (range: OR, 1.38; 95% CI, 1.02-1.88 to OR, 3.13; 95% CI, 2.35-4.15)

When assessing tolerability, the researchers found that overall, triptans were associated with the higher ORs for any adverse events (AE) with a trend of dose-response relationship. Lasmiditan (in the ditan class) was associated with the highest risk for AEs among all treatments. Most of the AEs were mild to moderate and included chest pain, tightness, heaviness, and pressure.

Dr. Yang and colleagues note that, “although these two new classes of antimigraine drugs may not be as efficacious as triptans, these novel abortive agents without cardiovascular risks might offer an alternative to current specific migraine treatments for patients at risk of cardiovascular disease.”
 

Balancing efficacy and tolerability

“When choosing an acute medication for a patient there is always a balance between efficacy and tolerability,” headache specialist and associate director of North Shore Headache and Spine Lauren Natbony, MD, said in an interview.

“A medication can only be effective if a patient is able to tolerate it and will actually use it,” Dr. Natbony said.

With respect to the current review, Dr. Natbony pointed out, “response to acute therapy can differ between migraine attacks and may be based on variables not controlled for, such as how early in an attack the medication was taken, associated symptoms such as nausea that may make oral medications less efficacious, etc.”

The authors acknowledge that the focus on short-term responses and AEs after a single dose is a limitation of the study. They also pointed out what they considered to be a strength of the study, which was its network meta-analysis design. According to the authors, this design allowed for “multiple direct and indirect comparisons, ranking the efficacy and safety of individual pharmacologic interventions and providing more precise estimates than those of RCTs and traditional meta-analysis.”

Funding for this study was provided through grants from the Ministry of Science and Technology, Taiwan; the Brain Research Center; and National Yang Ming Chiao Tung University.

Dr. Yang has received personal fees and grants from various pharmaceutical companies. He has also received grants from the Taiwan Ministry of Technology and Science, the Brain Research Center, National Yang Ming Chiao Tung University, and Taipei Veterans General Hospital outside the submitted work. The other authors and Dr. Natbony disclosed no relevant financial relationships.

New classes of antimigraine drugs demonstrate efficacy and improved tolerability for patients with chronic migraine, a new systematic review and meta-analysis finds.

“[T]he lack of cardiovascular risks of these new classes of migraine-specific treatments may provide alternative treatment options for individuals for whom currently available acute treatments have failed or for those with cardiovascular contraindications,” write lead author Chun-Pai Yang, MD, PhD, of Taichung (Taiwan) Veterans General Hospital and colleagues, in the paper, published online in JAMA Network Open.
 

Methods

The new study compared the outcomes for acute migraine management using the ditan, lasmiditan (a 5-hydroxytryptamine [5HT]1F–receptor agonist), and the two gepants, rimegepant, and ubrogepant (calcitonin gene–related peptide [CGRP] antagonists), with standard triptan (selective 5-HT1B/1D–receptor agonist) therapy.

The researchers evaluated 64 double-blind randomized clinical trials which included 46,442 patients, the majority of whom (74%-87%) were women with an age range of 36-43 years.

The primary outcome evaluated was the odds ratio for freedom from pain at 2 hours after a single dose and secondary outcomes were the OR for pain relief at 2 hours following a dose, as well as any adverse events.
 

Results

Dr. Yang and colleagues found that virtually all medications with widespread clinical use, regardless of class, were associated with higher ORs for pain freedom when compared with placebo.

Compared to ditan and gepant agents, however, triptans were associated with significantly higher ORs for pain freedom. The odds ratio ranges were 1.72-3.40 for lasmiditan, 1.58-3.13 for rimegepant, and 1.54-3.05 for ubrogepant.

With respect to pain relief at 2 hours, while all medications were more effective than placebo, triptans were associated with higher ORs when compared with the other drug classes: lasmiditan (range: OR, 1.46; 95% confidence interval, 1.09-1.96 to OR, 3.31; 95% CI, 2.41-4.55), rimegepant (range: OR, 1.33; 95% CI, 1.01-1.76 to OR, 3.01; 95% CI, 2.33-3.88), and ubrogepant (range: OR, 1.38; 95% CI, 1.02-1.88 to OR, 3.13; 95% CI, 2.35-4.15)

When assessing tolerability, the researchers found that overall, triptans were associated with the higher ORs for any adverse events (AE) with a trend of dose-response relationship. Lasmiditan (in the ditan class) was associated with the highest risk for AEs among all treatments. Most of the AEs were mild to moderate and included chest pain, tightness, heaviness, and pressure.

Dr. Yang and colleagues note that, “although these two new classes of antimigraine drugs may not be as efficacious as triptans, these novel abortive agents without cardiovascular risks might offer an alternative to current specific migraine treatments for patients at risk of cardiovascular disease.”
 

Balancing efficacy and tolerability

“When choosing an acute medication for a patient there is always a balance between efficacy and tolerability,” headache specialist and associate director of North Shore Headache and Spine Lauren Natbony, MD, said in an interview.

“A medication can only be effective if a patient is able to tolerate it and will actually use it,” Dr. Natbony said.

With respect to the current review, Dr. Natbony pointed out, “response to acute therapy can differ between migraine attacks and may be based on variables not controlled for, such as how early in an attack the medication was taken, associated symptoms such as nausea that may make oral medications less efficacious, etc.”

The authors acknowledge that the focus on short-term responses and AEs after a single dose is a limitation of the study. They also pointed out what they considered to be a strength of the study, which was its network meta-analysis design. According to the authors, this design allowed for “multiple direct and indirect comparisons, ranking the efficacy and safety of individual pharmacologic interventions and providing more precise estimates than those of RCTs and traditional meta-analysis.”

Funding for this study was provided through grants from the Ministry of Science and Technology, Taiwan; the Brain Research Center; and National Yang Ming Chiao Tung University.

Dr. Yang has received personal fees and grants from various pharmaceutical companies. He has also received grants from the Taiwan Ministry of Technology and Science, the Brain Research Center, National Yang Ming Chiao Tung University, and Taipei Veterans General Hospital outside the submitted work. The other authors and Dr. Natbony disclosed no relevant financial relationships.

Individuals with substance use disorders (SUDs) have a twofold increased risk for COVID-related hospitalization and death even after vaccination, new research shows.

Investigators analyzed data on over 10,000 vaccinated individuals with various SUDs and almost 600,000 vaccinated individuals without an SUD. They found about twice as many individuals with an SUD had a breakthrough COVID-19 infection as their counterparts without an SUD, at 7% versus 3.6%, respectively.

Worrisome phase

SUDs are “often associated with multiple comorbid conditions that are known risk factors for severe outcome of COVID-19 infection,” the investigators note.

Research published early in the pandemic showed patients with SUDs, including alcohol, cannabis, cocaine, opioid, and tobacco use disorders, were “at increased risk for COVID-19 infection and associated severe outcomes, especially among African Americans,” they add.

To date, no research has focused on the potential risk for COVID in individuals with SUDs following vaccination. In addition, although vaccines are “very effective,” breakthrough infections have been recorded, “highlighting the need to identify populations that might be most vulnerable, as we have entered a worrisome new phase of the pandemic,” the authors write.

For the study, researchers used a data analytics platform that included de-identified information from 63 health care organizations across the U.S. to estimate the risk for breakthrough COVID-19 among vaccinated patients with SUD (n = 30,183; mean age 59.3, 51.4% male, 63.2% White, 26.2% African American), compared with vaccinated individuals without SUDs (n = 549,189; mean age 54.7, 43.2% male, 63.4% White, 14.3% African American) between December 2020 and August 2021.

They also conducted statistical analyses to examine how the rate of breakthrough cases changed over that timeframe.

The cohorts were matched by demographics, adverse socioeconomic determinants of health, lifetime medical and psychiatric comorbidities, and vaccine type.

Among vaccinated SUD patients, three-quarters received the Pfizer-BioNTech vaccine, one-fifth received the Moderna vaccine, and 3.3% received the Johnson & Johnson vaccine.

In contrast, among the vaccinated non-SUD population, almost all (88.2%) received the Pfizer-BioNTech vaccine, 10% received Moderna, and only 1.2% received the Johnson & Johnson vaccine.
 

Underlying drivers

The prevalence of adverse socioeconomic determinants of health was higher in vaccinated individuals with SUDs compared to those without (7.9% vs. 1.2%, respectively). Moreover, vaccinated patients with SUD had a higher lifetime prevalence of all comorbidities as well as transplants (all Ps < .001).

The risk for breakthrough infection was significantly higher in vaccinated individuals with SUDs compared to those without (all Ps < .001).

After controlling for adverse socioeconomic determinants of health and comorbid medical conditions, the risk for breakthrough infection “no longer differed in SUD compared to non-SUD cohorts, except for patients with cannabis use disorder, who remained at significantly increased risk,” the authors report.

In both populations, the rate of breakthrough infections “steadily increased” between January and August 2021.

The risk for hospitalization and death was higher among those with breakthrough infections, compared with those in the matched cohort without breakthrough infections, but the risk for hospitalization and death were higher in the SUD compared with the non-SUD population.

In the SUD patients, after matching an array of demographic, socioeconomic, and medical factors as well as vaccine type, only cannabis use disorder was associated with a higher risk in African Americans, compared with matched Caucasians (HR = 1.63; 95% confidence interval, 1.06-2.51).

“When we adjusted the data to account for comorbidities and for socioeconomic background, we no longer saw a difference between those with substance use disorders and those without – the only exception to this was for people with cannabis use disorder,” said Dr. Volkow.

“This suggests that these factors, which are often associated with substance use disorders, are likely the underlying drivers for the increased risk,” she continued.

She added that it is important for other studies to investigate why individuals with cannabis use disorder had a higher risk for breakthrough infections.
 

Good news, bad news

Commenting for this news organization, Anna Lembke, MD, professor of psychiatry and behavioral sciences, Stanford (Calif.) University, said the study is important and contains good news and bad news.

The good news, she said, “is that, after controlling for comorbidities and socioeconomic variables, patients with SUDs are no more likely than patients without SUDs to get COVID after getting vaccinated, and the bad news is that if vaccinated patients with SUDs do get COVID, they’re more likely to end up hospitalized or die from it,” said Dr. Lembke, who was not involved with the study.

“The take-home message for clinicians is that if your vaccinated patient with an SUD gets COVID, be on the alert for a more complicated medical outcome and a higher risk of death,” warned Dr. Lembke.

This study was supported by the U.S. National Institute on Drug Abuse, the U.S. National Institute of Aging, and the Clinical and Translational Science Collaborative (CTSC) of Cleveland. No disclosures were listed on the original study. Dr. Lembke has disclosed no relevant financial relationships.

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

Individuals with substance use disorders (SUDs) have a twofold increased risk for COVID-related hospitalization and death even after vaccination, new research shows.

Investigators analyzed data on over 10,000 vaccinated individuals with various SUDs and almost 600,000 vaccinated individuals without an SUD. They found about twice as many individuals with an SUD had a breakthrough COVID-19 infection as their counterparts without an SUD, at 7% versus 3.6%, respectively.

Worrisome phase

SUDs are “often associated with multiple comorbid conditions that are known risk factors for severe outcome of COVID-19 infection,” the investigators note.

Research published early in the pandemic showed patients with SUDs, including alcohol, cannabis, cocaine, opioid, and tobacco use disorders, were “at increased risk for COVID-19 infection and associated severe outcomes, especially among African Americans,” they add.

To date, no research has focused on the potential risk for COVID in individuals with SUDs following vaccination. In addition, although vaccines are “very effective,” breakthrough infections have been recorded, “highlighting the need to identify populations that might be most vulnerable, as we have entered a worrisome new phase of the pandemic,” the authors write.

For the study, researchers used a data analytics platform that included de-identified information from 63 health care organizations across the U.S. to estimate the risk for breakthrough COVID-19 among vaccinated patients with SUD (n = 30,183; mean age 59.3, 51.4% male, 63.2% White, 26.2% African American), compared with vaccinated individuals without SUDs (n = 549,189; mean age 54.7, 43.2% male, 63.4% White, 14.3% African American) between December 2020 and August 2021.

They also conducted statistical analyses to examine how the rate of breakthrough cases changed over that timeframe.

The cohorts were matched by demographics, adverse socioeconomic determinants of health, lifetime medical and psychiatric comorbidities, and vaccine type.

Among vaccinated SUD patients, three-quarters received the Pfizer-BioNTech vaccine, one-fifth received the Moderna vaccine, and 3.3% received the Johnson & Johnson vaccine.

In contrast, among the vaccinated non-SUD population, almost all (88.2%) received the Pfizer-BioNTech vaccine, 10% received Moderna, and only 1.2% received the Johnson & Johnson vaccine.
 

Underlying drivers

The prevalence of adverse socioeconomic determinants of health was higher in vaccinated individuals with SUDs compared to those without (7.9% vs. 1.2%, respectively). Moreover, vaccinated patients with SUD had a higher lifetime prevalence of all comorbidities as well as transplants (all Ps < .001).

