Illinois has a new law designed to boost the mental health care workforce at a time when it has been devastated by the COVID-19 pandemic, say state leaders.

Governor J.B. Pritzker (D) signed the legislation, which took effect on June 10.

The law seeks to attract psychologists, social workers, and counselors who have left the workforce within the past 5 years by temporarily ending relicensing requirements, including the need for continuing education credit completion, passing new exams, and fee payments. It also eases the process for those practicing in other states to become licensed in Illinois.

State legislators said there is currently a crushing need for mental health providers, estimating that there are only 14 behavioral health care professionals for every 10,000 Illinois residents. The preamble to the law noted that there will be 8,353 unfilled mental health care jobs in Illinois by 2026.

“We need a mental health care workforce that is robust enough to get people help when they need it – not after months on a waiting list,” Governor Pritzker said in news release. “This legislation invests in mental health infrastructure – and that infrastructure is people,” he added.
 

Grant pathway

“Being told you have to wait weeks – or months – for care is extremely discouraging,” State Senator Laura Fine (D), a lead sponsor of the legislation, noted in the release.

“We need to support people struggling with mental and behavioral health issues, as well as address difficulties our mental health providers are facing trying to see as many patients as possible,” said Senator Fine.

Marvin Lindsey, CEO of the Community Behavioral Healthcare Association, added that the law would “accelerate the process for out-of-state professionals to obtain their Illinois licensure and [increase] the pipeline and diversity of the behavioral health workforce by implementing a funding mechanism that supports new or existing licensure training of interns.”

The law sets up a grant pathway for community mental health centers, which often serve as training sites. The grants would provide funds to establish or enhance training and supervision of interns and behavioral health providers-in-training seeking to become licensed clinical social workers, licensed clinical professional counselors, or licensed marriage and family therapists.

The money for those grants still has to be appropriated.

The law will also allow patient visits at Specialized Mental Health Rehabilitation Facilities conducted by either a psychiatrist or an advanced practice registered mental health or psychiatric nurse.

Finally, it would establish tax credits for employers who hire individuals in recovery from a substance use disorder or a behavioral disorder. Beginning in January 2023, employers will be eligible for up to $2,000 in credits per employee hired.

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

Illinois has a new law designed to boost the mental health care workforce at a time when it has been devastated by the COVID-19 pandemic, say state leaders.

Governor J.B. Pritzker (D) signed the legislation, which took effect on June 10.

The law seeks to attract psychologists, social workers, and counselors who have left the workforce within the past 5 years by temporarily ending relicensing requirements, including the need for continuing education credit completion, passing new exams, and fee payments. It also eases the process for those practicing in other states to become licensed in Illinois.

State legislators said there is currently a crushing need for mental health providers, estimating that there are only 14 behavioral health care professionals for every 10,000 Illinois residents. The preamble to the law noted that there will be 8,353 unfilled mental health care jobs in Illinois by 2026.

“We need a mental health care workforce that is robust enough to get people help when they need it – not after months on a waiting list,” Governor Pritzker said in news release. “This legislation invests in mental health infrastructure – and that infrastructure is people,” he added.
 

Grant pathway

“Being told you have to wait weeks – or months – for care is extremely discouraging,” State Senator Laura Fine (D), a lead sponsor of the legislation, noted in the release.

“We need to support people struggling with mental and behavioral health issues, as well as address difficulties our mental health providers are facing trying to see as many patients as possible,” said Senator Fine.

Marvin Lindsey, CEO of the Community Behavioral Healthcare Association, added that the law would “accelerate the process for out-of-state professionals to obtain their Illinois licensure and [increase] the pipeline and diversity of the behavioral health workforce by implementing a funding mechanism that supports new or existing licensure training of interns.”

The law sets up a grant pathway for community mental health centers, which often serve as training sites. The grants would provide funds to establish or enhance training and supervision of interns and behavioral health providers-in-training seeking to become licensed clinical social workers, licensed clinical professional counselors, or licensed marriage and family therapists.

The money for those grants still has to be appropriated.

The law will also allow patient visits at Specialized Mental Health Rehabilitation Facilities conducted by either a psychiatrist or an advanced practice registered mental health or psychiatric nurse.

Finally, it would establish tax credits for employers who hire individuals in recovery from a substance use disorder or a behavioral disorder. Beginning in January 2023, employers will be eligible for up to $2,000 in credits per employee hired.

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

Illinois has a new law designed to boost the mental health care workforce at a time when it has been devastated by the COVID-19 pandemic, say state leaders.

Governor J.B. Pritzker (D) signed the legislation, which took effect on June 10.

The law seeks to attract psychologists, social workers, and counselors who have left the workforce within the past 5 years by temporarily ending relicensing requirements, including the need for continuing education credit completion, passing new exams, and fee payments. It also eases the process for those practicing in other states to become licensed in Illinois.

State legislators said there is currently a crushing need for mental health providers, estimating that there are only 14 behavioral health care professionals for every 10,000 Illinois residents. The preamble to the law noted that there will be 8,353 unfilled mental health care jobs in Illinois by 2026.

“We need a mental health care workforce that is robust enough to get people help when they need it – not after months on a waiting list,” Governor Pritzker said in news release. “This legislation invests in mental health infrastructure – and that infrastructure is people,” he added.
 

Grant pathway

“Being told you have to wait weeks – or months – for care is extremely discouraging,” State Senator Laura Fine (D), a lead sponsor of the legislation, noted in the release.

“We need to support people struggling with mental and behavioral health issues, as well as address difficulties our mental health providers are facing trying to see as many patients as possible,” said Senator Fine.

Marvin Lindsey, CEO of the Community Behavioral Healthcare Association, added that the law would “accelerate the process for out-of-state professionals to obtain their Illinois licensure and [increase] the pipeline and diversity of the behavioral health workforce by implementing a funding mechanism that supports new or existing licensure training of interns.”

The law sets up a grant pathway for community mental health centers, which often serve as training sites. The grants would provide funds to establish or enhance training and supervision of interns and behavioral health providers-in-training seeking to become licensed clinical social workers, licensed clinical professional counselors, or licensed marriage and family therapists.

The money for those grants still has to be appropriated.

The law will also allow patient visits at Specialized Mental Health Rehabilitation Facilities conducted by either a psychiatrist or an advanced practice registered mental health or psychiatric nurse.

Finally, it would establish tax credits for employers who hire individuals in recovery from a substance use disorder or a behavioral disorder. Beginning in January 2023, employers will be eligible for up to $2,000 in credits per employee hired.

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

Ventricular arrhythmias more commonly occur on days when there are higher levels of air pollution, especially with fine particulate matter (PM), a new study suggests.

The investigators studied the relationship between air pollution and ventricular arrhythmias in Piacenza, Italy by examining 5-year data on patients who received an implantable cardioverter defibrillator (ICD).

Thomas321/iStock/Getty Images Plus

They found a significant association between PM2.5 levels and ventricular arrhythmias, especially those treated with direct current shock. Moreover, higher levels of PM2.5 and PM10 were associated with increased risk of all ventricular arrhythmias.

“These data confirm that environmental pollution is not only a climate emergency but also a public health problem,” lead author Alessia Zanni, currently at Maggiore Hospital, Bologna, Italy, and previously at Piacenza Hospital, said in an interview.

“The study suggests that the survival of patients with heart disease is affected not only by pharmacological therapies and advances in cardiology, but also by the air that they breathe,” she said.

The results were presented at European Society of Cardiology Heart Failure 2022.
 

More ED visits

The World Health Organization estimates around 7 million people die every year from exposure to polluted air, “as 91% of the world’s population lives in areas where air contaminants exceed safety levels,” Dr. Zanni said. Furthermore, “air pollution has been defined as the fourth-highest ranking risk factor for mortality – more important than LDL cholesterol, obesity, physical activity, or alcohol use.”

She noted that Piacenza has “historically been very attentive to the issues of early defibrillation and cardiac arrest.” Her group had previously found a correlation between out-of-hospital cardiac arrests and air pollution in the general population.

Moreover, her group recently observed that ED visits for patients with ICDs “tended to cluster; on some special days, many patients with ICDs had cardiac arrhythmias, and during those days, air pollution levels were particularly high.”

Her group therefore decided to compare the concentration of air pollutants on days when patients suffered from an arrhythmia event versus pollution levels on days without an arrhythmia, she said.
 

Further piece in a complex puzzle

The researchers studied 146 patients with ICDs between January 2013 and December 2017, assigning exposures (short, mid, and long term) to these patients based on their residential addresses.

They extracted day-by-day urban PM10, PM2.5, CO, NO₂, and O₃ levels from the Environmental Protection Agency monitoring stations and then, using time-stratified case-crossover analysis methodology, they calculated the association of ventricular arrhythmia onset with 0- to 7-day moving averages of the various air pollutants prior to the event.

Patients had received their ICD to control cardiac dysfunction brought on by previous myocardial infarction (n = 93), genetic or inflammatory conditions (n = 53), secondary prevention after a lethal arrhythmia (n = 67), and primary prevention (n = 79).

Of the 440 ventricular arrhythmias recorded, 322 were treated with antitachycardia pacing, while the remaining 118 were treated with direct current shock.

The researchers found a significant association between PM2.5 levels and ventricular arrhythmia treated with shock, corresponding to a 15% increased risk or every additional 10mg/m³ (P < .019).

They also found that, when PM2.5 concentrations were elevated by 1 mg/m³ for an entire week, compared with average levels, there was a 2.4% higher likelihood of ventricular arrhythmias, regardless of the temperature, and when PM10 was 1 mg/m³ above average for a week, there was a 2.1% increased risk for arrhythmias (odds ratio, 1,024; 95% confidence interval, 1,009-1,040] and OR, 1,021; 95% CI, 1,009-1,033, respectively), Dr. Zanni reported.

“Since the majority of out-of-hospital cardiac arrest causes still remain unclear, our data add a further piece to the complex puzzle of cardiac arrest triggers,” Dr. Zanni commented. “We think that particulate matter can cause acute inflammation of the heart muscle and potentially act as a trigger for lethal cardiac arrhythmias.

“As these toxic particles are emitted from power plants, industries, and cars, we think that cardiovascular research should highlight these new findings to promote green projects among the general population, clarifying the risks to the health of the human being, and we think strategies to prevent air pollutant exposure in high-risk patients [with previous cardiac disease] should be developed,” she added.

Further, “we advise patients at risk, during days with high PM2.5 (> 35 mg/m³) and PM10 (> 50 mg/m³) to use a mask of the N95 type outdoors, to reduce time spent outdoors – particularly in traffic – and to improve home air filtration,” Dr. Zanni said.
 

Entering the mainstream

In a comment, Joel Kaufman, MD, MPH, professor of internal medicine and environmental health, University of Washington, Seattle, said the study “adds to a fairly substantial literature already on this topic of short-term exposure to air pollution.”

The evidence that air pollutants “can be a trigger of worsening of cardiovascular disease is fairly consistent at this time, and although the effect sizes are small, they are consistent,” said Dr. Kaufman, who was the chair of the writing group for the American Heart Association’s 2020 policy statement, “Guidance to Reduce Cardiovascular Burden of Ambient Air Pollutants.”

“The research into this issue has become clearer during the past 10 years but still is not in the mainstream of most cardiologists’ awareness. They tend to focus more on controlling cholesterol and performing procedures, etc., but there are modifiable risk factors like air pollution that are increasingly recognized as being part of the picture,” said Dr. Kaufman, who was not involved with the current study.

Dr. Zanni added: “It is important that politics work hand in hand with the scientific community in order to win the battle against global warming, which will reduce the number of cardiovascular deaths – the leading cause of death worldwide – as well as environmental integrity.”

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Dr. Zanni and coauthors and Dr. Kaufman reported no relevant financial relationships.

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

Ventricular arrhythmias more commonly occur on days when there are higher levels of air pollution, especially with fine particulate matter (PM), a new study suggests.

The investigators studied the relationship between air pollution and ventricular arrhythmias in Piacenza, Italy by examining 5-year data on patients who received an implantable cardioverter defibrillator (ICD).

Thomas321/iStock/Getty Images Plus

They found a significant association between PM2.5 levels and ventricular arrhythmias, especially those treated with direct current shock. Moreover, higher levels of PM2.5 and PM10 were associated with increased risk of all ventricular arrhythmias.

“These data confirm that environmental pollution is not only a climate emergency but also a public health problem,” lead author Alessia Zanni, currently at Maggiore Hospital, Bologna, Italy, and previously at Piacenza Hospital, said in an interview.

“The study suggests that the survival of patients with heart disease is affected not only by pharmacological therapies and advances in cardiology, but also by the air that they breathe,” she said.

The results were presented at European Society of Cardiology Heart Failure 2022.
 

More ED visits

The World Health Organization estimates around 7 million people die every year from exposure to polluted air, “as 91% of the world’s population lives in areas where air contaminants exceed safety levels,” Dr. Zanni said. Furthermore, “air pollution has been defined as the fourth-highest ranking risk factor for mortality – more important than LDL cholesterol, obesity, physical activity, or alcohol use.”

She noted that Piacenza has “historically been very attentive to the issues of early defibrillation and cardiac arrest.” Her group had previously found a correlation between out-of-hospital cardiac arrests and air pollution in the general population.

Moreover, her group recently observed that ED visits for patients with ICDs “tended to cluster; on some special days, many patients with ICDs had cardiac arrhythmias, and during those days, air pollution levels were particularly high.”

Her group therefore decided to compare the concentration of air pollutants on days when patients suffered from an arrhythmia event versus pollution levels on days without an arrhythmia, she said.
 

Further piece in a complex puzzle

The researchers studied 146 patients with ICDs between January 2013 and December 2017, assigning exposures (short, mid, and long term) to these patients based on their residential addresses.

They extracted day-by-day urban PM10, PM2.5, CO, NO₂, and O₃ levels from the Environmental Protection Agency monitoring stations and then, using time-stratified case-crossover analysis methodology, they calculated the association of ventricular arrhythmia onset with 0- to 7-day moving averages of the various air pollutants prior to the event.

Patients had received their ICD to control cardiac dysfunction brought on by previous myocardial infarction (n = 93), genetic or inflammatory conditions (n = 53), secondary prevention after a lethal arrhythmia (n = 67), and primary prevention (n = 79).

Of the 440 ventricular arrhythmias recorded, 322 were treated with antitachycardia pacing, while the remaining 118 were treated with direct current shock.

The researchers found a significant association between PM2.5 levels and ventricular arrhythmia treated with shock, corresponding to a 15% increased risk or every additional 10mg/m³ (P < .019).

They also found that, when PM2.5 concentrations were elevated by 1 mg/m³ for an entire week, compared with average levels, there was a 2.4% higher likelihood of ventricular arrhythmias, regardless of the temperature, and when PM10 was 1 mg/m³ above average for a week, there was a 2.1% increased risk for arrhythmias (odds ratio, 1,024; 95% confidence interval, 1,009-1,040] and OR, 1,021; 95% CI, 1,009-1,033, respectively), Dr. Zanni reported.

“Since the majority of out-of-hospital cardiac arrest causes still remain unclear, our data add a further piece to the complex puzzle of cardiac arrest triggers,” Dr. Zanni commented. “We think that particulate matter can cause acute inflammation of the heart muscle and potentially act as a trigger for lethal cardiac arrhythmias.

“As these toxic particles are emitted from power plants, industries, and cars, we think that cardiovascular research should highlight these new findings to promote green projects among the general population, clarifying the risks to the health of the human being, and we think strategies to prevent air pollutant exposure in high-risk patients [with previous cardiac disease] should be developed,” she added.

Further, “we advise patients at risk, during days with high PM2.5 (> 35 mg/m³) and PM10 (> 50 mg/m³) to use a mask of the N95 type outdoors, to reduce time spent outdoors – particularly in traffic – and to improve home air filtration,” Dr. Zanni said.
 

Entering the mainstream

In a comment, Joel Kaufman, MD, MPH, professor of internal medicine and environmental health, University of Washington, Seattle, said the study “adds to a fairly substantial literature already on this topic of short-term exposure to air pollution.”

