MDedge Emergency Medicine

Almost one-third of patients with chronic pain report using medical cannabis to manage that pain, with more than half of them decreasing use of other pain medications, including opioids, new research shows.

“That patients report substituting cannabis for pain medicines so much really underscores the need for research on the benefits and risks of using cannabis for chronic pain,” lead author Mark C. Bicket, MD, PhD, assistant professor, department of anesthesiology, and director, Opioid Prescribing Engagement Network, University of Michigan, Ann Arbor, said in an interview.

However, he added, the question is whether they’re turning to cannabis and away from other pain treatments. “What’s not clear and one of the gaps that we wanted to address in the study was if medical cannabis use is changing the use of other treatments for chronic pain,” said Dr. Bicket.

The study was published online in JAMA Network Open.
 

Decreased opioid use

The survey included a representative sample of 1724 American adults aged 18 years or older with chronic noncancer pain living in areas with a medical cannabis program.

Respondents were asked about their use of three categories of pain treatments. This included medical cannabis; pharmacologic treatments including prescription opioids, nonopioid analgesics, and over-the-counter analgesics; and common nonpharmacologic treatments such as physical therapy, meditation, and cognitive-behavioral therapy (CBT).

Just over 96% of respondents completed the full survey. About 57% of the sample was female and the mean age of the study sample was 52.3 years.

Among study participants, 31% (95% CI, 28.2% - 34.1%) reported having ever used cannabis to manage pain; 25.9% (95% confidence interval, 23.2%-28.8%) reported use in the past 12 months, and 23.2% (95% CI, 20.6%-26%) reported use in the past 30 days.

“This translates into a large number of individuals who are using cannabis in an intended medical way” to treat chronic condition such as low back pain, migraine, and fibromyalgia, said Dr. Bicket.

More than half of survey respondents reported their medical cannabis use led to a decrease in prescription opioid use, prescription nonopioid use and use of over-the-counter medications.

Dr. Bicket noted “almost no one” said medical cannabis use led to higher use of these drugs.

As for nonpharmacologic treatments, 38.7% reported their use of cannabis led to decreased use of physical therapy, 19.1% to lower use of meditation, and 26% to less CBT. At the same time, 5.9%, 23.7% and 17.1%, respectively, reported it led to increased use of physical therapy, meditation, and CBT.

Medical cannabis is regulated at a state level. On a federal level, it’s considered a Schedule I substance, which means it’s deemed not to have a therapeutic use, although some groups are trying to change that categorization, said Dr. Bicket.

As a result, cannabis products “are quite variable” in terms of how they’re used (smoked, eaten etc.) and in their composition, including percentage of cannabidiol and tetrahydrocannabinol.

“We really don’t have a good sense of the relative risks and benefits that could come from cannabis as a treatment for chronic pain,” said Dr. Bicket. “As a physician, it’s difficult to have discussions with patients because I’m not able to understand the products they’re using based on this regulatory environment we have.”

He added clinicians “are operating in an area of uncertainty right now.”

What’s needed is research to determine how safe and effective medical cannabis is for chronic pain, he said.
 

Pain a leading indication

Commenting on the findings, Jason W. Busse, PhD, professor, department of anesthesia, and associate director, Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ont., said the study reinforces results of some prior research.

“It gives us current information certainly highlighting the high rate of use of medical cannabis among individuals with chronic pain once it becomes legally available.”

In addition, this high rate of use “means we desperately need information about the benefits and harms” of medical marijuana, he said.

Dr. Busse noted the survey didn’t provide information on the types of cannabis being used or the mode of administration. Oil drops and sprays cause less pulmonary harm than smoked versions, he said. It’s also not clear from the survey if participants are taking formulations with high levels of tetrahydrocannabinol that are associated with greater risk of harm.

He noted cannabis may interact with prescription drugs to make them less effective or, in some cases, to augment their adverse effects.

Dr. Busse pointed out some patients could be using fewer opioids because providers are under “enormous pressure” to reduce prescriptions of these drugs in the wake of spikes in opioid overdoses and deaths.

Chronic pain is “absolutely the leading indication” for medical marijuana, said Dr. Busse. U.S. reimbursement data suggest up to 65% of individuals get cannabis to treat a listed indication for chronic pain.

He said he hopes this new study will increase interest in funding new trials “so we can have better evidence to guide practice to help patients make decisions.”

The study received support from the National Institute on Drug Abuse. Dr. Bicket reported receiving personal fees from Axial Healthcare as well as grants from the National Institutes of Health, the Centers for Disease Control and Prevention, Michigan Department of Health and Human Services, Arnold Foundation, and the Patient-Centered Outcomes Research Institute outside the submitted work. Dr. Busse reported no relevant financial relationships.

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

Almost one-third of patients with chronic pain report using medical cannabis to manage that pain, with more than half of them decreasing use of other pain medications, including opioids, new research shows.

“That patients report substituting cannabis for pain medicines so much really underscores the need for research on the benefits and risks of using cannabis for chronic pain,” lead author Mark C. Bicket, MD, PhD, assistant professor, department of anesthesiology, and director, Opioid Prescribing Engagement Network, University of Michigan, Ann Arbor, said in an interview.

However, he added, the question is whether they’re turning to cannabis and away from other pain treatments. “What’s not clear and one of the gaps that we wanted to address in the study was if medical cannabis use is changing the use of other treatments for chronic pain,” said Dr. Bicket.

The study was published online in JAMA Network Open.
 

Decreased opioid use

The survey included a representative sample of 1724 American adults aged 18 years or older with chronic noncancer pain living in areas with a medical cannabis program.

Respondents were asked about their use of three categories of pain treatments. This included medical cannabis; pharmacologic treatments including prescription opioids, nonopioid analgesics, and over-the-counter analgesics; and common nonpharmacologic treatments such as physical therapy, meditation, and cognitive-behavioral therapy (CBT).

Just over 96% of respondents completed the full survey. About 57% of the sample was female and the mean age of the study sample was 52.3 years.

Among study participants, 31% (95% CI, 28.2% - 34.1%) reported having ever used cannabis to manage pain; 25.9% (95% confidence interval, 23.2%-28.8%) reported use in the past 12 months, and 23.2% (95% CI, 20.6%-26%) reported use in the past 30 days.

“This translates into a large number of individuals who are using cannabis in an intended medical way” to treat chronic condition such as low back pain, migraine, and fibromyalgia, said Dr. Bicket.

More than half of survey respondents reported their medical cannabis use led to a decrease in prescription opioid use, prescription nonopioid use and use of over-the-counter medications.

Dr. Bicket noted “almost no one” said medical cannabis use led to higher use of these drugs.

As for nonpharmacologic treatments, 38.7% reported their use of cannabis led to decreased use of physical therapy, 19.1% to lower use of meditation, and 26% to less CBT. At the same time, 5.9%, 23.7% and 17.1%, respectively, reported it led to increased use of physical therapy, meditation, and CBT.

Medical cannabis is regulated at a state level. On a federal level, it’s considered a Schedule I substance, which means it’s deemed not to have a therapeutic use, although some groups are trying to change that categorization, said Dr. Bicket.

As a result, cannabis products “are quite variable” in terms of how they’re used (smoked, eaten etc.) and in their composition, including percentage of cannabidiol and tetrahydrocannabinol.

“We really don’t have a good sense of the relative risks and benefits that could come from cannabis as a treatment for chronic pain,” said Dr. Bicket. “As a physician, it’s difficult to have discussions with patients because I’m not able to understand the products they’re using based on this regulatory environment we have.”

He added clinicians “are operating in an area of uncertainty right now.”

What’s needed is research to determine how safe and effective medical cannabis is for chronic pain, he said.
 

Pain a leading indication

Commenting on the findings, Jason W. Busse, PhD, professor, department of anesthesia, and associate director, Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ont., said the study reinforces results of some prior research.

“It gives us current information certainly highlighting the high rate of use of medical cannabis among individuals with chronic pain once it becomes legally available.”

In addition, this high rate of use “means we desperately need information about the benefits and harms” of medical marijuana, he said.

Dr. Busse noted the survey didn’t provide information on the types of cannabis being used or the mode of administration. Oil drops and sprays cause less pulmonary harm than smoked versions, he said. It’s also not clear from the survey if participants are taking formulations with high levels of tetrahydrocannabinol that are associated with greater risk of harm.

He noted cannabis may interact with prescription drugs to make them less effective or, in some cases, to augment their adverse effects.

Dr. Busse pointed out some patients could be using fewer opioids because providers are under “enormous pressure” to reduce prescriptions of these drugs in the wake of spikes in opioid overdoses and deaths.

Chronic pain is “absolutely the leading indication” for medical marijuana, said Dr. Busse. U.S. reimbursement data suggest up to 65% of individuals get cannabis to treat a listed indication for chronic pain.

He said he hopes this new study will increase interest in funding new trials “so we can have better evidence to guide practice to help patients make decisions.”

The study received support from the National Institute on Drug Abuse. Dr. Bicket reported receiving personal fees from Axial Healthcare as well as grants from the National Institutes of Health, the Centers for Disease Control and Prevention, Michigan Department of Health and Human Services, Arnold Foundation, and the Patient-Centered Outcomes Research Institute outside the submitted work. Dr. Busse reported no relevant financial relationships.

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

Almost one-third of patients with chronic pain report using medical cannabis to manage that pain, with more than half of them decreasing use of other pain medications, including opioids, new research shows.

“That patients report substituting cannabis for pain medicines so much really underscores the need for research on the benefits and risks of using cannabis for chronic pain,” lead author Mark C. Bicket, MD, PhD, assistant professor, department of anesthesiology, and director, Opioid Prescribing Engagement Network, University of Michigan, Ann Arbor, said in an interview.

However, he added, the question is whether they’re turning to cannabis and away from other pain treatments. “What’s not clear and one of the gaps that we wanted to address in the study was if medical cannabis use is changing the use of other treatments for chronic pain,” said Dr. Bicket.

The study was published online in JAMA Network Open.
 

Decreased opioid use

The survey included a representative sample of 1724 American adults aged 18 years or older with chronic noncancer pain living in areas with a medical cannabis program.

Respondents were asked about their use of three categories of pain treatments. This included medical cannabis; pharmacologic treatments including prescription opioids, nonopioid analgesics, and over-the-counter analgesics; and common nonpharmacologic treatments such as physical therapy, meditation, and cognitive-behavioral therapy (CBT).

Just over 96% of respondents completed the full survey. About 57% of the sample was female and the mean age of the study sample was 52.3 years.

Among study participants, 31% (95% CI, 28.2% - 34.1%) reported having ever used cannabis to manage pain; 25.9% (95% confidence interval, 23.2%-28.8%) reported use in the past 12 months, and 23.2% (95% CI, 20.6%-26%) reported use in the past 30 days.

“This translates into a large number of individuals who are using cannabis in an intended medical way” to treat chronic condition such as low back pain, migraine, and fibromyalgia, said Dr. Bicket.

More than half of survey respondents reported their medical cannabis use led to a decrease in prescription opioid use, prescription nonopioid use and use of over-the-counter medications.

Dr. Bicket noted “almost no one” said medical cannabis use led to higher use of these drugs.

As for nonpharmacologic treatments, 38.7% reported their use of cannabis led to decreased use of physical therapy, 19.1% to lower use of meditation, and 26% to less CBT. At the same time, 5.9%, 23.7% and 17.1%, respectively, reported it led to increased use of physical therapy, meditation, and CBT.

Medical cannabis is regulated at a state level. On a federal level, it’s considered a Schedule I substance, which means it’s deemed not to have a therapeutic use, although some groups are trying to change that categorization, said Dr. Bicket.

As a result, cannabis products “are quite variable” in terms of how they’re used (smoked, eaten etc.) and in their composition, including percentage of cannabidiol and tetrahydrocannabinol.

“We really don’t have a good sense of the relative risks and benefits that could come from cannabis as a treatment for chronic pain,” said Dr. Bicket. “As a physician, it’s difficult to have discussions with patients because I’m not able to understand the products they’re using based on this regulatory environment we have.”

He added clinicians “are operating in an area of uncertainty right now.”

What’s needed is research to determine how safe and effective medical cannabis is for chronic pain, he said.
 

Pain a leading indication

Commenting on the findings, Jason W. Busse, PhD, professor, department of anesthesia, and associate director, Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ont., said the study reinforces results of some prior research.

“It gives us current information certainly highlighting the high rate of use of medical cannabis among individuals with chronic pain once it becomes legally available.”

In addition, this high rate of use “means we desperately need information about the benefits and harms” of medical marijuana, he said.

Dr. Busse noted the survey didn’t provide information on the types of cannabis being used or the mode of administration. Oil drops and sprays cause less pulmonary harm than smoked versions, he said. It’s also not clear from the survey if participants are taking formulations with high levels of tetrahydrocannabinol that are associated with greater risk of harm.

He noted cannabis may interact with prescription drugs to make them less effective or, in some cases, to augment their adverse effects.

Dr. Busse pointed out some patients could be using fewer opioids because providers are under “enormous pressure” to reduce prescriptions of these drugs in the wake of spikes in opioid overdoses and deaths.

Chronic pain is “absolutely the leading indication” for medical marijuana, said Dr. Busse. U.S. reimbursement data suggest up to 65% of individuals get cannabis to treat a listed indication for chronic pain.

He said he hopes this new study will increase interest in funding new trials “so we can have better evidence to guide practice to help patients make decisions.”

The study received support from the National Institute on Drug Abuse. Dr. Bicket reported receiving personal fees from Axial Healthcare as well as grants from the National Institutes of Health, the Centers for Disease Control and Prevention, Michigan Department of Health and Human Services, Arnold Foundation, and the Patient-Centered Outcomes Research Institute outside the submitted work. Dr. Busse reported no relevant financial relationships.

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

High levels of triglyceride molecules in LDL cholesterol are “robustly” linked with an increased risk of atherosclerotic cardiovascular disease, according to a study that used two different methods in two separate cohorts from a large European population study plus a meta-analysis to verify the results.

“There have been some studies in the past, as you can see from our meta-analysis, that found a similar association, but I don’t think most people are convinced that there is really this relationship, and certainly I was not convinced,” lead investigator Børge G. Nordestgaard, MD, DMSc, professor at the University of Copenhagen, said in an interview.

The study enrolled 68,290 patients from the Copenhagen General Population study; 38,081 were assigned to direct automated assay to measure their LDL triglycerides and 30,208 had nuclear magnetic resonance (NMR) spectroscopy. Median follow-up was 3 and 9.2 years for the respective cohorts.