The risk for breakthrough infection was significantly higher in vaccinated individuals with SUDs compared to those without (all Ps < .001).

After controlling for adverse socioeconomic determinants of health and comorbid medical conditions, the risk for breakthrough infection “no longer differed in SUD compared to non-SUD cohorts, except for patients with cannabis use disorder, who remained at significantly increased risk,” the authors report.

In both populations, the rate of breakthrough infections “steadily increased” between January and August 2021.

The risk for hospitalization and death was higher among those with breakthrough infections, compared with those in the matched cohort without breakthrough infections, but the risk for hospitalization and death were higher in the SUD compared with the non-SUD population.

In the SUD patients, after matching an array of demographic, socioeconomic, and medical factors as well as vaccine type, only cannabis use disorder was associated with a higher risk in African Americans, compared with matched Caucasians (HR = 1.63; 95% confidence interval, 1.06-2.51).

“When we adjusted the data to account for comorbidities and for socioeconomic background, we no longer saw a difference between those with substance use disorders and those without – the only exception to this was for people with cannabis use disorder,” said Dr. Volkow.

“This suggests that these factors, which are often associated with substance use disorders, are likely the underlying drivers for the increased risk,” she continued.

She added that it is important for other studies to investigate why individuals with cannabis use disorder had a higher risk for breakthrough infections.
 

Good news, bad news

Commenting for this news organization, Anna Lembke, MD, professor of psychiatry and behavioral sciences, Stanford (Calif.) University, said the study is important and contains good news and bad news.

The good news, she said, “is that, after controlling for comorbidities and socioeconomic variables, patients with SUDs are no more likely than patients without SUDs to get COVID after getting vaccinated, and the bad news is that if vaccinated patients with SUDs do get COVID, they’re more likely to end up hospitalized or die from it,” said Dr. Lembke, who was not involved with the study.

“The take-home message for clinicians is that if your vaccinated patient with an SUD gets COVID, be on the alert for a more complicated medical outcome and a higher risk of death,” warned Dr. Lembke.

This study was supported by the U.S. National Institute on Drug Abuse, the U.S. National Institute of Aging, and the Clinical and Translational Science Collaborative (CTSC) of Cleveland. No disclosures were listed on the original study. Dr. Lembke has disclosed no relevant financial relationships.

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

Individuals with substance use disorders (SUDs) have a twofold increased risk for COVID-related hospitalization and death even after vaccination, new research shows.

Investigators analyzed data on over 10,000 vaccinated individuals with various SUDs and almost 600,000 vaccinated individuals without an SUD. They found about twice as many individuals with an SUD had a breakthrough COVID-19 infection as their counterparts without an SUD, at 7% versus 3.6%, respectively.

Worrisome phase

SUDs are “often associated with multiple comorbid conditions that are known risk factors for severe outcome of COVID-19 infection,” the investigators note.

Research published early in the pandemic showed patients with SUDs, including alcohol, cannabis, cocaine, opioid, and tobacco use disorders, were “at increased risk for COVID-19 infection and associated severe outcomes, especially among African Americans,” they add.

To date, no research has focused on the potential risk for COVID in individuals with SUDs following vaccination. In addition, although vaccines are “very effective,” breakthrough infections have been recorded, “highlighting the need to identify populations that might be most vulnerable, as we have entered a worrisome new phase of the pandemic,” the authors write.

For the study, researchers used a data analytics platform that included de-identified information from 63 health care organizations across the U.S. to estimate the risk for breakthrough COVID-19 among vaccinated patients with SUD (n = 30,183; mean age 59.3, 51.4% male, 63.2% White, 26.2% African American), compared with vaccinated individuals without SUDs (n = 549,189; mean age 54.7, 43.2% male, 63.4% White, 14.3% African American) between December 2020 and August 2021.

They also conducted statistical analyses to examine how the rate of breakthrough cases changed over that timeframe.

The cohorts were matched by demographics, adverse socioeconomic determinants of health, lifetime medical and psychiatric comorbidities, and vaccine type.

Among vaccinated SUD patients, three-quarters received the Pfizer-BioNTech vaccine, one-fifth received the Moderna vaccine, and 3.3% received the Johnson & Johnson vaccine.

In contrast, among the vaccinated non-SUD population, almost all (88.2%) received the Pfizer-BioNTech vaccine, 10% received Moderna, and only 1.2% received the Johnson & Johnson vaccine.
 

Underlying drivers

The prevalence of adverse socioeconomic determinants of health was higher in vaccinated individuals with SUDs compared to those without (7.9% vs. 1.2%, respectively). Moreover, vaccinated patients with SUD had a higher lifetime prevalence of all comorbidities as well as transplants (all Ps < .001).

The risk for breakthrough infection was significantly higher in vaccinated individuals with SUDs compared to those without (all Ps < .001).

After controlling for adverse socioeconomic determinants of health and comorbid medical conditions, the risk for breakthrough infection “no longer differed in SUD compared to non-SUD cohorts, except for patients with cannabis use disorder, who remained at significantly increased risk,” the authors report.

In both populations, the rate of breakthrough infections “steadily increased” between January and August 2021.

The risk for hospitalization and death was higher among those with breakthrough infections, compared with those in the matched cohort without breakthrough infections, but the risk for hospitalization and death were higher in the SUD compared with the non-SUD population.

In the SUD patients, after matching an array of demographic, socioeconomic, and medical factors as well as vaccine type, only cannabis use disorder was associated with a higher risk in African Americans, compared with matched Caucasians (HR = 1.63; 95% confidence interval, 1.06-2.51).

“When we adjusted the data to account for comorbidities and for socioeconomic background, we no longer saw a difference between those with substance use disorders and those without – the only exception to this was for people with cannabis use disorder,” said Dr. Volkow.

“This suggests that these factors, which are often associated with substance use disorders, are likely the underlying drivers for the increased risk,” she continued.

She added that it is important for other studies to investigate why individuals with cannabis use disorder had a higher risk for breakthrough infections.
 

Good news, bad news

Commenting for this news organization, Anna Lembke, MD, professor of psychiatry and behavioral sciences, Stanford (Calif.) University, said the study is important and contains good news and bad news.

The good news, she said, “is that, after controlling for comorbidities and socioeconomic variables, patients with SUDs are no more likely than patients without SUDs to get COVID after getting vaccinated, and the bad news is that if vaccinated patients with SUDs do get COVID, they’re more likely to end up hospitalized or die from it,” said Dr. Lembke, who was not involved with the study.

“The take-home message for clinicians is that if your vaccinated patient with an SUD gets COVID, be on the alert for a more complicated medical outcome and a higher risk of death,” warned Dr. Lembke.

This study was supported by the U.S. National Institute on Drug Abuse, the U.S. National Institute of Aging, and the Clinical and Translational Science Collaborative (CTSC) of Cleveland. No disclosures were listed on the original study. Dr. Lembke has disclosed no relevant financial relationships.

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

An 8-month high-intensity resistance and impact training program (HiRIT, Onero) led to greater gains in lumbar spine bone mineral density (BMD) and leg/back strength than a low-intensity Pilates-based program (Buff Bones).
 

BeyondImages/Getty Images

These findings are from the Medication and Exercise for Osteoporosis (MEDEX-OP) trial, which included 115 postmenopausal women with low bone mass. Patients were randomly assigned to attend either the HiRIT or Pilates-based exercise program. The participants attended supervised 45-min sessions twice weekly.

HiRIT was better than the low-intensity Pilates-based exercise program for enhancing bone mass, muscle strength, functional performance, and stature, the researchers reported. The low-intensity program did improve function, but to a lesser extent

Of the 115 participants, most (86) were not taking osteoporosis medicine. For the 29 women who were receiving it, the medication appeared to enhance the effect of exercise.

Melanie Fischbacher, PhD candidate, Griffith University, Gold Coast, Australia, presented these findings in an oral session at the annual meeting of the American Society for Bone and Mineral Research; the study was also published in the Journal of Bone and Mineral Research.

The study’s senior author, Belinda R. Beck, PhD, director of the Bone Clinic in Brisbane, Australia, developed the Onero HiRIT program and has licensed it to others in Australia.

“It is a very effective program and we have shown it can be undertaken safely, but it must be supervised because of the heavy weights and high-risk clientele,” Beck stressed to this news organization.

“This is not a program you should just hand to a patient and tell them to do in a gym,” she said.

“Both forms of exercise in our study were beneficial for functional outcomes but Onero improved back extensor strength, mobility and stature considerably more than Buff Bones,” Ms. Fischbacher said in an interview.

Nevertheless, “the contribution of functional capacity to risk of falling and fracture cannot be overstated, and bone medications do not address function,” she noted.

“More trials combining bone medication and bone-targeted exercise are needed,” the researchers concluded.

Compliance stands out, study supports high-intensity exercise

Kristen M. Beavers, PhD, MPH, RD, who was not involved with this research, told this news organization that participant compliance in the study really stands out.

“Compliance to an 8-month, 2 day/week high-intensity resistance training program among older women with low bone mass was quite good in this study [>80%], with very few adverse events reported,” said Dr. Beavers, of the department of health and exercise science, Wake Forest University, Winston Salem, N.C.

“A lot of individuals wouldn’t even consider recommending this type/intensity of exercise to this population, because they are worried it is too risky and/or the uptake will be low,” she said.

Although the benefit in BMD and strength wasn’t seen universally across all bone/muscle outcomes assessed, the findings do reinforce the idea that high-intensity exercise is more efficacious for bone health than low-intensity exercise, she noted.

“The possible additive effect of high-intensity exercise when combined with medication is worth confirming in larger, adequately designed/powered studies,” according to Dr. Beavers.

“The general consensus in the field is that higher-intensity exercise is more osteogenic than low-intensity exercise, but improving muscle mass, quality, and function (including balance) are also important to reduce the risk of falls, which is a major contributor to incident fracture,” she noted.

Exercise, even low-intensity exercise, reduces the risk for falls, as shown in a recent meta-analysis, she added. This is something antiresorptive medications don’t do.
 

Building on the LIFTMOR and LIFTMOR-M Trials

Previously, the Australian group showed that HiRIT is efficacious and safe for bone formation in individuals with low to very low bone mass – in postmenopausal women in the LIFTMOR study (J Bone Miner Res. 2017 Oct 4 .doi: 10.1002/jbmr.3284), and in men in the LIFTMOR-M study.

The current study compared two exercise programs. The researchers randomly assigned 86 women who were not taking antiresorptive medication to the high-intensity (42) or low-intensity (44) exercise program. They also assigned 29 women who were receiving antiresorptive medication to the high-intensity (15) or low-intensity (14) exercise program.

In the high-intensity exercise plus medication subgroup, the women were taking denosumab (12), risedronate (2) or alendronate (1). In the low-intensity exercise plus medication subgroup, the women were taking denosumab (9), risedronate (1), alendronate (3), or zoledronic acid (1).

The mean age of the women was 64-68 years. The mean lumbar spine T score was –1.5 to –2.3, and the mean femoral neck T score was –1.7 to –2.0 (determined by dual-energy x-ray absorptiometry) .

The HiRIT training program consisted of three free-weight resistance training exercises (deadlift, back squat, overhead press), one high-impact exercise (jump drop), and two balance exercises. The exercises varied each session.

The low-intensity training consisted of bone-specific Pilates-based exercises performed on the mat; standing weight-bearing exercise with 1-kg dumbbells; and impact exercises, such as heel drops and stomping.

At 8 months, compared with women in the low-intensity exercise program, those in the HiRIT program demonstrated greater improvement in lumbar spine BMD (1.9% vs. 0.1%) and stature (0.2 cm vs. 0.0 cm), muscle strength, and functional performance.

Functional performance improved with both exercise programs, but the HiRIT program led to greater leg and back muscle strength and better results in the five times sit-to-stand test (P < .05).

HiRIT plus bone medication improved BMD at the femoral neck and total hip, whereas HiRIT alone did not. Low-intensity exercise plus bone medication improved BMD at the lumbar spine and total hip, whereas low-intensity exercise alone did not.

The retention rate was 90%. The rate of exercise compliance was 83% in the high-intensity group and 82% in the low-intensity group.

Thirty falls were reported by 24 participants (21%). One fracture occurred in each exercise group. Three adverse events occurred in the low-intensity group, and four occurred in the high-intensity group.

Dr. Beck owns the Bone Clinic and sells licenses to the Onero program. The other researchers disclosed no relevant financial relationships.

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

An 8-month high-intensity resistance and impact training program (HiRIT, Onero) led to greater gains in lumbar spine bone mineral density (BMD) and leg/back strength than a low-intensity Pilates-based program (Buff Bones).
 