The evidence that air pollutants “can be a trigger of worsening of cardiovascular disease is fairly consistent at this time, and although the effect sizes are small, they are consistent,” said Dr. Kaufman, who was the chair of the writing group for the American Heart Association’s 2020 policy statement, “Guidance to Reduce Cardiovascular Burden of Ambient Air Pollutants.”

“The research into this issue has become clearer during the past 10 years but still is not in the mainstream of most cardiologists’ awareness. They tend to focus more on controlling cholesterol and performing procedures, etc., but there are modifiable risk factors like air pollution that are increasingly recognized as being part of the picture,” said Dr. Kaufman, who was not involved with the current study.

Dr. Zanni added: “It is important that politics work hand in hand with the scientific community in order to win the battle against global warming, which will reduce the number of cardiovascular deaths – the leading cause of death worldwide – as well as environmental integrity.”

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Dr. Zanni and coauthors and Dr. Kaufman reported no relevant financial relationships.

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

Ventricular arrhythmias more commonly occur on days when there are higher levels of air pollution, especially with fine particulate matter (PM), a new study suggests.

The investigators studied the relationship between air pollution and ventricular arrhythmias in Piacenza, Italy by examining 5-year data on patients who received an implantable cardioverter defibrillator (ICD).

Thomas321/iStock/Getty Images Plus

They found a significant association between PM2.5 levels and ventricular arrhythmias, especially those treated with direct current shock. Moreover, higher levels of PM2.5 and PM10 were associated with increased risk of all ventricular arrhythmias.

“These data confirm that environmental pollution is not only a climate emergency but also a public health problem,” lead author Alessia Zanni, currently at Maggiore Hospital, Bologna, Italy, and previously at Piacenza Hospital, said in an interview.

“The study suggests that the survival of patients with heart disease is affected not only by pharmacological therapies and advances in cardiology, but also by the air that they breathe,” she said.

The results were presented at European Society of Cardiology Heart Failure 2022.
 

More ED visits

The World Health Organization estimates around 7 million people die every year from exposure to polluted air, “as 91% of the world’s population lives in areas where air contaminants exceed safety levels,” Dr. Zanni said. Furthermore, “air pollution has been defined as the fourth-highest ranking risk factor for mortality – more important than LDL cholesterol, obesity, physical activity, or alcohol use.”

She noted that Piacenza has “historically been very attentive to the issues of early defibrillation and cardiac arrest.” Her group had previously found a correlation between out-of-hospital cardiac arrests and air pollution in the general population.

Moreover, her group recently observed that ED visits for patients with ICDs “tended to cluster; on some special days, many patients with ICDs had cardiac arrhythmias, and during those days, air pollution levels were particularly high.”

Her group therefore decided to compare the concentration of air pollutants on days when patients suffered from an arrhythmia event versus pollution levels on days without an arrhythmia, she said.
 

Further piece in a complex puzzle

The researchers studied 146 patients with ICDs between January 2013 and December 2017, assigning exposures (short, mid, and long term) to these patients based on their residential addresses.

They extracted day-by-day urban PM10, PM2.5, CO, NO₂, and O₃ levels from the Environmental Protection Agency monitoring stations and then, using time-stratified case-crossover analysis methodology, they calculated the association of ventricular arrhythmia onset with 0- to 7-day moving averages of the various air pollutants prior to the event.

Patients had received their ICD to control cardiac dysfunction brought on by previous myocardial infarction (n = 93), genetic or inflammatory conditions (n = 53), secondary prevention after a lethal arrhythmia (n = 67), and primary prevention (n = 79).

Of the 440 ventricular arrhythmias recorded, 322 were treated with antitachycardia pacing, while the remaining 118 were treated with direct current shock.

The researchers found a significant association between PM2.5 levels and ventricular arrhythmia treated with shock, corresponding to a 15% increased risk or every additional 10mg/m³ (P < .019).

They also found that, when PM2.5 concentrations were elevated by 1 mg/m³ for an entire week, compared with average levels, there was a 2.4% higher likelihood of ventricular arrhythmias, regardless of the temperature, and when PM10 was 1 mg/m³ above average for a week, there was a 2.1% increased risk for arrhythmias (odds ratio, 1,024; 95% confidence interval, 1,009-1,040] and OR, 1,021; 95% CI, 1,009-1,033, respectively), Dr. Zanni reported.

“Since the majority of out-of-hospital cardiac arrest causes still remain unclear, our data add a further piece to the complex puzzle of cardiac arrest triggers,” Dr. Zanni commented. “We think that particulate matter can cause acute inflammation of the heart muscle and potentially act as a trigger for lethal cardiac arrhythmias.

“As these toxic particles are emitted from power plants, industries, and cars, we think that cardiovascular research should highlight these new findings to promote green projects among the general population, clarifying the risks to the health of the human being, and we think strategies to prevent air pollutant exposure in high-risk patients [with previous cardiac disease] should be developed,” she added.

Further, “we advise patients at risk, during days with high PM2.5 (> 35 mg/m³) and PM10 (> 50 mg/m³) to use a mask of the N95 type outdoors, to reduce time spent outdoors – particularly in traffic – and to improve home air filtration,” Dr. Zanni said.
 

Entering the mainstream

In a comment, Joel Kaufman, MD, MPH, professor of internal medicine and environmental health, University of Washington, Seattle, said the study “adds to a fairly substantial literature already on this topic of short-term exposure to air pollution.”

The evidence that air pollutants “can be a trigger of worsening of cardiovascular disease is fairly consistent at this time, and although the effect sizes are small, they are consistent,” said Dr. Kaufman, who was the chair of the writing group for the American Heart Association’s 2020 policy statement, “Guidance to Reduce Cardiovascular Burden of Ambient Air Pollutants.”

“The research into this issue has become clearer during the past 10 years but still is not in the mainstream of most cardiologists’ awareness. They tend to focus more on controlling cholesterol and performing procedures, etc., but there are modifiable risk factors like air pollution that are increasingly recognized as being part of the picture,” said Dr. Kaufman, who was not involved with the current study.

Dr. Zanni added: “It is important that politics work hand in hand with the scientific community in order to win the battle against global warming, which will reduce the number of cardiovascular deaths – the leading cause of death worldwide – as well as environmental integrity.”

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Dr. Zanni and coauthors and Dr. Kaufman reported no relevant financial relationships.

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

ATLANTA -- Liquid formulations of levothyroxine offer the possibility of allowing patients with hypothyroidism to take their medication with meals or coffee and skip the currently recommended 30- to 60-minute waiting period before doing either, new data suggest.

amenic181/Getty Images

Because food, coffee, and certain medications can interfere with intestinal absorption of levothyroxine (also known as LT4), current guidelines recommend that the drug be taken in a fasting state, typically 30-60 minutes before breakfast. However, compliance may be difficult for some patients.

Now, a potential solution may come from new evidence that liquid levothyroxine formulations that bypass the gastric dissolution phase of absorption may mitigate the interference with food and coffee.

Findings from two bioavailability studies showing no difference in comparisons of Thyquidity (levothyroxine sodium oral solution, Vertice Pharma) with or without waiting periods before consuming coffee or a high-fat meal were presented at the annual meeting of the Endocrine Society (ENDO 2022), by Vertice Pharma Medical Director Kris Washington, PharmD.

And just last month, similar data were published in Thyroid for another levothyroxine oral solution, Tirosint-SOL (IBSA). No difference in pharmacokinetic properties were found with this product with a shorter versus a longer waiting period before consuming a high-fat meal.
 

Liquid thyroxine may be less affected by food/drink but is expensive

Both products have been approved by the U.S. Food and Drug Administration, but current labeling for both still calls for a 30- to 60-minute waiting period between taking the medication and eating or drinking. Thyquidity is an oral solution of 100 µg/mL levothyroxine sodium that has been shown to be bioequivalent to one of the most popular branded levothyroxine tablets, Synthroid (AbbVie), under fasting conditions. Tirosint-SOL is also an oral solution that comes in 15 different dosage ampules.

“It is important to note that while these findings are exciting and encouraging, we do want you to continue to follow the current FDA-approved label for Thyquidity, recommending that it be taken on an empty stomach 30-60 minutes prior to breakfast and that patients continue to follow all other label instructions,” Dr. Washington said during a press briefing at ENDO 2022.

When asked whether the new data would be submitted to the FDA for a possible amendment to this message, she replied: “We’re still discussing that. We’re exploring all options. ... This is fairly new data. ... It makes sense and certainly solves a lot of the challenges for people who can’t swallow or don’t choose to swallow, or the challenges of splitting or crushing with tablets.”

Asked to comment, Benjamin J. Gigliotti, MD, a clinical thyroidologist at the University of Rochester, New York, told this news organization: “Liquid levothyroxine has the potential to be a clinically useful formulation,” noting that these recent data corroborate prior findings from Europe and elsewhere that liquid levothyroxine is absorbed more rapidly and thus may be less impacted by food or beverages.

However, Dr. Gigliotti also pointed out, “I don’t think malabsorption is a major contributor to suboptimal treatment because if [patients] malabsorb the hormone, we typically just increase their dose a little bit or ask them to take it separately, and that works just fine for most people.”

And the higher cost of the liquid products is a major issue, he noted. 

A quick search on GoodRx shows that the lowest price of Tirosint-SOL is $115.52 for a 1 month supply and Thyquidity is $181.04/month. “In the few patients where I tried to obtain Tirosint-SOL, it was not covered by insurance, even with a prior authorization,” Dr. Gigliotti commented.

In contrast, generic levothyroxine tablets are about $4/month, while a common brand name of levothyroxine tablets are $47.81/month.

“Until these liquid formulations are more widely covered by insurance for a reasonable copay, or come down in price compared to generic levothyroxine tablets, most of my patients have voiced that they’d rather deal with the inconveniences of a tablet compared to higher medication cost, especially with rising economic insecurity imposed by the COVID-19 pandemic and recent world events,” Dr. Gigliotti said.
 

Bioequivalence with shorter versus longer waits before coffee/breakfast

The Thyquidity coffee study was a single-center open-label, randomized, crossover study of 40 healthy adults randomized after a 10-hour overnight fast to 600 µg Thyquidity with water under fasting conditions or to the same dose given 5 minutes prior to drinking an 8-ounce cup of American coffee without milk or sweeteners. After a 40-day washout period, the same participants received the other treatment.

Mean serum thyroxine (T4) concentrations over 48 hours were nearly identical, demonstrating comparable bioavailability. Pharmacokinetics parameters, including area under the curve (AUC) and Cmax, were also comparable for both groups. The geometric least square mean ratios for baseline-adjusted LT4 were 96.0% for Cmax and 94% for AUC. And the corresponding 90% confidence intervals fell within the 80%-125% FDA acceptance range for absence of a food effect on bioavailability, said Dr. Washington when presenting the findings.

There was one adverse event, a decrease in blood glucose level, which was deemed to be mild and unrelated to study treatment. No deaths, serious adverse events, or discontinuations due to adverse events were reported. There were no significant changes in vital signs or on ECG.

In the second Thyquidity study of 38 healthy adults, after a 10-hour fast, the same doses were given 10 or 30 minutes prior to the consumption of a 950-calorie standardized high-fat breakfast.

Again, over 48 hours, mean serum T4 levels were comparable between the two groups. The geometric least squares mean ratios for both AUC and Cmax for baseline-adjusted LT4 were 88.7% and 85.1%, respectively. Again, the corresponding 90% confidence intervals fell within the FDA’s noninterference definition, again demonstrating lack of a food effect on bioavailability, Dr. Washington noted.

Four adverse events were reported in three participants, with three deemed to be possibly related to the medication. All were isolated lab abnormalities without clinical symptoms and deemed to be mild. Three were normal on repeat testing.

There were no deaths or serious adverse events or study discontinuations for adverse events and no significant findings for vital signs or on ECG.
 

Similar findings for Tirosint-SOL but longer-term studies needed

The recently published Tirosint-SOL study included 36 healthy volunteers randomized to single 600-µg doses of the LT4 oral solution after a 10-hour fast, either 15 or 30 minutes before eating a standardized high-fat, high-calorie meal. Mean serum total thyroxine concentration profiles were similar for both the 15- and 30-minute waits, with similar AUCs.

Geometric mean ratios for AUCs at 48 and 72 hours were 90% and 92%, respectively, and the 90% confidence intervals fell within the 80%-125% FDA boundaries, suggesting similar exposures whether taken 15 or 30 minutes before a meal.

Senior author Francesco S. Celi, MD, chair of the division of endocrinology, diabetes, and metabolism at Virginia Commonwealth University, Richmond, told this news organization: “There is an interest in providing more opportunities for patients and improving adherence to the medication. ... Whatever makes life a bit easier for patients and results in a more predictable response to treatment means down the road there will be fewer visits to the doctor to make adjustments.”

However, he said that in addition to the cost and reimbursement issue, all of these studies have been short term and not conducted in real-life settings.

“Another question is: What happens if the patient goes on low-dose LT4? The studies were conducted on much higher pharmacologic doses. But at least from a safety standpoint, there’s no specific concern.”

Dr. Washington is an employee of Vertice Pharma. Dr. Celi has received unrestricted research grants and worked as a consultant for IBSA. Dr. Gigliotti has reported no relevant financial relationships.

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

ATLANTA -- Liquid formulations of levothyroxine offer the possibility of allowing patients with hypothyroidism to take their medication with meals or coffee and skip the currently recommended 30- to 60-minute waiting period before doing either, new data suggest.

amenic181/Getty Images

Because food, coffee, and certain medications can interfere with intestinal absorption of levothyroxine (also known as LT4), current guidelines recommend that the drug be taken in a fasting state, typically 30-60 minutes before breakfast. However, compliance may be difficult for some patients.

Now, a potential solution may come from new evidence that liquid levothyroxine formulations that bypass the gastric dissolution phase of absorption may mitigate the interference with food and coffee.

Findings from two bioavailability studies showing no difference in comparisons of Thyquidity (levothyroxine sodium oral solution, Vertice Pharma) with or without waiting periods before consuming coffee or a high-fat meal were presented at the annual meeting of the Endocrine Society (ENDO 2022), by Vertice Pharma Medical Director Kris Washington, PharmD.

And just last month, similar data were published in Thyroid for another levothyroxine oral solution, Tirosint-SOL (IBSA). No difference in pharmacokinetic properties were found with this product with a shorter versus a longer waiting period before consuming a high-fat meal.
 

Liquid thyroxine may be less affected by food/drink but is expensive

Both products have been approved by the U.S. Food and Drug Administration, but current labeling for both still calls for a 30- to 60-minute waiting period between taking the medication and eating or drinking. Thyquidity is an oral solution of 100 µg/mL levothyroxine sodium that has been shown to be bioequivalent to one of the most popular branded levothyroxine tablets, Synthroid (AbbVie), under fasting conditions. Tirosint-SOL is also an oral solution that comes in 15 different dosage ampules.

“It is important to note that while these findings are exciting and encouraging, we do want you to continue to follow the current FDA-approved label for Thyquidity, recommending that it be taken on an empty stomach 30-60 minutes prior to breakfast and that patients continue to follow all other label instructions,” Dr. Washington said during a press briefing at ENDO 2022.

When asked whether the new data would be submitted to the FDA for a possible amendment to this message, she replied: “We’re still discussing that. We’re exploring all options. ... This is fairly new data. ... It makes sense and certainly solves a lot of the challenges for people who can’t swallow or don’t choose to swallow, or the challenges of splitting or crushing with tablets.”

Asked to comment, Benjamin J. Gigliotti, MD, a clinical thyroidologist at the University of Rochester, New York, told this news organization: “Liquid levothyroxine has the potential to be a clinically useful formulation,” noting that these recent data corroborate prior findings from Europe and elsewhere that liquid levothyroxine is absorbed more rapidly and thus may be less impacted by food or beverages.

However, Dr. Gigliotti also pointed out, “I don’t think malabsorption is a major contributor to suboptimal treatment because if [patients] malabsorb the hormone, we typically just increase their dose a little bit or ask them to take it separately, and that works just fine for most people.”