LDL triglycerides carry higher ASCVD risk

In the automated assay group, each 0.1-mmol/L (9 mg/dL)–higher direct LDL triglycerides carried a 22%-38% higher risk for the following outcomes: ASCVD (hazard ratio, 1.26; 95% confidence interval, 1.17-1.35); ischemic heart disease (HR, 1.27; 95% CI, 1.16-1.39); myocardial infarction (HR, 1.28; 95% CI, 1.11-1.48); ischemic stroke (HR, 1.22; 95% CI, 1.08-1.38); and peripheral artery disease (HR, 1.38; 95% CI, 1.21-1.58).

In the group that had NMR spectroscopy to measure LDL triglycerides, risks were similar, ranging from HRs of 1.13 (95% CI, 1.05-1.23) for ischemic stroke to 1.41 (95% CI, 1.31-1.52) for myocardial infarction. The investigators noted that apolipoprotein B levels didn’t entirely explain these results.

The meta-analysis included 18 studies that evaluated varying cardiovascular disease outcomes. It compared random-effects risk ratios for the highest quartile vs. the lowest quartile of LDL triglycerides. They were 1.50 (95% CI, 1.35-1.66) for ASCVD (four studies, 71,526 individuals, 8,576 events); 1.62 (95% CI, 1.37-1.93) for ischemic heart disease (six studies, 107,538 individuals, 9,734 events); 1.30 (95% CI, 1.13-1.49) for ischemic stroke (four studies, 78,026 individuals, 4,273 events); and 1.53 (95% CI, 1.29-1.81) for peripheral artery disease (four studies, 107,511 individuals, 1,848 events). The study was published online in the Journal of the American College of Cardiology.

Results confirm hypothesis the study sought to disprove

The purpose of the study was to actually disprove the hypothesis that the study ended up confirming, Dr. Nordestgaard said. “When we started this study, my idea was that we wanted to show that LDL triglyceride was not related to these diseases, because that didn’t make sense to me,” he said. “I’m so used to the thinking that the cholesterol content of these particles drive atherosclerosis and therefore atherosclerotic cardiovascular disease.”

He noted that LDL can carry both cholesterol and triglycerides, and that larger remnant lipoproteins can carry a substantial amount of triglycerides and a lesser amount of cholesterol. “Those remnants actually transfer into LDL, so they somewhat bring the triglycerides molecules into LDL,” Dr. Nordestgaard said.

The direct automated assay test used in the study to measure LDL triglycerides is not approved for use in the United States by the Food and Drug Administration, according to Denka, the manufacturer of the test.

The use of the Copenhagen General Population Study cohorts is a strength of the study because it has 100% follow-up with all patients, Dr. Nordestgaard said. The meta-analysis is another strength. “So we can show real clearly, not only in our two prospective studies, but also added to the former ones in the literature: All say exactly the same thing: High LDL triglycerides carry a high risk for ASCVD and its components.”

A limitation Dr. Nordestgaard acknowledged: The study doesn’t explain the causal relationship between high LDL triglycerides and ASCVD. But the study provides “very sound evidence that there’s a relationship,” he added. The study population was also a White, Danish population that lacked ethnic and racial diversity.

Next step is finding a treatment

The Danish study essentially confirms what the Atherosclerosis Risk in Community Study (ARIC) found with regard to LDL triglycerides, said Christie M. Ballantyne, MD, chief of cardiology at Baylor College of Medicine in Houston, and an ARIC investigator. 

This study is the “first step” to coming up with a test to identify risk, he said. “These data are pretty convincing, when you throw in the data in this study plus all the meta-analyses data, that LDL triglycerides, when they’re elevated, identify individuals at increased risk for an atherosclerotic cardiovascular event.”

The next step, he said, is coming up with a treatment for people with elevated HDL triglyceride. “That’s where we don’t have as much data because this test hasn’t been used. I’m pretty sure that statins are going to work fine for these people, because they lower LDL cholesterol and they also lower triglycerides, and some of the data have shown already that they reduce the LDL remnant,” Dr. Ballantyne said.

The Danish study provides enough of a basis for pursuing future studies to better understand the effect of statins on LDL triglyceride levels, Dr. Ballantyne added.

The study received funding from the Novo Nordisk Foundation and the Danish Heart Foundation, along with institutional support. Dr. Nordestgaard has no relevant disclosures. Dr. Ballantyne disclosed receiving research support from Denka.

High levels of triglyceride molecules in LDL cholesterol are “robustly” linked with an increased risk of atherosclerotic cardiovascular disease, according to a study that used two different methods in two separate cohorts from a large European population study plus a meta-analysis to verify the results.

“There have been some studies in the past, as you can see from our meta-analysis, that found a similar association, but I don’t think most people are convinced that there is really this relationship, and certainly I was not convinced,” lead investigator Børge G. Nordestgaard, MD, DMSc, professor at the University of Copenhagen, said in an interview.

The study enrolled 68,290 patients from the Copenhagen General Population study; 38,081 were assigned to direct automated assay to measure their LDL triglycerides and 30,208 had nuclear magnetic resonance (NMR) spectroscopy. Median follow-up was 3 and 9.2 years for the respective cohorts.

LDL triglycerides carry higher ASCVD risk

In the automated assay group, each 0.1-mmol/L (9 mg/dL)–higher direct LDL triglycerides carried a 22%-38% higher risk for the following outcomes: ASCVD (hazard ratio, 1.26; 95% confidence interval, 1.17-1.35); ischemic heart disease (HR, 1.27; 95% CI, 1.16-1.39); myocardial infarction (HR, 1.28; 95% CI, 1.11-1.48); ischemic stroke (HR, 1.22; 95% CI, 1.08-1.38); and peripheral artery disease (HR, 1.38; 95% CI, 1.21-1.58).

In the group that had NMR spectroscopy to measure LDL triglycerides, risks were similar, ranging from HRs of 1.13 (95% CI, 1.05-1.23) for ischemic stroke to 1.41 (95% CI, 1.31-1.52) for myocardial infarction. The investigators noted that apolipoprotein B levels didn’t entirely explain these results.

The meta-analysis included 18 studies that evaluated varying cardiovascular disease outcomes. It compared random-effects risk ratios for the highest quartile vs. the lowest quartile of LDL triglycerides. They were 1.50 (95% CI, 1.35-1.66) for ASCVD (four studies, 71,526 individuals, 8,576 events); 1.62 (95% CI, 1.37-1.93) for ischemic heart disease (six studies, 107,538 individuals, 9,734 events); 1.30 (95% CI, 1.13-1.49) for ischemic stroke (four studies, 78,026 individuals, 4,273 events); and 1.53 (95% CI, 1.29-1.81) for peripheral artery disease (four studies, 107,511 individuals, 1,848 events). The study was published online in the Journal of the American College of Cardiology.

Results confirm hypothesis the study sought to disprove

The purpose of the study was to actually disprove the hypothesis that the study ended up confirming, Dr. Nordestgaard said. “When we started this study, my idea was that we wanted to show that LDL triglyceride was not related to these diseases, because that didn’t make sense to me,” he said. “I’m so used to the thinking that the cholesterol content of these particles drive atherosclerosis and therefore atherosclerotic cardiovascular disease.”

He noted that LDL can carry both cholesterol and triglycerides, and that larger remnant lipoproteins can carry a substantial amount of triglycerides and a lesser amount of cholesterol. “Those remnants actually transfer into LDL, so they somewhat bring the triglycerides molecules into LDL,” Dr. Nordestgaard said.

The direct automated assay test used in the study to measure LDL triglycerides is not approved for use in the United States by the Food and Drug Administration, according to Denka, the manufacturer of the test.

The use of the Copenhagen General Population Study cohorts is a strength of the study because it has 100% follow-up with all patients, Dr. Nordestgaard said. The meta-analysis is another strength. “So we can show real clearly, not only in our two prospective studies, but also added to the former ones in the literature: All say exactly the same thing: High LDL triglycerides carry a high risk for ASCVD and its components.”

A limitation Dr. Nordestgaard acknowledged: The study doesn’t explain the causal relationship between high LDL triglycerides and ASCVD. But the study provides “very sound evidence that there’s a relationship,” he added. The study population was also a White, Danish population that lacked ethnic and racial diversity.

Next step is finding a treatment

The Danish study essentially confirms what the Atherosclerosis Risk in Community Study (ARIC) found with regard to LDL triglycerides, said Christie M. Ballantyne, MD, chief of cardiology at Baylor College of Medicine in Houston, and an ARIC investigator. 

This study is the “first step” to coming up with a test to identify risk, he said. “These data are pretty convincing, when you throw in the data in this study plus all the meta-analyses data, that LDL triglycerides, when they’re elevated, identify individuals at increased risk for an atherosclerotic cardiovascular event.”

The next step, he said, is coming up with a treatment for people with elevated HDL triglyceride. “That’s where we don’t have as much data because this test hasn’t been used. I’m pretty sure that statins are going to work fine for these people, because they lower LDL cholesterol and they also lower triglycerides, and some of the data have shown already that they reduce the LDL remnant,” Dr. Ballantyne said.

The Danish study provides enough of a basis for pursuing future studies to better understand the effect of statins on LDL triglyceride levels, Dr. Ballantyne added.

The study received funding from the Novo Nordisk Foundation and the Danish Heart Foundation, along with institutional support. Dr. Nordestgaard has no relevant disclosures. Dr. Ballantyne disclosed receiving research support from Denka.

High levels of triglyceride molecules in LDL cholesterol are “robustly” linked with an increased risk of atherosclerotic cardiovascular disease, according to a study that used two different methods in two separate cohorts from a large European population study plus a meta-analysis to verify the results.

“There have been some studies in the past, as you can see from our meta-analysis, that found a similar association, but I don’t think most people are convinced that there is really this relationship, and certainly I was not convinced,” lead investigator Børge G. Nordestgaard, MD, DMSc, professor at the University of Copenhagen, said in an interview.

The study enrolled 68,290 patients from the Copenhagen General Population study; 38,081 were assigned to direct automated assay to measure their LDL triglycerides and 30,208 had nuclear magnetic resonance (NMR) spectroscopy. Median follow-up was 3 and 9.2 years for the respective cohorts.

LDL triglycerides carry higher ASCVD risk

In the automated assay group, each 0.1-mmol/L (9 mg/dL)–higher direct LDL triglycerides carried a 22%-38% higher risk for the following outcomes: ASCVD (hazard ratio, 1.26; 95% confidence interval, 1.17-1.35); ischemic heart disease (HR, 1.27; 95% CI, 1.16-1.39); myocardial infarction (HR, 1.28; 95% CI, 1.11-1.48); ischemic stroke (HR, 1.22; 95% CI, 1.08-1.38); and peripheral artery disease (HR, 1.38; 95% CI, 1.21-1.58).

In the group that had NMR spectroscopy to measure LDL triglycerides, risks were similar, ranging from HRs of 1.13 (95% CI, 1.05-1.23) for ischemic stroke to 1.41 (95% CI, 1.31-1.52) for myocardial infarction. The investigators noted that apolipoprotein B levels didn’t entirely explain these results.

The meta-analysis included 18 studies that evaluated varying cardiovascular disease outcomes. It compared random-effects risk ratios for the highest quartile vs. the lowest quartile of LDL triglycerides. They were 1.50 (95% CI, 1.35-1.66) for ASCVD (four studies, 71,526 individuals, 8,576 events); 1.62 (95% CI, 1.37-1.93) for ischemic heart disease (six studies, 107,538 individuals, 9,734 events); 1.30 (95% CI, 1.13-1.49) for ischemic stroke (four studies, 78,026 individuals, 4,273 events); and 1.53 (95% CI, 1.29-1.81) for peripheral artery disease (four studies, 107,511 individuals, 1,848 events). The study was published online in the Journal of the American College of Cardiology.

Results confirm hypothesis the study sought to disprove

The purpose of the study was to actually disprove the hypothesis that the study ended up confirming, Dr. Nordestgaard said. “When we started this study, my idea was that we wanted to show that LDL triglyceride was not related to these diseases, because that didn’t make sense to me,” he said. “I’m so used to the thinking that the cholesterol content of these particles drive atherosclerosis and therefore atherosclerotic cardiovascular disease.”

He noted that LDL can carry both cholesterol and triglycerides, and that larger remnant lipoproteins can carry a substantial amount of triglycerides and a lesser amount of cholesterol. “Those remnants actually transfer into LDL, so they somewhat bring the triglycerides molecules into LDL,” Dr. Nordestgaard said.

The direct automated assay test used in the study to measure LDL triglycerides is not approved for use in the United States by the Food and Drug Administration, according to Denka, the manufacturer of the test.

The use of the Copenhagen General Population Study cohorts is a strength of the study because it has 100% follow-up with all patients, Dr. Nordestgaard said. The meta-analysis is another strength. “So we can show real clearly, not only in our two prospective studies, but also added to the former ones in the literature: All say exactly the same thing: High LDL triglycerides carry a high risk for ASCVD and its components.”

A limitation Dr. Nordestgaard acknowledged: The study doesn’t explain the causal relationship between high LDL triglycerides and ASCVD. But the study provides “very sound evidence that there’s a relationship,” he added. The study population was also a White, Danish population that lacked ethnic and racial diversity.

Next step is finding a treatment

The Danish study essentially confirms what the Atherosclerosis Risk in Community Study (ARIC) found with regard to LDL triglycerides, said Christie M. Ballantyne, MD, chief of cardiology at Baylor College of Medicine in Houston, and an ARIC investigator. 

This study is the “first step” to coming up with a test to identify risk, he said. “These data are pretty convincing, when you throw in the data in this study plus all the meta-analyses data, that LDL triglycerides, when they’re elevated, identify individuals at increased risk for an atherosclerotic cardiovascular event.”

The next step, he said, is coming up with a treatment for people with elevated HDL triglyceride. “That’s where we don’t have as much data because this test hasn’t been used. I’m pretty sure that statins are going to work fine for these people, because they lower LDL cholesterol and they also lower triglycerides, and some of the data have shown already that they reduce the LDL remnant,” Dr. Ballantyne said.

The Danish study provides enough of a basis for pursuing future studies to better understand the effect of statins on LDL triglyceride levels, Dr. Ballantyne added.

The study received funding from the Novo Nordisk Foundation and the Danish Heart Foundation, along with institutional support. Dr. Nordestgaard has no relevant disclosures. Dr. Ballantyne disclosed receiving research support from Denka.

I received a call late one night from a colleague in the emergency department of the children’s hospital. “This 2-year-old has a fever, cough, red eyes, and an impressive rash. I’ve personally never seen a case of measles, but I’m worried given that this child has never received the MMR vaccine.”