BeyondImages/Getty Images

These findings are from the Medication and Exercise for Osteoporosis (MEDEX-OP) trial, which included 115 postmenopausal women with low bone mass. Patients were randomly assigned to attend either the HiRIT or Pilates-based exercise program. The participants attended supervised 45-min sessions twice weekly.

HiRIT was better than the low-intensity Pilates-based exercise program for enhancing bone mass, muscle strength, functional performance, and stature, the researchers reported. The low-intensity program did improve function, but to a lesser extent

Of the 115 participants, most (86) were not taking osteoporosis medicine. For the 29 women who were receiving it, the medication appeared to enhance the effect of exercise.

Melanie Fischbacher, PhD candidate, Griffith University, Gold Coast, Australia, presented these findings in an oral session at the annual meeting of the American Society for Bone and Mineral Research; the study was also published in the Journal of Bone and Mineral Research.

The study’s senior author, Belinda R. Beck, PhD, director of the Bone Clinic in Brisbane, Australia, developed the Onero HiRIT program and has licensed it to others in Australia.

“It is a very effective program and we have shown it can be undertaken safely, but it must be supervised because of the heavy weights and high-risk clientele,” Beck stressed to this news organization.

“This is not a program you should just hand to a patient and tell them to do in a gym,” she said.

“Both forms of exercise in our study were beneficial for functional outcomes but Onero improved back extensor strength, mobility and stature considerably more than Buff Bones,” Ms. Fischbacher said in an interview.

Nevertheless, “the contribution of functional capacity to risk of falling and fracture cannot be overstated, and bone medications do not address function,” she noted.

“More trials combining bone medication and bone-targeted exercise are needed,” the researchers concluded.

Compliance stands out, study supports high-intensity exercise

Kristen M. Beavers, PhD, MPH, RD, who was not involved with this research, told this news organization that participant compliance in the study really stands out.

“Compliance to an 8-month, 2 day/week high-intensity resistance training program among older women with low bone mass was quite good in this study [>80%], with very few adverse events reported,” said Dr. Beavers, of the department of health and exercise science, Wake Forest University, Winston Salem, N.C.

“A lot of individuals wouldn’t even consider recommending this type/intensity of exercise to this population, because they are worried it is too risky and/or the uptake will be low,” she said.

Although the benefit in BMD and strength wasn’t seen universally across all bone/muscle outcomes assessed, the findings do reinforce the idea that high-intensity exercise is more efficacious for bone health than low-intensity exercise, she noted.

“The possible additive effect of high-intensity exercise when combined with medication is worth confirming in larger, adequately designed/powered studies,” according to Dr. Beavers.

“The general consensus in the field is that higher-intensity exercise is more osteogenic than low-intensity exercise, but improving muscle mass, quality, and function (including balance) are also important to reduce the risk of falls, which is a major contributor to incident fracture,” she noted.

Exercise, even low-intensity exercise, reduces the risk for falls, as shown in a recent meta-analysis, she added. This is something antiresorptive medications don’t do.
 

Building on the LIFTMOR and LIFTMOR-M Trials

Previously, the Australian group showed that HiRIT is efficacious and safe for bone formation in individuals with low to very low bone mass – in postmenopausal women in the LIFTMOR study (J Bone Miner Res. 2017 Oct 4 .doi: 10.1002/jbmr.3284), and in men in the LIFTMOR-M study.

The current study compared two exercise programs. The researchers randomly assigned 86 women who were not taking antiresorptive medication to the high-intensity (42) or low-intensity (44) exercise program. They also assigned 29 women who were receiving antiresorptive medication to the high-intensity (15) or low-intensity (14) exercise program.

In the high-intensity exercise plus medication subgroup, the women were taking denosumab (12), risedronate (2) or alendronate (1). In the low-intensity exercise plus medication subgroup, the women were taking denosumab (9), risedronate (1), alendronate (3), or zoledronic acid (1).

The mean age of the women was 64-68 years. The mean lumbar spine T score was –1.5 to –2.3, and the mean femoral neck T score was –1.7 to –2.0 (determined by dual-energy x-ray absorptiometry) .

The HiRIT training program consisted of three free-weight resistance training exercises (deadlift, back squat, overhead press), one high-impact exercise (jump drop), and two balance exercises. The exercises varied each session.

The low-intensity training consisted of bone-specific Pilates-based exercises performed on the mat; standing weight-bearing exercise with 1-kg dumbbells; and impact exercises, such as heel drops and stomping.

At 8 months, compared with women in the low-intensity exercise program, those in the HiRIT program demonstrated greater improvement in lumbar spine BMD (1.9% vs. 0.1%) and stature (0.2 cm vs. 0.0 cm), muscle strength, and functional performance.

Functional performance improved with both exercise programs, but the HiRIT program led to greater leg and back muscle strength and better results in the five times sit-to-stand test (P < .05).

HiRIT plus bone medication improved BMD at the femoral neck and total hip, whereas HiRIT alone did not. Low-intensity exercise plus bone medication improved BMD at the lumbar spine and total hip, whereas low-intensity exercise alone did not.

The retention rate was 90%. The rate of exercise compliance was 83% in the high-intensity group and 82% in the low-intensity group.

Thirty falls were reported by 24 participants (21%). One fracture occurred in each exercise group. Three adverse events occurred in the low-intensity group, and four occurred in the high-intensity group.

Dr. Beck owns the Bone Clinic and sells licenses to the Onero program. The other researchers disclosed no relevant financial relationships.

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

An 8-month high-intensity resistance and impact training program (HiRIT, Onero) led to greater gains in lumbar spine bone mineral density (BMD) and leg/back strength than a low-intensity Pilates-based program (Buff Bones).
 

BeyondImages/Getty Images

These findings are from the Medication and Exercise for Osteoporosis (MEDEX-OP) trial, which included 115 postmenopausal women with low bone mass. Patients were randomly assigned to attend either the HiRIT or Pilates-based exercise program. The participants attended supervised 45-min sessions twice weekly.

HiRIT was better than the low-intensity Pilates-based exercise program for enhancing bone mass, muscle strength, functional performance, and stature, the researchers reported. The low-intensity program did improve function, but to a lesser extent

Of the 115 participants, most (86) were not taking osteoporosis medicine. For the 29 women who were receiving it, the medication appeared to enhance the effect of exercise.

Melanie Fischbacher, PhD candidate, Griffith University, Gold Coast, Australia, presented these findings in an oral session at the annual meeting of the American Society for Bone and Mineral Research; the study was also published in the Journal of Bone and Mineral Research.

The study’s senior author, Belinda R. Beck, PhD, director of the Bone Clinic in Brisbane, Australia, developed the Onero HiRIT program and has licensed it to others in Australia.

“It is a very effective program and we have shown it can be undertaken safely, but it must be supervised because of the heavy weights and high-risk clientele,” Beck stressed to this news organization.

“This is not a program you should just hand to a patient and tell them to do in a gym,” she said.

“Both forms of exercise in our study were beneficial for functional outcomes but Onero improved back extensor strength, mobility and stature considerably more than Buff Bones,” Ms. Fischbacher said in an interview.

Nevertheless, “the contribution of functional capacity to risk of falling and fracture cannot be overstated, and bone medications do not address function,” she noted.

“More trials combining bone medication and bone-targeted exercise are needed,” the researchers concluded.

Compliance stands out, study supports high-intensity exercise

Kristen M. Beavers, PhD, MPH, RD, who was not involved with this research, told this news organization that participant compliance in the study really stands out.

“Compliance to an 8-month, 2 day/week high-intensity resistance training program among older women with low bone mass was quite good in this study [>80%], with very few adverse events reported,” said Dr. Beavers, of the department of health and exercise science, Wake Forest University, Winston Salem, N.C.

“A lot of individuals wouldn’t even consider recommending this type/intensity of exercise to this population, because they are worried it is too risky and/or the uptake will be low,” she said.

Although the benefit in BMD and strength wasn’t seen universally across all bone/muscle outcomes assessed, the findings do reinforce the idea that high-intensity exercise is more efficacious for bone health than low-intensity exercise, she noted.

“The possible additive effect of high-intensity exercise when combined with medication is worth confirming in larger, adequately designed/powered studies,” according to Dr. Beavers.

“The general consensus in the field is that higher-intensity exercise is more osteogenic than low-intensity exercise, but improving muscle mass, quality, and function (including balance) are also important to reduce the risk of falls, which is a major contributor to incident fracture,” she noted.

Exercise, even low-intensity exercise, reduces the risk for falls, as shown in a recent meta-analysis, she added. This is something antiresorptive medications don’t do.
 

Building on the LIFTMOR and LIFTMOR-M Trials

Previously, the Australian group showed that HiRIT is efficacious and safe for bone formation in individuals with low to very low bone mass – in postmenopausal women in the LIFTMOR study (J Bone Miner Res. 2017 Oct 4 .doi: 10.1002/jbmr.3284), and in men in the LIFTMOR-M study.

The current study compared two exercise programs. The researchers randomly assigned 86 women who were not taking antiresorptive medication to the high-intensity (42) or low-intensity (44) exercise program. They also assigned 29 women who were receiving antiresorptive medication to the high-intensity (15) or low-intensity (14) exercise program.

In the high-intensity exercise plus medication subgroup, the women were taking denosumab (12), risedronate (2) or alendronate (1). In the low-intensity exercise plus medication subgroup, the women were taking denosumab (9), risedronate (1), alendronate (3), or zoledronic acid (1).

The mean age of the women was 64-68 years. The mean lumbar spine T score was –1.5 to –2.3, and the mean femoral neck T score was –1.7 to –2.0 (determined by dual-energy x-ray absorptiometry) .

The HiRIT training program consisted of three free-weight resistance training exercises (deadlift, back squat, overhead press), one high-impact exercise (jump drop), and two balance exercises. The exercises varied each session.

The low-intensity training consisted of bone-specific Pilates-based exercises performed on the mat; standing weight-bearing exercise with 1-kg dumbbells; and impact exercises, such as heel drops and stomping.

At 8 months, compared with women in the low-intensity exercise program, those in the HiRIT program demonstrated greater improvement in lumbar spine BMD (1.9% vs. 0.1%) and stature (0.2 cm vs. 0.0 cm), muscle strength, and functional performance.

Functional performance improved with both exercise programs, but the HiRIT program led to greater leg and back muscle strength and better results in the five times sit-to-stand test (P < .05).

HiRIT plus bone medication improved BMD at the femoral neck and total hip, whereas HiRIT alone did not. Low-intensity exercise plus bone medication improved BMD at the lumbar spine and total hip, whereas low-intensity exercise alone did not.

The retention rate was 90%. The rate of exercise compliance was 83% in the high-intensity group and 82% in the low-intensity group.

Thirty falls were reported by 24 participants (21%). One fracture occurred in each exercise group. Three adverse events occurred in the low-intensity group, and four occurred in the high-intensity group.

Dr. Beck owns the Bone Clinic and sells licenses to the Onero program. The other researchers disclosed no relevant financial relationships.

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

COVID-19 has killed Native Americans at twice the rate of White Americans, underscoring the health inequities and deep-rooted distrust tribal nations have of federal government entities.

And yet, Native Americans have the highest vaccination rates of any major racial or ethnic group in the United States. Like many other tribal nations, the Navajo had to embrace Western science to reclaim its social customs and ceremonies. “We’re a very social culture, so having to isolate really impacted our mental health,” said Mary Hasbah Roessel, MD, DLFAPA, a Navajo psychiatrist who is affiliated with Santa Fe Indian Hospital in New Mexico.

The Navajo nation occupies the largest Native American reservation in the United States, spanning New Mexico, Arizona, and Utah. As of mid-October, the nation had reported more than 34,000 COVID-19 cases and 1,400 deaths in its jurisdiction.

In an interview with this news organization, Dr. Roessel described the partnerships that mobilized a nation of more than 250,000 individuals to get vaccinated.

Question: Why has the death rate been so high in the Navajo nation?

Answer: A lot of health disparities before the pandemic were blatantly revealed during COVID. Only 40% of people on the reservation had running water. Having to stay home and isolate led to food insecurity. Further insecurity issues affected our ability to stay healthy, such as having good sanitation. There’s a lot of poverty, a high unemployment rate. Some people had to go to work off reservation and were potentially bringing the virus home. A lot of generations live in the same household. Elders were vulnerable to getting the infection, and there was little ability to isolate if someone wasn’t having symptoms. Hospitals nearby didn’t have ICUs.

Therefore, the rate of cases skyrocketed early on. We were disproportionately affected. The Navajo nation per capita had the highest rate of cases in any state.
 

Q: What changes took place within the Navajo nation to get people vaccinated? What role did the federal Indian Health Service have in promoting this?

A: There had to be a shift in acceptance of the vaccinations. I think what particularly helped the Navajo nation was seeing the IHS rise up and provide access for treatments and vaccinations early on.