And the higher cost of the liquid products is a major issue, he noted. 

A quick search on GoodRx shows that the lowest price of Tirosint-SOL is $115.52 for a 1 month supply and Thyquidity is $181.04/month. “In the few patients where I tried to obtain Tirosint-SOL, it was not covered by insurance, even with a prior authorization,” Dr. Gigliotti commented.

In contrast, generic levothyroxine tablets are about $4/month, while a common brand name of levothyroxine tablets are $47.81/month.

“Until these liquid formulations are more widely covered by insurance for a reasonable copay, or come down in price compared to generic levothyroxine tablets, most of my patients have voiced that they’d rather deal with the inconveniences of a tablet compared to higher medication cost, especially with rising economic insecurity imposed by the COVID-19 pandemic and recent world events,” Dr. Gigliotti said.
 

Bioequivalence with shorter versus longer waits before coffee/breakfast

The Thyquidity coffee study was a single-center open-label, randomized, crossover study of 40 healthy adults randomized after a 10-hour overnight fast to 600 µg Thyquidity with water under fasting conditions or to the same dose given 5 minutes prior to drinking an 8-ounce cup of American coffee without milk or sweeteners. After a 40-day washout period, the same participants received the other treatment.

Mean serum thyroxine (T4) concentrations over 48 hours were nearly identical, demonstrating comparable bioavailability. Pharmacokinetics parameters, including area under the curve (AUC) and Cmax, were also comparable for both groups. The geometric least square mean ratios for baseline-adjusted LT4 were 96.0% for Cmax and 94% for AUC. And the corresponding 90% confidence intervals fell within the 80%-125% FDA acceptance range for absence of a food effect on bioavailability, said Dr. Washington when presenting the findings.

There was one adverse event, a decrease in blood glucose level, which was deemed to be mild and unrelated to study treatment. No deaths, serious adverse events, or discontinuations due to adverse events were reported. There were no significant changes in vital signs or on ECG.

In the second Thyquidity study of 38 healthy adults, after a 10-hour fast, the same doses were given 10 or 30 minutes prior to the consumption of a 950-calorie standardized high-fat breakfast.

Again, over 48 hours, mean serum T4 levels were comparable between the two groups. The geometric least squares mean ratios for both AUC and Cmax for baseline-adjusted LT4 were 88.7% and 85.1%, respectively. Again, the corresponding 90% confidence intervals fell within the FDA’s noninterference definition, again demonstrating lack of a food effect on bioavailability, Dr. Washington noted.

Four adverse events were reported in three participants, with three deemed to be possibly related to the medication. All were isolated lab abnormalities without clinical symptoms and deemed to be mild. Three were normal on repeat testing.

There were no deaths or serious adverse events or study discontinuations for adverse events and no significant findings for vital signs or on ECG.
 

Similar findings for Tirosint-SOL but longer-term studies needed

The recently published Tirosint-SOL study included 36 healthy volunteers randomized to single 600-µg doses of the LT4 oral solution after a 10-hour fast, either 15 or 30 minutes before eating a standardized high-fat, high-calorie meal. Mean serum total thyroxine concentration profiles were similar for both the 15- and 30-minute waits, with similar AUCs.

Geometric mean ratios for AUCs at 48 and 72 hours were 90% and 92%, respectively, and the 90% confidence intervals fell within the 80%-125% FDA boundaries, suggesting similar exposures whether taken 15 or 30 minutes before a meal.

Senior author Francesco S. Celi, MD, chair of the division of endocrinology, diabetes, and metabolism at Virginia Commonwealth University, Richmond, told this news organization: “There is an interest in providing more opportunities for patients and improving adherence to the medication. ... Whatever makes life a bit easier for patients and results in a more predictable response to treatment means down the road there will be fewer visits to the doctor to make adjustments.”

However, he said that in addition to the cost and reimbursement issue, all of these studies have been short term and not conducted in real-life settings.

“Another question is: What happens if the patient goes on low-dose LT4? The studies were conducted on much higher pharmacologic doses. But at least from a safety standpoint, there’s no specific concern.”

Dr. Washington is an employee of Vertice Pharma. Dr. Celi has received unrestricted research grants and worked as a consultant for IBSA. Dr. Gigliotti has reported no relevant financial relationships.

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

ATLANTA -- Liquid formulations of levothyroxine offer the possibility of allowing patients with hypothyroidism to take their medication with meals or coffee and skip the currently recommended 30- to 60-minute waiting period before doing either, new data suggest.

amenic181/Getty Images

Because food, coffee, and certain medications can interfere with intestinal absorption of levothyroxine (also known as LT4), current guidelines recommend that the drug be taken in a fasting state, typically 30-60 minutes before breakfast. However, compliance may be difficult for some patients.

Now, a potential solution may come from new evidence that liquid levothyroxine formulations that bypass the gastric dissolution phase of absorption may mitigate the interference with food and coffee.

Findings from two bioavailability studies showing no difference in comparisons of Thyquidity (levothyroxine sodium oral solution, Vertice Pharma) with or without waiting periods before consuming coffee or a high-fat meal were presented at the annual meeting of the Endocrine Society (ENDO 2022), by Vertice Pharma Medical Director Kris Washington, PharmD.

And just last month, similar data were published in Thyroid for another levothyroxine oral solution, Tirosint-SOL (IBSA). No difference in pharmacokinetic properties were found with this product with a shorter versus a longer waiting period before consuming a high-fat meal.
 

Liquid thyroxine may be less affected by food/drink but is expensive

Both products have been approved by the U.S. Food and Drug Administration, but current labeling for both still calls for a 30- to 60-minute waiting period between taking the medication and eating or drinking. Thyquidity is an oral solution of 100 µg/mL levothyroxine sodium that has been shown to be bioequivalent to one of the most popular branded levothyroxine tablets, Synthroid (AbbVie), under fasting conditions. Tirosint-SOL is also an oral solution that comes in 15 different dosage ampules.

“It is important to note that while these findings are exciting and encouraging, we do want you to continue to follow the current FDA-approved label for Thyquidity, recommending that it be taken on an empty stomach 30-60 minutes prior to breakfast and that patients continue to follow all other label instructions,” Dr. Washington said during a press briefing at ENDO 2022.

When asked whether the new data would be submitted to the FDA for a possible amendment to this message, she replied: “We’re still discussing that. We’re exploring all options. ... This is fairly new data. ... It makes sense and certainly solves a lot of the challenges for people who can’t swallow or don’t choose to swallow, or the challenges of splitting or crushing with tablets.”

Asked to comment, Benjamin J. Gigliotti, MD, a clinical thyroidologist at the University of Rochester, New York, told this news organization: “Liquid levothyroxine has the potential to be a clinically useful formulation,” noting that these recent data corroborate prior findings from Europe and elsewhere that liquid levothyroxine is absorbed more rapidly and thus may be less impacted by food or beverages.

However, Dr. Gigliotti also pointed out, “I don’t think malabsorption is a major contributor to suboptimal treatment because if [patients] malabsorb the hormone, we typically just increase their dose a little bit or ask them to take it separately, and that works just fine for most people.”

And the higher cost of the liquid products is a major issue, he noted. 

A quick search on GoodRx shows that the lowest price of Tirosint-SOL is $115.52 for a 1 month supply and Thyquidity is $181.04/month. “In the few patients where I tried to obtain Tirosint-SOL, it was not covered by insurance, even with a prior authorization,” Dr. Gigliotti commented.

In contrast, generic levothyroxine tablets are about $4/month, while a common brand name of levothyroxine tablets are $47.81/month.

“Until these liquid formulations are more widely covered by insurance for a reasonable copay, or come down in price compared to generic levothyroxine tablets, most of my patients have voiced that they’d rather deal with the inconveniences of a tablet compared to higher medication cost, especially with rising economic insecurity imposed by the COVID-19 pandemic and recent world events,” Dr. Gigliotti said.
 

Bioequivalence with shorter versus longer waits before coffee/breakfast

The Thyquidity coffee study was a single-center open-label, randomized, crossover study of 40 healthy adults randomized after a 10-hour overnight fast to 600 µg Thyquidity with water under fasting conditions or to the same dose given 5 minutes prior to drinking an 8-ounce cup of American coffee without milk or sweeteners. After a 40-day washout period, the same participants received the other treatment.

Mean serum thyroxine (T4) concentrations over 48 hours were nearly identical, demonstrating comparable bioavailability. Pharmacokinetics parameters, including area under the curve (AUC) and Cmax, were also comparable for both groups. The geometric least square mean ratios for baseline-adjusted LT4 were 96.0% for Cmax and 94% for AUC. And the corresponding 90% confidence intervals fell within the 80%-125% FDA acceptance range for absence of a food effect on bioavailability, said Dr. Washington when presenting the findings.

There was one adverse event, a decrease in blood glucose level, which was deemed to be mild and unrelated to study treatment. No deaths, serious adverse events, or discontinuations due to adverse events were reported. There were no significant changes in vital signs or on ECG.

In the second Thyquidity study of 38 healthy adults, after a 10-hour fast, the same doses were given 10 or 30 minutes prior to the consumption of a 950-calorie standardized high-fat breakfast.

Again, over 48 hours, mean serum T4 levels were comparable between the two groups. The geometric least squares mean ratios for both AUC and Cmax for baseline-adjusted LT4 were 88.7% and 85.1%, respectively. Again, the corresponding 90% confidence intervals fell within the FDA’s noninterference definition, again demonstrating lack of a food effect on bioavailability, Dr. Washington noted.

Four adverse events were reported in three participants, with three deemed to be possibly related to the medication. All were isolated lab abnormalities without clinical symptoms and deemed to be mild. Three were normal on repeat testing.

There were no deaths or serious adverse events or study discontinuations for adverse events and no significant findings for vital signs or on ECG.
 

Similar findings for Tirosint-SOL but longer-term studies needed

The recently published Tirosint-SOL study included 36 healthy volunteers randomized to single 600-µg doses of the LT4 oral solution after a 10-hour fast, either 15 or 30 minutes before eating a standardized high-fat, high-calorie meal. Mean serum total thyroxine concentration profiles were similar for both the 15- and 30-minute waits, with similar AUCs.

Geometric mean ratios for AUCs at 48 and 72 hours were 90% and 92%, respectively, and the 90% confidence intervals fell within the 80%-125% FDA boundaries, suggesting similar exposures whether taken 15 or 30 minutes before a meal.

Senior author Francesco S. Celi, MD, chair of the division of endocrinology, diabetes, and metabolism at Virginia Commonwealth University, Richmond, told this news organization: “There is an interest in providing more opportunities for patients and improving adherence to the medication. ... Whatever makes life a bit easier for patients and results in a more predictable response to treatment means down the road there will be fewer visits to the doctor to make adjustments.”

However, he said that in addition to the cost and reimbursement issue, all of these studies have been short term and not conducted in real-life settings.

“Another question is: What happens if the patient goes on low-dose LT4? The studies were conducted on much higher pharmacologic doses. But at least from a safety standpoint, there’s no specific concern.”

Dr. Washington is an employee of Vertice Pharma. Dr. Celi has received unrestricted research grants and worked as a consultant for IBSA. Dr. Gigliotti has reported no relevant financial relationships.

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

The brachial plexus is a group of interwoven nerves arising from the cervical spinal cord and coursing through the neck, shoulder, and axilla with terminal branches extending to the distal arm.¹ Disorders of the brachial plexus are more rare than other isolated peripheral nerve disorders, trauma being the most common etiology.¹ Traction, neoplasms, radiation exposure, external compression, and inflammatory processes, such as Parsonage-Turner syndrome, have also been described as less common etiologies.²

Rhabdomyolysis, a condition in which muscle breakdown occurs, is an uncommon and perhaps underrecognized cause of brachial plexopathy. Rhabdomyolysis is often caused by muscle overuse, trauma, prolonged immobilization, drugs, or toxins. Substances indicated as precipitating factors include alcohol, opioids, cocaine, and amphetamines.^3,4 As rhabdomyolysis progresses, swelling and edema can compress surrounding structures. Therefore, in cases of rhabdomyolysis involving the muscles of the neck and shoulder girdle, external compression of the brachial plexus can potentially cause brachial plexopathy. Rare cases of this phenomenon occurring as a sequela of substance use have been described.^1,5-9 Few cases have been reported in the literature.

The following case report describes a patient who experienced rhabdomyolysis following use of crack cocaine contaminated with fentanyl, which subsequently caused bilateral brachial plexopathy. 

Case Presentation

A 68-year-old male patient with a history of polysubstance use disorder presented to the emergency department with complete loss of sensory and motor function of both arms. He had fallen asleep on his couch the previous evening with his arms crossed over his chest in the prone position. He reported using crack cocaine earlier that day that was later discovered to be contaminated with fentanyl. The patient reported using no other substances, including alcohol. When he woke about 7 hours later, the patient’s arms were completely paralyzed.

On admission, the patient presented with an agitated mental status. The patient presented with 0/5 strength bilaterally in the upper extremities (UEs) accompanied by numbness and tingling. Radial pulses were palpable in both arms. All UE reflexes were absent, but patellar reflex was intact bilaterally. On hospital day 2, the patient was awake, alert, and oriented to person, place, and time and could provide a full history. The patient’s cranial nerves were intact with shoulder shrug testing mildly weak at 4/5 strength. The patient had 0/5 strength bilaterally and bilateral absent reflexes in the UEs. Sensation was markedly decreased, as he was unable to feel temperature, pinprick sensation, or general touch in both UEs. Coordination of the UEs could not be tested due to weakness. No response could be elicited from the median or ulnar nerve bilaterally on somatosensory evoked potential study. The lower extremities were intact to movement, sensation, coordination, and reflexes.

Serum electrolytes and glucose levels were normal. The creatine phosphokinase (CPK) level was elevated at 21,292 IU/L. Creatinine and blood urea nitrogen levels were elevated at 1.7 mg/dL and 32 mg/dL, respectively. Serum B12, thyroid-stimulating hormone, and hemoglobin A_1c levels were normal. Urine drug screen was positive for cocaine metabolite and fentanyl but negative for other substances, including alcohol. The patient stated emphatically he had only used crack cocaine, so it was presumed that the crack cocaine had been contaminated with fentanyl.

Computed tomography (CT) of the head was normal and revealed no acute intracranial process. Further imaging studies included magnetic resonance imaging (MRI) of the brain and spinal cord and subsequently of the brachial plexus. There was no evidence of a spinal cord or intracranial lesion. However, there was abnormal signal in the lower neck greater on the right side suggesting an edematous inflammatory process involving part of the shoulder girdle musculature. This included the trapezius, levator scapula, rhomboid, and serratus anterior muscles, as well as prominent fluid signal in the right supraclavicular fossa. The abnormal signal was less prominent on the left and involved the serratus anterior muscle. To a lesser extent, there also was involvement of the distal attachment site of the anterior and middle scalene muscles on the right greater than the left. It is presumed that muscular edema resulted in partial narrowing of the thoracic outlet bilaterally with corresponding mass effect on the traversing brachial plexus, resulting in the patient’s symptoms (Figure).

Discussion

Rhabdomyolysis is a condition defined by myocyte necrosis that results in release of cellular contents and local edema. Inciting events may be traumatic, metabolic, ischemic, or substance induced. Common substances indicated include cocaine, amphetamines, acetaminophen, opioids, and alcohol.¹⁰ It classically presents with muscle pain and a marked elevation in serum CPK level, but other metabolic disturbances, acute kidney injury, or toxic hepatitis may also occur. A more uncommon sequela of rhabdomyolysis is plexopathy caused by edematous swelling and compression of the surrounding structures.

Rare cases of brachial plexopathy caused by rhabdomyolysis following substance use have been described. In many of these cases, rhabdomyolysis occurred after alcohol use with or without concurrent use of prescription opioids or heroin.^7-9 One case following use of 3,4-methylenedioxy-N-methylamptamine (MDMA) and marijuana use was reported.¹ Another case of concurrent brachial plexopathy and Horner syndrome in a 29-year-old male patient following ingestion of alcohol and opioids has also been described.⁵ The rate of occurrence of this phenomenon in the general population is unknown.