By the end of the call, I was worried too. Measles is a febrile respiratory illness classically accompanied by cough, coryza, conjunctivitis, and a characteristic maculopapular rash that begins on the face and spreads to the trunk and limbs. It is also highly contagious: 90% percent of susceptible, exposed individuals become infected.

Admittedly, measles is rare. Just 118 cases were reported in the United States in 2022, but 83 of those were in Columbus just 3 hours from where my colleague and I live and work. According to City of Columbus officials, the outbreak occurred almost exclusively in unimmunized children, the majority of whom were 5 years and younger. An unexpectedly high number of children were hospitalized. Typically, one in five people with measles will require hospitalization. In this outbreak, 33 children have been hospitalized as of Jan. 10.

Public health experts warn that 2023 could be much worse unless we increase measles immunization rates in the United States and globally. Immunization of around 95% of eligible people with two doses of measles-containing vaccine is associated with herd immunity. Globally, we’re falling short. Only 81% of the world’s children have received their first measle vaccine dose and only 71% have received the second dose. These are the lowest coverage rates for measles vaccine since 2008.

A 2022 joint press release from the Centers for Disease Control and Prevention and the World Health Organization noted that “measles anywhere is a threat everywhere, as the virus can quickly spread to multiple communities and across international borders.” Some prior measles outbreaks in the United States have started with a case in an international traveler or a U.S. resident who contracted measles during travel abroad.

In the United States, the number of children immunized with multiple routine vaccines has fallen in the last couple of years, in part because of pandemic-related disruptions in health care delivery. Increasing vaccine hesitancy, fueled by debates over the COVID-19 vaccine, may be slowing catch-up immunization in kids who fell behind.

Investigators from Emory University, Atlanta, and Marshfield Clinic Research Institute recently estimated that 9,145,026 U.S. children are susceptible to measles. If pandemic-level immunization rates continue without effective catch-up immunization, that number could rise to more than 15 million.

School vaccination requirements support efforts to ensure that kids are protected against vaccine-preventable diseases, but some data suggest that opposition to requiring MMR vaccine to attend public school is growing. According to a 2022 Kaiser Family Foundation Vaccine Monitor survey, 28% of U.S. adults – and 35% of parents of children under 18 – now say that parents should be able to decide to not vaccinate their children for measles, mumps, and rubella. That’s up from 16% of adults and 23% of parents in a 2019 Pew Research Center poll.

Public confidence in the benefits of MMR has also dropped modestly. About 85% of adults surveyed said that the benefits of MMR vaccine outweigh the risk, down from 88% in 2019. Among adults not vaccinated against COVID-19, only 70% said that benefits of these vaccines outweigh the risks.

While the WHO ramps up efforts to improve measles vaccination globally, pediatric clinicians can take steps now to mitigate the risk of measles outbreaks in their own communities. Query health records to understand how many eligible children in your practice have not yet received MMR vaccine. Notify families that vaccination is strongly recommended and make scheduling an appointment to receive vaccine easy. Some practices may have the bandwidth to offer evening and weekend hours for vaccine catch-up visits.

Curious about immunization rates in your state? The American Academy of Pediatrics has an interactive map that reports immunization coverage levels by state and provides comparisons to national rates and goals.

Prompt recognition and isolation of individuals with measles, along with prophylaxis of susceptible contacts, can limit community transmission. Measles can resemble other illnesses associated with fever and rash. Washington state has developed a screening tool to assist with recognition of measles. The CDC also has a measles outbreak toolkit that includes resources that outline clinical features and diagnoses, as well as strategies for talking to parents about vaccines.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She is a member of the AAP’s Committee on Infectious Diseases and one of the lead authors of the AAP’s Recommendations for Prevention and Control of Influenza in Children, 2022-2023. The opinions expressed in this article are her own. Dr. Bryant disclosed that she has served as an investigator on clinical trials funded by Pfizer, Enanta, and Gilead. Email her at [email protected].

I received a call late one night from a colleague in the emergency department of the children’s hospital. “This 2-year-old has a fever, cough, red eyes, and an impressive rash. I’ve personally never seen a case of measles, but I’m worried given that this child has never received the MMR vaccine.”

By the end of the call, I was worried too. Measles is a febrile respiratory illness classically accompanied by cough, coryza, conjunctivitis, and a characteristic maculopapular rash that begins on the face and spreads to the trunk and limbs. It is also highly contagious: 90% percent of susceptible, exposed individuals become infected.

Admittedly, measles is rare. Just 118 cases were reported in the United States in 2022, but 83 of those were in Columbus just 3 hours from where my colleague and I live and work. According to City of Columbus officials, the outbreak occurred almost exclusively in unimmunized children, the majority of whom were 5 years and younger. An unexpectedly high number of children were hospitalized. Typically, one in five people with measles will require hospitalization. In this outbreak, 33 children have been hospitalized as of Jan. 10.

Public health experts warn that 2023 could be much worse unless we increase measles immunization rates in the United States and globally. Immunization of around 95% of eligible people with two doses of measles-containing vaccine is associated with herd immunity. Globally, we’re falling short. Only 81% of the world’s children have received their first measle vaccine dose and only 71% have received the second dose. These are the lowest coverage rates for measles vaccine since 2008.

A 2022 joint press release from the Centers for Disease Control and Prevention and the World Health Organization noted that “measles anywhere is a threat everywhere, as the virus can quickly spread to multiple communities and across international borders.” Some prior measles outbreaks in the United States have started with a case in an international traveler or a U.S. resident who contracted measles during travel abroad.

In the United States, the number of children immunized with multiple routine vaccines has fallen in the last couple of years, in part because of pandemic-related disruptions in health care delivery. Increasing vaccine hesitancy, fueled by debates over the COVID-19 vaccine, may be slowing catch-up immunization in kids who fell behind.

Investigators from Emory University, Atlanta, and Marshfield Clinic Research Institute recently estimated that 9,145,026 U.S. children are susceptible to measles. If pandemic-level immunization rates continue without effective catch-up immunization, that number could rise to more than 15 million.

School vaccination requirements support efforts to ensure that kids are protected against vaccine-preventable diseases, but some data suggest that opposition to requiring MMR vaccine to attend public school is growing. According to a 2022 Kaiser Family Foundation Vaccine Monitor survey, 28% of U.S. adults – and 35% of parents of children under 18 – now say that parents should be able to decide to not vaccinate their children for measles, mumps, and rubella. That’s up from 16% of adults and 23% of parents in a 2019 Pew Research Center poll.

Public confidence in the benefits of MMR has also dropped modestly. About 85% of adults surveyed said that the benefits of MMR vaccine outweigh the risk, down from 88% in 2019. Among adults not vaccinated against COVID-19, only 70% said that benefits of these vaccines outweigh the risks.

While the WHO ramps up efforts to improve measles vaccination globally, pediatric clinicians can take steps now to mitigate the risk of measles outbreaks in their own communities. Query health records to understand how many eligible children in your practice have not yet received MMR vaccine. Notify families that vaccination is strongly recommended and make scheduling an appointment to receive vaccine easy. Some practices may have the bandwidth to offer evening and weekend hours for vaccine catch-up visits.

Curious about immunization rates in your state? The American Academy of Pediatrics has an interactive map that reports immunization coverage levels by state and provides comparisons to national rates and goals.

Prompt recognition and isolation of individuals with measles, along with prophylaxis of susceptible contacts, can limit community transmission. Measles can resemble other illnesses associated with fever and rash. Washington state has developed a screening tool to assist with recognition of measles. The CDC also has a measles outbreak toolkit that includes resources that outline clinical features and diagnoses, as well as strategies for talking to parents about vaccines.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She is a member of the AAP’s Committee on Infectious Diseases and one of the lead authors of the AAP’s Recommendations for Prevention and Control of Influenza in Children, 2022-2023. The opinions expressed in this article are her own. Dr. Bryant disclosed that she has served as an investigator on clinical trials funded by Pfizer, Enanta, and Gilead. Email her at [email protected].

I received a call late one night from a colleague in the emergency department of the children’s hospital. “This 2-year-old has a fever, cough, red eyes, and an impressive rash. I’ve personally never seen a case of measles, but I’m worried given that this child has never received the MMR vaccine.”

By the end of the call, I was worried too. Measles is a febrile respiratory illness classically accompanied by cough, coryza, conjunctivitis, and a characteristic maculopapular rash that begins on the face and spreads to the trunk and limbs. It is also highly contagious: 90% percent of susceptible, exposed individuals become infected.

Admittedly, measles is rare. Just 118 cases were reported in the United States in 2022, but 83 of those were in Columbus just 3 hours from where my colleague and I live and work. According to City of Columbus officials, the outbreak occurred almost exclusively in unimmunized children, the majority of whom were 5 years and younger. An unexpectedly high number of children were hospitalized. Typically, one in five people with measles will require hospitalization. In this outbreak, 33 children have been hospitalized as of Jan. 10.

Public health experts warn that 2023 could be much worse unless we increase measles immunization rates in the United States and globally. Immunization of around 95% of eligible people with two doses of measles-containing vaccine is associated with herd immunity. Globally, we’re falling short. Only 81% of the world’s children have received their first measle vaccine dose and only 71% have received the second dose. These are the lowest coverage rates for measles vaccine since 2008.

A 2022 joint press release from the Centers for Disease Control and Prevention and the World Health Organization noted that “measles anywhere is a threat everywhere, as the virus can quickly spread to multiple communities and across international borders.” Some prior measles outbreaks in the United States have started with a case in an international traveler or a U.S. resident who contracted measles during travel abroad.

In the United States, the number of children immunized with multiple routine vaccines has fallen in the last couple of years, in part because of pandemic-related disruptions in health care delivery. Increasing vaccine hesitancy, fueled by debates over the COVID-19 vaccine, may be slowing catch-up immunization in kids who fell behind.

Investigators from Emory University, Atlanta, and Marshfield Clinic Research Institute recently estimated that 9,145,026 U.S. children are susceptible to measles. If pandemic-level immunization rates continue without effective catch-up immunization, that number could rise to more than 15 million.

School vaccination requirements support efforts to ensure that kids are protected against vaccine-preventable diseases, but some data suggest that opposition to requiring MMR vaccine to attend public school is growing. According to a 2022 Kaiser Family Foundation Vaccine Monitor survey, 28% of U.S. adults – and 35% of parents of children under 18 – now say that parents should be able to decide to not vaccinate their children for measles, mumps, and rubella. That’s up from 16% of adults and 23% of parents in a 2019 Pew Research Center poll.

Public confidence in the benefits of MMR has also dropped modestly. About 85% of adults surveyed said that the benefits of MMR vaccine outweigh the risk, down from 88% in 2019. Among adults not vaccinated against COVID-19, only 70% said that benefits of these vaccines outweigh the risks.

While the WHO ramps up efforts to improve measles vaccination globally, pediatric clinicians can take steps now to mitigate the risk of measles outbreaks in their own communities. Query health records to understand how many eligible children in your practice have not yet received MMR vaccine. Notify families that vaccination is strongly recommended and make scheduling an appointment to receive vaccine easy. Some practices may have the bandwidth to offer evening and weekend hours for vaccine catch-up visits.

Curious about immunization rates in your state? The American Academy of Pediatrics has an interactive map that reports immunization coverage levels by state and provides comparisons to national rates and goals.

Prompt recognition and isolation of individuals with measles, along with prophylaxis of susceptible contacts, can limit community transmission. Measles can resemble other illnesses associated with fever and rash. Washington state has developed a screening tool to assist with recognition of measles. The CDC also has a measles outbreak toolkit that includes resources that outline clinical features and diagnoses, as well as strategies for talking to parents about vaccines.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She is a member of the AAP’s Committee on Infectious Diseases and one of the lead authors of the AAP’s Recommendations for Prevention and Control of Influenza in Children, 2022-2023. The opinions expressed in this article are her own. Dr. Bryant disclosed that she has served as an investigator on clinical trials funded by Pfizer, Enanta, and Gilead. Email her at [email protected].

The newest subvariant of Omicron, XBB.1.5, is so transmissible that everybody is at risk of catching it, even if they’ve already been infected and are fully vaccinated, a health expert told USA Today.

“It’s crazy infectious,” said Paula Cannon, PhD, a virologist at the University of Southern California, Los Angeles. “All the things that have protected you for the past couple of years, I don’t think are going to protect you against this new crop of variants.” 

XBB.1.5 is spreading quickly in the United States. It accounted for 27.6% of cases in the country in the week ending on Jan. 7, up from about 1% of cases at one point in December, according to the Centers for Disease Control and Prevention. It’s especially prevalent in the Northeast, now accounting for more than 70% of the cases in that region.

It’s spreading across the globe, too. Maria Van Kerkhove, PhD, technical lead of the World Health Organization, has called XBB.1.5 is “the most transmissible subvariant that has been detected yet.” 

Ashish Jha, MD, the White House COVID-19 response coordinator, tweeted a few days ago that the spread of XBB.1.5 is “stunning” but cautioned that it’s unclear if the symptoms of infection will be more severe than for previous variants.

“Whether we’ll have an XBB.1.5 wave (and if yes, how big) will depend on many factors including immunity of the population, people’s actions, etc.,” he tweeted. 

He urged people to get up to date on their boosters, wear a snug-fitting mask, and avoid crowded indoor spaces. He noted that people who haven’t been infected recently or haven’t gotten the bivalent booster likely have little protection against infection.

The symptoms for XBB.1.5 appear to be the same as for other versions of COVID-19. However, it’s less common for people infected with XBB.1.5 to report losing their sense of taste and smell, USA Today reported.

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

The newest subvariant of Omicron, XBB.1.5, is so transmissible that everybody is at risk of catching it, even if they’ve already been infected and are fully vaccinated, a health expert told USA Today.

“It’s crazy infectious,” said Paula Cannon, PhD, a virologist at the University of Southern California, Los Angeles. “All the things that have protected you for the past couple of years, I don’t think are going to protect you against this new crop of variants.” 

XBB.1.5 is spreading quickly in the United States. It accounted for 27.6% of cases in the country in the week ending on Jan. 7, up from about 1% of cases at one point in December, according to the Centers for Disease Control and Prevention. It’s especially prevalent in the Northeast, now accounting for more than 70% of the cases in that region.

It’s spreading across the globe, too. Maria Van Kerkhove, PhD, technical lead of the World Health Organization, has called XBB.1.5 is “the most transmissible subvariant that has been detected yet.” 