With the IHS, we went into a disaster response mode with all-hands-on deck meetings. We had to figure out how we could access mass vaccination clinics. Partnering with the Navajo Department of Health, we did that right away with hospitals and small clinics across the Navajo nation. Casinos owned by tribal entities that closed during COVID reopened and were used as vaccination clinics.

Vaccinations were sent to us fairly quickly. I ended up getting vaccinated in December 2020, when it was first rolled out.

Native and Navajo individuals have been reluctant to rely on government services. Because IHS came through with the vaccines, COVID reduced that stigma to access its services. Even the Navajo Department of Health partnered with the Indian Health Service to provide culturally relevant campaigns that explain why the vaccine is valuable.

I think because people were so impacted, they saw something valuable with the vaccine. Given the education and access, people were ready to get vaccinated. They realized if a whole household got vaccinated, they could see early on that they could be social again.
 

Q: What cultural factors have been contributing to this positive development?

A: In our Navajo culture, we’ve dealt with monsters before. We talk about that in terms of how we teach our young people to be strong and resilient. We talked about this virus as being another monster we had to tackle and control. The teaching was along those lines. We’ve dealt with this before, and we can handle it. We’re resilient. Our culture is very strong in that way. So how do we do it? We have to partner; we have to embrace Western medicine to return back to the ceremonies we want to have again and be social again. We focus on positive things, so if we see something as potentially positive, such as the vaccine, we see that and know that’s something to help us come into our life again.

Q: I would expect that protecting elders in the tribe would be a big incentive in taking the vaccine.

A: Yes, we didn’t want to lose our language and culture, and we wanted to protect our elders. Having a way to do that was very important as well. They were among the first to get vaccinated.

Q: What is the current vaccination rate in the Navajo nation?

A: I think it’s in the upper 80th percentile. It’s very high.

Q: What have been the biggest takeaways so far, and what are your hopes for the future?

A: Even though the Navajo Nation has been impacted and devastated with the loss of elders and knowledge keepers, we still have our culture and ceremonies intact to the point that we know we can be resilient get through this difficult time.

Through collaborations with the federal and state governments and the clinics, we see that things are different now. Going forward, my hope is these partnerships will continue, that we’ll build those relationships and not be so siloed in our care. When the New Mexico Department of Health rolled out its first vaccination clinic, for example, we jumped on and saw how they did it. We were then able to do our own, collaborating with the state.

We also saw how important our culture was, how it helped our Navajo people through these difficult times.

Dr. Roessel, a distinguished fellow of the American Psychiatric Association, has special expertise in cultural psychiatry. Her childhood was spent growing up in the Navajo nation with her grandfather, who was a Navajo medicine man. Her psychiatric practice focuses on integrating Indigenous knowledge and principles.

References

American Public Media Research Lab. “The Color of Coronavirus: COVID-19 Deaths by Race and Ethnicity in the U.S.” 2021 Mar 5.

Centers for Disease Control and Prevention. “Demographic Characteristics of People Receiving COVID-19 Vaccinations in the United States.” Data as of 2021 Oct 14.

Navajo Nation. Indian Health Service. U.S. Department of Health & Human Services.

The Navajo Nation’s Office of the President and Vice President. “11 New Cases, 32,735 Recoveries, and Six Recent Deaths Related to COVID-19.” 2021 Oct 13.

Navajo Nation Government web page.

COVID-19 has killed Native Americans at twice the rate of White Americans, underscoring the health inequities and deep-rooted distrust tribal nations have of federal government entities.

And yet, Native Americans have the highest vaccination rates of any major racial or ethnic group in the United States. Like many other tribal nations, the Navajo had to embrace Western science to reclaim its social customs and ceremonies. “We’re a very social culture, so having to isolate really impacted our mental health,” said Mary Hasbah Roessel, MD, DLFAPA, a Navajo psychiatrist who is affiliated with Santa Fe Indian Hospital in New Mexico.

The Navajo nation occupies the largest Native American reservation in the United States, spanning New Mexico, Arizona, and Utah. As of mid-October, the nation had reported more than 34,000 COVID-19 cases and 1,400 deaths in its jurisdiction.

In an interview with this news organization, Dr. Roessel described the partnerships that mobilized a nation of more than 250,000 individuals to get vaccinated.

Question: Why has the death rate been so high in the Navajo nation?

Answer: A lot of health disparities before the pandemic were blatantly revealed during COVID. Only 40% of people on the reservation had running water. Having to stay home and isolate led to food insecurity. Further insecurity issues affected our ability to stay healthy, such as having good sanitation. There’s a lot of poverty, a high unemployment rate. Some people had to go to work off reservation and were potentially bringing the virus home. A lot of generations live in the same household. Elders were vulnerable to getting the infection, and there was little ability to isolate if someone wasn’t having symptoms. Hospitals nearby didn’t have ICUs.

Therefore, the rate of cases skyrocketed early on. We were disproportionately affected. The Navajo nation per capita had the highest rate of cases in any state.
 

Q: What changes took place within the Navajo nation to get people vaccinated? What role did the federal Indian Health Service have in promoting this?

A: There had to be a shift in acceptance of the vaccinations. I think what particularly helped the Navajo nation was seeing the IHS rise up and provide access for treatments and vaccinations early on.

With the IHS, we went into a disaster response mode with all-hands-on deck meetings. We had to figure out how we could access mass vaccination clinics. Partnering with the Navajo Department of Health, we did that right away with hospitals and small clinics across the Navajo nation. Casinos owned by tribal entities that closed during COVID reopened and were used as vaccination clinics.

Vaccinations were sent to us fairly quickly. I ended up getting vaccinated in December 2020, when it was first rolled out.

Native and Navajo individuals have been reluctant to rely on government services. Because IHS came through with the vaccines, COVID reduced that stigma to access its services. Even the Navajo Department of Health partnered with the Indian Health Service to provide culturally relevant campaigns that explain why the vaccine is valuable.

I think because people were so impacted, they saw something valuable with the vaccine. Given the education and access, people were ready to get vaccinated. They realized if a whole household got vaccinated, they could see early on that they could be social again.
 

Q: What cultural factors have been contributing to this positive development?

A: In our Navajo culture, we’ve dealt with monsters before. We talk about that in terms of how we teach our young people to be strong and resilient. We talked about this virus as being another monster we had to tackle and control. The teaching was along those lines. We’ve dealt with this before, and we can handle it. We’re resilient. Our culture is very strong in that way. So how do we do it? We have to partner; we have to embrace Western medicine to return back to the ceremonies we want to have again and be social again. We focus on positive things, so if we see something as potentially positive, such as the vaccine, we see that and know that’s something to help us come into our life again.

Q: I would expect that protecting elders in the tribe would be a big incentive in taking the vaccine.

A: Yes, we didn’t want to lose our language and culture, and we wanted to protect our elders. Having a way to do that was very important as well. They were among the first to get vaccinated.

Q: What is the current vaccination rate in the Navajo nation?

A: I think it’s in the upper 80th percentile. It’s very high.

Q: What have been the biggest takeaways so far, and what are your hopes for the future?

A: Even though the Navajo Nation has been impacted and devastated with the loss of elders and knowledge keepers, we still have our culture and ceremonies intact to the point that we know we can be resilient get through this difficult time.

Through collaborations with the federal and state governments and the clinics, we see that things are different now. Going forward, my hope is these partnerships will continue, that we’ll build those relationships and not be so siloed in our care. When the New Mexico Department of Health rolled out its first vaccination clinic, for example, we jumped on and saw how they did it. We were then able to do our own, collaborating with the state.

We also saw how important our culture was, how it helped our Navajo people through these difficult times.

Dr. Roessel, a distinguished fellow of the American Psychiatric Association, has special expertise in cultural psychiatry. Her childhood was spent growing up in the Navajo nation with her grandfather, who was a Navajo medicine man. Her psychiatric practice focuses on integrating Indigenous knowledge and principles.

References

American Public Media Research Lab. “The Color of Coronavirus: COVID-19 Deaths by Race and Ethnicity in the U.S.” 2021 Mar 5.

Centers for Disease Control and Prevention. “Demographic Characteristics of People Receiving COVID-19 Vaccinations in the United States.” Data as of 2021 Oct 14.

Navajo Nation. Indian Health Service. U.S. Department of Health & Human Services.

The Navajo Nation’s Office of the President and Vice President. “11 New Cases, 32,735 Recoveries, and Six Recent Deaths Related to COVID-19.” 2021 Oct 13.

Navajo Nation Government web page.

COVID-19 has killed Native Americans at twice the rate of White Americans, underscoring the health inequities and deep-rooted distrust tribal nations have of federal government entities.

And yet, Native Americans have the highest vaccination rates of any major racial or ethnic group in the United States. Like many other tribal nations, the Navajo had to embrace Western science to reclaim its social customs and ceremonies. “We’re a very social culture, so having to isolate really impacted our mental health,” said Mary Hasbah Roessel, MD, DLFAPA, a Navajo psychiatrist who is affiliated with Santa Fe Indian Hospital in New Mexico.

The Navajo nation occupies the largest Native American reservation in the United States, spanning New Mexico, Arizona, and Utah. As of mid-October, the nation had reported more than 34,000 COVID-19 cases and 1,400 deaths in its jurisdiction.

In an interview with this news organization, Dr. Roessel described the partnerships that mobilized a nation of more than 250,000 individuals to get vaccinated.

Question: Why has the death rate been so high in the Navajo nation?

Answer: A lot of health disparities before the pandemic were blatantly revealed during COVID. Only 40% of people on the reservation had running water. Having to stay home and isolate led to food insecurity. Further insecurity issues affected our ability to stay healthy, such as having good sanitation. There’s a lot of poverty, a high unemployment rate. Some people had to go to work off reservation and were potentially bringing the virus home. A lot of generations live in the same household. Elders were vulnerable to getting the infection, and there was little ability to isolate if someone wasn’t having symptoms. Hospitals nearby didn’t have ICUs.

Therefore, the rate of cases skyrocketed early on. We were disproportionately affected. The Navajo nation per capita had the highest rate of cases in any state.
 

Q: What changes took place within the Navajo nation to get people vaccinated? What role did the federal Indian Health Service have in promoting this?

A: There had to be a shift in acceptance of the vaccinations. I think what particularly helped the Navajo nation was seeing the IHS rise up and provide access for treatments and vaccinations early on.

With the IHS, we went into a disaster response mode with all-hands-on deck meetings. We had to figure out how we could access mass vaccination clinics. Partnering with the Navajo Department of Health, we did that right away with hospitals and small clinics across the Navajo nation. Casinos owned by tribal entities that closed during COVID reopened and were used as vaccination clinics.

Vaccinations were sent to us fairly quickly. I ended up getting vaccinated in December 2020, when it was first rolled out.

Native and Navajo individuals have been reluctant to rely on government services. Because IHS came through with the vaccines, COVID reduced that stigma to access its services. Even the Navajo Department of Health partnered with the Indian Health Service to provide culturally relevant campaigns that explain why the vaccine is valuable.

I think because people were so impacted, they saw something valuable with the vaccine. Given the education and access, people were ready to get vaccinated. They realized if a whole household got vaccinated, they could see early on that they could be social again.
 

Q: What cultural factors have been contributing to this positive development?

A: In our Navajo culture, we’ve dealt with monsters before. We talk about that in terms of how we teach our young people to be strong and resilient. We talked about this virus as being another monster we had to tackle and control. The teaching was along those lines. We’ve dealt with this before, and we can handle it. We’re resilient. Our culture is very strong in that way. So how do we do it? We have to partner; we have to embrace Western medicine to return back to the ceremonies we want to have again and be social again. We focus on positive things, so if we see something as potentially positive, such as the vaccine, we see that and know that’s something to help us come into our life again.

Q: I would expect that protecting elders in the tribe would be a big incentive in taking the vaccine.

A: Yes, we didn’t want to lose our language and culture, and we wanted to protect our elders. Having a way to do that was very important as well. They were among the first to get vaccinated.

Q: What is the current vaccination rate in the Navajo nation?

A: I think it’s in the upper 80th percentile. It’s very high.

Q: What have been the biggest takeaways so far, and what are your hopes for the future?

A: Even though the Navajo Nation has been impacted and devastated with the loss of elders and knowledge keepers, we still have our culture and ceremonies intact to the point that we know we can be resilient get through this difficult time.

Through collaborations with the federal and state governments and the clinics, we see that things are different now. Going forward, my hope is these partnerships will continue, that we’ll build those relationships and not be so siloed in our care. When the New Mexico Department of Health rolled out its first vaccination clinic, for example, we jumped on and saw how they did it. We were then able to do our own, collaborating with the state.

We also saw how important our culture was, how it helped our Navajo people through these difficult times.

Dr. Roessel, a distinguished fellow of the American Psychiatric Association, has special expertise in cultural psychiatry. Her childhood was spent growing up in the Navajo nation with her grandfather, who was a Navajo medicine man. Her psychiatric practice focuses on integrating Indigenous knowledge and principles.