In the case of our patient, cocaine metabolite and fentanyl were the only substances found on urine drug screen. The patient had used crack cocaine that had presumably been contaminated with fentanyl, a high potency synthetic opioid. The rate of fentanyl contamination of street drugs is variable. It is a subject of high concern, considering the increasing rates of synthetic opioid overdose-related deaths. According to the US Centers for Disease Control and Prevention, synthetic opioids have played a role in the increasing rates of cocaine-related overdose deaths. Conversely, in more than half of all overdose deaths involving fentanyl derivatives, patients also tested positive for cocaine, methamphetamine, or heroin. In recent studies conducted in various cities in the northeastern US, rates of fentanyl metabolite detection were much higher than rates of reported fentanyl use.¹¹ Cases of crack cocaine contamination with fentanyl derivatives have been reported in Canada and Washington.¹²

The pathophysiology of rhabdomyolysis caused by substance use has not been definitively identified, but it is hypothesized that the cause is 2-fold. The first insult is the direct toxicity of the substances to myocytes.^8,9 The second factor is prolonged immobilization in a position that compresses the affected musculature and blood supply, causing both mechanical stress and ischemia to the muscles and brachial plexus. This prolonged immobilization can frequently follow use of substances, such as alcohol or opioids.⁹ Cases have been reported wherein rhabdomyolysis causing brachial plexopathy occurred despite relatively normal positioning of the arms and shoulders during sleep.⁹ In our case, the patient had fallen asleep with his arms crossed over his chest in the prone position with his head turned, though he could not recall to which side. Although he stated that he had slept in this position regularly, the effects of fentanyl may have prevented the patient from waking to adjust his posture. This position had potential to compress the musculature of the neck and shoulders and restrict blood flow, resulting in the focal rhabdomyolysis seen in this patient. In theory, the position could also cause a stretch injury of the brachial plexus, although a pure stretch injury would more likely present unilaterally and without evidence of rhabdomyolysis.

Chronic ethanol use may have been a major contributor by both sensitizing the muscles to toxicity of other substances and induction of CYP450 enzymes that are normally responsible for metabolizing other drugs.⁸ Alcohol also inhibits gluconeogenesis and leads to hyperpolarization of myocytes, further contributing to their susceptibility to damage.⁹ Our patient had a prior history of alcohol use years before this event, but not at the time of this event.

Our patient had other known risk factors for rhabdomyolysis, including his long-term statin therapy, but it is unclear whether these were contributing factors in his case.¹⁰ Of the medications that are known to cause rhabdomyolysis, statins are among the most commonly described, although the mechanism through which this process occurs is not clear. A case of rhabdomyolysis following use of cocaine and heroin in a patient on long-standing statin therapy has been described.¹³ Our review of the literature found no cases of statin-induced rhabdomyolysis associated with brachial plexopathy. It is possible that concurrent statin therapy has an additive effect to other substances in inducing rhabdomyolysis.

Parsonage-Turner syndrome, also known as neuralgic amyotrophy, should also be included in the differential diagnosis. While there have been multiple etiologies proposed for Parsonage-Turner syndrome, it is generally thought to begin as a primary inflammatory process targeting the brachial plexus. One case report describes Parsonage-Turner syndrome progressing to secondary rhabdomyolysis.⁶ In this case, no primary etiology was identified, so the Parsonage-Turner syndrome diagnosis was made with secondary rhabdomyolysis.⁶ We believe it is possible that this case and others may have been misdiagnosed as Parsonage-Turner syndrome.

Conclusions

This case report adds to the literature describing focal rhabdomyolysis causing secondary bilateral brachial plexopathy after substance use. Further research is needed to establish a definitive pathophysiology as well as treatment guidelines. Evidence-based treatment could mean better outcomes and quicker recoveries for future patients with this condition.

The brachial plexus is a group of interwoven nerves arising from the cervical spinal cord and coursing through the neck, shoulder, and axilla with terminal branches extending to the distal arm.¹ Disorders of the brachial plexus are more rare than other isolated peripheral nerve disorders, trauma being the most common etiology.¹ Traction, neoplasms, radiation exposure, external compression, and inflammatory processes, such as Parsonage-Turner syndrome, have also been described as less common etiologies.²

Rhabdomyolysis, a condition in which muscle breakdown occurs, is an uncommon and perhaps underrecognized cause of brachial plexopathy. Rhabdomyolysis is often caused by muscle overuse, trauma, prolonged immobilization, drugs, or toxins. Substances indicated as precipitating factors include alcohol, opioids, cocaine, and amphetamines.^3,4 As rhabdomyolysis progresses, swelling and edema can compress surrounding structures. Therefore, in cases of rhabdomyolysis involving the muscles of the neck and shoulder girdle, external compression of the brachial plexus can potentially cause brachial plexopathy. Rare cases of this phenomenon occurring as a sequela of substance use have been described.^1,5-9 Few cases have been reported in the literature.

The following case report describes a patient who experienced rhabdomyolysis following use of crack cocaine contaminated with fentanyl, which subsequently caused bilateral brachial plexopathy. 

Case Presentation

A 68-year-old male patient with a history of polysubstance use disorder presented to the emergency department with complete loss of sensory and motor function of both arms. He had fallen asleep on his couch the previous evening with his arms crossed over his chest in the prone position. He reported using crack cocaine earlier that day that was later discovered to be contaminated with fentanyl. The patient reported using no other substances, including alcohol. When he woke about 7 hours later, the patient’s arms were completely paralyzed.

On admission, the patient presented with an agitated mental status. The patient presented with 0/5 strength bilaterally in the upper extremities (UEs) accompanied by numbness and tingling. Radial pulses were palpable in both arms. All UE reflexes were absent, but patellar reflex was intact bilaterally. On hospital day 2, the patient was awake, alert, and oriented to person, place, and time and could provide a full history. The patient’s cranial nerves were intact with shoulder shrug testing mildly weak at 4/5 strength. The patient had 0/5 strength bilaterally and bilateral absent reflexes in the UEs. Sensation was markedly decreased, as he was unable to feel temperature, pinprick sensation, or general touch in both UEs. Coordination of the UEs could not be tested due to weakness. No response could be elicited from the median or ulnar nerve bilaterally on somatosensory evoked potential study. The lower extremities were intact to movement, sensation, coordination, and reflexes.

Serum electrolytes and glucose levels were normal. The creatine phosphokinase (CPK) level was elevated at 21,292 IU/L. Creatinine and blood urea nitrogen levels were elevated at 1.7 mg/dL and 32 mg/dL, respectively. Serum B12, thyroid-stimulating hormone, and hemoglobin A_1c levels were normal. Urine drug screen was positive for cocaine metabolite and fentanyl but negative for other substances, including alcohol. The patient stated emphatically he had only used crack cocaine, so it was presumed that the crack cocaine had been contaminated with fentanyl.

Computed tomography (CT) of the head was normal and revealed no acute intracranial process. Further imaging studies included magnetic resonance imaging (MRI) of the brain and spinal cord and subsequently of the brachial plexus. There was no evidence of a spinal cord or intracranial lesion. However, there was abnormal signal in the lower neck greater on the right side suggesting an edematous inflammatory process involving part of the shoulder girdle musculature. This included the trapezius, levator scapula, rhomboid, and serratus anterior muscles, as well as prominent fluid signal in the right supraclavicular fossa. The abnormal signal was less prominent on the left and involved the serratus anterior muscle. To a lesser extent, there also was involvement of the distal attachment site of the anterior and middle scalene muscles on the right greater than the left. It is presumed that muscular edema resulted in partial narrowing of the thoracic outlet bilaterally with corresponding mass effect on the traversing brachial plexus, resulting in the patient’s symptoms (Figure).

Discussion

Rhabdomyolysis is a condition defined by myocyte necrosis that results in release of cellular contents and local edema. Inciting events may be traumatic, metabolic, ischemic, or substance induced. Common substances indicated include cocaine, amphetamines, acetaminophen, opioids, and alcohol.¹⁰ It classically presents with muscle pain and a marked elevation in serum CPK level, but other metabolic disturbances, acute kidney injury, or toxic hepatitis may also occur. A more uncommon sequela of rhabdomyolysis is plexopathy caused by edematous swelling and compression of the surrounding structures.

Rare cases of brachial plexopathy caused by rhabdomyolysis following substance use have been described. In many of these cases, rhabdomyolysis occurred after alcohol use with or without concurrent use of prescription opioids or heroin.^7-9 One case following use of 3,4-methylenedioxy-N-methylamptamine (MDMA) and marijuana use was reported.¹ Another case of concurrent brachial plexopathy and Horner syndrome in a 29-year-old male patient following ingestion of alcohol and opioids has also been described.⁵ The rate of occurrence of this phenomenon in the general population is unknown.

In the case of our patient, cocaine metabolite and fentanyl were the only substances found on urine drug screen. The patient had used crack cocaine that had presumably been contaminated with fentanyl, a high potency synthetic opioid. The rate of fentanyl contamination of street drugs is variable. It is a subject of high concern, considering the increasing rates of synthetic opioid overdose-related deaths. According to the US Centers for Disease Control and Prevention, synthetic opioids have played a role in the increasing rates of cocaine-related overdose deaths. Conversely, in more than half of all overdose deaths involving fentanyl derivatives, patients also tested positive for cocaine, methamphetamine, or heroin. In recent studies conducted in various cities in the northeastern US, rates of fentanyl metabolite detection were much higher than rates of reported fentanyl use.¹¹ Cases of crack cocaine contamination with fentanyl derivatives have been reported in Canada and Washington.¹²

The pathophysiology of rhabdomyolysis caused by substance use has not been definitively identified, but it is hypothesized that the cause is 2-fold. The first insult is the direct toxicity of the substances to myocytes.^8,9 The second factor is prolonged immobilization in a position that compresses the affected musculature and blood supply, causing both mechanical stress and ischemia to the muscles and brachial plexus. This prolonged immobilization can frequently follow use of substances, such as alcohol or opioids.⁹ Cases have been reported wherein rhabdomyolysis causing brachial plexopathy occurred despite relatively normal positioning of the arms and shoulders during sleep.⁹ In our case, the patient had fallen asleep with his arms crossed over his chest in the prone position with his head turned, though he could not recall to which side. Although he stated that he had slept in this position regularly, the effects of fentanyl may have prevented the patient from waking to adjust his posture. This position had potential to compress the musculature of the neck and shoulders and restrict blood flow, resulting in the focal rhabdomyolysis seen in this patient. In theory, the position could also cause a stretch injury of the brachial plexus, although a pure stretch injury would more likely present unilaterally and without evidence of rhabdomyolysis.

Chronic ethanol use may have been a major contributor by both sensitizing the muscles to toxicity of other substances and induction of CYP450 enzymes that are normally responsible for metabolizing other drugs.⁸ Alcohol also inhibits gluconeogenesis and leads to hyperpolarization of myocytes, further contributing to their susceptibility to damage.⁹ Our patient had a prior history of alcohol use years before this event, but not at the time of this event.

Our patient had other known risk factors for rhabdomyolysis, including his long-term statin therapy, but it is unclear whether these were contributing factors in his case.¹⁰ Of the medications that are known to cause rhabdomyolysis, statins are among the most commonly described, although the mechanism through which this process occurs is not clear. A case of rhabdomyolysis following use of cocaine and heroin in a patient on long-standing statin therapy has been described.¹³ Our review of the literature found no cases of statin-induced rhabdomyolysis associated with brachial plexopathy. It is possible that concurrent statin therapy has an additive effect to other substances in inducing rhabdomyolysis.

Parsonage-Turner syndrome, also known as neuralgic amyotrophy, should also be included in the differential diagnosis. While there have been multiple etiologies proposed for Parsonage-Turner syndrome, it is generally thought to begin as a primary inflammatory process targeting the brachial plexus. One case report describes Parsonage-Turner syndrome progressing to secondary rhabdomyolysis.⁶ In this case, no primary etiology was identified, so the Parsonage-Turner syndrome diagnosis was made with secondary rhabdomyolysis.⁶ We believe it is possible that this case and others may have been misdiagnosed as Parsonage-Turner syndrome.

Conclusions

This case report adds to the literature describing focal rhabdomyolysis causing secondary bilateral brachial plexopathy after substance use. Further research is needed to establish a definitive pathophysiology as well as treatment guidelines. Evidence-based treatment could mean better outcomes and quicker recoveries for future patients with this condition.

The brachial plexus is a group of interwoven nerves arising from the cervical spinal cord and coursing through the neck, shoulder, and axilla with terminal branches extending to the distal arm.¹ Disorders of the brachial plexus are more rare than other isolated peripheral nerve disorders, trauma being the most common etiology.¹ Traction, neoplasms, radiation exposure, external compression, and inflammatory processes, such as Parsonage-Turner syndrome, have also been described as less common etiologies.²

Rhabdomyolysis, a condition in which muscle breakdown occurs, is an uncommon and perhaps underrecognized cause of brachial plexopathy. Rhabdomyolysis is often caused by muscle overuse, trauma, prolonged immobilization, drugs, or toxins. Substances indicated as precipitating factors include alcohol, opioids, cocaine, and amphetamines.^3,4 As rhabdomyolysis progresses, swelling and edema can compress surrounding structures. Therefore, in cases of rhabdomyolysis involving the muscles of the neck and shoulder girdle, external compression of the brachial plexus can potentially cause brachial plexopathy. Rare cases of this phenomenon occurring as a sequela of substance use have been described.^1,5-9 Few cases have been reported in the literature.

The following case report describes a patient who experienced rhabdomyolysis following use of crack cocaine contaminated with fentanyl, which subsequently caused bilateral brachial plexopathy. 

Case Presentation

A 68-year-old male patient with a history of polysubstance use disorder presented to the emergency department with complete loss of sensory and motor function of both arms. He had fallen asleep on his couch the previous evening with his arms crossed over his chest in the prone position. He reported using crack cocaine earlier that day that was later discovered to be contaminated with fentanyl. The patient reported using no other substances, including alcohol. When he woke about 7 hours later, the patient’s arms were completely paralyzed.

On admission, the patient presented with an agitated mental status. The patient presented with 0/5 strength bilaterally in the upper extremities (UEs) accompanied by numbness and tingling. Radial pulses were palpable in both arms. All UE reflexes were absent, but patellar reflex was intact bilaterally. On hospital day 2, the patient was awake, alert, and oriented to person, place, and time and could provide a full history. The patient’s cranial nerves were intact with shoulder shrug testing mildly weak at 4/5 strength. The patient had 0/5 strength bilaterally and bilateral absent reflexes in the UEs. Sensation was markedly decreased, as he was unable to feel temperature, pinprick sensation, or general touch in both UEs. Coordination of the UEs could not be tested due to weakness. No response could be elicited from the median or ulnar nerve bilaterally on somatosensory evoked potential study. The lower extremities were intact to movement, sensation, coordination, and reflexes.

Serum electrolytes and glucose levels were normal. The creatine phosphokinase (CPK) level was elevated at 21,292 IU/L. Creatinine and blood urea nitrogen levels were elevated at 1.7 mg/dL and 32 mg/dL, respectively. Serum B12, thyroid-stimulating hormone, and hemoglobin A_1c levels were normal. Urine drug screen was positive for cocaine metabolite and fentanyl but negative for other substances, including alcohol. The patient stated emphatically he had only used crack cocaine, so it was presumed that the crack cocaine had been contaminated with fentanyl.

Computed tomography (CT) of the head was normal and revealed no acute intracranial process. Further imaging studies included magnetic resonance imaging (MRI) of the brain and spinal cord and subsequently of the brachial plexus. There was no evidence of a spinal cord or intracranial lesion. However, there was abnormal signal in the lower neck greater on the right side suggesting an edematous inflammatory process involving part of the shoulder girdle musculature. This included the trapezius, levator scapula, rhomboid, and serratus anterior muscles, as well as prominent fluid signal in the right supraclavicular fossa. The abnormal signal was less prominent on the left and involved the serratus anterior muscle. To a lesser extent, there also was involvement of the distal attachment site of the anterior and middle scalene muscles on the right greater than the left. It is presumed that muscular edema resulted in partial narrowing of the thoracic outlet bilaterally with corresponding mass effect on the traversing brachial plexus, resulting in the patient’s symptoms (Figure).