Ashish Jha, MD, the White House COVID-19 response coordinator, tweeted a few days ago that the spread of XBB.1.5 is “stunning” but cautioned that it’s unclear if the symptoms of infection will be more severe than for previous variants.

“Whether we’ll have an XBB.1.5 wave (and if yes, how big) will depend on many factors including immunity of the population, people’s actions, etc.,” he tweeted. 

He urged people to get up to date on their boosters, wear a snug-fitting mask, and avoid crowded indoor spaces. He noted that people who haven’t been infected recently or haven’t gotten the bivalent booster likely have little protection against infection.

The symptoms for XBB.1.5 appear to be the same as for other versions of COVID-19. However, it’s less common for people infected with XBB.1.5 to report losing their sense of taste and smell, USA Today reported.

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

The newest subvariant of Omicron, XBB.1.5, is so transmissible that everybody is at risk of catching it, even if they’ve already been infected and are fully vaccinated, a health expert told USA Today.

“It’s crazy infectious,” said Paula Cannon, PhD, a virologist at the University of Southern California, Los Angeles. “All the things that have protected you for the past couple of years, I don’t think are going to protect you against this new crop of variants.” 

XBB.1.5 is spreading quickly in the United States. It accounted for 27.6% of cases in the country in the week ending on Jan. 7, up from about 1% of cases at one point in December, according to the Centers for Disease Control and Prevention. It’s especially prevalent in the Northeast, now accounting for more than 70% of the cases in that region.

It’s spreading across the globe, too. Maria Van Kerkhove, PhD, technical lead of the World Health Organization, has called XBB.1.5 is “the most transmissible subvariant that has been detected yet.” 

Ashish Jha, MD, the White House COVID-19 response coordinator, tweeted a few days ago that the spread of XBB.1.5 is “stunning” but cautioned that it’s unclear if the symptoms of infection will be more severe than for previous variants.

“Whether we’ll have an XBB.1.5 wave (and if yes, how big) will depend on many factors including immunity of the population, people’s actions, etc.,” he tweeted. 

He urged people to get up to date on their boosters, wear a snug-fitting mask, and avoid crowded indoor spaces. He noted that people who haven’t been infected recently or haven’t gotten the bivalent booster likely have little protection against infection.

The symptoms for XBB.1.5 appear to be the same as for other versions of COVID-19. However, it’s less common for people infected with XBB.1.5 to report losing their sense of taste and smell, USA Today reported.

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

The SARS-CoV-2 virus can be found throughout the entire body and remain present for more than 7 months, researchers discovered.

A study on the subject was published in the journal Nature. The researchers completed autopsies from April 2020 to March 2021 of 44 unvaccinated people who had severe COVID-19. The median age was 62.5 years old, and 30% were female. Extensive brain sampling was done for 11 cases.

Because of its nature as a respiratory illness, SARS-CoV-2 was most widespread in the respiratory system such as in the lungs. But it was also found in 79 other body locations, including the heart, kidneys, liver, muscles, nerves, reproductive tract, and eyes. 

The researchers said their work shows the SARS-CoV-2 “is capable of infecting and replicating within the human brain.” They also said their results indicate the virus spreads via the blood early during infection, which “seeds the virus throughout the body following infection of the respiratory tract.”

The authors noted that, while the virus was found outside the respiratory tract, they did not find signs of inflammation beyond the respiratory system.

The results will help narrow down treatments for long COVID, and particularly support the idea of using the antiviral drug Paxlovid to treat long COVID, according to a blog post from the National Institute of Allergy and Infectious Diseases. A clinical trial is already underway examining the treatment, and results are expected in January 2024.

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

The SARS-CoV-2 virus can be found throughout the entire body and remain present for more than 7 months, researchers discovered.

A study on the subject was published in the journal Nature. The researchers completed autopsies from April 2020 to March 2021 of 44 unvaccinated people who had severe COVID-19. The median age was 62.5 years old, and 30% were female. Extensive brain sampling was done for 11 cases.

Because of its nature as a respiratory illness, SARS-CoV-2 was most widespread in the respiratory system such as in the lungs. But it was also found in 79 other body locations, including the heart, kidneys, liver, muscles, nerves, reproductive tract, and eyes. 

The researchers said their work shows the SARS-CoV-2 “is capable of infecting and replicating within the human brain.” They also said their results indicate the virus spreads via the blood early during infection, which “seeds the virus throughout the body following infection of the respiratory tract.”

The authors noted that, while the virus was found outside the respiratory tract, they did not find signs of inflammation beyond the respiratory system.

The results will help narrow down treatments for long COVID, and particularly support the idea of using the antiviral drug Paxlovid to treat long COVID, according to a blog post from the National Institute of Allergy and Infectious Diseases. A clinical trial is already underway examining the treatment, and results are expected in January 2024.

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

The SARS-CoV-2 virus can be found throughout the entire body and remain present for more than 7 months, researchers discovered.

A study on the subject was published in the journal Nature. The researchers completed autopsies from April 2020 to March 2021 of 44 unvaccinated people who had severe COVID-19. The median age was 62.5 years old, and 30% were female. Extensive brain sampling was done for 11 cases.

Because of its nature as a respiratory illness, SARS-CoV-2 was most widespread in the respiratory system such as in the lungs. But it was also found in 79 other body locations, including the heart, kidneys, liver, muscles, nerves, reproductive tract, and eyes. 

The researchers said their work shows the SARS-CoV-2 “is capable of infecting and replicating within the human brain.” They also said their results indicate the virus spreads via the blood early during infection, which “seeds the virus throughout the body following infection of the respiratory tract.”

The authors noted that, while the virus was found outside the respiratory tract, they did not find signs of inflammation beyond the respiratory system.

The results will help narrow down treatments for long COVID, and particularly support the idea of using the antiviral drug Paxlovid to treat long COVID, according to a blog post from the National Institute of Allergy and Infectious Diseases. A clinical trial is already underway examining the treatment, and results are expected in January 2024.

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

Multisystem inflammatory syndrome in children (MIS-C) is more common than previously thought. This pediatric illness occurs 2-6 weeks after being infected with COVID-19. 

For every 100 COVID-19 hospitalizations, there were 17 MIS-C hospitalizations, a new study found. The illness is rare, but it causes dangerous multiorgan dysfunction and frequently requires a stay in the ICU. According to the Centers for Disease Control and Prevention, there have been at least 9,333 cases nationwide and 76 deaths from MIS-C.

Researchers said their findings were in such contrast to previous MIS-C research that it may render the old research “misleading.”

The analysis was powered by improved data extracted from hospital billing systems. Previous analyses of MIS-C were limited to voluntarily reported cases, which is likely the reason for the undercount.

The study reported a mortality rate for people with the most severe cases (affecting six to eight organs) of 5.8%. The authors of a companion editorial to the study said the mortality rate was low when considering the widespread impacts, “reflecting the rapid reversibility of MIS-C” with treatment. 

Differences in MIS-C cases were also found based on children’s race and ethnicity. Black patients were more likely to have severe cases affecting more organs, compared to white patients.

The study included 4,107 MIS-C cases, using data from 2021 for patients younger than 21 years old. The median age was 9 years old. 

The findings provide direction for further research, the editorial writers suggested.

Questions that need to be answered include asking why Black children with MIS-C are more likely to have a higher number of organ systems affected.

“Identifying patient biological or socioeconomic factors that can be targeted for treatment or prevention should be pursued,” they wrote.

The CDC says symptoms of MIS-C are an ongoing fever plus more than one of the following: stomach pain, bloodshot eyes, diarrhea, dizziness or lightheadedness (signs of low blood pressure), skin rash, or vomiting.

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

Multisystem inflammatory syndrome in children (MIS-C) is more common than previously thought. This pediatric illness occurs 2-6 weeks after being infected with COVID-19. 

For every 100 COVID-19 hospitalizations, there were 17 MIS-C hospitalizations, a new study found. The illness is rare, but it causes dangerous multiorgan dysfunction and frequently requires a stay in the ICU. According to the Centers for Disease Control and Prevention, there have been at least 9,333 cases nationwide and 76 deaths from MIS-C.

Researchers said their findings were in such contrast to previous MIS-C research that it may render the old research “misleading.”

The analysis was powered by improved data extracted from hospital billing systems. Previous analyses of MIS-C were limited to voluntarily reported cases, which is likely the reason for the undercount.

The study reported a mortality rate for people with the most severe cases (affecting six to eight organs) of 5.8%. The authors of a companion editorial to the study said the mortality rate was low when considering the widespread impacts, “reflecting the rapid reversibility of MIS-C” with treatment. 

Differences in MIS-C cases were also found based on children’s race and ethnicity. Black patients were more likely to have severe cases affecting more organs, compared to white patients.

The study included 4,107 MIS-C cases, using data from 2021 for patients younger than 21 years old. The median age was 9 years old. 

The findings provide direction for further research, the editorial writers suggested.

Questions that need to be answered include asking why Black children with MIS-C are more likely to have a higher number of organ systems affected.

“Identifying patient biological or socioeconomic factors that can be targeted for treatment or prevention should be pursued,” they wrote.

The CDC says symptoms of MIS-C are an ongoing fever plus more than one of the following: stomach pain, bloodshot eyes, diarrhea, dizziness or lightheadedness (signs of low blood pressure), skin rash, or vomiting.

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

Multisystem inflammatory syndrome in children (MIS-C) is more common than previously thought. This pediatric illness occurs 2-6 weeks after being infected with COVID-19. 

For every 100 COVID-19 hospitalizations, there were 17 MIS-C hospitalizations, a new study found. The illness is rare, but it causes dangerous multiorgan dysfunction and frequently requires a stay in the ICU. According to the Centers for Disease Control and Prevention, there have been at least 9,333 cases nationwide and 76 deaths from MIS-C.

Researchers said their findings were in such contrast to previous MIS-C research that it may render the old research “misleading.”

The analysis was powered by improved data extracted from hospital billing systems. Previous analyses of MIS-C were limited to voluntarily reported cases, which is likely the reason for the undercount.

The study reported a mortality rate for people with the most severe cases (affecting six to eight organs) of 5.8%. The authors of a companion editorial to the study said the mortality rate was low when considering the widespread impacts, “reflecting the rapid reversibility of MIS-C” with treatment. 

Differences in MIS-C cases were also found based on children’s race and ethnicity. Black patients were more likely to have severe cases affecting more organs, compared to white patients.

The study included 4,107 MIS-C cases, using data from 2021 for patients younger than 21 years old. The median age was 9 years old. 

The findings provide direction for further research, the editorial writers suggested.

Questions that need to be answered include asking why Black children with MIS-C are more likely to have a higher number of organ systems affected.

“Identifying patient biological or socioeconomic factors that can be targeted for treatment or prevention should be pursued,” they wrote.

The CDC says symptoms of MIS-C are an ongoing fever plus more than one of the following: stomach pain, bloodshot eyes, diarrhea, dizziness or lightheadedness (signs of low blood pressure), skin rash, or vomiting.

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

Peripheral airway response to methacholine was similar among obese adults with and without asthma, although forced expiratory volume was lower for those with asthma, based on data from 53 individuals.

Obesity remains a risk factor for asthma, and obese individuals with asthma tend to have worse control and more severe disease, compared with nonobese asthma patients, wrote Anne E. Dixon, BM, BCh, of the University of Vermont, Burlington, and colleagues.

Previous studies have shown that airway reactivity can occur in obese individuals without airway inflammation, but studies characterizing obese asthma based on lung function are lacking, they said. “Combining spirometry and oscillometry might reveal abnormalities in lung mechanics particularly pertinent to people with obesity and asthma,” the researchers noted.

In a cross-sectional study published in the journal CHEST, the researchers reviewed data from 31 obese adults with asthma and 22 obese adults without asthma. The participants were aged 18 years and older, with forced expiratory volume (FEV₁) of at least 60% of predicted. All had class III obesity, with an average BMI of 47.2 kg/m² for those with asthma and 46.7 kg/m² for nonasthma controls. Demographic characteristics were similar between the groups.

Airway reactivity was defined as a 20% decrease in FEV₁ and/or a 50% change in resistance or reactance at 5 Hz (R5 and X5), at a concentration of 16 mg/mL or less of methacholine. Patients were assessed using spirometry and oscillometry.

Overall, most obese individuals with and without asthma showed significant changes in peripheral airway resistance. For those with asthma, the resistance at 5 Hz, measured by oscillometry, increased by 52% in response to the PC20 methacholine challenge, with an area under the reactance curve (AX) of 361%. For controls without asthma, the resistance at 5 Hz increased by 45%, with an AX of 268% in response to 16 mg/mL of methacholine.

This finding suggests that obesity predisposes individuals to peripheral airway reactivity regardless of asthma status, the researchers wrote in their discussion.

The researchers also identified two distinct groups of asthma patients categorized by respiratory system impedance based on more concordant vs. discordant bronchoconstriction in the central and peripheral airways. The baseline AX for these two groups was 11.8 and 46.7, respectively, with interquartile ranges of 9.9-23.4 and 23.2-53.7, respectively.

The discordant group included only women, and these patients reported significantly more gastroesophageal reflux, increased chest tightness, and more wheezing and asthma exacerbations than the concordant group, which may be related to air trapping, shown on previous studies of obese individuals with asthma, the researchers wrote.

The findings were limited by several factors, including the measurement of airway impedance only at the peak methacholine dose and the measurement of oscillometry after spirometry, the researchers noted. Other limitations included the relatively small study population at a single center, and the focus on obese individuals only.

More research is needed in larger and more diverse patient populations, but the results support the characterization of a subgroup of obese asthma patients with significant peripheral airway dysfunction, the researchers wrote.

“Oscillometry testing can reveal a physiologic phenotype of asthma in obesity that may be related to worse symptoms and more severe disease, and also reveal subclinical abnormalities in people with obesity, but without clinically diagnosed lung disease,” they concluded.

The study was supported in part by the National Institutes of Health. The researchers declared no financial conflicts.

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

Peripheral airway response to methacholine was similar among obese adults with and without asthma, although forced expiratory volume was lower for those with asthma, based on data from 53 individuals.

Obesity remains a risk factor for asthma, and obese individuals with asthma tend to have worse control and more severe disease, compared with nonobese asthma patients, wrote Anne E. Dixon, BM, BCh, of the University of Vermont, Burlington, and colleagues.

Previous studies have shown that airway reactivity can occur in obese individuals without airway inflammation, but studies characterizing obese asthma based on lung function are lacking, they said. “Combining spirometry and oscillometry might reveal abnormalities in lung mechanics particularly pertinent to people with obesity and asthma,” the researchers noted.