References

American Public Media Research Lab. “The Color of Coronavirus: COVID-19 Deaths by Race and Ethnicity in the U.S.” 2021 Mar 5.

Centers for Disease Control and Prevention. “Demographic Characteristics of People Receiving COVID-19 Vaccinations in the United States.” Data as of 2021 Oct 14.

Navajo Nation. Indian Health Service. U.S. Department of Health & Human Services.

The Navajo Nation’s Office of the President and Vice President. “11 New Cases, 32,735 Recoveries, and Six Recent Deaths Related to COVID-19.” 2021 Oct 13.

Navajo Nation Government web page.

In patients with basal cell carcinoma (BCC), watchful waiting may be more suitable than active treatment for patients with asymptomatic nodular or superficial BCC and a limited life expectancy, according to a study published in JAMA Dermatology.

“Patient preferences, treatment goals, and the option for proceeding with a watchful waiting approach should be discussed as part of personalized shared decision-making,” wrote Marieke van Winden, MD, MSc, of Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues. “In patients with a limited life expectancy and asymptomatic low-risk tumors, the time to benefit from treatment might exceed life expectancy, and watchful waiting should be discussed as a potentially appropriate approach.”

As little research has been undertaken on watchful waiting in patients with BCC, the expected tumor growth, progression and the chance of developing symptoms while taking this approach are poorly understood. Patients with limited life expectancy might not live long enough to develop BCC symptoms and may benefit more from watchful waiting than active treatment, authors of the study wrote.

This observational cohort study evaluated the reasons for watchful waiting, along with the natural course of 280 BCCs in 89 patients (53% men, median age 83 years) who chose this approach. Patients had one or more untreated BCCs for at least 3 months and the median follow-up was 9 months. The researchers also looked at the reasons for initiating later treatment.

Patient-related factors, including limited life expectancy, comorbidity prioritizations, and frailty, were the most important reasons to choose watchful waiting in 83% of patients, followed by tumor-related factors in 55% of patients. Of the tumors, 47% increased in size. The estimated tumor diameter increase in 1 year was 4.46 mm for infiltrative/micronodular BCCs and 1.06 mm for nodular, superficial, or clinical BCCs. Tumor growth was not associated with initial tumor size and location.

The most common reasons to initiate active treatment were tumor burden, resolved reasons for watchful waiting, and reevaluation of patient-related factors.

“All patients should be followed up regularly to determine whether a watchful waiting approach is still suited and if patients still prefer watchful waiting to reconsider the consequences of refraining from treatment,” the authors wrote.

In an accompanying editorial, Mackenzie R. Wehner, MD, MPhil, of the University of Texas MD Anderson Cancer Center in Houston, said that, while the observational and retrospective design was a limitation of the study, this allowed the authors to observe patients avoiding or delaying treatment for BCC in real clinical practice.

The study “shows that few patients developed new symptoms, and few patients who decided to treat after a delay had more invasive interventions than originally anticipated, an encouraging result as we continue to study the option and hone the details of active surveillance in BCC,” Dr. Wehner wrote. “It is important to note that the authors did not perform actual active surveillance. This study did not prospectively enroll patients and see them in follow-up at set times, nor did it have prespecified end points for recommending treatment.”

“Before evidence-based active surveillance in BCC can become a viable option, prospective studies of active surveillance, with specified follow-up times and clear outcome measures, are needed,” Dr. Wehner wrote.

Dr. van Winden did not report any conflicts of interest.

In patients with basal cell carcinoma (BCC), watchful waiting may be more suitable than active treatment for patients with asymptomatic nodular or superficial BCC and a limited life expectancy, according to a study published in JAMA Dermatology.

“Patient preferences, treatment goals, and the option for proceeding with a watchful waiting approach should be discussed as part of personalized shared decision-making,” wrote Marieke van Winden, MD, MSc, of Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues. “In patients with a limited life expectancy and asymptomatic low-risk tumors, the time to benefit from treatment might exceed life expectancy, and watchful waiting should be discussed as a potentially appropriate approach.”

As little research has been undertaken on watchful waiting in patients with BCC, the expected tumor growth, progression and the chance of developing symptoms while taking this approach are poorly understood. Patients with limited life expectancy might not live long enough to develop BCC symptoms and may benefit more from watchful waiting than active treatment, authors of the study wrote.

This observational cohort study evaluated the reasons for watchful waiting, along with the natural course of 280 BCCs in 89 patients (53% men, median age 83 years) who chose this approach. Patients had one or more untreated BCCs for at least 3 months and the median follow-up was 9 months. The researchers also looked at the reasons for initiating later treatment.

Patient-related factors, including limited life expectancy, comorbidity prioritizations, and frailty, were the most important reasons to choose watchful waiting in 83% of patients, followed by tumor-related factors in 55% of patients. Of the tumors, 47% increased in size. The estimated tumor diameter increase in 1 year was 4.46 mm for infiltrative/micronodular BCCs and 1.06 mm for nodular, superficial, or clinical BCCs. Tumor growth was not associated with initial tumor size and location.

The most common reasons to initiate active treatment were tumor burden, resolved reasons for watchful waiting, and reevaluation of patient-related factors.

“All patients should be followed up regularly to determine whether a watchful waiting approach is still suited and if patients still prefer watchful waiting to reconsider the consequences of refraining from treatment,” the authors wrote.

In an accompanying editorial, Mackenzie R. Wehner, MD, MPhil, of the University of Texas MD Anderson Cancer Center in Houston, said that, while the observational and retrospective design was a limitation of the study, this allowed the authors to observe patients avoiding or delaying treatment for BCC in real clinical practice.

The study “shows that few patients developed new symptoms, and few patients who decided to treat after a delay had more invasive interventions than originally anticipated, an encouraging result as we continue to study the option and hone the details of active surveillance in BCC,” Dr. Wehner wrote. “It is important to note that the authors did not perform actual active surveillance. This study did not prospectively enroll patients and see them in follow-up at set times, nor did it have prespecified end points for recommending treatment.”

“Before evidence-based active surveillance in BCC can become a viable option, prospective studies of active surveillance, with specified follow-up times and clear outcome measures, are needed,” Dr. Wehner wrote.

Dr. van Winden did not report any conflicts of interest.

In patients with basal cell carcinoma (BCC), watchful waiting may be more suitable than active treatment for patients with asymptomatic nodular or superficial BCC and a limited life expectancy, according to a study published in JAMA Dermatology.

“Patient preferences, treatment goals, and the option for proceeding with a watchful waiting approach should be discussed as part of personalized shared decision-making,” wrote Marieke van Winden, MD, MSc, of Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues. “In patients with a limited life expectancy and asymptomatic low-risk tumors, the time to benefit from treatment might exceed life expectancy, and watchful waiting should be discussed as a potentially appropriate approach.”

As little research has been undertaken on watchful waiting in patients with BCC, the expected tumor growth, progression and the chance of developing symptoms while taking this approach are poorly understood. Patients with limited life expectancy might not live long enough to develop BCC symptoms and may benefit more from watchful waiting than active treatment, authors of the study wrote.

This observational cohort study evaluated the reasons for watchful waiting, along with the natural course of 280 BCCs in 89 patients (53% men, median age 83 years) who chose this approach. Patients had one or more untreated BCCs for at least 3 months and the median follow-up was 9 months. The researchers also looked at the reasons for initiating later treatment.

Patient-related factors, including limited life expectancy, comorbidity prioritizations, and frailty, were the most important reasons to choose watchful waiting in 83% of patients, followed by tumor-related factors in 55% of patients. Of the tumors, 47% increased in size. The estimated tumor diameter increase in 1 year was 4.46 mm for infiltrative/micronodular BCCs and 1.06 mm for nodular, superficial, or clinical BCCs. Tumor growth was not associated with initial tumor size and location.

The most common reasons to initiate active treatment were tumor burden, resolved reasons for watchful waiting, and reevaluation of patient-related factors.

“All patients should be followed up regularly to determine whether a watchful waiting approach is still suited and if patients still prefer watchful waiting to reconsider the consequences of refraining from treatment,” the authors wrote.

In an accompanying editorial, Mackenzie R. Wehner, MD, MPhil, of the University of Texas MD Anderson Cancer Center in Houston, said that, while the observational and retrospective design was a limitation of the study, this allowed the authors to observe patients avoiding or delaying treatment for BCC in real clinical practice.

The study “shows that few patients developed new symptoms, and few patients who decided to treat after a delay had more invasive interventions than originally anticipated, an encouraging result as we continue to study the option and hone the details of active surveillance in BCC,” Dr. Wehner wrote. “It is important to note that the authors did not perform actual active surveillance. This study did not prospectively enroll patients and see them in follow-up at set times, nor did it have prespecified end points for recommending treatment.”

“Before evidence-based active surveillance in BCC can become a viable option, prospective studies of active surveillance, with specified follow-up times and clear outcome measures, are needed,” Dr. Wehner wrote.

Dr. van Winden did not report any conflicts of interest.

A new U.S. government study shows it isn’t risky and may even be a good idea to mix, rather than match, COVID-19 vaccines when getting a booster dose.

The study also shows mixing different kinds of vaccines appears to spur the body to make higher levels of virus-blocking antibodies than they would have gotten by boosting with a dose of the vaccine the person already had.

If regulators endorse the study findings, it should make getting a COVID-19 booster as easy as getting a yearly influenza vaccine.

“Currently when you go to do your flu shot nobody asks you what kind you had last year. Nobody cares what you had last year. And we were hoping that that was the same — that we would be able to boost regardless of what you had [previously],” said the study’s senior author, John Beigel, MD, who is associate director for clinical research in the division of microbiology and infectious diseases at the National Institutes of Health.

“But we needed to have the data,” he said.

Studies have suggested that higher antibody levels translate into better protection against disease, though the exact level that confers protection is not yet known.

“The antibody responses are so much higher [with mix and match], it’s really impressive,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University in Nashville, who was not involved in the study.

Dr. Shaffner said if the U.S. Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) sign off on the approach, he would especially recommend that people who got the Johnson & Johnson vaccine follow up with a dose of an mRNA vaccine from Pfizer or Moderna.

“It is a broader stimulation of the immune system, and I think that broader stimulation is advantageous,” he said.

Minimal side effects

The preprint study was published late Oct. 13 in medRxiv ahead of peer review, just before a slate of meetings involving vaccine experts that advise the FDA and CDC. 

These experts are tasked with trying to figure out whether additional shots of Moderna and Johnson & Johnson vaccines are safe and effective for boosting immunity against COVID-19.

The FDA’s panel is the Vaccines and Related Biological Products Advisory Committee (VRBPAC), and the CDC’s panel is the Advisory Committee on Immunization Practices (ACIP). 

During the pandemic, they have been meeting almost in lock step to tackle important vaccine-related questions.

“We got this data out because we knew VRBPAC was coming and we knew ACIP was going to grapple with these issues,” Dr. Beigel said.

He noted that these are just the first results. The study will continue for a year, and the researchers aim to deeply characterize the breadth and depth of the immune response to all nine of the different vaccine combinations included in the study.

The study included 458 participants at 10 study sites around the country who had been fully vaccinated with one of the three COVID-19 vaccines authorized for use in the United States: Moderna, Johnson & Johnson, or Pfizer-BioNTech. 

About 150 study participants were recruited from each group. Everyone in the study had finished their primary series at least 12 weeks before starting the study. None had a prior SARS-CoV-2 infection.

About 50 participants from each vaccine group were randomly assigned to get a third (booster) dose of either the same vaccine as the one they had already received, or a different vaccine, creating nine possible combinations of shots.

About half of study participants reported mild side effects — including pain at the injection site, fatigue, headache, and muscle aches.

Two study participants had serious medical problems during the study, but they were judged to be unrelated to vaccination. One study participant experienced kidney failure after their muscles broke down following a fall. The other experienced cholecystitis, or an inflamed gallbladder. 

Up to 1 month after the booster shots, no other serious adverse events were seen.

The study didn’t look at whether people got COVID-19, so it’s not possible to say that they were better protected against disease after their boosters.

Increase in antibodies

But all the groups saw substantial increases in their antibody levels, which is thought to indicate that they were better protected.

Overall, groups that got the same vaccine as their primary series saw 4 to 20-fold increases in their antibody levels. Groups that got different shots than the ones in their primary series got 6 to 76 fold increases in their antibody levels.

People who had originally gotten a Johnson & Johnson vaccine saw far bigger increases in antibodies, and were more likely to see a protective rise in antibodies if they got a second dose of an mRNA vaccine.

Dr. Schaffner noted that European countries had already been mixing the vaccine doses this way, giving people who had received the AstraZeneca vaccine, which is similar to the Johnson & Johnson shot, another dose of an mRNA vaccine.

German Chancellor Angela Merkel received a Moderna vaccine for her second dose after an initial shot of the Oxford-AstraZeneca vaccines, for example.