Discussion

Rhabdomyolysis is a condition defined by myocyte necrosis that results in release of cellular contents and local edema. Inciting events may be traumatic, metabolic, ischemic, or substance induced. Common substances indicated include cocaine, amphetamines, acetaminophen, opioids, and alcohol.¹⁰ It classically presents with muscle pain and a marked elevation in serum CPK level, but other metabolic disturbances, acute kidney injury, or toxic hepatitis may also occur. A more uncommon sequela of rhabdomyolysis is plexopathy caused by edematous swelling and compression of the surrounding structures.

Rare cases of brachial plexopathy caused by rhabdomyolysis following substance use have been described. In many of these cases, rhabdomyolysis occurred after alcohol use with or without concurrent use of prescription opioids or heroin.^7-9 One case following use of 3,4-methylenedioxy-N-methylamptamine (MDMA) and marijuana use was reported.¹ Another case of concurrent brachial plexopathy and Horner syndrome in a 29-year-old male patient following ingestion of alcohol and opioids has also been described.⁵ The rate of occurrence of this phenomenon in the general population is unknown.

In the case of our patient, cocaine metabolite and fentanyl were the only substances found on urine drug screen. The patient had used crack cocaine that had presumably been contaminated with fentanyl, a high potency synthetic opioid. The rate of fentanyl contamination of street drugs is variable. It is a subject of high concern, considering the increasing rates of synthetic opioid overdose-related deaths. According to the US Centers for Disease Control and Prevention, synthetic opioids have played a role in the increasing rates of cocaine-related overdose deaths. Conversely, in more than half of all overdose deaths involving fentanyl derivatives, patients also tested positive for cocaine, methamphetamine, or heroin. In recent studies conducted in various cities in the northeastern US, rates of fentanyl metabolite detection were much higher than rates of reported fentanyl use.¹¹ Cases of crack cocaine contamination with fentanyl derivatives have been reported in Canada and Washington.¹²

The pathophysiology of rhabdomyolysis caused by substance use has not been definitively identified, but it is hypothesized that the cause is 2-fold. The first insult is the direct toxicity of the substances to myocytes.^8,9 The second factor is prolonged immobilization in a position that compresses the affected musculature and blood supply, causing both mechanical stress and ischemia to the muscles and brachial plexus. This prolonged immobilization can frequently follow use of substances, such as alcohol or opioids.⁹ Cases have been reported wherein rhabdomyolysis causing brachial plexopathy occurred despite relatively normal positioning of the arms and shoulders during sleep.⁹ In our case, the patient had fallen asleep with his arms crossed over his chest in the prone position with his head turned, though he could not recall to which side. Although he stated that he had slept in this position regularly, the effects of fentanyl may have prevented the patient from waking to adjust his posture. This position had potential to compress the musculature of the neck and shoulders and restrict blood flow, resulting in the focal rhabdomyolysis seen in this patient. In theory, the position could also cause a stretch injury of the brachial plexus, although a pure stretch injury would more likely present unilaterally and without evidence of rhabdomyolysis.

Chronic ethanol use may have been a major contributor by both sensitizing the muscles to toxicity of other substances and induction of CYP450 enzymes that are normally responsible for metabolizing other drugs.⁸ Alcohol also inhibits gluconeogenesis and leads to hyperpolarization of myocytes, further contributing to their susceptibility to damage.⁹ Our patient had a prior history of alcohol use years before this event, but not at the time of this event.

Our patient had other known risk factors for rhabdomyolysis, including his long-term statin therapy, but it is unclear whether these were contributing factors in his case.¹⁰ Of the medications that are known to cause rhabdomyolysis, statins are among the most commonly described, although the mechanism through which this process occurs is not clear. A case of rhabdomyolysis following use of cocaine and heroin in a patient on long-standing statin therapy has been described.¹³ Our review of the literature found no cases of statin-induced rhabdomyolysis associated with brachial plexopathy. It is possible that concurrent statin therapy has an additive effect to other substances in inducing rhabdomyolysis.

Parsonage-Turner syndrome, also known as neuralgic amyotrophy, should also be included in the differential diagnosis. While there have been multiple etiologies proposed for Parsonage-Turner syndrome, it is generally thought to begin as a primary inflammatory process targeting the brachial plexus. One case report describes Parsonage-Turner syndrome progressing to secondary rhabdomyolysis.⁶ In this case, no primary etiology was identified, so the Parsonage-Turner syndrome diagnosis was made with secondary rhabdomyolysis.⁶ We believe it is possible that this case and others may have been misdiagnosed as Parsonage-Turner syndrome.

Conclusions

This case report adds to the literature describing focal rhabdomyolysis causing secondary bilateral brachial plexopathy after substance use. Further research is needed to establish a definitive pathophysiology as well as treatment guidelines. Evidence-based treatment could mean better outcomes and quicker recoveries for future patients with this condition.

The U.S. National Lipid Association has issued a new scientific statement on the management of patients with statin intolerance, which recommends different strategies to help patients stay on statin medications, and also suggests alternatives that can be used in patients who really cannot tolerate statin drugs.

The statement was published online in the Journal of Clinical Lipidology.  

It notes that, although statins are generally well tolerated, statin intolerance is reported in 5%-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes.

RogerAshford/Thinkstock

The statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a “nocebo” effect, basically the patient expectation of harm resulting in perceived side effects.

To identify a tolerable statin regimen, it recommends that clinicians consider using several different strategies (different statin, dose, and/or dosing frequency), and to classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest-approved daily dosage.

The statement says that nonstatin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy, and in these cases, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored.

In high and very high-risk patients who are statin intolerant, clinicians should consider initiating nonstatin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins, it suggests.

“There is strong evidence that statins reduce risk of cardiovascular events particularly in patients with atherosclerotic cardiovascular disease, but recent research shows that only about half of patients with ASCVD are on a statin,” Kevin C. Maki, PhD, coauthor of the statement and current president of the National Lipid Association, said in an interview.

“There is an urgent problem with underutilization of statins and undertreatment of ASCVD. And we know that perceived side effects associated with statins are a common reason for discontinuation of these drugs and the consequent failure to manage ASCVD adequately,” he said.  

Dr. Maki noted that the NLA’s first message is that, when experiencing symptoms taking statins, a large majority of patients can still tolerate a statin. “They can try a different agent or a different dose. But for those who still can’t tolerate a statin, we then recommend nonstatin therapies and we favor those therapies with evidence from randomized trials.”

He pointed out that many patients who believe they are experiencing side effects from taking statins still experience the same effects on a placebo, a condition known as the nocebo effect.

“Several studies have shown that the nocebo effect is very common and accounts for more than half of perceived statin side effects. It is therefore estimated that many of the complaints of statin intolerance are probably not directly related to the pharmacodynamic actions of the drugs,” Dr. Maki said.

One recent study on the nocebo effect, the SAMSON study, suggested that 90% of symptoms attributed to statins were elicited by placebo tablets too.

But Dr. Maki added that it can be a losing battle for the clinician if patients think their symptoms are related to taking a statin.

“We suggest that clinicians inform patients that most people can tolerate a statin – maybe with a different agent or an alternative dose – and it is really important to lower LDL cholesterol as that will lower the risk of MI and stroke, so we need to find a regimen that works for each individual,” he said. “Most people can find a regimen that works. If this means taking a lower dose of a statin, they can take some additional therapy as well. This is a better situation than stopping taking statins altogether and allowing ASCVD to progress.”

Dr. Maki stressed that statins should still be the first choice as they are effective, taken orally, and inexpensive.

“Other medications do not have all these advantages. For example, PCSK9 inhibitors are very effective but they are expensive and injectable,” he noted. “And while ezetimibe [Zetia] is now generic so inexpensive, it has a more modest effect on LDL-lowering compared to statins, so by itself it is not normally enough for most patients to get to their target LDL, but it is an option for use in combination with a statin.”

He added that the NLA message is to do everything possible to keep patients on a statin, especially patients with preexisting ASCVD.

“We would like these patients to be on high-intensity statins. If they really can’t tolerate this, then they could be on a low-intensity statin plus an additional agent.”

Commenting on the NLA statement, SAMSON study coauthor James Howard, MB BChir, PhD, Imperial College London, said he had reservations about some of the recommendations.

“Whilst I think it is great news that the existence and importance of the nocebo effect is increasingly recognized in international guidelines and statements, I think we need to be very careful about recommending reduced doses and frequencies of statins,” Dr. Howard said.

“Studies such as SAMSON and StatinWISE indicate the vast majority of side effects reported by patients taking statins are not caused by the statin molecule, but instead are caused by either the nocebo effect, or ever-present background symptoms that are wrongly attributed to the statins,” he commented. “Therefore, to recommend that the correct approach in a patient with a history of MI suffering symptoms on 80 mg of atorvastatin is to reduce the dose or try alternate daily dosing. This reinforces the view that these drugs are side-effect prone and need to be carefully titrated.”

Dr. Howard suggested that patients should be educated on the possibility of the nocebo effect or background symptoms and encouraged to retrial statins at the same dose. “If that doesn’t work, then formal recording with a symptom diary might help patients recognize background symptoms,” he added.

Dr. Howard noted that, if symptoms still persist, an “n-of-1” trial could be conducted, in which the patient rotates between multiple periods of taking a statin and a placebo, but he acknowledged that this is expensive and time consuming. 

Also commenting, Steve Nissen, MD, Cleveland Clinic, said he thought the NLA statement was “reasonable and thoughtful.”

“Regardless of whether the symptoms are due to the nocebo effect or not, some patients will just not take a statin no matter how hard you try to convince them to persevere, so we do need alternatives,” Dr. Nissen said.

He noted that current alternatives would include the PCSK9 inhibitors and ezetimibe, but a future candidate could be the oral bempedoic acid (Nexletol), which is currently being evaluated in a large outcomes trial (CLEAR Outcomes).

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

The U.S. National Lipid Association has issued a new scientific statement on the management of patients with statin intolerance, which recommends different strategies to help patients stay on statin medications, and also suggests alternatives that can be used in patients who really cannot tolerate statin drugs.

The statement was published online in the Journal of Clinical Lipidology.  

It notes that, although statins are generally well tolerated, statin intolerance is reported in 5%-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes.

RogerAshford/Thinkstock

The statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a “nocebo” effect, basically the patient expectation of harm resulting in perceived side effects.

To identify a tolerable statin regimen, it recommends that clinicians consider using several different strategies (different statin, dose, and/or dosing frequency), and to classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest-approved daily dosage.

The statement says that nonstatin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy, and in these cases, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored.

In high and very high-risk patients who are statin intolerant, clinicians should consider initiating nonstatin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins, it suggests.

“There is strong evidence that statins reduce risk of cardiovascular events particularly in patients with atherosclerotic cardiovascular disease, but recent research shows that only about half of patients with ASCVD are on a statin,” Kevin C. Maki, PhD, coauthor of the statement and current president of the National Lipid Association, said in an interview.

“There is an urgent problem with underutilization of statins and undertreatment of ASCVD. And we know that perceived side effects associated with statins are a common reason for discontinuation of these drugs and the consequent failure to manage ASCVD adequately,” he said.  

Dr. Maki noted that the NLA’s first message is that, when experiencing symptoms taking statins, a large majority of patients can still tolerate a statin. “They can try a different agent or a different dose. But for those who still can’t tolerate a statin, we then recommend nonstatin therapies and we favor those therapies with evidence from randomized trials.”

He pointed out that many patients who believe they are experiencing side effects from taking statins still experience the same effects on a placebo, a condition known as the nocebo effect.

“Several studies have shown that the nocebo effect is very common and accounts for more than half of perceived statin side effects. It is therefore estimated that many of the complaints of statin intolerance are probably not directly related to the pharmacodynamic actions of the drugs,” Dr. Maki said.

One recent study on the nocebo effect, the SAMSON study, suggested that 90% of symptoms attributed to statins were elicited by placebo tablets too.

But Dr. Maki added that it can be a losing battle for the clinician if patients think their symptoms are related to taking a statin.

“We suggest that clinicians inform patients that most people can tolerate a statin – maybe with a different agent or an alternative dose – and it is really important to lower LDL cholesterol as that will lower the risk of MI and stroke, so we need to find a regimen that works for each individual,” he said. “Most people can find a regimen that works. If this means taking a lower dose of a statin, they can take some additional therapy as well. This is a better situation than stopping taking statins altogether and allowing ASCVD to progress.”

Dr. Maki stressed that statins should still be the first choice as they are effective, taken orally, and inexpensive.

“Other medications do not have all these advantages. For example, PCSK9 inhibitors are very effective but they are expensive and injectable,” he noted. “And while ezetimibe [Zetia] is now generic so inexpensive, it has a more modest effect on LDL-lowering compared to statins, so by itself it is not normally enough for most patients to get to their target LDL, but it is an option for use in combination with a statin.”

He added that the NLA message is to do everything possible to keep patients on a statin, especially patients with preexisting ASCVD.

“We would like these patients to be on high-intensity statins. If they really can’t tolerate this, then they could be on a low-intensity statin plus an additional agent.”

Commenting on the NLA statement, SAMSON study coauthor James Howard, MB BChir, PhD, Imperial College London, said he had reservations about some of the recommendations.

“Whilst I think it is great news that the existence and importance of the nocebo effect is increasingly recognized in international guidelines and statements, I think we need to be very careful about recommending reduced doses and frequencies of statins,” Dr. Howard said.

“Studies such as SAMSON and StatinWISE indicate the vast majority of side effects reported by patients taking statins are not caused by the statin molecule, but instead are caused by either the nocebo effect, or ever-present background symptoms that are wrongly attributed to the statins,” he commented. “Therefore, to recommend that the correct approach in a patient with a history of MI suffering symptoms on 80 mg of atorvastatin is to reduce the dose or try alternate daily dosing. This reinforces the view that these drugs are side-effect prone and need to be carefully titrated.”

Dr. Howard suggested that patients should be educated on the possibility of the nocebo effect or background symptoms and encouraged to retrial statins at the same dose. “If that doesn’t work, then formal recording with a symptom diary might help patients recognize background symptoms,” he added.

Dr. Howard noted that, if symptoms still persist, an “n-of-1” trial could be conducted, in which the patient rotates between multiple periods of taking a statin and a placebo, but he acknowledged that this is expensive and time consuming. 

Also commenting, Steve Nissen, MD, Cleveland Clinic, said he thought the NLA statement was “reasonable and thoughtful.”

“Regardless of whether the symptoms are due to the nocebo effect or not, some patients will just not take a statin no matter how hard you try to convince them to persevere, so we do need alternatives,” Dr. Nissen said.

He noted that current alternatives would include the PCSK9 inhibitors and ezetimibe, but a future candidate could be the oral bempedoic acid (Nexletol), which is currently being evaluated in a large outcomes trial (CLEAR Outcomes).

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

The U.S. National Lipid Association has issued a new scientific statement on the management of patients with statin intolerance, which recommends different strategies to help patients stay on statin medications, and also suggests alternatives that can be used in patients who really cannot tolerate statin drugs.

The statement was published online in the Journal of Clinical Lipidology.  

It notes that, although statins are generally well tolerated, statin intolerance is reported in 5%-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes.

RogerAshford/Thinkstock

The statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a “nocebo” effect, basically the patient expectation of harm resulting in perceived side effects.

To identify a tolerable statin regimen, it recommends that clinicians consider using several different strategies (different statin, dose, and/or dosing frequency), and to classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest-approved daily dosage.

The statement says that nonstatin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy, and in these cases, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored.

In high and very high-risk patients who are statin intolerant, clinicians should consider initiating nonstatin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins, it suggests.