In a cross-sectional study published in the journal CHEST, the researchers reviewed data from 31 obese adults with asthma and 22 obese adults without asthma. The participants were aged 18 years and older, with forced expiratory volume (FEV₁) of at least 60% of predicted. All had class III obesity, with an average BMI of 47.2 kg/m² for those with asthma and 46.7 kg/m² for nonasthma controls. Demographic characteristics were similar between the groups.

Airway reactivity was defined as a 20% decrease in FEV₁ and/or a 50% change in resistance or reactance at 5 Hz (R5 and X5), at a concentration of 16 mg/mL or less of methacholine. Patients were assessed using spirometry and oscillometry.

Overall, most obese individuals with and without asthma showed significant changes in peripheral airway resistance. For those with asthma, the resistance at 5 Hz, measured by oscillometry, increased by 52% in response to the PC20 methacholine challenge, with an area under the reactance curve (AX) of 361%. For controls without asthma, the resistance at 5 Hz increased by 45%, with an AX of 268% in response to 16 mg/mL of methacholine.

This finding suggests that obesity predisposes individuals to peripheral airway reactivity regardless of asthma status, the researchers wrote in their discussion.

The researchers also identified two distinct groups of asthma patients categorized by respiratory system impedance based on more concordant vs. discordant bronchoconstriction in the central and peripheral airways. The baseline AX for these two groups was 11.8 and 46.7, respectively, with interquartile ranges of 9.9-23.4 and 23.2-53.7, respectively.

The discordant group included only women, and these patients reported significantly more gastroesophageal reflux, increased chest tightness, and more wheezing and asthma exacerbations than the concordant group, which may be related to air trapping, shown on previous studies of obese individuals with asthma, the researchers wrote.

The findings were limited by several factors, including the measurement of airway impedance only at the peak methacholine dose and the measurement of oscillometry after spirometry, the researchers noted. Other limitations included the relatively small study population at a single center, and the focus on obese individuals only.

More research is needed in larger and more diverse patient populations, but the results support the characterization of a subgroup of obese asthma patients with significant peripheral airway dysfunction, the researchers wrote.

“Oscillometry testing can reveal a physiologic phenotype of asthma in obesity that may be related to worse symptoms and more severe disease, and also reveal subclinical abnormalities in people with obesity, but without clinically diagnosed lung disease,” they concluded.

The study was supported in part by the National Institutes of Health. The researchers declared no financial conflicts.

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

Peripheral airway response to methacholine was similar among obese adults with and without asthma, although forced expiratory volume was lower for those with asthma, based on data from 53 individuals.

Obesity remains a risk factor for asthma, and obese individuals with asthma tend to have worse control and more severe disease, compared with nonobese asthma patients, wrote Anne E. Dixon, BM, BCh, of the University of Vermont, Burlington, and colleagues.

Previous studies have shown that airway reactivity can occur in obese individuals without airway inflammation, but studies characterizing obese asthma based on lung function are lacking, they said. “Combining spirometry and oscillometry might reveal abnormalities in lung mechanics particularly pertinent to people with obesity and asthma,” the researchers noted.

In a cross-sectional study published in the journal CHEST, the researchers reviewed data from 31 obese adults with asthma and 22 obese adults without asthma. The participants were aged 18 years and older, with forced expiratory volume (FEV₁) of at least 60% of predicted. All had class III obesity, with an average BMI of 47.2 kg/m² for those with asthma and 46.7 kg/m² for nonasthma controls. Demographic characteristics were similar between the groups.

Airway reactivity was defined as a 20% decrease in FEV₁ and/or a 50% change in resistance or reactance at 5 Hz (R5 and X5), at a concentration of 16 mg/mL or less of methacholine. Patients were assessed using spirometry and oscillometry.

Overall, most obese individuals with and without asthma showed significant changes in peripheral airway resistance. For those with asthma, the resistance at 5 Hz, measured by oscillometry, increased by 52% in response to the PC20 methacholine challenge, with an area under the reactance curve (AX) of 361%. For controls without asthma, the resistance at 5 Hz increased by 45%, with an AX of 268% in response to 16 mg/mL of methacholine.

This finding suggests that obesity predisposes individuals to peripheral airway reactivity regardless of asthma status, the researchers wrote in their discussion.

The researchers also identified two distinct groups of asthma patients categorized by respiratory system impedance based on more concordant vs. discordant bronchoconstriction in the central and peripheral airways. The baseline AX for these two groups was 11.8 and 46.7, respectively, with interquartile ranges of 9.9-23.4 and 23.2-53.7, respectively.

The discordant group included only women, and these patients reported significantly more gastroesophageal reflux, increased chest tightness, and more wheezing and asthma exacerbations than the concordant group, which may be related to air trapping, shown on previous studies of obese individuals with asthma, the researchers wrote.

The findings were limited by several factors, including the measurement of airway impedance only at the peak methacholine dose and the measurement of oscillometry after spirometry, the researchers noted. Other limitations included the relatively small study population at a single center, and the focus on obese individuals only.

More research is needed in larger and more diverse patient populations, but the results support the characterization of a subgroup of obese asthma patients with significant peripheral airway dysfunction, the researchers wrote.

“Oscillometry testing can reveal a physiologic phenotype of asthma in obesity that may be related to worse symptoms and more severe disease, and also reveal subclinical abnormalities in people with obesity, but without clinically diagnosed lung disease,” they concluded.

The study was supported in part by the National Institutes of Health. The researchers declared no financial conflicts.

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

If you smoke, vape, or ingest cannabis, your anesthesiologist should know before you undergo a surgical procedure, according to new medical guidelines.

All patients who undergo procedures that require regional or general anesthesia should be asked if, how often, and in what forms they use the drug, according to recommendations from the American Society of Regional Anesthesia and Pain Medicine.

One reason: Patients who regularly use cannabis may experience worse pain and nausea after surgery and may require more opioid analgesia, the group said.

The society’s recommendations – published in Regional Anesthesia and Pain Medicine – are the first guidelines in the United States to cover cannabis use as it relates to surgery, the group said.
 

Possible interactions

Use of cannabis has increased in recent years, and researchers have been concerned that the drug may interact with anesthesia and complicate pain management. Few studies have evaluated interactions between cannabis and anesthetic agents, however, according to the authors of the new guidelines.

“With the rising prevalence of both medical and recreational cannabis use in the general population, anesthesiologists, surgeons, and perioperative physicians must have an understanding of the effects of cannabis on physiology in order to provide safe perioperative care,” the guideline said.

“Before surgery, anesthesiologists should ask patients if they use cannabis – whether medicinally or recreationally – and be prepared to possibly change the anesthesia plan or delay the procedure in certain situations,” Samer Narouze, MD, PhD, ASRA president and senior author of the guidelines, said in a news release about the recommendations.

Although some patients may use cannabis to relieve pain, research shows that “regular users may have more pain and nausea after surgery, not less, and may need more medications, including opioids, to manage the discomfort,” said Dr. Narouze, chairman of the Center for Pain Medicine at Western Reserve Hospital in Cuyahoga Falls, Ohio.
 

Risks for vomiting, heart attack

The new recommendations were created by a committee of 13 experts, including anesthesiologists, chronic pain physicians, and a patient advocate. Shalini Shah, MD, vice chair of anesthesiology at the University of California, Irvine, was lead author of the document.

Four of 21 recommendations were classified as grade A, meaning that following them would be expected to provide substantial benefits. Those recommendations are to screen all patients before surgery; postpone elective surgery for patients who have altered mental status or impaired decision-making capacity at the time of surgery; counsel frequent, heavy users about the potential for cannabis use to impair postoperative pain control; and counsel pregnant patients about the risks of cannabis use to unborn children.

The authors cited studies to support their recommendations, including one showing that long-term cannabis use was associated with a 20% increase in the incidence of postoperative nausea and vomiting, a leading complaint of surgery patients. Other research has shown that cannabis use is linked to more pain and use of opioids after surgery.

Other recommendations include delaying elective surgery for at least 2 hours after a patient has smoked cannabis, owing to an increased risk for heart attack, and considering adjustment of ventilation settings during surgery for regular smokers of cannabis. Research has shown that smoking cannabis may be a rare trigger for myocardial infarction and is associated with airway inflammation and self-reported respiratory symptoms.

Nevertheless, doctors should not conduct universal toxicology screening, given a lack of evidence supporting this practice, the guideline stated.

The authors did not have enough information to make recommendations about reducing cannabis use before surgery or adjusting opioid prescriptions after surgery for patients who use cannabis, they said.

Kenneth Finn, MD, president of the American Board of Pain Medicine, welcomed the publication of the new guidelines. Dr. Finn, who practices at Springs Rehabilitation in Colorado Springs, has edited a textbook about cannabis in medicine and founded the International Academy on the Science and Impact of Cannabis.

“The vast majority of medical providers really have no idea about cannabis and what its impacts are on the human body,” Dr. Finn said.

For one, it can interact with numerous other drugs, including warfarin.

Guideline coauthor Eugene R. Viscusi, MD, professor of anesthesiology at the Sidney Kimmel Medical College, Philadelphia, emphasized that, while cannabis may be perceived as “natural,” it should not be considered differently from manufactured drugs.

Cannabis and cannabinoids represent “a class of very potent and pharmacologically active compounds,” Dr. Viscusi said in an interview. While researchers continue to assess possible medically beneficial effects of cannabis compounds, clinicians also need to be aware of the risks.

“The literature continues to emerge, and while we are always hopeful for good news, as physicians, we need to be very well versed on potential risks, especially in a high-risk situation like surgery,” he said.

Dr. Shah has consulted for companies that develop medical devices and drugs. Dr. Finn is the editor of the textbook, “Cannabis in Medicine: An Evidence-Based Approach” (Springer: New York, 2020), for which he receives royalties.

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

If you smoke, vape, or ingest cannabis, your anesthesiologist should know before you undergo a surgical procedure, according to new medical guidelines.

All patients who undergo procedures that require regional or general anesthesia should be asked if, how often, and in what forms they use the drug, according to recommendations from the American Society of Regional Anesthesia and Pain Medicine.

One reason: Patients who regularly use cannabis may experience worse pain and nausea after surgery and may require more opioid analgesia, the group said.

The society’s recommendations – published in Regional Anesthesia and Pain Medicine – are the first guidelines in the United States to cover cannabis use as it relates to surgery, the group said.
 

Possible interactions

Use of cannabis has increased in recent years, and researchers have been concerned that the drug may interact with anesthesia and complicate pain management. Few studies have evaluated interactions between cannabis and anesthetic agents, however, according to the authors of the new guidelines.

“With the rising prevalence of both medical and recreational cannabis use in the general population, anesthesiologists, surgeons, and perioperative physicians must have an understanding of the effects of cannabis on physiology in order to provide safe perioperative care,” the guideline said.

“Before surgery, anesthesiologists should ask patients if they use cannabis – whether medicinally or recreationally – and be prepared to possibly change the anesthesia plan or delay the procedure in certain situations,” Samer Narouze, MD, PhD, ASRA president and senior author of the guidelines, said in a news release about the recommendations.

Although some patients may use cannabis to relieve pain, research shows that “regular users may have more pain and nausea after surgery, not less, and may need more medications, including opioids, to manage the discomfort,” said Dr. Narouze, chairman of the Center for Pain Medicine at Western Reserve Hospital in Cuyahoga Falls, Ohio.
 

Risks for vomiting, heart attack

The new recommendations were created by a committee of 13 experts, including anesthesiologists, chronic pain physicians, and a patient advocate. Shalini Shah, MD, vice chair of anesthesiology at the University of California, Irvine, was lead author of the document.

Four of 21 recommendations were classified as grade A, meaning that following them would be expected to provide substantial benefits. Those recommendations are to screen all patients before surgery; postpone elective surgery for patients who have altered mental status or impaired decision-making capacity at the time of surgery; counsel frequent, heavy users about the potential for cannabis use to impair postoperative pain control; and counsel pregnant patients about the risks of cannabis use to unborn children.

The authors cited studies to support their recommendations, including one showing that long-term cannabis use was associated with a 20% increase in the incidence of postoperative nausea and vomiting, a leading complaint of surgery patients. Other research has shown that cannabis use is linked to more pain and use of opioids after surgery.

Other recommendations include delaying elective surgery for at least 2 hours after a patient has smoked cannabis, owing to an increased risk for heart attack, and considering adjustment of ventilation settings during surgery for regular smokers of cannabis. Research has shown that smoking cannabis may be a rare trigger for myocardial infarction and is associated with airway inflammation and self-reported respiratory symptoms.

Nevertheless, doctors should not conduct universal toxicology screening, given a lack of evidence supporting this practice, the guideline stated.

The authors did not have enough information to make recommendations about reducing cannabis use before surgery or adjusting opioid prescriptions after surgery for patients who use cannabis, they said.

Kenneth Finn, MD, president of the American Board of Pain Medicine, welcomed the publication of the new guidelines. Dr. Finn, who practices at Springs Rehabilitation in Colorado Springs, has edited a textbook about cannabis in medicine and founded the International Academy on the Science and Impact of Cannabis.

“The vast majority of medical providers really have no idea about cannabis and what its impacts are on the human body,” Dr. Finn said.

For one, it can interact with numerous other drugs, including warfarin.

Guideline coauthor Eugene R. Viscusi, MD, professor of anesthesiology at the Sidney Kimmel Medical College, Philadelphia, emphasized that, while cannabis may be perceived as “natural,” it should not be considered differently from manufactured drugs.

Cannabis and cannabinoids represent “a class of very potent and pharmacologically active compounds,” Dr. Viscusi said in an interview. While researchers continue to assess possible medically beneficial effects of cannabis compounds, clinicians also need to be aware of the risks.

“The literature continues to emerge, and while we are always hopeful for good news, as physicians, we need to be very well versed on potential risks, especially in a high-risk situation like surgery,” he said.

Dr. Shah has consulted for companies that develop medical devices and drugs. Dr. Finn is the editor of the textbook, “Cannabis in Medicine: An Evidence-Based Approach” (Springer: New York, 2020), for which he receives royalties.

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

If you smoke, vape, or ingest cannabis, your anesthesiologist should know before you undergo a surgical procedure, according to new medical guidelines.

All patients who undergo procedures that require regional or general anesthesia should be asked if, how often, and in what forms they use the drug, according to recommendations from the American Society of Regional Anesthesia and Pain Medicine.

One reason: Patients who regularly use cannabis may experience worse pain and nausea after surgery and may require more opioid analgesia, the group said.