No safety signals related to mixing vaccines has been seen in countries that routinely use the approach for their initial series.

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

A new U.S. government study shows it isn’t risky and may even be a good idea to mix, rather than match, COVID-19 vaccines when getting a booster dose.

The study also shows mixing different kinds of vaccines appears to spur the body to make higher levels of virus-blocking antibodies than they would have gotten by boosting with a dose of the vaccine the person already had.

If regulators endorse the study findings, it should make getting a COVID-19 booster as easy as getting a yearly influenza vaccine.

“Currently when you go to do your flu shot nobody asks you what kind you had last year. Nobody cares what you had last year. And we were hoping that that was the same — that we would be able to boost regardless of what you had [previously],” said the study’s senior author, John Beigel, MD, who is associate director for clinical research in the division of microbiology and infectious diseases at the National Institutes of Health.

“But we needed to have the data,” he said.

Studies have suggested that higher antibody levels translate into better protection against disease, though the exact level that confers protection is not yet known.

“The antibody responses are so much higher [with mix and match], it’s really impressive,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University in Nashville, who was not involved in the study.

Dr. Shaffner said if the U.S. Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) sign off on the approach, he would especially recommend that people who got the Johnson & Johnson vaccine follow up with a dose of an mRNA vaccine from Pfizer or Moderna.

“It is a broader stimulation of the immune system, and I think that broader stimulation is advantageous,” he said.

Minimal side effects

The preprint study was published late Oct. 13 in medRxiv ahead of peer review, just before a slate of meetings involving vaccine experts that advise the FDA and CDC. 

These experts are tasked with trying to figure out whether additional shots of Moderna and Johnson & Johnson vaccines are safe and effective for boosting immunity against COVID-19.

The FDA’s panel is the Vaccines and Related Biological Products Advisory Committee (VRBPAC), and the CDC’s panel is the Advisory Committee on Immunization Practices (ACIP). 

During the pandemic, they have been meeting almost in lock step to tackle important vaccine-related questions.

“We got this data out because we knew VRBPAC was coming and we knew ACIP was going to grapple with these issues,” Dr. Beigel said.

He noted that these are just the first results. The study will continue for a year, and the researchers aim to deeply characterize the breadth and depth of the immune response to all nine of the different vaccine combinations included in the study.

The study included 458 participants at 10 study sites around the country who had been fully vaccinated with one of the three COVID-19 vaccines authorized for use in the United States: Moderna, Johnson & Johnson, or Pfizer-BioNTech. 

About 150 study participants were recruited from each group. Everyone in the study had finished their primary series at least 12 weeks before starting the study. None had a prior SARS-CoV-2 infection.

About 50 participants from each vaccine group were randomly assigned to get a third (booster) dose of either the same vaccine as the one they had already received, or a different vaccine, creating nine possible combinations of shots.

About half of study participants reported mild side effects — including pain at the injection site, fatigue, headache, and muscle aches.

Two study participants had serious medical problems during the study, but they were judged to be unrelated to vaccination. One study participant experienced kidney failure after their muscles broke down following a fall. The other experienced cholecystitis, or an inflamed gallbladder. 

Up to 1 month after the booster shots, no other serious adverse events were seen.

The study didn’t look at whether people got COVID-19, so it’s not possible to say that they were better protected against disease after their boosters.

Increase in antibodies

But all the groups saw substantial increases in their antibody levels, which is thought to indicate that they were better protected.

Overall, groups that got the same vaccine as their primary series saw 4 to 20-fold increases in their antibody levels. Groups that got different shots than the ones in their primary series got 6 to 76 fold increases in their antibody levels.

People who had originally gotten a Johnson & Johnson vaccine saw far bigger increases in antibodies, and were more likely to see a protective rise in antibodies if they got a second dose of an mRNA vaccine.

Dr. Schaffner noted that European countries had already been mixing the vaccine doses this way, giving people who had received the AstraZeneca vaccine, which is similar to the Johnson & Johnson shot, another dose of an mRNA vaccine.

German Chancellor Angela Merkel received a Moderna vaccine for her second dose after an initial shot of the Oxford-AstraZeneca vaccines, for example.

No safety signals related to mixing vaccines has been seen in countries that routinely use the approach for their initial series.

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

A new U.S. government study shows it isn’t risky and may even be a good idea to mix, rather than match, COVID-19 vaccines when getting a booster dose.

The study also shows mixing different kinds of vaccines appears to spur the body to make higher levels of virus-blocking antibodies than they would have gotten by boosting with a dose of the vaccine the person already had.

If regulators endorse the study findings, it should make getting a COVID-19 booster as easy as getting a yearly influenza vaccine.

“Currently when you go to do your flu shot nobody asks you what kind you had last year. Nobody cares what you had last year. And we were hoping that that was the same — that we would be able to boost regardless of what you had [previously],” said the study’s senior author, John Beigel, MD, who is associate director for clinical research in the division of microbiology and infectious diseases at the National Institutes of Health.

“But we needed to have the data,” he said.

Studies have suggested that higher antibody levels translate into better protection against disease, though the exact level that confers protection is not yet known.

“The antibody responses are so much higher [with mix and match], it’s really impressive,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University in Nashville, who was not involved in the study.

Dr. Shaffner said if the U.S. Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) sign off on the approach, he would especially recommend that people who got the Johnson & Johnson vaccine follow up with a dose of an mRNA vaccine from Pfizer or Moderna.

“It is a broader stimulation of the immune system, and I think that broader stimulation is advantageous,” he said.

Minimal side effects

The preprint study was published late Oct. 13 in medRxiv ahead of peer review, just before a slate of meetings involving vaccine experts that advise the FDA and CDC. 

These experts are tasked with trying to figure out whether additional shots of Moderna and Johnson & Johnson vaccines are safe and effective for boosting immunity against COVID-19.

The FDA’s panel is the Vaccines and Related Biological Products Advisory Committee (VRBPAC), and the CDC’s panel is the Advisory Committee on Immunization Practices (ACIP). 

During the pandemic, they have been meeting almost in lock step to tackle important vaccine-related questions.

“We got this data out because we knew VRBPAC was coming and we knew ACIP was going to grapple with these issues,” Dr. Beigel said.

He noted that these are just the first results. The study will continue for a year, and the researchers aim to deeply characterize the breadth and depth of the immune response to all nine of the different vaccine combinations included in the study.

The study included 458 participants at 10 study sites around the country who had been fully vaccinated with one of the three COVID-19 vaccines authorized for use in the United States: Moderna, Johnson & Johnson, or Pfizer-BioNTech. 

About 150 study participants were recruited from each group. Everyone in the study had finished their primary series at least 12 weeks before starting the study. None had a prior SARS-CoV-2 infection.

About 50 participants from each vaccine group were randomly assigned to get a third (booster) dose of either the same vaccine as the one they had already received, or a different vaccine, creating nine possible combinations of shots.

About half of study participants reported mild side effects — including pain at the injection site, fatigue, headache, and muscle aches.

Two study participants had serious medical problems during the study, but they were judged to be unrelated to vaccination. One study participant experienced kidney failure after their muscles broke down following a fall. The other experienced cholecystitis, or an inflamed gallbladder. 

Up to 1 month after the booster shots, no other serious adverse events were seen.

The study didn’t look at whether people got COVID-19, so it’s not possible to say that they were better protected against disease after their boosters.

Increase in antibodies

But all the groups saw substantial increases in their antibody levels, which is thought to indicate that they were better protected.

Overall, groups that got the same vaccine as their primary series saw 4 to 20-fold increases in their antibody levels. Groups that got different shots than the ones in their primary series got 6 to 76 fold increases in their antibody levels.

People who had originally gotten a Johnson & Johnson vaccine saw far bigger increases in antibodies, and were more likely to see a protective rise in antibodies if they got a second dose of an mRNA vaccine.

Dr. Schaffner noted that European countries had already been mixing the vaccine doses this way, giving people who had received the AstraZeneca vaccine, which is similar to the Johnson & Johnson shot, another dose of an mRNA vaccine.

German Chancellor Angela Merkel received a Moderna vaccine for her second dose after an initial shot of the Oxford-AstraZeneca vaccines, for example.

No safety signals related to mixing vaccines has been seen in countries that routinely use the approach for their initial series.

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

New draft recommendations from the U.S. Preventive Services Task Force (USPSTF) on the use of aspirin for the primary prevention of cardiovascular disease (CVD) have been released and appear to limit the population in which it should be considered.  

David Sucsy/iStockphoto

“The USPSTF concludes with moderate certainty that aspirin use for the primary prevention of CVD events in adults ages 40 to 59 years who have a 10% or greater 10-year CVD risk has a small net benefit,” the recommendation notes. They conclude that for these patients, the decision to use aspirin “should be an individual one.”

“Persons who are not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit,” they note.

For older individuals, however, “The USPSTF concludes with moderate certainty that initiating aspirin use for the primary prevention of CVD events in adults age 60 years or older has no net benefit,” the task force concludes.

The new recommendations were posted online Oct. 12 and will be available for public comment until November 8. Once it is finalized, the recommendation will replace the 2016 USPSTF recommendation on aspirin use to prevent CVD and colorectal cancer (CRC), they note.

In that document, the task force recommended initiating low-dose aspirin for the primary prevention of both CVD and CRC in adults 50-59 years of age who had a 10% or greater 10-year CVD risk, were not at increased risk for bleeding, had a life expectancy of at least 10 years, and were willing to take daily low-dose aspirin for at least 10 years, with the decision to start being an individual one.

For older and younger patients, they found at that time that the evidence was “insufficient to assess the balance of benefits and harms of initiating aspirin use for the primary prevention of CVD and CRC in adults younger than age 50 years or adults aged 70 years or older.”

In the new draft document, “the USPSTF has changed the age ranges and grades of its recommendation on aspirin use.” Besides the recommendations for CVD prevention, they have also changed the previous recommendation of aspirin for the prevention of CRC given evidence generated from large primary CVD prevention trials.

“Based on new analyses of the evidence from primary CVD prevention populations, longer-term follow-up data from the Women’s Health Study (WHS) (JE Buring, personal communication, November 23, 2020), and new trial evidence, the USPSTF concluded that the evidence is inadequate that low-dose aspirin use reduces CRC incidence or mortality,” it states.  
 

Optimum dose

On the optimum dose for primary CVD prevention, the task force says the benefit appears similar for a low dose (≤100 mg/d) and all doses that have been studied in CVD prevention trials (50 to 500 mg/d). “A pragmatic approach would be to use 81 mg/d, which is the most commonly prescribed dose in the United States,” it states.

The USPSTF recommends using the ACC/AHA Pooled Cohort Equations to estimate cardiovascular risk but it points out that these equations are imperfect for risk prediction at the individual level, and suggests using these risk estimates as a starting point to discuss with appropriate candidates their desire for daily aspirin use. The benefits of initiating aspirin use are greater for individuals at higher risk for CVD events (eg, those with >15% or >20% 10-year CVD risk), they note.

“Decisions about initiating aspirin use should be based on shared decision-making between clinicians and patients about the potential benefits and harms. Persons who place a higher value on the potential benefits than the potential harms may choose to initiate low-dose aspirin use. Persons who place a higher value on the potential harms or on the burden of taking a daily preventive medication than the potential benefits may choose not to initiate low-dose aspirin use,” the task force says.

It also points out that the risk for bleeding increases modestly with advancing age. “For persons who have initiated aspirin use, the net benefits continue to accrue over time in the absence of a bleeding event. The net benefits, however, become smaller with advancing age because of an increased risk for bleeding, so modeling data suggest that it may be reasonable to consider stopping aspirin use around age 75 years,” it states.
 

Systematic review

The updated draft recommendations are based on a new systematic review commissioned by the USPSTF on the effectiveness of aspirin to reduce the risk of CVD events (myocardial infarction and stroke), cardiovascular mortality, and all-cause mortality in persons without a history of CVD.

The systematic review also investigated the effect of aspirin use on CRC incidence and mortality in primary CVD prevention populations, as well as the harms, particularly bleeding harms, associated with aspirin use.

In addition to the systematic evidence review, the USPSTF commissioned a microsimulation modeling study to assess the net balance of benefits and harms from aspirin use for primary prevention of CVD and CRC, stratified by age, sex, and CVD risk level. Modeling study parameter inputs were informed by the results of the systematic review, and the primary outcomes were net benefits expressed as quality-adjusted life-years and life-years. 

The USPSTF found 13 randomized clinical trials (RCTs) that reported on the benefits of aspirin use for the primary prevention of cardiovascular morbidity and mortality. The total number of participants was 161,680, and most trials used low-dose aspirin of 100 mg/d or less or aspirin every other day. The 13 primary prevention trials included a balanced number of male and female participants and included a broad distribution of ages, with mean age ranging from 53 years in the Physicians’ Health Study to 74 years in the ASPREE trial.