“There is strong evidence that statins reduce risk of cardiovascular events particularly in patients with atherosclerotic cardiovascular disease, but recent research shows that only about half of patients with ASCVD are on a statin,” Kevin C. Maki, PhD, coauthor of the statement and current president of the National Lipid Association, said in an interview.

“There is an urgent problem with underutilization of statins and undertreatment of ASCVD. And we know that perceived side effects associated with statins are a common reason for discontinuation of these drugs and the consequent failure to manage ASCVD adequately,” he said.  

Dr. Maki noted that the NLA’s first message is that, when experiencing symptoms taking statins, a large majority of patients can still tolerate a statin. “They can try a different agent or a different dose. But for those who still can’t tolerate a statin, we then recommend nonstatin therapies and we favor those therapies with evidence from randomized trials.”

He pointed out that many patients who believe they are experiencing side effects from taking statins still experience the same effects on a placebo, a condition known as the nocebo effect.

“Several studies have shown that the nocebo effect is very common and accounts for more than half of perceived statin side effects. It is therefore estimated that many of the complaints of statin intolerance are probably not directly related to the pharmacodynamic actions of the drugs,” Dr. Maki said.

One recent study on the nocebo effect, the SAMSON study, suggested that 90% of symptoms attributed to statins were elicited by placebo tablets too.

But Dr. Maki added that it can be a losing battle for the clinician if patients think their symptoms are related to taking a statin.

“We suggest that clinicians inform patients that most people can tolerate a statin – maybe with a different agent or an alternative dose – and it is really important to lower LDL cholesterol as that will lower the risk of MI and stroke, so we need to find a regimen that works for each individual,” he said. “Most people can find a regimen that works. If this means taking a lower dose of a statin, they can take some additional therapy as well. This is a better situation than stopping taking statins altogether and allowing ASCVD to progress.”

Dr. Maki stressed that statins should still be the first choice as they are effective, taken orally, and inexpensive.

“Other medications do not have all these advantages. For example, PCSK9 inhibitors are very effective but they are expensive and injectable,” he noted. “And while ezetimibe [Zetia] is now generic so inexpensive, it has a more modest effect on LDL-lowering compared to statins, so by itself it is not normally enough for most patients to get to their target LDL, but it is an option for use in combination with a statin.”

He added that the NLA message is to do everything possible to keep patients on a statin, especially patients with preexisting ASCVD.

“We would like these patients to be on high-intensity statins. If they really can’t tolerate this, then they could be on a low-intensity statin plus an additional agent.”

Commenting on the NLA statement, SAMSON study coauthor James Howard, MB BChir, PhD, Imperial College London, said he had reservations about some of the recommendations.

“Whilst I think it is great news that the existence and importance of the nocebo effect is increasingly recognized in international guidelines and statements, I think we need to be very careful about recommending reduced doses and frequencies of statins,” Dr. Howard said.

“Studies such as SAMSON and StatinWISE indicate the vast majority of side effects reported by patients taking statins are not caused by the statin molecule, but instead are caused by either the nocebo effect, or ever-present background symptoms that are wrongly attributed to the statins,” he commented. “Therefore, to recommend that the correct approach in a patient with a history of MI suffering symptoms on 80 mg of atorvastatin is to reduce the dose or try alternate daily dosing. This reinforces the view that these drugs are side-effect prone and need to be carefully titrated.”

Dr. Howard suggested that patients should be educated on the possibility of the nocebo effect or background symptoms and encouraged to retrial statins at the same dose. “If that doesn’t work, then formal recording with a symptom diary might help patients recognize background symptoms,” he added.

Dr. Howard noted that, if symptoms still persist, an “n-of-1” trial could be conducted, in which the patient rotates between multiple periods of taking a statin and a placebo, but he acknowledged that this is expensive and time consuming. 

Also commenting, Steve Nissen, MD, Cleveland Clinic, said he thought the NLA statement was “reasonable and thoughtful.”

“Regardless of whether the symptoms are due to the nocebo effect or not, some patients will just not take a statin no matter how hard you try to convince them to persevere, so we do need alternatives,” Dr. Nissen said.

He noted that current alternatives would include the PCSK9 inhibitors and ezetimibe, but a future candidate could be the oral bempedoic acid (Nexletol), which is currently being evaluated in a large outcomes trial (CLEAR Outcomes).

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

The number of pediatric hepatitis cases has remained steady since 2017, new research from the Centers for Disease Control and Prevention suggests, despite the recent investigation into children with hepatitis of unknown cause. The study also found that there was no indication of elevated rates of adenovirus type 40/41 infection in children.

But Rohit Kohli, MBBS, MS, chief of the Division of Gastroenterology, Hepatology, and Nutrition at the Children’s Hospital Los Angeles, California, says that although the study is “well-designed and robust,” that does not mean that these hepatitis cases of unknown origin are no longer a concern. He was not involved with the CDC research. “As a clinician, I’m still worried,” he said. “Why I feel like this is not conclusive is that there are other data from entities like the United Kingdom Health Security Agency that are incongruent with [these findings],” he said.

The research was published in the CDC’s Morbidity and Mortality Weekly Report.

In November 2021, the Alabama Department of Public Health began an investigation with the CDC after a cluster of children were admitted to a children’s hospital in the state with severe hepatitis, who all tested positive for adenovirus. When the United Kingdom’s Health Security Agency announced an investigation into similar cases in early April 2022, the CDC decided to expand their search nationally.

Now, as of June 15, the agency is investigating 290 cases in 41 states and U.S. territories. Worldwide, 650 cases in 33 countries have been reported, according to the most recent update by the World Health Organization on May 27, 2022. At least 38 patients have needed liver transplants, and nine deaths have been reported to WHO.

In its most recent press call on the topic, the CDC announced that it’s aware of six deaths in the United States through May 20, 2022. The COVID-19 vaccine has been ruled out as a potential cause because the majority of affected children are unvaccinated or are too young to receive the vaccine. Adenovirus infection remains a leading suspect in these sick children because the virus has been detected in 60.8% of tested cases, WHO reports.

Investigators have detected an increase in reported pediatric hepatitis cases, compared with prior years in the United Kingdom, but it was not clear whether that same pattern would be found in the United States. Neither pediatric hepatitis nor adenovirus type 40/41 are reportable conditions in the United States. In the May 20 CDC press call, Umesh Parashar, MD, chief of the CDC’s Viral Gastroenteritis Branch, said that an estimated 1,500-2,000 children aged younger than 10 are hospitalized in the United States for hepatitis every year. “That’s a fairly large number,” he said, and it might make it difficult to detect a small increase in cases.

To better estimate trends in pediatric hepatitis and adenovirus infection in the United States, investigators collected available data on emergency department (ED) visits, hospitalizations, and liver transplants associated with hepatitis in children as well as adenovirus stool testing results. Researchers used four large databases: the National Syndromic Surveillance Program; the Premier Healthcare Database Special Release; the Organ Procurement and Transplant Network; and Labcorp, which is a large commercial lab network.

To account for changes in health care utilization in the first year of the COVID-19 pandemic, the team compared hepatitis-associated ED visits, hospitalizations, and liver transplants from October 2021 to March 2022 versus the same months (January to March and October to December) in 2017, 2018, and 2019. For adenovirus stool testing, results from October 2021 to March 2022 were compared with the same calendar months (October to March) from 2017-2018, 2018-2019, and 2019-2020, to help control for seasonality.

• Weekly ED visits with hepatitis-associated discharge codes
• Hepatitis-associated monthly hospitalizations in children aged 0-4 years (22 vs. 19.5; P = .26)
• Hepatitis-associated monthly hospitalization in children aged 5-11 years (12 vs. 10.5; P = .42)
• Monthly liver transplants (5 vs. 4; P = .19)
• Percentage of stool specimens positive for adenovirus types 40/41, though the number of specimens tested was highest in March 2022

The authors acknowledged that pediatric hepatitis is rare, so it may be difficult tease out small changes in the number of cases. Also, data on hospitalizations and liver transplants have a 2- to 3-month reporting delay, so the case counts for March 2022 “might be underreported,” they wrote. Mr. Kohli noted that because hepatitis and adenovirus are not reportable conditions, the analysis relied on retrospective data from insurance companies and electronic medical records. Retrospective data are inherently limited, compared with prospective analyses, he said, and it’s possible that certain cases could be included in more than one database and thus be double-counted, whereas other cases could be missed entirely.

These findings also conflict with data from the United Kingdom, which in May reported that the average number of hepatitis cases had increased, compared with previous years, he said. More data are needed, he said, and he is involved with a study with the North American Society for Pediatric Gastroenterology and the American Association for the Study of Liver Diseases that is also collecting data to try to understand whether there has been an uptick in pediatric hepatitis cases. The study will collect patient data directly from hospitals as well as include additional pathology data, such as biopsy results.

“We should not be inhibited to look further academically – and public health–wise – while we take into cognizance this very good, robust attempt from the CDC,” he said.

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

The number of pediatric hepatitis cases has remained steady since 2017, new research from the Centers for Disease Control and Prevention suggests, despite the recent investigation into children with hepatitis of unknown cause. The study also found that there was no indication of elevated rates of adenovirus type 40/41 infection in children.

But Rohit Kohli, MBBS, MS, chief of the Division of Gastroenterology, Hepatology, and Nutrition at the Children’s Hospital Los Angeles, California, says that although the study is “well-designed and robust,” that does not mean that these hepatitis cases of unknown origin are no longer a concern. He was not involved with the CDC research. “As a clinician, I’m still worried,” he said. “Why I feel like this is not conclusive is that there are other data from entities like the United Kingdom Health Security Agency that are incongruent with [these findings],” he said.

The research was published in the CDC’s Morbidity and Mortality Weekly Report.

In November 2021, the Alabama Department of Public Health began an investigation with the CDC after a cluster of children were admitted to a children’s hospital in the state with severe hepatitis, who all tested positive for adenovirus. When the United Kingdom’s Health Security Agency announced an investigation into similar cases in early April 2022, the CDC decided to expand their search nationally.

Now, as of June 15, the agency is investigating 290 cases in 41 states and U.S. territories. Worldwide, 650 cases in 33 countries have been reported, according to the most recent update by the World Health Organization on May 27, 2022. At least 38 patients have needed liver transplants, and nine deaths have been reported to WHO.

In its most recent press call on the topic, the CDC announced that it’s aware of six deaths in the United States through May 20, 2022. The COVID-19 vaccine has been ruled out as a potential cause because the majority of affected children are unvaccinated or are too young to receive the vaccine. Adenovirus infection remains a leading suspect in these sick children because the virus has been detected in 60.8% of tested cases, WHO reports.

Investigators have detected an increase in reported pediatric hepatitis cases, compared with prior years in the United Kingdom, but it was not clear whether that same pattern would be found in the United States. Neither pediatric hepatitis nor adenovirus type 40/41 are reportable conditions in the United States. In the May 20 CDC press call, Umesh Parashar, MD, chief of the CDC’s Viral Gastroenteritis Branch, said that an estimated 1,500-2,000 children aged younger than 10 are hospitalized in the United States for hepatitis every year. “That’s a fairly large number,” he said, and it might make it difficult to detect a small increase in cases.

To better estimate trends in pediatric hepatitis and adenovirus infection in the United States, investigators collected available data on emergency department (ED) visits, hospitalizations, and liver transplants associated with hepatitis in children as well as adenovirus stool testing results. Researchers used four large databases: the National Syndromic Surveillance Program; the Premier Healthcare Database Special Release; the Organ Procurement and Transplant Network; and Labcorp, which is a large commercial lab network.

To account for changes in health care utilization in the first year of the COVID-19 pandemic, the team compared hepatitis-associated ED visits, hospitalizations, and liver transplants from October 2021 to March 2022 versus the same months (January to March and October to December) in 2017, 2018, and 2019. For adenovirus stool testing, results from October 2021 to March 2022 were compared with the same calendar months (October to March) from 2017-2018, 2018-2019, and 2019-2020, to help control for seasonality.

• Weekly ED visits with hepatitis-associated discharge codes
• Hepatitis-associated monthly hospitalizations in children aged 0-4 years (22 vs. 19.5; P = .26)
• Hepatitis-associated monthly hospitalization in children aged 5-11 years (12 vs. 10.5; P = .42)
• Monthly liver transplants (5 vs. 4; P = .19)
• Percentage of stool specimens positive for adenovirus types 40/41, though the number of specimens tested was highest in March 2022

The authors acknowledged that pediatric hepatitis is rare, so it may be difficult tease out small changes in the number of cases. Also, data on hospitalizations and liver transplants have a 2- to 3-month reporting delay, so the case counts for March 2022 “might be underreported,” they wrote. Mr. Kohli noted that because hepatitis and adenovirus are not reportable conditions, the analysis relied on retrospective data from insurance companies and electronic medical records. Retrospective data are inherently limited, compared with prospective analyses, he said, and it’s possible that certain cases could be included in more than one database and thus be double-counted, whereas other cases could be missed entirely.

These findings also conflict with data from the United Kingdom, which in May reported that the average number of hepatitis cases had increased, compared with previous years, he said. More data are needed, he said, and he is involved with a study with the North American Society for Pediatric Gastroenterology and the American Association for the Study of Liver Diseases that is also collecting data to try to understand whether there has been an uptick in pediatric hepatitis cases. The study will collect patient data directly from hospitals as well as include additional pathology data, such as biopsy results.

“We should not be inhibited to look further academically – and public health–wise – while we take into cognizance this very good, robust attempt from the CDC,” he said.

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

The number of pediatric hepatitis cases has remained steady since 2017, new research from the Centers for Disease Control and Prevention suggests, despite the recent investigation into children with hepatitis of unknown cause. The study also found that there was no indication of elevated rates of adenovirus type 40/41 infection in children.

But Rohit Kohli, MBBS, MS, chief of the Division of Gastroenterology, Hepatology, and Nutrition at the Children’s Hospital Los Angeles, California, says that although the study is “well-designed and robust,” that does not mean that these hepatitis cases of unknown origin are no longer a concern. He was not involved with the CDC research. “As a clinician, I’m still worried,” he said. “Why I feel like this is not conclusive is that there are other data from entities like the United Kingdom Health Security Agency that are incongruent with [these findings],” he said.

The research was published in the CDC’s Morbidity and Mortality Weekly Report.

In November 2021, the Alabama Department of Public Health began an investigation with the CDC after a cluster of children were admitted to a children’s hospital in the state with severe hepatitis, who all tested positive for adenovirus. When the United Kingdom’s Health Security Agency announced an investigation into similar cases in early April 2022, the CDC decided to expand their search nationally.

Now, as of June 15, the agency is investigating 290 cases in 41 states and U.S. territories. Worldwide, 650 cases in 33 countries have been reported, according to the most recent update by the World Health Organization on May 27, 2022. At least 38 patients have needed liver transplants, and nine deaths have been reported to WHO.

In its most recent press call on the topic, the CDC announced that it’s aware of six deaths in the United States through May 20, 2022. The COVID-19 vaccine has been ruled out as a potential cause because the majority of affected children are unvaccinated or are too young to receive the vaccine. Adenovirus infection remains a leading suspect in these sick children because the virus has been detected in 60.8% of tested cases, WHO reports.

Investigators have detected an increase in reported pediatric hepatitis cases, compared with prior years in the United Kingdom, but it was not clear whether that same pattern would be found in the United States. Neither pediatric hepatitis nor adenovirus type 40/41 are reportable conditions in the United States. In the May 20 CDC press call, Umesh Parashar, MD, chief of the CDC’s Viral Gastroenteritis Branch, said that an estimated 1,500-2,000 children aged younger than 10 are hospitalized in the United States for hepatitis every year. “That’s a fairly large number,” he said, and it might make it difficult to detect a small increase in cases.

To better estimate trends in pediatric hepatitis and adenovirus infection in the United States, investigators collected available data on emergency department (ED) visits, hospitalizations, and liver transplants associated with hepatitis in children as well as adenovirus stool testing results. Researchers used four large databases: the National Syndromic Surveillance Program; the Premier Healthcare Database Special Release; the Organ Procurement and Transplant Network; and Labcorp, which is a large commercial lab network.