The society’s recommendations – published in Regional Anesthesia and Pain Medicine – are the first guidelines in the United States to cover cannabis use as it relates to surgery, the group said.
 

Possible interactions

Use of cannabis has increased in recent years, and researchers have been concerned that the drug may interact with anesthesia and complicate pain management. Few studies have evaluated interactions between cannabis and anesthetic agents, however, according to the authors of the new guidelines.

“With the rising prevalence of both medical and recreational cannabis use in the general population, anesthesiologists, surgeons, and perioperative physicians must have an understanding of the effects of cannabis on physiology in order to provide safe perioperative care,” the guideline said.

“Before surgery, anesthesiologists should ask patients if they use cannabis – whether medicinally or recreationally – and be prepared to possibly change the anesthesia plan or delay the procedure in certain situations,” Samer Narouze, MD, PhD, ASRA president and senior author of the guidelines, said in a news release about the recommendations.

Although some patients may use cannabis to relieve pain, research shows that “regular users may have more pain and nausea after surgery, not less, and may need more medications, including opioids, to manage the discomfort,” said Dr. Narouze, chairman of the Center for Pain Medicine at Western Reserve Hospital in Cuyahoga Falls, Ohio.
 

Risks for vomiting, heart attack

The new recommendations were created by a committee of 13 experts, including anesthesiologists, chronic pain physicians, and a patient advocate. Shalini Shah, MD, vice chair of anesthesiology at the University of California, Irvine, was lead author of the document.

Four of 21 recommendations were classified as grade A, meaning that following them would be expected to provide substantial benefits. Those recommendations are to screen all patients before surgery; postpone elective surgery for patients who have altered mental status or impaired decision-making capacity at the time of surgery; counsel frequent, heavy users about the potential for cannabis use to impair postoperative pain control; and counsel pregnant patients about the risks of cannabis use to unborn children.

The authors cited studies to support their recommendations, including one showing that long-term cannabis use was associated with a 20% increase in the incidence of postoperative nausea and vomiting, a leading complaint of surgery patients. Other research has shown that cannabis use is linked to more pain and use of opioids after surgery.

Other recommendations include delaying elective surgery for at least 2 hours after a patient has smoked cannabis, owing to an increased risk for heart attack, and considering adjustment of ventilation settings during surgery for regular smokers of cannabis. Research has shown that smoking cannabis may be a rare trigger for myocardial infarction and is associated with airway inflammation and self-reported respiratory symptoms.

Nevertheless, doctors should not conduct universal toxicology screening, given a lack of evidence supporting this practice, the guideline stated.

The authors did not have enough information to make recommendations about reducing cannabis use before surgery or adjusting opioid prescriptions after surgery for patients who use cannabis, they said.

Kenneth Finn, MD, president of the American Board of Pain Medicine, welcomed the publication of the new guidelines. Dr. Finn, who practices at Springs Rehabilitation in Colorado Springs, has edited a textbook about cannabis in medicine and founded the International Academy on the Science and Impact of Cannabis.

“The vast majority of medical providers really have no idea about cannabis and what its impacts are on the human body,” Dr. Finn said.

For one, it can interact with numerous other drugs, including warfarin.

Guideline coauthor Eugene R. Viscusi, MD, professor of anesthesiology at the Sidney Kimmel Medical College, Philadelphia, emphasized that, while cannabis may be perceived as “natural,” it should not be considered differently from manufactured drugs.

Cannabis and cannabinoids represent “a class of very potent and pharmacologically active compounds,” Dr. Viscusi said in an interview. While researchers continue to assess possible medically beneficial effects of cannabis compounds, clinicians also need to be aware of the risks.

“The literature continues to emerge, and while we are always hopeful for good news, as physicians, we need to be very well versed on potential risks, especially in a high-risk situation like surgery,” he said.

Dr. Shah has consulted for companies that develop medical devices and drugs. Dr. Finn is the editor of the textbook, “Cannabis in Medicine: An Evidence-Based Approach” (Springer: New York, 2020), for which he receives royalties.

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

Readjudication of mortality data from the FOURIER trial suggests a higher risk for cardiovascular death with evolocumab (Repatha) among patients with established atherosclerotic cardiovascular disease than originally reported for the first-in-class PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor.

The Restoring Invisible and Abandoned Trials (RIAT) investigators launched this review in 2018, citing “significant inconsistencies and misreporting” between information in death narratives in the trial’s clinical study report (CSR) and the 2017 New England Journal of Medicine publication of the primary trial results.

“After readjudication, deaths of cardiac origin were numerically higher in the evolocumab group than in the placebo group in the FOURIER trial, suggesting possible cardiac harm,” the researchers conclude in the new report published online in BMJ Open. “At the time the trial was terminated early, a non-significantly higher risk of cardiovascular mortality was observed with evolocumab, which was numerically greater in our adjudication.

“Our findings indicate that complete restoration of all clinical outcomes from the FOURIER trial is required,” they wrote. “Meanwhile, clinicians should be skeptical about benefits vs harms of prescribing evolocumab for patients with established atherosclerotic cardiovascular disease.”

Asked to comment on the reanalysis, FOURIER lead investigator Marc Sabatine, MD, MPH, a professor of medicine at Harvard Medical School and the Lewis Dexter distinguished chair in cardiovascular medicine at Brigham and Women’s Hospital, both in Boston, said: “It’s hard to call this science. I think it lacks all scientific rigor and is fundamentally flawed and, because their process was flawed, it has led them to erroneous conclusions.”

Reached for comment, Sanjay Kaul, MD, a cardiologist and professor of medicine at Cedars-Sinai Medical Center in Los Angeles, who was not involved with either study, said: “If I were to describe this in one sentence, I would say much ado about nothing. A tempest in a teapot.”
 

Evaluating hard outcomes

The Food and Drug Administration approved evolocumab in 2015 for lowering LDL cholesterol levels, but without results from any trial evaluating hard outcomes.

As previously reported in 2017, FOURIER showed that adding evolocumab to high-intensity statins slashed LDL cholesterol by 59% and was associated with a 15% reduction in the primary composite cardiovascular events endpoint, compared with placebo, but numerically more all-cause and CV mortality.

The NEJM data analysis reported the risk for cardiovascular mortality was 5% (hazard ratio, 1.05; 95% confidence interval, 0.88-1.25), whereas the new review found a still nonsignificant 20% relative risk (R95% CI, 0.95-1.51).

Cardiac deaths were also numerically higher in the evolocumab group (113 vs. 88), corresponding to a 28% higher relative risk (95% CI, 0.97-1.69). Vascular deaths were similar at 37 in both groups (RR, 1.00; 95% CI, 0.63-1.58).

For 360 of the 870 deaths, the cause of death adjudicated by the FOURIER clinical events committee differs from that identified by the local clinical investigators in the CSR death narrative, the authors said.

The RIAT investigators found 11 more deaths from myocardial infarction in the evolocumab group (36 vs. 25 in NEJM) and 3 fewer deaths in the placebo group (27 vs. 30). In addition, their review indicated that deaths as a result of cardiac failure in the evolocumab group were almost double those in the placebo group, at 31 versus 16, respectively.
 

An ‘obvious disconnect’

Thomas L. Perry, MD, a coauthor of the BMJ Open paper and a general internist in the department of anesthesiology, pharmacology, and therapeutics at the University of British Columbia, Vancouver, said in an interview that the team repeatedly sought information from the FOURIER investigators but never received a response.

They petitioned and received the FOURIER CSR from the European Medicines Agency and Health Canada and made a similar request with the FDA but were told in October 2019 it would take up to 7 years to release the information. Case report forms were also requested but not received from all three agencies.

Dr. Perry noted that no autopsies were performed in the trial, a claim Dr. Sabatine rejected, and that their review of the death narratives in the CSR found 91 deaths classified by the local investigator as “undetermined” but subsequently adjudicated by the FOURIER clinical events committee as “sudden cardiac” deaths without any documented evidence to support the change.

At his request, Dr. Perry said they included two case examples (figures 1 and 2) in the BMJ Open paper of the “obvious disconnect” in death endpoints. Both of these were identified by the local investigator as a myocardial infarction but later “misreported” according to Dr. Perry, as a sudden cardiac death and noncardiovascular death (trauma), respectively.

“What’s so important about this is not only that it throws into doubt the reliability of what the people at Harvard and elsewhere reported in the New England Journal of Medicine in 2017, but also raises a question about any other large study like this where you rely on supposedly ethical local investigators to run the trial well and to report accurately what happens to people,” Dr. Perry said in an interview.

Although he never prescribed evolocumab after the initial results were published, Dr. Perry said he’s even less convinced of a benefit now. “Basically, I don’t believe that they are telling us the facts. I have no reason to say there’s an element of deliberately misleading us. I think it’s sloppiness, incompetence, laziness.”

Dr. Perry also favors readjudication of the mortality data in the ODYSSEY trial, which showed an all-cause mortality benefit with the PCSK9 inhibitor alirocumab (Praluent).
 

The ‘full picture’

Dr. Sabatine explained that when a patient had a cardiovascular event, including a death, it triggered the collection of a full dossier containing all available source documents, such as discharge summaries, laboratory and imaging data, and autopsy reports, that were independently reviewed by two board certified physicians blinded to treatment. To suggest, as the RIAT investigators have, that no autopsies were performed is “obviously ridiculous and wrong.”

In contrast, he said the new analysis was post hoc, involved unblinded individuals, and relied on serious adverse event narratives, which include a small text box that must be filled out with the site’s initial impression of the case and sent within 24 hours of the event.

Further, when the FOURIER investigators pulled the dossiers for the two more egregious examples cited in the paper, they found that the first patient died in his sleep at home. “The investigator then just said, ‘oh, I assume it’s an MI,’ but there’s no biochemical data, there’s no ECGs, there’s nothing to make the diagnosis of MI. So that’s why that is a sudden cardiac death per the FDA definition,” Dr. Sabatine said.

When the FOURIER investigators reviewed the full dossier for the second case example, they found the patient had slipped in his kitchen at home, sustained a serious head trauma, was brought into the emergency department, and died.

“That’s why we rely on the source documents. That gives the full picture,” he said. The FDA also reviewed the death narratives.

“They comment, ironically, that they were surprised at the inconsistencies between the investigator-reported causes of death and the central events committee-adjudicated ones, making it sound like something nefarious has happened. But that’s the whole point of adjudication, right? That you have a central events committee that reviews and then classifies based on all the data,” Dr. Sabatine said.

Dr. Sabatine said he sees no reason to reevaluate the ODYSSEY mortality data and that the RIAT analysis should not change the overall interpretation of FOURIER.

“I think this is in fact a disservice to the medical community because it’s not real science,” he said. “It’s just sensationalism and sends the wrong message. But I completely stand by the results that we published, as the FDA has.”

Dr. Kaul also thought the new analysis doesn’t materially change the overall benefit–risk balance. He observed that there isn’t a major difference between the reanalysis and the original evaluation. Total mortality was similar and, for cardiovascular deaths, the original NEJM paper lists 251 for evolocumab versus 240 for placebo and the reanalysis lists 150 versus 125, respectively.

Undetermined deaths were 144 for evolocumab and 164 for placebo in the reanalysis. “The conservative approach is to count them as presumed cardiovascular deaths,” Dr. Kaul said. “So, if you do the math and add those undetermined as cardiovascular deaths, we get a total of 294 (150 + 144) versus 289 (125 + 164). That’s five excess deaths with evolocumab.”
 

Open access

Although the RIAT group has called for the public release of the FOURIER data, commercial and legal issues will complicate that process, Steven Grover, MD, professor of medicine and director of the comprehensive health improvement program at McGill University, Montreal, said in an interview. Amgen is back in court over patent protection, filing an appeal with the Supreme Court after losing in the lower courts in a protracted battle, Reuters reported.

“One thing that’s for sure after they’ve raised questions about the results of this study [is that] somebody needs to take a good hard look at the adjudicated results,” said Dr. Grover, who coauthored several iterations of the Canadian Cardiovascular Society dyslipidemia guidelines, including the latest in 2021.

“I think the thing that got so many of us back in 2017 when the study was first published is the mortality data stuck out like a sore thumb,” he said in an interview. “It didn’t have to be statistically significant, but it did need to move in the same direction as the nonfatal coronary events. That’s what we’ve seen happen time and again and, in this case, it was going in the opposite direction.”

Dr. Sabatine said he doesn’t know whether the data will be released but that the FOURIER trialists plan to submit a rebuttal to BMJ Open to the RIAT analysis, which has caused a stir on CardioTwitter. “Now that people live with tweets of information, it necessitates then dispelling the misinformation that comes out. So yes, we will draft a rebuttal pointing out all the flaws in this analysis.”

Dr. Kaul commented that the FDA’s response not to provide the data was “rather curious” and that Dr. Sabatine and colleagues had the opportunity to address the RIAT group’s concerns, but the paper notes they did not even bother to respond. “You can’t be holier than thou in medicine. You have to treat every question with respect and humility and can’t be dismissive. ... He could have nipped the evil in the bud, so to speak.”

The study was funded by a grant from the University of Maryland, Baltimore. The authors, Dr. Kaul, and Dr. Grover reported having no relevant financial relationships.

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

Readjudication of mortality data from the FOURIER trial suggests a higher risk for cardiovascular death with evolocumab (Repatha) among patients with established atherosclerotic cardiovascular disease than originally reported for the first-in-class PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor.

The Restoring Invisible and Abandoned Trials (RIAT) investigators launched this review in 2018, citing “significant inconsistencies and misreporting” between information in death narratives in the trial’s clinical study report (CSR) and the 2017 New England Journal of Medicine publication of the primary trial results.

“After readjudication, deaths of cardiac origin were numerically higher in the evolocumab group than in the placebo group in the FOURIER trial, suggesting possible cardiac harm,” the researchers conclude in the new report published online in BMJ Open. “At the time the trial was terminated early, a non-significantly higher risk of cardiovascular mortality was observed with evolocumab, which was numerically greater in our adjudication.

“Our findings indicate that complete restoration of all clinical outcomes from the FOURIER trial is required,” they wrote. “Meanwhile, clinicians should be skeptical about benefits vs harms of prescribing evolocumab for patients with established atherosclerotic cardiovascular disease.”

Asked to comment on the reanalysis, FOURIER lead investigator Marc Sabatine, MD, MPH, a professor of medicine at Harvard Medical School and the Lewis Dexter distinguished chair in cardiovascular medicine at Brigham and Women’s Hospital, both in Boston, said: “It’s hard to call this science. I think it lacks all scientific rigor and is fundamentally flawed and, because their process was flawed, it has led them to erroneous conclusions.”