This body of evidence shows that aspirin use for primary prevention of CVD is associated with a decreased risk of myocardial infarction and stroke but not cardiovascular mortality or all-cause mortality. Results are quite similar when including studies using all doses of aspirin compared with studies using low-dose aspirin.

The USPSTF reviewed 14 RCTs in CVD primary prevention populations that reported on the bleeding harms of aspirin.

When looking at studies reporting on the harms of low-dose aspirin use (≤100 mg/d), which is most relevant to current practice, a pooled analysis of 10 trials showed that aspirin use was associated with a 58% increase in major gastrointestinal bleeding, and a pooled analysis of 11 trials showed a 31% increase in intracranial bleeds in the aspirin group compared with the control group. Low-dose aspirin use was not associated with a statistically significant increase in risk of fatal hemorrhagic stroke.

Data suggested that the increased risk of bleeding associated with aspirin use occurs relatively quickly after initiating aspirin, and data do not suggest that aspirin has a differential relative bleeding risk based on age, sex, presence of diabetes, level of CVD risk, or race or ethnicity. Although the increase in relative risk does not appear to differ based on age, the absolute risk of bleeding, and thus the magnitude of bleeding harm, does increase with age, and more so in adults age 60 years or older, they note.

The microsimulation model to estimate the magnitude of net benefit of low-dose aspirin use incorporated findings from the systematic review.

Modeling data demonstrated that aspirin use in both men and women ages 40-59 years with 10% or greater 10-year CVD risk generally provides a modest net benefit in both quality-adjusted life-years and life-years gained. Initiation of aspirin use in persons aged 60-69 years results in quality-adjusted life-years gained that range from slightly negative to slightly positive depending on CVD risk level, and life-years gained are generally negative.

In persons aged 70-79 years, initiation of aspirin use results in a loss of both quality-adjusted life-years and life-years at essentially all CVD risk levels modeled (ie, up to 20% 10-year CVD risk).

The USPSTF thus determined that aspirin use has a small net benefit in persons aged 40-59 years with 10% or greater 10-year CVD risk, and initiation of aspirin use has no net benefit in persons age 60 years or older.

When looking at net lifetime benefit of continuous aspirin use until stopping at age 65, 70, 75, 80, or 85 years, modeling data suggest that there is generally little incremental lifetime net benefit in continuing aspirin use beyond the age of 75-80 years.

The task force points out that the net benefit of continuing aspirin use by a person in their 60s or 70s is not the same as the net benefit of initiating aspirin use by a person in their 60s or 70s. This is because, in part, of the fact that CVD risk is heavily influenced by age. Persons who meet the eligibility criteria for aspirin use at a younger age (ie, ≥10% 10-year CVD risk in their 40s or 50s) typically have even higher CVD risk by their 60s or 70s compared with persons who first reach a 10% or greater 10-year CVD risk in their 60s or 70s, and may gain more benefit by continuing aspirin use than a person at lower risk might gain by initiating aspirin use, the USPSTF explains.

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

New draft recommendations from the U.S. Preventive Services Task Force (USPSTF) on the use of aspirin for the primary prevention of cardiovascular disease (CVD) have been released and appear to limit the population in which it should be considered.  

David Sucsy/iStockphoto

“The USPSTF concludes with moderate certainty that aspirin use for the primary prevention of CVD events in adults ages 40 to 59 years who have a 10% or greater 10-year CVD risk has a small net benefit,” the recommendation notes. They conclude that for these patients, the decision to use aspirin “should be an individual one.”

“Persons who are not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit,” they note.

For older individuals, however, “The USPSTF concludes with moderate certainty that initiating aspirin use for the primary prevention of CVD events in adults age 60 years or older has no net benefit,” the task force concludes.

The new recommendations were posted online Oct. 12 and will be available for public comment until November 8. Once it is finalized, the recommendation will replace the 2016 USPSTF recommendation on aspirin use to prevent CVD and colorectal cancer (CRC), they note.

In that document, the task force recommended initiating low-dose aspirin for the primary prevention of both CVD and CRC in adults 50-59 years of age who had a 10% or greater 10-year CVD risk, were not at increased risk for bleeding, had a life expectancy of at least 10 years, and were willing to take daily low-dose aspirin for at least 10 years, with the decision to start being an individual one.

For older and younger patients, they found at that time that the evidence was “insufficient to assess the balance of benefits and harms of initiating aspirin use for the primary prevention of CVD and CRC in adults younger than age 50 years or adults aged 70 years or older.”

In the new draft document, “the USPSTF has changed the age ranges and grades of its recommendation on aspirin use.” Besides the recommendations for CVD prevention, they have also changed the previous recommendation of aspirin for the prevention of CRC given evidence generated from large primary CVD prevention trials.

“Based on new analyses of the evidence from primary CVD prevention populations, longer-term follow-up data from the Women’s Health Study (WHS) (JE Buring, personal communication, November 23, 2020), and new trial evidence, the USPSTF concluded that the evidence is inadequate that low-dose aspirin use reduces CRC incidence or mortality,” it states.  
 

Optimum dose

On the optimum dose for primary CVD prevention, the task force says the benefit appears similar for a low dose (≤100 mg/d) and all doses that have been studied in CVD prevention trials (50 to 500 mg/d). “A pragmatic approach would be to use 81 mg/d, which is the most commonly prescribed dose in the United States,” it states.

The USPSTF recommends using the ACC/AHA Pooled Cohort Equations to estimate cardiovascular risk but it points out that these equations are imperfect for risk prediction at the individual level, and suggests using these risk estimates as a starting point to discuss with appropriate candidates their desire for daily aspirin use. The benefits of initiating aspirin use are greater for individuals at higher risk for CVD events (eg, those with >15% or >20% 10-year CVD risk), they note.

“Decisions about initiating aspirin use should be based on shared decision-making between clinicians and patients about the potential benefits and harms. Persons who place a higher value on the potential benefits than the potential harms may choose to initiate low-dose aspirin use. Persons who place a higher value on the potential harms or on the burden of taking a daily preventive medication than the potential benefits may choose not to initiate low-dose aspirin use,” the task force says.

It also points out that the risk for bleeding increases modestly with advancing age. “For persons who have initiated aspirin use, the net benefits continue to accrue over time in the absence of a bleeding event. The net benefits, however, become smaller with advancing age because of an increased risk for bleeding, so modeling data suggest that it may be reasonable to consider stopping aspirin use around age 75 years,” it states.
 

Systematic review

The updated draft recommendations are based on a new systematic review commissioned by the USPSTF on the effectiveness of aspirin to reduce the risk of CVD events (myocardial infarction and stroke), cardiovascular mortality, and all-cause mortality in persons without a history of CVD.

The systematic review also investigated the effect of aspirin use on CRC incidence and mortality in primary CVD prevention populations, as well as the harms, particularly bleeding harms, associated with aspirin use.

In addition to the systematic evidence review, the USPSTF commissioned a microsimulation modeling study to assess the net balance of benefits and harms from aspirin use for primary prevention of CVD and CRC, stratified by age, sex, and CVD risk level. Modeling study parameter inputs were informed by the results of the systematic review, and the primary outcomes were net benefits expressed as quality-adjusted life-years and life-years. 

The USPSTF found 13 randomized clinical trials (RCTs) that reported on the benefits of aspirin use for the primary prevention of cardiovascular morbidity and mortality. The total number of participants was 161,680, and most trials used low-dose aspirin of 100 mg/d or less or aspirin every other day. The 13 primary prevention trials included a balanced number of male and female participants and included a broad distribution of ages, with mean age ranging from 53 years in the Physicians’ Health Study to 74 years in the ASPREE trial.

This body of evidence shows that aspirin use for primary prevention of CVD is associated with a decreased risk of myocardial infarction and stroke but not cardiovascular mortality or all-cause mortality. Results are quite similar when including studies using all doses of aspirin compared with studies using low-dose aspirin.

The USPSTF reviewed 14 RCTs in CVD primary prevention populations that reported on the bleeding harms of aspirin.

When looking at studies reporting on the harms of low-dose aspirin use (≤100 mg/d), which is most relevant to current practice, a pooled analysis of 10 trials showed that aspirin use was associated with a 58% increase in major gastrointestinal bleeding, and a pooled analysis of 11 trials showed a 31% increase in intracranial bleeds in the aspirin group compared with the control group. Low-dose aspirin use was not associated with a statistically significant increase in risk of fatal hemorrhagic stroke.

Data suggested that the increased risk of bleeding associated with aspirin use occurs relatively quickly after initiating aspirin, and data do not suggest that aspirin has a differential relative bleeding risk based on age, sex, presence of diabetes, level of CVD risk, or race or ethnicity. Although the increase in relative risk does not appear to differ based on age, the absolute risk of bleeding, and thus the magnitude of bleeding harm, does increase with age, and more so in adults age 60 years or older, they note.

The microsimulation model to estimate the magnitude of net benefit of low-dose aspirin use incorporated findings from the systematic review.

Modeling data demonstrated that aspirin use in both men and women ages 40-59 years with 10% or greater 10-year CVD risk generally provides a modest net benefit in both quality-adjusted life-years and life-years gained. Initiation of aspirin use in persons aged 60-69 years results in quality-adjusted life-years gained that range from slightly negative to slightly positive depending on CVD risk level, and life-years gained are generally negative.

In persons aged 70-79 years, initiation of aspirin use results in a loss of both quality-adjusted life-years and life-years at essentially all CVD risk levels modeled (ie, up to 20% 10-year CVD risk).

The USPSTF thus determined that aspirin use has a small net benefit in persons aged 40-59 years with 10% or greater 10-year CVD risk, and initiation of aspirin use has no net benefit in persons age 60 years or older.

When looking at net lifetime benefit of continuous aspirin use until stopping at age 65, 70, 75, 80, or 85 years, modeling data suggest that there is generally little incremental lifetime net benefit in continuing aspirin use beyond the age of 75-80 years.

The task force points out that the net benefit of continuing aspirin use by a person in their 60s or 70s is not the same as the net benefit of initiating aspirin use by a person in their 60s or 70s. This is because, in part, of the fact that CVD risk is heavily influenced by age. Persons who meet the eligibility criteria for aspirin use at a younger age (ie, ≥10% 10-year CVD risk in their 40s or 50s) typically have even higher CVD risk by their 60s or 70s compared with persons who first reach a 10% or greater 10-year CVD risk in their 60s or 70s, and may gain more benefit by continuing aspirin use than a person at lower risk might gain by initiating aspirin use, the USPSTF explains.

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

New draft recommendations from the U.S. Preventive Services Task Force (USPSTF) on the use of aspirin for the primary prevention of cardiovascular disease (CVD) have been released and appear to limit the population in which it should be considered.  

David Sucsy/iStockphoto

“The USPSTF concludes with moderate certainty that aspirin use for the primary prevention of CVD events in adults ages 40 to 59 years who have a 10% or greater 10-year CVD risk has a small net benefit,” the recommendation notes. They conclude that for these patients, the decision to use aspirin “should be an individual one.”

“Persons who are not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit,” they note.

For older individuals, however, “The USPSTF concludes with moderate certainty that initiating aspirin use for the primary prevention of CVD events in adults age 60 years or older has no net benefit,” the task force concludes.

The new recommendations were posted online Oct. 12 and will be available for public comment until November 8. Once it is finalized, the recommendation will replace the 2016 USPSTF recommendation on aspirin use to prevent CVD and colorectal cancer (CRC), they note.

In that document, the task force recommended initiating low-dose aspirin for the primary prevention of both CVD and CRC in adults 50-59 years of age who had a 10% or greater 10-year CVD risk, were not at increased risk for bleeding, had a life expectancy of at least 10 years, and were willing to take daily low-dose aspirin for at least 10 years, with the decision to start being an individual one.

For older and younger patients, they found at that time that the evidence was “insufficient to assess the balance of benefits and harms of initiating aspirin use for the primary prevention of CVD and CRC in adults younger than age 50 years or adults aged 70 years or older.”

In the new draft document, “the USPSTF has changed the age ranges and grades of its recommendation on aspirin use.” Besides the recommendations for CVD prevention, they have also changed the previous recommendation of aspirin for the prevention of CRC given evidence generated from large primary CVD prevention trials.

“Based on new analyses of the evidence from primary CVD prevention populations, longer-term follow-up data from the Women’s Health Study (WHS) (JE Buring, personal communication, November 23, 2020), and new trial evidence, the USPSTF concluded that the evidence is inadequate that low-dose aspirin use reduces CRC incidence or mortality,” it states.  
 

Optimum dose

On the optimum dose for primary CVD prevention, the task force says the benefit appears similar for a low dose (≤100 mg/d) and all doses that have been studied in CVD prevention trials (50 to 500 mg/d). “A pragmatic approach would be to use 81 mg/d, which is the most commonly prescribed dose in the United States,” it states.