To account for changes in health care utilization in the first year of the COVID-19 pandemic, the team compared hepatitis-associated ED visits, hospitalizations, and liver transplants from October 2021 to March 2022 versus the same months (January to March and October to December) in 2017, 2018, and 2019. For adenovirus stool testing, results from October 2021 to March 2022 were compared with the same calendar months (October to March) from 2017-2018, 2018-2019, and 2019-2020, to help control for seasonality.

• Weekly ED visits with hepatitis-associated discharge codes
• Hepatitis-associated monthly hospitalizations in children aged 0-4 years (22 vs. 19.5; P = .26)
• Hepatitis-associated monthly hospitalization in children aged 5-11 years (12 vs. 10.5; P = .42)
• Monthly liver transplants (5 vs. 4; P = .19)
• Percentage of stool specimens positive for adenovirus types 40/41, though the number of specimens tested was highest in March 2022

The authors acknowledged that pediatric hepatitis is rare, so it may be difficult tease out small changes in the number of cases. Also, data on hospitalizations and liver transplants have a 2- to 3-month reporting delay, so the case counts for March 2022 “might be underreported,” they wrote. Mr. Kohli noted that because hepatitis and adenovirus are not reportable conditions, the analysis relied on retrospective data from insurance companies and electronic medical records. Retrospective data are inherently limited, compared with prospective analyses, he said, and it’s possible that certain cases could be included in more than one database and thus be double-counted, whereas other cases could be missed entirely.

These findings also conflict with data from the United Kingdom, which in May reported that the average number of hepatitis cases had increased, compared with previous years, he said. More data are needed, he said, and he is involved with a study with the North American Society for Pediatric Gastroenterology and the American Association for the Study of Liver Diseases that is also collecting data to try to understand whether there has been an uptick in pediatric hepatitis cases. The study will collect patient data directly from hospitals as well as include additional pathology data, such as biopsy results.

“We should not be inhibited to look further academically – and public health–wise – while we take into cognizance this very good, robust attempt from the CDC,” he said.

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

The World Health Organization has announced that it will rename the monkeypox virus after a group of scientists voiced concerns that the name is “discriminatory and stigmatizing.”

The virus has infected more than 1,600 people in 39 countries so far this year, the WHO said, including 32 countries where the virus isn’t typically detected.

“WHO is working with partners and experts from around the world on changing the name of monkeypox virus, its clades, and the disease it causes,” Tedros Adhanom Ghebreyesus, PhD, the WHO’s director-general, said during a press briefing.

“We will make announcements about the new names as soon as possible,” he said.

Last week, more than 30 international scientists urged the public health community to change the name of the virus. The scientists posted a letter on June 10, which included support from the Africa Centres for Disease Control and Prevention, noting that the name should change with the ongoing transmission among humans this year.

“The prevailing perception in the international media and scientific literature is that MPXV is endemic in people in some African countries. However, it is well established that nearly all MPXV outbreaks in Africa prior to the 2022 outbreak have been the result of spillover from animals and humans and only rarely have there been reports of sustained human-to-human transmissions,” they wrote.

“In the context of the current global outbreak, continued reference to, and nomenclature of this virus being African is not only inaccurate but is also discriminatory and stigmatizing,” they added.

As one example, they noted, news outlets have used images of African patients to depict the pox lesions, although most stories about the current outbreak have focused on the global north. The Foreign Press Association of Africa has urged the global media to stop using images of Black people to highlight the outbreak in Europe.

“Although the origin of the new global MPXV outbreak is still unknown, there is growing evidence that the most likely scenario is that cross-continent, cryptic human transmission has been ongoing for longer than previously thought,” they wrote.

The WHO has listed two known clades of the monkeypox virus in recent updates – “one identified in West Africa and one in the Congo Basin region.” The group of scientists wrote that this approach is “counter to the best practice of avoiding geographic locations in the nomenclature of diseases and disease groups.”

The scientists proposed a new classification that would name three clades in order of detection – 1, 2, and 3 – for the viral genomes detected in Central Africa, Western Africa, and the localized spillover events detected this year in global north countries. More genome sequencing could uncover additional clades, they noted.

Even within the most recent clade, there is already notable diversity among the genomes, the scientists said. Like the new naming convention adopted for the coronavirus pandemic, the nomenclature for human monkeypox could be donated as “A.1, A.2, A.1.1,” they wrote.

The largest current outbreak is in the United Kingdom, where health officials have detected 524 cases, according to the latest update from the U.K. Health Security Agency.

As of June 15, 72 cases have been reported in the United States, including 15 in California and 15 in New York, according to the latest Centers for Disease Control and Prevention data.

Also on June 15, the WHO published interim guidance on the use of smallpox vaccines for monkeypox. The WHO doesn’t recommend mass vaccination against monkeypox and said vaccines should be used on a case-by-case basis.

The WHO will convene an emergency meeting next week to determine whether the spread of the virus should be considered a global public health emergency.

“The global outbreak of monkeypox is clearly unusual and concerning,” Dr. Tedros said June 15. “It’s for that reason that I have decided to convene the emergency committee under the International Health Regulations next week to assess whether this outbreak represents a public health emergency of international concern.”

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

The World Health Organization has announced that it will rename the monkeypox virus after a group of scientists voiced concerns that the name is “discriminatory and stigmatizing.”

The virus has infected more than 1,600 people in 39 countries so far this year, the WHO said, including 32 countries where the virus isn’t typically detected.

“WHO is working with partners and experts from around the world on changing the name of monkeypox virus, its clades, and the disease it causes,” Tedros Adhanom Ghebreyesus, PhD, the WHO’s director-general, said during a press briefing.

“We will make announcements about the new names as soon as possible,” he said.

Last week, more than 30 international scientists urged the public health community to change the name of the virus. The scientists posted a letter on June 10, which included support from the Africa Centres for Disease Control and Prevention, noting that the name should change with the ongoing transmission among humans this year.

“The prevailing perception in the international media and scientific literature is that MPXV is endemic in people in some African countries. However, it is well established that nearly all MPXV outbreaks in Africa prior to the 2022 outbreak have been the result of spillover from animals and humans and only rarely have there been reports of sustained human-to-human transmissions,” they wrote.

“In the context of the current global outbreak, continued reference to, and nomenclature of this virus being African is not only inaccurate but is also discriminatory and stigmatizing,” they added.

As one example, they noted, news outlets have used images of African patients to depict the pox lesions, although most stories about the current outbreak have focused on the global north. The Foreign Press Association of Africa has urged the global media to stop using images of Black people to highlight the outbreak in Europe.

“Although the origin of the new global MPXV outbreak is still unknown, there is growing evidence that the most likely scenario is that cross-continent, cryptic human transmission has been ongoing for longer than previously thought,” they wrote.

The WHO has listed two known clades of the monkeypox virus in recent updates – “one identified in West Africa and one in the Congo Basin region.” The group of scientists wrote that this approach is “counter to the best practice of avoiding geographic locations in the nomenclature of diseases and disease groups.”

The scientists proposed a new classification that would name three clades in order of detection – 1, 2, and 3 – for the viral genomes detected in Central Africa, Western Africa, and the localized spillover events detected this year in global north countries. More genome sequencing could uncover additional clades, they noted.

Even within the most recent clade, there is already notable diversity among the genomes, the scientists said. Like the new naming convention adopted for the coronavirus pandemic, the nomenclature for human monkeypox could be donated as “A.1, A.2, A.1.1,” they wrote.

The largest current outbreak is in the United Kingdom, where health officials have detected 524 cases, according to the latest update from the U.K. Health Security Agency.

As of June 15, 72 cases have been reported in the United States, including 15 in California and 15 in New York, according to the latest Centers for Disease Control and Prevention data.

Also on June 15, the WHO published interim guidance on the use of smallpox vaccines for monkeypox. The WHO doesn’t recommend mass vaccination against monkeypox and said vaccines should be used on a case-by-case basis.

The WHO will convene an emergency meeting next week to determine whether the spread of the virus should be considered a global public health emergency.

“The global outbreak of monkeypox is clearly unusual and concerning,” Dr. Tedros said June 15. “It’s for that reason that I have decided to convene the emergency committee under the International Health Regulations next week to assess whether this outbreak represents a public health emergency of international concern.”

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

The World Health Organization has announced that it will rename the monkeypox virus after a group of scientists voiced concerns that the name is “discriminatory and stigmatizing.”

The virus has infected more than 1,600 people in 39 countries so far this year, the WHO said, including 32 countries where the virus isn’t typically detected.

“WHO is working with partners and experts from around the world on changing the name of monkeypox virus, its clades, and the disease it causes,” Tedros Adhanom Ghebreyesus, PhD, the WHO’s director-general, said during a press briefing.

“We will make announcements about the new names as soon as possible,” he said.

Last week, more than 30 international scientists urged the public health community to change the name of the virus. The scientists posted a letter on June 10, which included support from the Africa Centres for Disease Control and Prevention, noting that the name should change with the ongoing transmission among humans this year.

“The prevailing perception in the international media and scientific literature is that MPXV is endemic in people in some African countries. However, it is well established that nearly all MPXV outbreaks in Africa prior to the 2022 outbreak have been the result of spillover from animals and humans and only rarely have there been reports of sustained human-to-human transmissions,” they wrote.

“In the context of the current global outbreak, continued reference to, and nomenclature of this virus being African is not only inaccurate but is also discriminatory and stigmatizing,” they added.

As one example, they noted, news outlets have used images of African patients to depict the pox lesions, although most stories about the current outbreak have focused on the global north. The Foreign Press Association of Africa has urged the global media to stop using images of Black people to highlight the outbreak in Europe.

“Although the origin of the new global MPXV outbreak is still unknown, there is growing evidence that the most likely scenario is that cross-continent, cryptic human transmission has been ongoing for longer than previously thought,” they wrote.

The WHO has listed two known clades of the monkeypox virus in recent updates – “one identified in West Africa and one in the Congo Basin region.” The group of scientists wrote that this approach is “counter to the best practice of avoiding geographic locations in the nomenclature of diseases and disease groups.”

The scientists proposed a new classification that would name three clades in order of detection – 1, 2, and 3 – for the viral genomes detected in Central Africa, Western Africa, and the localized spillover events detected this year in global north countries. More genome sequencing could uncover additional clades, they noted.

Even within the most recent clade, there is already notable diversity among the genomes, the scientists said. Like the new naming convention adopted for the coronavirus pandemic, the nomenclature for human monkeypox could be donated as “A.1, A.2, A.1.1,” they wrote.

The largest current outbreak is in the United Kingdom, where health officials have detected 524 cases, according to the latest update from the U.K. Health Security Agency.

As of June 15, 72 cases have been reported in the United States, including 15 in California and 15 in New York, according to the latest Centers for Disease Control and Prevention data.

Also on June 15, the WHO published interim guidance on the use of smallpox vaccines for monkeypox. The WHO doesn’t recommend mass vaccination against monkeypox and said vaccines should be used on a case-by-case basis.

The WHO will convene an emergency meeting next week to determine whether the spread of the virus should be considered a global public health emergency.

“The global outbreak of monkeypox is clearly unusual and concerning,” Dr. Tedros said June 15. “It’s for that reason that I have decided to convene the emergency committee under the International Health Regulations next week to assess whether this outbreak represents a public health emergency of international concern.”

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

A small blood sample and 24 hours might be all that’s needed to find out how strong the immune system is against a first or repeat coronavirus infections.

Scientists created a test that indirectly measures T-cell response – an important, long-term component of immunity that can last long after antibody levels fall off – to a challenge by the virus in whole blood.

The test mimics what can be done in a formal laboratory now but avoids some complicated steps and specialized training for lab personnel. This test, researchers said, is faster, can scale up to test many more people, and can be adapted to detect viral mutations as they emerge in the future.

The study explaining how all this works was published online in Nature Biotechnology.

The test, called dqTACT, could help predict the likelihood of “breakthrough” infections in people who are fully vaccinated and could help determine how frequently people who are immunocompromised might need to be revaccinated, the authors noted.

Infection with the coronavirus and other viruses can trigger a one-two punch from the immunity system – a fast antibody response followed by longer-lasting cellular immunity, including T cells, which “remember” the virus. Cellular immunity can trigger a quick response if the same virus ever shows up again.

The new test adds synthetic viral peptides – strings of amino acids that make up proteins – from the coronavirus to a blood sample. If there is no T-cell reaction within 24 hours, the test is negative. If the peptides trigger T cells, the test can measure the strength of the immune response.

The researchers validated the new test against traditional laboratory testing in 91 people, about half of whom never had COVID-19 and another half who were infected and recovered. The results matched well.

They also found the test predicted immune strength up to 8 months following a second dose of COVID-19 vaccine. Furthermore, T-cell response was greater among people who received two doses of a vaccine versus others who received only one immunization.

Studies are ongoing and designed to meet authorization requirements as part of future licensing from the Food and Drug Administration.

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

A small blood sample and 24 hours might be all that’s needed to find out how strong the immune system is against a first or repeat coronavirus infections.

Scientists created a test that indirectly measures T-cell response – an important, long-term component of immunity that can last long after antibody levels fall off – to a challenge by the virus in whole blood.

The test mimics what can be done in a formal laboratory now but avoids some complicated steps and specialized training for lab personnel. This test, researchers said, is faster, can scale up to test many more people, and can be adapted to detect viral mutations as they emerge in the future.

The study explaining how all this works was published online in Nature Biotechnology.

The test, called dqTACT, could help predict the likelihood of “breakthrough” infections in people who are fully vaccinated and could help determine how frequently people who are immunocompromised might need to be revaccinated, the authors noted.

Infection with the coronavirus and other viruses can trigger a one-two punch from the immunity system – a fast antibody response followed by longer-lasting cellular immunity, including T cells, which “remember” the virus. Cellular immunity can trigger a quick response if the same virus ever shows up again.

The new test adds synthetic viral peptides – strings of amino acids that make up proteins – from the coronavirus to a blood sample. If there is no T-cell reaction within 24 hours, the test is negative. If the peptides trigger T cells, the test can measure the strength of the immune response.

The researchers validated the new test against traditional laboratory testing in 91 people, about half of whom never had COVID-19 and another half who were infected and recovered. The results matched well.

They also found the test predicted immune strength up to 8 months following a second dose of COVID-19 vaccine. Furthermore, T-cell response was greater among people who received two doses of a vaccine versus others who received only one immunization.

Studies are ongoing and designed to meet authorization requirements as part of future licensing from the Food and Drug Administration.

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

A small blood sample and 24 hours might be all that’s needed to find out how strong the immune system is against a first or repeat coronavirus infections.

Scientists created a test that indirectly measures T-cell response – an important, long-term component of immunity that can last long after antibody levels fall off – to a challenge by the virus in whole blood.

The test mimics what can be done in a formal laboratory now but avoids some complicated steps and specialized training for lab personnel. This test, researchers said, is faster, can scale up to test many more people, and can be adapted to detect viral mutations as they emerge in the future.

The study explaining how all this works was published online in Nature Biotechnology.

The test, called dqTACT, could help predict the likelihood of “breakthrough” infections in people who are fully vaccinated and could help determine how frequently people who are immunocompromised might need to be revaccinated, the authors noted.

Infection with the coronavirus and other viruses can trigger a one-two punch from the immunity system – a fast antibody response followed by longer-lasting cellular immunity, including T cells, which “remember” the virus. Cellular immunity can trigger a quick response if the same virus ever shows up again.

The new test adds synthetic viral peptides – strings of amino acids that make up proteins – from the coronavirus to a blood sample. If there is no T-cell reaction within 24 hours, the test is negative. If the peptides trigger T cells, the test can measure the strength of the immune response.

The researchers validated the new test against traditional laboratory testing in 91 people, about half of whom never had COVID-19 and another half who were infected and recovered. The results matched well.