Reached for comment, Sanjay Kaul, MD, a cardiologist and professor of medicine at Cedars-Sinai Medical Center in Los Angeles, who was not involved with either study, said: “If I were to describe this in one sentence, I would say much ado about nothing. A tempest in a teapot.”
 

Evaluating hard outcomes

The Food and Drug Administration approved evolocumab in 2015 for lowering LDL cholesterol levels, but without results from any trial evaluating hard outcomes.

As previously reported in 2017, FOURIER showed that adding evolocumab to high-intensity statins slashed LDL cholesterol by 59% and was associated with a 15% reduction in the primary composite cardiovascular events endpoint, compared with placebo, but numerically more all-cause and CV mortality.

The NEJM data analysis reported the risk for cardiovascular mortality was 5% (hazard ratio, 1.05; 95% confidence interval, 0.88-1.25), whereas the new review found a still nonsignificant 20% relative risk (R95% CI, 0.95-1.51).

Cardiac deaths were also numerically higher in the evolocumab group (113 vs. 88), corresponding to a 28% higher relative risk (95% CI, 0.97-1.69). Vascular deaths were similar at 37 in both groups (RR, 1.00; 95% CI, 0.63-1.58).

For 360 of the 870 deaths, the cause of death adjudicated by the FOURIER clinical events committee differs from that identified by the local clinical investigators in the CSR death narrative, the authors said.

The RIAT investigators found 11 more deaths from myocardial infarction in the evolocumab group (36 vs. 25 in NEJM) and 3 fewer deaths in the placebo group (27 vs. 30). In addition, their review indicated that deaths as a result of cardiac failure in the evolocumab group were almost double those in the placebo group, at 31 versus 16, respectively.
 

An ‘obvious disconnect’

Thomas L. Perry, MD, a coauthor of the BMJ Open paper and a general internist in the department of anesthesiology, pharmacology, and therapeutics at the University of British Columbia, Vancouver, said in an interview that the team repeatedly sought information from the FOURIER investigators but never received a response.

They petitioned and received the FOURIER CSR from the European Medicines Agency and Health Canada and made a similar request with the FDA but were told in October 2019 it would take up to 7 years to release the information. Case report forms were also requested but not received from all three agencies.

Dr. Perry noted that no autopsies were performed in the trial, a claim Dr. Sabatine rejected, and that their review of the death narratives in the CSR found 91 deaths classified by the local investigator as “undetermined” but subsequently adjudicated by the FOURIER clinical events committee as “sudden cardiac” deaths without any documented evidence to support the change.

At his request, Dr. Perry said they included two case examples (figures 1 and 2) in the BMJ Open paper of the “obvious disconnect” in death endpoints. Both of these were identified by the local investigator as a myocardial infarction but later “misreported” according to Dr. Perry, as a sudden cardiac death and noncardiovascular death (trauma), respectively.

“What’s so important about this is not only that it throws into doubt the reliability of what the people at Harvard and elsewhere reported in the New England Journal of Medicine in 2017, but also raises a question about any other large study like this where you rely on supposedly ethical local investigators to run the trial well and to report accurately what happens to people,” Dr. Perry said in an interview.

Although he never prescribed evolocumab after the initial results were published, Dr. Perry said he’s even less convinced of a benefit now. “Basically, I don’t believe that they are telling us the facts. I have no reason to say there’s an element of deliberately misleading us. I think it’s sloppiness, incompetence, laziness.”

Dr. Perry also favors readjudication of the mortality data in the ODYSSEY trial, which showed an all-cause mortality benefit with the PCSK9 inhibitor alirocumab (Praluent).
 

The ‘full picture’

Dr. Sabatine explained that when a patient had a cardiovascular event, including a death, it triggered the collection of a full dossier containing all available source documents, such as discharge summaries, laboratory and imaging data, and autopsy reports, that were independently reviewed by two board certified physicians blinded to treatment. To suggest, as the RIAT investigators have, that no autopsies were performed is “obviously ridiculous and wrong.”

In contrast, he said the new analysis was post hoc, involved unblinded individuals, and relied on serious adverse event narratives, which include a small text box that must be filled out with the site’s initial impression of the case and sent within 24 hours of the event.

Further, when the FOURIER investigators pulled the dossiers for the two more egregious examples cited in the paper, they found that the first patient died in his sleep at home. “The investigator then just said, ‘oh, I assume it’s an MI,’ but there’s no biochemical data, there’s no ECGs, there’s nothing to make the diagnosis of MI. So that’s why that is a sudden cardiac death per the FDA definition,” Dr. Sabatine said.

When the FOURIER investigators reviewed the full dossier for the second case example, they found the patient had slipped in his kitchen at home, sustained a serious head trauma, was brought into the emergency department, and died.

“That’s why we rely on the source documents. That gives the full picture,” he said. The FDA also reviewed the death narratives.

“They comment, ironically, that they were surprised at the inconsistencies between the investigator-reported causes of death and the central events committee-adjudicated ones, making it sound like something nefarious has happened. But that’s the whole point of adjudication, right? That you have a central events committee that reviews and then classifies based on all the data,” Dr. Sabatine said.

Dr. Sabatine said he sees no reason to reevaluate the ODYSSEY mortality data and that the RIAT analysis should not change the overall interpretation of FOURIER.

“I think this is in fact a disservice to the medical community because it’s not real science,” he said. “It’s just sensationalism and sends the wrong message. But I completely stand by the results that we published, as the FDA has.”

Dr. Kaul also thought the new analysis doesn’t materially change the overall benefit–risk balance. He observed that there isn’t a major difference between the reanalysis and the original evaluation. Total mortality was similar and, for cardiovascular deaths, the original NEJM paper lists 251 for evolocumab versus 240 for placebo and the reanalysis lists 150 versus 125, respectively.

Undetermined deaths were 144 for evolocumab and 164 for placebo in the reanalysis. “The conservative approach is to count them as presumed cardiovascular deaths,” Dr. Kaul said. “So, if you do the math and add those undetermined as cardiovascular deaths, we get a total of 294 (150 + 144) versus 289 (125 + 164). That’s five excess deaths with evolocumab.”
 

Open access

Although the RIAT group has called for the public release of the FOURIER data, commercial and legal issues will complicate that process, Steven Grover, MD, professor of medicine and director of the comprehensive health improvement program at McGill University, Montreal, said in an interview. Amgen is back in court over patent protection, filing an appeal with the Supreme Court after losing in the lower courts in a protracted battle, Reuters reported.

“One thing that’s for sure after they’ve raised questions about the results of this study [is that] somebody needs to take a good hard look at the adjudicated results,” said Dr. Grover, who coauthored several iterations of the Canadian Cardiovascular Society dyslipidemia guidelines, including the latest in 2021.

“I think the thing that got so many of us back in 2017 when the study was first published is the mortality data stuck out like a sore thumb,” he said in an interview. “It didn’t have to be statistically significant, but it did need to move in the same direction as the nonfatal coronary events. That’s what we’ve seen happen time and again and, in this case, it was going in the opposite direction.”

Dr. Sabatine said he doesn’t know whether the data will be released but that the FOURIER trialists plan to submit a rebuttal to BMJ Open to the RIAT analysis, which has caused a stir on CardioTwitter. “Now that people live with tweets of information, it necessitates then dispelling the misinformation that comes out. So yes, we will draft a rebuttal pointing out all the flaws in this analysis.”

Dr. Kaul commented that the FDA’s response not to provide the data was “rather curious” and that Dr. Sabatine and colleagues had the opportunity to address the RIAT group’s concerns, but the paper notes they did not even bother to respond. “You can’t be holier than thou in medicine. You have to treat every question with respect and humility and can’t be dismissive. ... He could have nipped the evil in the bud, so to speak.”

The study was funded by a grant from the University of Maryland, Baltimore. The authors, Dr. Kaul, and Dr. Grover reported having no relevant financial relationships.

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

Readjudication of mortality data from the FOURIER trial suggests a higher risk for cardiovascular death with evolocumab (Repatha) among patients with established atherosclerotic cardiovascular disease than originally reported for the first-in-class PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor.

The Restoring Invisible and Abandoned Trials (RIAT) investigators launched this review in 2018, citing “significant inconsistencies and misreporting” between information in death narratives in the trial’s clinical study report (CSR) and the 2017 New England Journal of Medicine publication of the primary trial results.

“After readjudication, deaths of cardiac origin were numerically higher in the evolocumab group than in the placebo group in the FOURIER trial, suggesting possible cardiac harm,” the researchers conclude in the new report published online in BMJ Open. “At the time the trial was terminated early, a non-significantly higher risk of cardiovascular mortality was observed with evolocumab, which was numerically greater in our adjudication.

“Our findings indicate that complete restoration of all clinical outcomes from the FOURIER trial is required,” they wrote. “Meanwhile, clinicians should be skeptical about benefits vs harms of prescribing evolocumab for patients with established atherosclerotic cardiovascular disease.”

Asked to comment on the reanalysis, FOURIER lead investigator Marc Sabatine, MD, MPH, a professor of medicine at Harvard Medical School and the Lewis Dexter distinguished chair in cardiovascular medicine at Brigham and Women’s Hospital, both in Boston, said: “It’s hard to call this science. I think it lacks all scientific rigor and is fundamentally flawed and, because their process was flawed, it has led them to erroneous conclusions.”

Reached for comment, Sanjay Kaul, MD, a cardiologist and professor of medicine at Cedars-Sinai Medical Center in Los Angeles, who was not involved with either study, said: “If I were to describe this in one sentence, I would say much ado about nothing. A tempest in a teapot.”
 

Evaluating hard outcomes

The Food and Drug Administration approved evolocumab in 2015 for lowering LDL cholesterol levels, but without results from any trial evaluating hard outcomes.

As previously reported in 2017, FOURIER showed that adding evolocumab to high-intensity statins slashed LDL cholesterol by 59% and was associated with a 15% reduction in the primary composite cardiovascular events endpoint, compared with placebo, but numerically more all-cause and CV mortality.

The NEJM data analysis reported the risk for cardiovascular mortality was 5% (hazard ratio, 1.05; 95% confidence interval, 0.88-1.25), whereas the new review found a still nonsignificant 20% relative risk (R95% CI, 0.95-1.51).

Cardiac deaths were also numerically higher in the evolocumab group (113 vs. 88), corresponding to a 28% higher relative risk (95% CI, 0.97-1.69). Vascular deaths were similar at 37 in both groups (RR, 1.00; 95% CI, 0.63-1.58).

For 360 of the 870 deaths, the cause of death adjudicated by the FOURIER clinical events committee differs from that identified by the local clinical investigators in the CSR death narrative, the authors said.

The RIAT investigators found 11 more deaths from myocardial infarction in the evolocumab group (36 vs. 25 in NEJM) and 3 fewer deaths in the placebo group (27 vs. 30). In addition, their review indicated that deaths as a result of cardiac failure in the evolocumab group were almost double those in the placebo group, at 31 versus 16, respectively.
 

An ‘obvious disconnect’

Thomas L. Perry, MD, a coauthor of the BMJ Open paper and a general internist in the department of anesthesiology, pharmacology, and therapeutics at the University of British Columbia, Vancouver, said in an interview that the team repeatedly sought information from the FOURIER investigators but never received a response.

They petitioned and received the FOURIER CSR from the European Medicines Agency and Health Canada and made a similar request with the FDA but were told in October 2019 it would take up to 7 years to release the information. Case report forms were also requested but not received from all three agencies.

Dr. Perry noted that no autopsies were performed in the trial, a claim Dr. Sabatine rejected, and that their review of the death narratives in the CSR found 91 deaths classified by the local investigator as “undetermined” but subsequently adjudicated by the FOURIER clinical events committee as “sudden cardiac” deaths without any documented evidence to support the change.

At his request, Dr. Perry said they included two case examples (figures 1 and 2) in the BMJ Open paper of the “obvious disconnect” in death endpoints. Both of these were identified by the local investigator as a myocardial infarction but later “misreported” according to Dr. Perry, as a sudden cardiac death and noncardiovascular death (trauma), respectively.

“What’s so important about this is not only that it throws into doubt the reliability of what the people at Harvard and elsewhere reported in the New England Journal of Medicine in 2017, but also raises a question about any other large study like this where you rely on supposedly ethical local investigators to run the trial well and to report accurately what happens to people,” Dr. Perry said in an interview.

Although he never prescribed evolocumab after the initial results were published, Dr. Perry said he’s even less convinced of a benefit now. “Basically, I don’t believe that they are telling us the facts. I have no reason to say there’s an element of deliberately misleading us. I think it’s sloppiness, incompetence, laziness.”

Dr. Perry also favors readjudication of the mortality data in the ODYSSEY trial, which showed an all-cause mortality benefit with the PCSK9 inhibitor alirocumab (Praluent).
 

The ‘full picture’

Dr. Sabatine explained that when a patient had a cardiovascular event, including a death, it triggered the collection of a full dossier containing all available source documents, such as discharge summaries, laboratory and imaging data, and autopsy reports, that were independently reviewed by two board certified physicians blinded to treatment. To suggest, as the RIAT investigators have, that no autopsies were performed is “obviously ridiculous and wrong.”

In contrast, he said the new analysis was post hoc, involved unblinded individuals, and relied on serious adverse event narratives, which include a small text box that must be filled out with the site’s initial impression of the case and sent within 24 hours of the event.

Further, when the FOURIER investigators pulled the dossiers for the two more egregious examples cited in the paper, they found that the first patient died in his sleep at home. “The investigator then just said, ‘oh, I assume it’s an MI,’ but there’s no biochemical data, there’s no ECGs, there’s nothing to make the diagnosis of MI. So that’s why that is a sudden cardiac death per the FDA definition,” Dr. Sabatine said.

When the FOURIER investigators reviewed the full dossier for the second case example, they found the patient had slipped in his kitchen at home, sustained a serious head trauma, was brought into the emergency department, and died.

“That’s why we rely on the source documents. That gives the full picture,” he said. The FDA also reviewed the death narratives.

“They comment, ironically, that they were surprised at the inconsistencies between the investigator-reported causes of death and the central events committee-adjudicated ones, making it sound like something nefarious has happened. But that’s the whole point of adjudication, right? That you have a central events committee that reviews and then classifies based on all the data,” Dr. Sabatine said.

Dr. Sabatine said he sees no reason to reevaluate the ODYSSEY mortality data and that the RIAT analysis should not change the overall interpretation of FOURIER.