The USPSTF recommends using the ACC/AHA Pooled Cohort Equations to estimate cardiovascular risk but it points out that these equations are imperfect for risk prediction at the individual level, and suggests using these risk estimates as a starting point to discuss with appropriate candidates their desire for daily aspirin use. The benefits of initiating aspirin use are greater for individuals at higher risk for CVD events (eg, those with >15% or >20% 10-year CVD risk), they note.

“Decisions about initiating aspirin use should be based on shared decision-making between clinicians and patients about the potential benefits and harms. Persons who place a higher value on the potential benefits than the potential harms may choose to initiate low-dose aspirin use. Persons who place a higher value on the potential harms or on the burden of taking a daily preventive medication than the potential benefits may choose not to initiate low-dose aspirin use,” the task force says.

It also points out that the risk for bleeding increases modestly with advancing age. “For persons who have initiated aspirin use, the net benefits continue to accrue over time in the absence of a bleeding event. The net benefits, however, become smaller with advancing age because of an increased risk for bleeding, so modeling data suggest that it may be reasonable to consider stopping aspirin use around age 75 years,” it states.
 

Systematic review

The updated draft recommendations are based on a new systematic review commissioned by the USPSTF on the effectiveness of aspirin to reduce the risk of CVD events (myocardial infarction and stroke), cardiovascular mortality, and all-cause mortality in persons without a history of CVD.

The systematic review also investigated the effect of aspirin use on CRC incidence and mortality in primary CVD prevention populations, as well as the harms, particularly bleeding harms, associated with aspirin use.

In addition to the systematic evidence review, the USPSTF commissioned a microsimulation modeling study to assess the net balance of benefits and harms from aspirin use for primary prevention of CVD and CRC, stratified by age, sex, and CVD risk level. Modeling study parameter inputs were informed by the results of the systematic review, and the primary outcomes were net benefits expressed as quality-adjusted life-years and life-years. 

The USPSTF found 13 randomized clinical trials (RCTs) that reported on the benefits of aspirin use for the primary prevention of cardiovascular morbidity and mortality. The total number of participants was 161,680, and most trials used low-dose aspirin of 100 mg/d or less or aspirin every other day. The 13 primary prevention trials included a balanced number of male and female participants and included a broad distribution of ages, with mean age ranging from 53 years in the Physicians’ Health Study to 74 years in the ASPREE trial.

This body of evidence shows that aspirin use for primary prevention of CVD is associated with a decreased risk of myocardial infarction and stroke but not cardiovascular mortality or all-cause mortality. Results are quite similar when including studies using all doses of aspirin compared with studies using low-dose aspirin.

The USPSTF reviewed 14 RCTs in CVD primary prevention populations that reported on the bleeding harms of aspirin.

When looking at studies reporting on the harms of low-dose aspirin use (≤100 mg/d), which is most relevant to current practice, a pooled analysis of 10 trials showed that aspirin use was associated with a 58% increase in major gastrointestinal bleeding, and a pooled analysis of 11 trials showed a 31% increase in intracranial bleeds in the aspirin group compared with the control group. Low-dose aspirin use was not associated with a statistically significant increase in risk of fatal hemorrhagic stroke.

Data suggested that the increased risk of bleeding associated with aspirin use occurs relatively quickly after initiating aspirin, and data do not suggest that aspirin has a differential relative bleeding risk based on age, sex, presence of diabetes, level of CVD risk, or race or ethnicity. Although the increase in relative risk does not appear to differ based on age, the absolute risk of bleeding, and thus the magnitude of bleeding harm, does increase with age, and more so in adults age 60 years or older, they note.

The microsimulation model to estimate the magnitude of net benefit of low-dose aspirin use incorporated findings from the systematic review.

Modeling data demonstrated that aspirin use in both men and women ages 40-59 years with 10% or greater 10-year CVD risk generally provides a modest net benefit in both quality-adjusted life-years and life-years gained. Initiation of aspirin use in persons aged 60-69 years results in quality-adjusted life-years gained that range from slightly negative to slightly positive depending on CVD risk level, and life-years gained are generally negative.

In persons aged 70-79 years, initiation of aspirin use results in a loss of both quality-adjusted life-years and life-years at essentially all CVD risk levels modeled (ie, up to 20% 10-year CVD risk).

The USPSTF thus determined that aspirin use has a small net benefit in persons aged 40-59 years with 10% or greater 10-year CVD risk, and initiation of aspirin use has no net benefit in persons age 60 years or older.

When looking at net lifetime benefit of continuous aspirin use until stopping at age 65, 70, 75, 80, or 85 years, modeling data suggest that there is generally little incremental lifetime net benefit in continuing aspirin use beyond the age of 75-80 years.

The task force points out that the net benefit of continuing aspirin use by a person in their 60s or 70s is not the same as the net benefit of initiating aspirin use by a person in their 60s or 70s. This is because, in part, of the fact that CVD risk is heavily influenced by age. Persons who meet the eligibility criteria for aspirin use at a younger age (ie, ≥10% 10-year CVD risk in their 40s or 50s) typically have even higher CVD risk by their 60s or 70s compared with persons who first reach a 10% or greater 10-year CVD risk in their 60s or 70s, and may gain more benefit by continuing aspirin use than a person at lower risk might gain by initiating aspirin use, the USPSTF explains.

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

The prevalence of homicide was 16% higher in pregnant women or postpartum women than nonpregnant or nonpostpartum women in the United States, according to 2018 and 2019 mortality data from the National Center for Health Statistics.

Homicide has long been identified as a leading cause of death during pregnancy, but homicide is not counted in estimates of maternal mortality, nor is it emphasized as a target for prevention and intervention, wrote Maeve Wallace, PhD, of Tulane University, New Orleans, and colleagues.

Data on maternal mortality (defined as “death while pregnant or within 42 days of the end of pregnancy from causes related to or aggravated by pregnancy”) were limited until the addition of pregnancy to the U.S. Standard Certificate of Death in 2003; all 50 states had adopted it by 2018, the researchers noted.

In a study published in Obstetrics & Gynecology, the researchers analyzed the first 2 years of nationally available data to identify pregnancy-associated mortality and characterize other risk factors such as age and race.

The researchers identified 4,705 female homicides in 2018 and 2019. Of these, 273 (5.8%) occurred in women who were pregnant or within a year of the end of pregnancy. Approximately half (50.2%) of the pregnant or postpartum victims were non-Hispanic Black, 30% were non-Hispanic white, 9.5% were Hispanic, and 10.3% were other races; approximately one-third (35.5%) were in the 20- to 24-year age group.

Overall, the ratio was 3.62 homicides per 100,000 live births among females who were either pregnant or within 1 year post partum, compared to 3.12 homicides per 100,000 live births in nonpregnant, nonpostpartum females aged 10-44 years (P = .05).

“Patterns were similar in further stratification by both race and age such that pregnancy was associated with more than a doubled risk of homicide among girls and women aged 10–24 in both the non-Hispanic White and non-Hispanic Black populations,” the researchers wrote.

The findings are consistent with previous studies, which “implicates health and social system failures. Although we are unable to directly evaluate the involvement of intimate partner violence (IPV) in this report, we did find that a majority of pregnancy-associated homicides occurred in the home, implicating the likelihood of involvement by persons known to the victim,” they noted. In addition, the data showed that approximately 70% of the incidents of homicide in pregnant and postpartum women involved a firearm, an increase over previous estimates.

The study findings were limited by several factors including the lack of circumstantial information and incomplete data on victim characteristics, the researchers noted. Other key limitations included the potential for false-positives and false-negatives when recording pregnancy status, which could lead to underestimates of pregnancy-associated homicides, and the lack of data on pregnancy outcomes for women who experienced live birth, abortion, or miscarriage within a year of death.

However, the results highlight the need for increased awareness and training of physicians in completing the pregnancy checkbox on death certificates, and the need for action on recommendations and interventions to prevent maternal deaths from homicide, they emphasized.

“Although encouraging, a commitment to the actual implementation of policies and investments known to be effective at protecting and the promoting the health and safety of girls and women must follow,” they concluded.
 

Data highlight disparities

“This study could not be done effectively prior to now, as the adoption of the pregnancy checkbox on the U.S. Standard Certificate of Death was only available in all 50 states as of 2018,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview.

“This study also demonstrates what was already known, which is that pregnancy is a high-risk time period for intimate partner violence, including homicide. The differences in homicide rates based on race and ethnicity also highlight the clear disparities in maternal mortality in the U.S. that are attributable to racism. There is more attention being paid to maternal mortality and the differential experience based on race, and this demonstrates that simply addressing medical management during pregnancy is not enough – we need to address root causes of racism if we truly want to reduce maternal mortality,” Dr. Prager said. 

“The primary take-home message for clinicians is to ascertain safety from every patient, and to try to reduce the impacts of racism on health care for patients, especially during pregnancy,” she said. 

Although more detailed records would help with elucidating causes versus associations, “more research is not the answer,” Dr. Prager stated. “The real solution here is to have better gun safety laws, and to put significant resources toward reducing the impacts of racism on health care and our society.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Prager had no financial conflicts to disclose, but serves on the editorial advisory board of Ob.Gyn News.

The prevalence of homicide was 16% higher in pregnant women or postpartum women than nonpregnant or nonpostpartum women in the United States, according to 2018 and 2019 mortality data from the National Center for Health Statistics.

Homicide has long been identified as a leading cause of death during pregnancy, but homicide is not counted in estimates of maternal mortality, nor is it emphasized as a target for prevention and intervention, wrote Maeve Wallace, PhD, of Tulane University, New Orleans, and colleagues.

Data on maternal mortality (defined as “death while pregnant or within 42 days of the end of pregnancy from causes related to or aggravated by pregnancy”) were limited until the addition of pregnancy to the U.S. Standard Certificate of Death in 2003; all 50 states had adopted it by 2018, the researchers noted.

In a study published in Obstetrics & Gynecology, the researchers analyzed the first 2 years of nationally available data to identify pregnancy-associated mortality and characterize other risk factors such as age and race.

The researchers identified 4,705 female homicides in 2018 and 2019. Of these, 273 (5.8%) occurred in women who were pregnant or within a year of the end of pregnancy. Approximately half (50.2%) of the pregnant or postpartum victims were non-Hispanic Black, 30% were non-Hispanic white, 9.5% were Hispanic, and 10.3% were other races; approximately one-third (35.5%) were in the 20- to 24-year age group.

Overall, the ratio was 3.62 homicides per 100,000 live births among females who were either pregnant or within 1 year post partum, compared to 3.12 homicides per 100,000 live births in nonpregnant, nonpostpartum females aged 10-44 years (P = .05).

“Patterns were similar in further stratification by both race and age such that pregnancy was associated with more than a doubled risk of homicide among girls and women aged 10–24 in both the non-Hispanic White and non-Hispanic Black populations,” the researchers wrote.

The findings are consistent with previous studies, which “implicates health and social system failures. Although we are unable to directly evaluate the involvement of intimate partner violence (IPV) in this report, we did find that a majority of pregnancy-associated homicides occurred in the home, implicating the likelihood of involvement by persons known to the victim,” they noted. In addition, the data showed that approximately 70% of the incidents of homicide in pregnant and postpartum women involved a firearm, an increase over previous estimates.

The study findings were limited by several factors including the lack of circumstantial information and incomplete data on victim characteristics, the researchers noted. Other key limitations included the potential for false-positives and false-negatives when recording pregnancy status, which could lead to underestimates of pregnancy-associated homicides, and the lack of data on pregnancy outcomes for women who experienced live birth, abortion, or miscarriage within a year of death.

However, the results highlight the need for increased awareness and training of physicians in completing the pregnancy checkbox on death certificates, and the need for action on recommendations and interventions to prevent maternal deaths from homicide, they emphasized.

“Although encouraging, a commitment to the actual implementation of policies and investments known to be effective at protecting and the promoting the health and safety of girls and women must follow,” they concluded.
 

Data highlight disparities

“This study could not be done effectively prior to now, as the adoption of the pregnancy checkbox on the U.S. Standard Certificate of Death was only available in all 50 states as of 2018,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview.

“This study also demonstrates what was already known, which is that pregnancy is a high-risk time period for intimate partner violence, including homicide. The differences in homicide rates based on race and ethnicity also highlight the clear disparities in maternal mortality in the U.S. that are attributable to racism. There is more attention being paid to maternal mortality and the differential experience based on race, and this demonstrates that simply addressing medical management during pregnancy is not enough – we need to address root causes of racism if we truly want to reduce maternal mortality,” Dr. Prager said. 

“The primary take-home message for clinicians is to ascertain safety from every patient, and to try to reduce the impacts of racism on health care for patients, especially during pregnancy,” she said. 

Although more detailed records would help with elucidating causes versus associations, “more research is not the answer,” Dr. Prager stated. “The real solution here is to have better gun safety laws, and to put significant resources toward reducing the impacts of racism on health care and our society.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Prager had no financial conflicts to disclose, but serves on the editorial advisory board of Ob.Gyn News.