“I think this is in fact a disservice to the medical community because it’s not real science,” he said. “It’s just sensationalism and sends the wrong message. But I completely stand by the results that we published, as the FDA has.”

Dr. Kaul also thought the new analysis doesn’t materially change the overall benefit–risk balance. He observed that there isn’t a major difference between the reanalysis and the original evaluation. Total mortality was similar and, for cardiovascular deaths, the original NEJM paper lists 251 for evolocumab versus 240 for placebo and the reanalysis lists 150 versus 125, respectively.

Undetermined deaths were 144 for evolocumab and 164 for placebo in the reanalysis. “The conservative approach is to count them as presumed cardiovascular deaths,” Dr. Kaul said. “So, if you do the math and add those undetermined as cardiovascular deaths, we get a total of 294 (150 + 144) versus 289 (125 + 164). That’s five excess deaths with evolocumab.”
 

Open access

Although the RIAT group has called for the public release of the FOURIER data, commercial and legal issues will complicate that process, Steven Grover, MD, professor of medicine and director of the comprehensive health improvement program at McGill University, Montreal, said in an interview. Amgen is back in court over patent protection, filing an appeal with the Supreme Court after losing in the lower courts in a protracted battle, Reuters reported.

“One thing that’s for sure after they’ve raised questions about the results of this study [is that] somebody needs to take a good hard look at the adjudicated results,” said Dr. Grover, who coauthored several iterations of the Canadian Cardiovascular Society dyslipidemia guidelines, including the latest in 2021.

“I think the thing that got so many of us back in 2017 when the study was first published is the mortality data stuck out like a sore thumb,” he said in an interview. “It didn’t have to be statistically significant, but it did need to move in the same direction as the nonfatal coronary events. That’s what we’ve seen happen time and again and, in this case, it was going in the opposite direction.”

Dr. Sabatine said he doesn’t know whether the data will be released but that the FOURIER trialists plan to submit a rebuttal to BMJ Open to the RIAT analysis, which has caused a stir on CardioTwitter. “Now that people live with tweets of information, it necessitates then dispelling the misinformation that comes out. So yes, we will draft a rebuttal pointing out all the flaws in this analysis.”

Dr. Kaul commented that the FDA’s response not to provide the data was “rather curious” and that Dr. Sabatine and colleagues had the opportunity to address the RIAT group’s concerns, but the paper notes they did not even bother to respond. “You can’t be holier than thou in medicine. You have to treat every question with respect and humility and can’t be dismissive. ... He could have nipped the evil in the bud, so to speak.”

The study was funded by a grant from the University of Maryland, Baltimore. The authors, Dr. Kaul, and Dr. Grover reported having no relevant financial relationships.

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

Participation in the first 2 years of Maryland’s Advanced Primary Care Program (MDPCP) was associated with better COVID-19 outcomes compared with a matched group not involved with the program, new data indicate.

The better outcomes were seen in higher vaccination rates and fewer infections, hospitalizations, and deaths from the disease, according to study authors, led by Emily Gruber, MBA, MPH, with the Maryland Primary Care Program, Maryland Department of Health in Baltimore.

The results were published online in JAMA Network Open.

The study population was divided into MDPCP participants (n = 208,146) and a matched cohort (n = 37,203) of beneficiaries not attributed to MDPCP practices but who met eligibility criteria for study participation from Jan. 1, 2020, through Dec. 31, 2021.
 

More vaccinations, more antibody treatments

Researchers broke down the comparisons of better outcomes: 84.47% of MDPCP beneficiaries were fully vaccinated vs. 77.93% of nonparticipating beneficiaries (P less than .001). COVID-19–positive program beneficiaries also received monoclonal antibody treatment more often (8.45% vs. 6.11%; P less than .001).

Plus, program participants received more care via telehealth (62.95% vs. 54.53%; P less than .001) compared with those not participating.

Regarding secondary outcomes, MDPCP beneficiaries had lower rates of COVID cases (6.55% vs. 7.09%; P less than .001), lower rates of COVID-19 hospitalizations (1.81% vs. 2.06%; P = .001), and lower rates of death due to COVID-19 (0.56% vs. 0.77%; P less than .001).
 

Program components

Enrollment in the MDPCP is voluntary, and primary care practices can apply each year to be part of the program.

The model integrates primary care and public health in the pandemic response. It was created by the Maryland Department of Health (MDH) and the Centers for Medicare & Medicaid Services (CMS).

It expands the role of primary care to include services such as expanded care management, integrated behavioral health, data-driven care, and screenings and referrals to address social needs.

Coauthor Howard Haft, MD, MMM, with the Maryland Department of Public Health, said in an interview that among the most important factors in the program’s success were giving providers vaccines to distribute and then giving providers data on how many patients are vaccinated, and who’s not vaccinated but at high risk, and how those rates compare to other practices.

As to whether this could be a widespread model, Dr. Haft said, “It’s highly replicable.”

“Every state in the nation overall has all of these resources. It’s a matter of having the operational and political will to put those resources together. Almost every state has the technological ability to use their health information exchange to help tie pieces together.”
 

Vaccines and testing made available to providers

Making ample vaccines and testing available to providers in their offices helped patients get those services in a place they trust, Dr. Haft said.

The model also included a payment system for providers that included a significant amount of non–visit-based payments when many locations were closed in the height of the pandemic.

“That helped financially,” as did providing free telehealth platforms to practices with training on how to use them, Dr. Haft said.
 

‘Innovative and important’

Renu Tipirneni, MD, an assistant professor of internal medicine at the University of Michigan and at the Institute for Healthcare Policy and Innovation in Ann Arbor, said Maryland is out front putting into practice what practices nationwide aspire to do – coordinating physical and mental health and social needs and integrating primary and public health. Dr. Tipirneni, who was not involved with the study, said she was impressed the researchers were able to show statistically significant improvement with COVID-19 outcomes in the first 2 years.

“In terms of health outcomes, we often have to wait longer to see good outcomes,” she said. “It’s a really innovative and important model.”

She said states can learn from each other and this model is an example.

Integrating primary care and public health and addressing social needs may be the biggest challenges for states, she said, as those realms typically have been siloed.

“But they may be the key components to achieving these outcomes,” she said.
 

Take-home message

The most important benefit of the program is that data suggest it saves lives, according to Dr. Haft. While the actual difference between COVID deaths in the program and nonprogram groups was small, multiplying that savings across the nation shows substantial potential benefit, he explained.

“At a time when we were losing lives at an unconscionable rate, we were able to make a difference in saving lives,” Dr. Haft said.

Authors report no relevant financial disclosures.

The study received financial support from the Maryland Department of Health.

Dr. Tiperneni is helping evaluate Michigan’s Medicaid contract.
 

Participation in the first 2 years of Maryland’s Advanced Primary Care Program (MDPCP) was associated with better COVID-19 outcomes compared with a matched group not involved with the program, new data indicate.

The better outcomes were seen in higher vaccination rates and fewer infections, hospitalizations, and deaths from the disease, according to study authors, led by Emily Gruber, MBA, MPH, with the Maryland Primary Care Program, Maryland Department of Health in Baltimore.

The results were published online in JAMA Network Open.

The study population was divided into MDPCP participants (n = 208,146) and a matched cohort (n = 37,203) of beneficiaries not attributed to MDPCP practices but who met eligibility criteria for study participation from Jan. 1, 2020, through Dec. 31, 2021.
 

More vaccinations, more antibody treatments

Researchers broke down the comparisons of better outcomes: 84.47% of MDPCP beneficiaries were fully vaccinated vs. 77.93% of nonparticipating beneficiaries (P less than .001). COVID-19–positive program beneficiaries also received monoclonal antibody treatment more often (8.45% vs. 6.11%; P less than .001).

Plus, program participants received more care via telehealth (62.95% vs. 54.53%; P less than .001) compared with those not participating.

Regarding secondary outcomes, MDPCP beneficiaries had lower rates of COVID cases (6.55% vs. 7.09%; P less than .001), lower rates of COVID-19 hospitalizations (1.81% vs. 2.06%; P = .001), and lower rates of death due to COVID-19 (0.56% vs. 0.77%; P less than .001).
 

Program components

Enrollment in the MDPCP is voluntary, and primary care practices can apply each year to be part of the program.

The model integrates primary care and public health in the pandemic response. It was created by the Maryland Department of Health (MDH) and the Centers for Medicare & Medicaid Services (CMS).

It expands the role of primary care to include services such as expanded care management, integrated behavioral health, data-driven care, and screenings and referrals to address social needs.

Coauthor Howard Haft, MD, MMM, with the Maryland Department of Public Health, said in an interview that among the most important factors in the program’s success were giving providers vaccines to distribute and then giving providers data on how many patients are vaccinated, and who’s not vaccinated but at high risk, and how those rates compare to other practices.

As to whether this could be a widespread model, Dr. Haft said, “It’s highly replicable.”

“Every state in the nation overall has all of these resources. It’s a matter of having the operational and political will to put those resources together. Almost every state has the technological ability to use their health information exchange to help tie pieces together.”
 

Vaccines and testing made available to providers

Making ample vaccines and testing available to providers in their offices helped patients get those services in a place they trust, Dr. Haft said.

The model also included a payment system for providers that included a significant amount of non–visit-based payments when many locations were closed in the height of the pandemic.

“That helped financially,” as did providing free telehealth platforms to practices with training on how to use them, Dr. Haft said.
 

‘Innovative and important’

Renu Tipirneni, MD, an assistant professor of internal medicine at the University of Michigan and at the Institute for Healthcare Policy and Innovation in Ann Arbor, said Maryland is out front putting into practice what practices nationwide aspire to do – coordinating physical and mental health and social needs and integrating primary and public health. Dr. Tipirneni, who was not involved with the study, said she was impressed the researchers were able to show statistically significant improvement with COVID-19 outcomes in the first 2 years.

“In terms of health outcomes, we often have to wait longer to see good outcomes,” she said. “It’s a really innovative and important model.”

She said states can learn from each other and this model is an example.

Integrating primary care and public health and addressing social needs may be the biggest challenges for states, she said, as those realms typically have been siloed.

“But they may be the key components to achieving these outcomes,” she said.
 

Take-home message

The most important benefit of the program is that data suggest it saves lives, according to Dr. Haft. While the actual difference between COVID deaths in the program and nonprogram groups was small, multiplying that savings across the nation shows substantial potential benefit, he explained.

“At a time when we were losing lives at an unconscionable rate, we were able to make a difference in saving lives,” Dr. Haft said.

Authors report no relevant financial disclosures.

The study received financial support from the Maryland Department of Health.

Dr. Tiperneni is helping evaluate Michigan’s Medicaid contract.
 

Participation in the first 2 years of Maryland’s Advanced Primary Care Program (MDPCP) was associated with better COVID-19 outcomes compared with a matched group not involved with the program, new data indicate.

The better outcomes were seen in higher vaccination rates and fewer infections, hospitalizations, and deaths from the disease, according to study authors, led by Emily Gruber, MBA, MPH, with the Maryland Primary Care Program, Maryland Department of Health in Baltimore.

The results were published online in JAMA Network Open.

The study population was divided into MDPCP participants (n = 208,146) and a matched cohort (n = 37,203) of beneficiaries not attributed to MDPCP practices but who met eligibility criteria for study participation from Jan. 1, 2020, through Dec. 31, 2021.
 

More vaccinations, more antibody treatments

Researchers broke down the comparisons of better outcomes: 84.47% of MDPCP beneficiaries were fully vaccinated vs. 77.93% of nonparticipating beneficiaries (P less than .001). COVID-19–positive program beneficiaries also received monoclonal antibody treatment more often (8.45% vs. 6.11%; P less than .001).

Plus, program participants received more care via telehealth (62.95% vs. 54.53%; P less than .001) compared with those not participating.

Regarding secondary outcomes, MDPCP beneficiaries had lower rates of COVID cases (6.55% vs. 7.09%; P less than .001), lower rates of COVID-19 hospitalizations (1.81% vs. 2.06%; P = .001), and lower rates of death due to COVID-19 (0.56% vs. 0.77%; P less than .001).
 

Program components

Enrollment in the MDPCP is voluntary, and primary care practices can apply each year to be part of the program.

The model integrates primary care and public health in the pandemic response. It was created by the Maryland Department of Health (MDH) and the Centers for Medicare & Medicaid Services (CMS).

It expands the role of primary care to include services such as expanded care management, integrated behavioral health, data-driven care, and screenings and referrals to address social needs.

Coauthor Howard Haft, MD, MMM, with the Maryland Department of Public Health, said in an interview that among the most important factors in the program’s success were giving providers vaccines to distribute and then giving providers data on how many patients are vaccinated, and who’s not vaccinated but at high risk, and how those rates compare to other practices.

As to whether this could be a widespread model, Dr. Haft said, “It’s highly replicable.”

“Every state in the nation overall has all of these resources. It’s a matter of having the operational and political will to put those resources together. Almost every state has the technological ability to use their health information exchange to help tie pieces together.”
 

Vaccines and testing made available to providers

Making ample vaccines and testing available to providers in their offices helped patients get those services in a place they trust, Dr. Haft said.

The model also included a payment system for providers that included a significant amount of non–visit-based payments when many locations were closed in the height of the pandemic.

“That helped financially,” as did providing free telehealth platforms to practices with training on how to use them, Dr. Haft said.
 

‘Innovative and important’

Renu Tipirneni, MD, an assistant professor of internal medicine at the University of Michigan and at the Institute for Healthcare Policy and Innovation in Ann Arbor, said Maryland is out front putting into practice what practices nationwide aspire to do – coordinating physical and mental health and social needs and integrating primary and public health. Dr. Tipirneni, who was not involved with the study, said she was impressed the researchers were able to show statistically significant improvement with COVID-19 outcomes in the first 2 years.

“In terms of health outcomes, we often have to wait longer to see good outcomes,” she said. “It’s a really innovative and important model.”

She said states can learn from each other and this model is an example.

Integrating primary care and public health and addressing social needs may be the biggest challenges for states, she said, as those realms typically have been siloed.

“But they may be the key components to achieving these outcomes,” she said.
 

Take-home message

The most important benefit of the program is that data suggest it saves lives, according to Dr. Haft. While the actual difference between COVID deaths in the program and nonprogram groups was small, multiplying that savings across the nation shows substantial potential benefit, he explained.

“At a time when we were losing lives at an unconscionable rate, we were able to make a difference in saving lives,” Dr. Haft said.

Authors report no relevant financial disclosures.

The study received financial support from the Maryland Department of Health.

Dr. Tiperneni is helping evaluate Michigan’s Medicaid contract.