They also found the test predicted immune strength up to 8 months following a second dose of COVID-19 vaccine. Furthermore, T-cell response was greater among people who received two doses of a vaccine versus others who received only one immunization.

Studies are ongoing and designed to meet authorization requirements as part of future licensing from the Food and Drug Administration.

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

Heads up, parents: Fisher-Price and the Consumer Product Safety Commission said on June 14 that, between 2009 and 2022, at least 13 infants died after falling asleep in the company’s rockers.

The deaths were linked to the Fisher-Price Infant-to-Toddler Rockers and the Newborn-to-Toddler Rockers, according to a statement from the CPSC and Fisher-Price.

The CPSC and Fisher-Price reminded parents and caregivers that products, namely “rockers, gliders, soothers, and swings,” should not be used for infant sleep and that parents and caregivers “should not leave infants in these products unsupervised, unrestrained, or with bedding material, due to the risk of suffocation.”

In 2019, the CPSC issued a recall for the Fisher-Price Rock ‘n Play Sleeper after more than 30 infant fatalities occurred after its 2009 introduction. And in 2021, a similar recall occurred after four infants, all of whom were under 4 months old, died between April 2019 and February 2020, according to The Associated Press.

The CPSC’s warning on the rockers was delayed because of a 1981 Gag Rule that prevented the agency from issuing a warning when they first became aware of the infant deaths associated with the rockers; the rule blocks the agency from doing so “without first seeking permission from the product’s maker,” CPSC Commissioner Richard Trumka said in the statement.

“When CPSC needs to warn the public about a pattern of death and injury tied to a product, it should be able to quickly issue that warning to prevent further loss of life. ... Here, the Gag Rule delayed our message to the public by 2 months.”

A new safety regulation enacted by the CPSC will take effect to prevent further harm from infant sleep products. Beginning June 23, 2022, all infant sleep products must have a sleep surface angle of 10 degrees or less, according to the agency. The Safe Sleep for Babies Act signed into law in 2021 follows the CPSC’s industry recommendations, according to NPR.

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

Heads up, parents: Fisher-Price and the Consumer Product Safety Commission said on June 14 that, between 2009 and 2022, at least 13 infants died after falling asleep in the company’s rockers.

The deaths were linked to the Fisher-Price Infant-to-Toddler Rockers and the Newborn-to-Toddler Rockers, according to a statement from the CPSC and Fisher-Price.

The CPSC and Fisher-Price reminded parents and caregivers that products, namely “rockers, gliders, soothers, and swings,” should not be used for infant sleep and that parents and caregivers “should not leave infants in these products unsupervised, unrestrained, or with bedding material, due to the risk of suffocation.”

In 2019, the CPSC issued a recall for the Fisher-Price Rock ‘n Play Sleeper after more than 30 infant fatalities occurred after its 2009 introduction. And in 2021, a similar recall occurred after four infants, all of whom were under 4 months old, died between April 2019 and February 2020, according to The Associated Press.

The CPSC’s warning on the rockers was delayed because of a 1981 Gag Rule that prevented the agency from issuing a warning when they first became aware of the infant deaths associated with the rockers; the rule blocks the agency from doing so “without first seeking permission from the product’s maker,” CPSC Commissioner Richard Trumka said in the statement.

“When CPSC needs to warn the public about a pattern of death and injury tied to a product, it should be able to quickly issue that warning to prevent further loss of life. ... Here, the Gag Rule delayed our message to the public by 2 months.”

A new safety regulation enacted by the CPSC will take effect to prevent further harm from infant sleep products. Beginning June 23, 2022, all infant sleep products must have a sleep surface angle of 10 degrees or less, according to the agency. The Safe Sleep for Babies Act signed into law in 2021 follows the CPSC’s industry recommendations, according to NPR.

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

Heads up, parents: Fisher-Price and the Consumer Product Safety Commission said on June 14 that, between 2009 and 2022, at least 13 infants died after falling asleep in the company’s rockers.

The deaths were linked to the Fisher-Price Infant-to-Toddler Rockers and the Newborn-to-Toddler Rockers, according to a statement from the CPSC and Fisher-Price.

The CPSC and Fisher-Price reminded parents and caregivers that products, namely “rockers, gliders, soothers, and swings,” should not be used for infant sleep and that parents and caregivers “should not leave infants in these products unsupervised, unrestrained, or with bedding material, due to the risk of suffocation.”

In 2019, the CPSC issued a recall for the Fisher-Price Rock ‘n Play Sleeper after more than 30 infant fatalities occurred after its 2009 introduction. And in 2021, a similar recall occurred after four infants, all of whom were under 4 months old, died between April 2019 and February 2020, according to The Associated Press.

The CPSC’s warning on the rockers was delayed because of a 1981 Gag Rule that prevented the agency from issuing a warning when they first became aware of the infant deaths associated with the rockers; the rule blocks the agency from doing so “without first seeking permission from the product’s maker,” CPSC Commissioner Richard Trumka said in the statement.

“When CPSC needs to warn the public about a pattern of death and injury tied to a product, it should be able to quickly issue that warning to prevent further loss of life. ... Here, the Gag Rule delayed our message to the public by 2 months.”

A new safety regulation enacted by the CPSC will take effect to prevent further harm from infant sleep products. Beginning June 23, 2022, all infant sleep products must have a sleep surface angle of 10 degrees or less, according to the agency. The Safe Sleep for Babies Act signed into law in 2021 follows the CPSC’s industry recommendations, according to NPR.

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

Glucocorticoids should be bridging therapies in the treatment of juvenile idiopathic arthritis–associated uveitis (JIAU) and idiopathic chronic anterior uveitis (CAU), according to recently released recommendations from the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC).

The recommendations cover literature from December 2014 to June 2020 and represent an update of previously published treatment guidelines from 2018. The MIWGUC work group that formulated the new recommendations consisted of eight pediatric rheumatologists and eight ophthalmologists with expertise in pediatric uveitis.

One major shift from the previous guidelines is the lack of distinction between JIAU and CAU, said lead author Ivan Foeldvari, MD, head of the Hamburg (Germany) Center for Pediatric and Adolescent Rheumatology.

“We are considering these two conditions equivalent regarding the ophthalmological presentation,” Dr. Foeldvari said in an interview.

These guidelines have also expanded possible treatment options for these conditions in light of data from clinical trials that have pointed to new options, Dr. Foeldvari noted.

The guidelines also present new options, compared with the 2019 American College of Rheumatology/Arthritis Foundation JIA-associated uveitis guideline. The data cutoff for that guideline was 2014. “Many key papers were published since 2014,” Dr. Foeldvari said.

Another major change is in the escalation of therapy, he noted.

“We view glucocorticoids as a bridging agent, which is very important to emphasize,” Dr. Foeldvari said. “We do not want oral glucocorticoids used as a monotherapy. If you consider a child who has severe uveitis and you want to give an oral glucocorticoid treatment, then it should be considered only for bridging. We suggest to start a DMARD [disease-modifying antirheumatic drug].”

The specific recommendation is that methotrexate be the first DMARD that clinicians choose after using glucocorticoids as a bridging therapy; adalimumab is recommended as the next treatment choice for patients who do not respond to methotrexate.

The working group also calls for limited use of topical glucocorticoids in the affected eye, he said.

“We recommend no more than two or three drops long term in the eye, because there are studies that show continuous local therapy is the main reason that children may develop blindness,” Dr. Foeldvari said. “With respect to oral corticosteroids, they have a lot of systemic effects. Those effects include a high risk of infection, weight gain, and growth disturbance.”

The new recommendations can guide treatment decisions for rheumatologists and ophthalmologists alike, according to Daniel J. Lovell, MD, MPH, the Joseph E. Levinson Endowed Chair of Pediatric Rheumatology and professor of pediatrics at the University of Cincinnati and Cincinnati Children’s Hospital Medical Center. He was one of the authors of the 2019 ACR/Arthritis Foundation guideline.

“We [rheumatologists] comanage these patients with ophthalmologists,” Dr. Lovell said in an interview. “Ophthalmologists are oftentimes not as experienced in using biologics or methotrexate in terms of monitoring for safety and dosing.”

Dr. Lovell pointed out that the key message from this set of recommendations is to curb the use of topical steroids.

“Topical steroids should be used sparingly and as monotherapy for a very short period of time,” Dr. Lovell said. “Any guidelines agree that if eye inflammation is still present at 3 months, we need to move beyond topical steroid monotherapy.”

These new recommendations from MIWGUC are fairly consistent with the 2019 ACR/Arthritis Foundation guideline, he noted.

“The differences are very minor,” Dr. Lovell said. “In both instances, systemic corticosteroids should be bridging therapy. If you have a patient who needs systemic corticosteroids in addition to topical at the same time, you should be talking about adding other anti-inflammatory treatments, such as traditional and/or biologic DMARDs. Both MIWGUC and the ACR guidelines agree on that.”

The 2019 ACR/Arthritis Foundation guideline did not mention rituximab as an option, nor Janus kinase (JAK) inhibitors, Dr. Lovell said, noting there was no literature on JAK inhibitors as a possible option for JIAU when the guideline was being formulated.

Both sets of guidelines point out that there is a dearth of literature with respect to determining the safe dose of maintenance topical corticosteroids, Dr. Lovell said.

“The ACR 2019 guidelines state you should add systemic therapy if there is persistent eye inflammation despite use of up to two drops per day of topical corticosteroids, while the European [MIWGUC] guideline states you can allow up to three drops,” he said. “In both instances, they are quoting the same two sources. Both guidelines indicate that the literature is very scant as to defining a true, safe dose of topical ocular corticosteroids. They differ by one drop allowed per day. In both instances, in the presence of active uveitis, at 3 months on topical steroid monotherapy, both [guidelines] strongly recommend adding systemic therapy.”

Marinka Twilt, MD, MSCE, PhD, associate professor in the department of pediatrics at the University of Calgary (Alta.), noted in an interview that these latest recommendations from MIWGUC have included consensus views on what to do if certain medications fail to lead to remission, which is not addressed in the 2019 ACR/Arthritis Foundation guideline.

“The new manuscript provides consensus on the use of abatacept, JAK inhibitors, and rituximab if patients are refractory to adalimumab and tocilizumab, which is not discussed in the 2019 recommendations,” Dr. Twilt said.

She also pointed out that these recommendations suggest adalimumab as treatment before infliximab, whereas the 2019 guideline did not recommend using one or the other first.

In compiling the recommendations, the authors received no outside financial support. Dr. Foeldvari is a member of advisory boards for Lilly, Pfizer, Novartis, and Medac. Dr. Lovell and Dr. Twilt disclosed no relevant financial relationships.

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

Glucocorticoids should be bridging therapies in the treatment of juvenile idiopathic arthritis–associated uveitis (JIAU) and idiopathic chronic anterior uveitis (CAU), according to recently released recommendations from the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC).

The recommendations cover literature from December 2014 to June 2020 and represent an update of previously published treatment guidelines from 2018. The MIWGUC work group that formulated the new recommendations consisted of eight pediatric rheumatologists and eight ophthalmologists with expertise in pediatric uveitis.

One major shift from the previous guidelines is the lack of distinction between JIAU and CAU, said lead author Ivan Foeldvari, MD, head of the Hamburg (Germany) Center for Pediatric and Adolescent Rheumatology.

“We are considering these two conditions equivalent regarding the ophthalmological presentation,” Dr. Foeldvari said in an interview.

These guidelines have also expanded possible treatment options for these conditions in light of data from clinical trials that have pointed to new options, Dr. Foeldvari noted.

The guidelines also present new options, compared with the 2019 American College of Rheumatology/Arthritis Foundation JIA-associated uveitis guideline. The data cutoff for that guideline was 2014. “Many key papers were published since 2014,” Dr. Foeldvari said.

Another major change is in the escalation of therapy, he noted.

“We view glucocorticoids as a bridging agent, which is very important to emphasize,” Dr. Foeldvari said. “We do not want oral glucocorticoids used as a monotherapy. If you consider a child who has severe uveitis and you want to give an oral glucocorticoid treatment, then it should be considered only for bridging. We suggest to start a DMARD [disease-modifying antirheumatic drug].”

The specific recommendation is that methotrexate be the first DMARD that clinicians choose after using glucocorticoids as a bridging therapy; adalimumab is recommended as the next treatment choice for patients who do not respond to methotrexate.

The working group also calls for limited use of topical glucocorticoids in the affected eye, he said.

“We recommend no more than two or three drops long term in the eye, because there are studies that show continuous local therapy is the main reason that children may develop blindness,” Dr. Foeldvari said. “With respect to oral corticosteroids, they have a lot of systemic effects. Those effects include a high risk of infection, weight gain, and growth disturbance.”

The new recommendations can guide treatment decisions for rheumatologists and ophthalmologists alike, according to Daniel J. Lovell, MD, MPH, the Joseph E. Levinson Endowed Chair of Pediatric Rheumatology and professor of pediatrics at the University of Cincinnati and Cincinnati Children’s Hospital Medical Center. He was one of the authors of the 2019 ACR/Arthritis Foundation guideline.

“We [rheumatologists] comanage these patients with ophthalmologists,” Dr. Lovell said in an interview. “Ophthalmologists are oftentimes not as experienced in using biologics or methotrexate in terms of monitoring for safety and dosing.”

Dr. Lovell pointed out that the key message from this set of recommendations is to curb the use of topical steroids.

“Topical steroids should be used sparingly and as monotherapy for a very short period of time,” Dr. Lovell said. “Any guidelines agree that if eye inflammation is still present at 3 months, we need to move beyond topical steroid monotherapy.”

These new recommendations from MIWGUC are fairly consistent with the 2019 ACR/Arthritis Foundation guideline, he noted.

“The differences are very minor,” Dr. Lovell said. “In both instances, systemic corticosteroids should be bridging therapy. If you have a patient who needs systemic corticosteroids in addition to topical at the same time, you should be talking about adding other anti-inflammatory treatments, such as traditional and/or biologic DMARDs. Both MIWGUC and the ACR guidelines agree on that.”

The 2019 ACR/Arthritis Foundation guideline did not mention rituximab as an option, nor Janus kinase (JAK) inhibitors, Dr. Lovell said, noting there was no literature on JAK inhibitors as a possible option for JIAU when the guideline was being formulated.

Both sets of guidelines point out that there is a dearth of literature with respect to determining the safe dose of maintenance topical corticosteroids, Dr. Lovell said.

“The ACR 2019 guidelines state you should add systemic therapy if there is persistent eye inflammation despite use of up to two drops per day of topical corticosteroids, while the European [MIWGUC] guideline states you can allow up to three drops,” he said. “In both instances, they are quoting the same two sources. Both guidelines indicate that the literature is very scant as to defining a true, safe dose of topical ocular corticosteroids. They differ by one drop allowed per day. In both instances, in the presence of active uveitis, at 3 months on topical steroid monotherapy, both [guidelines] strongly recommend adding systemic therapy.”

Marinka Twilt, MD, MSCE, PhD, associate professor in the department of pediatrics at the University of Calgary (Alta.), noted in an interview that these latest recommendations from MIWGUC have included consensus views on what to do if certain medications fail to lead to remission, which is not addressed in the 2019 ACR/Arthritis Foundation guideline.

“The new manuscript provides consensus on the use of abatacept, JAK inhibitors, and rituximab if patients are refractory to adalimumab and tocilizumab, which is not discussed in the 2019 recommendations,” Dr. Twilt said.

She also pointed out that these recommendations suggest adalimumab as treatment before infliximab, whereas the 2019 guideline did not recommend using one or the other first.

In compiling the recommendations, the authors received no outside financial support. Dr. Foeldvari is a member of advisory boards for Lilly, Pfizer, Novartis, and Medac. Dr. Lovell and Dr. Twilt disclosed no relevant financial relationships.

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

Glucocorticoids should be bridging therapies in the treatment of juvenile idiopathic arthritis–associated uveitis (JIAU) and idiopathic chronic anterior uveitis (CAU), according to recently released recommendations from the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC).

The recommendations cover literature from December 2014 to June 2020 and represent an update of previously published treatment guidelines from 2018. The MIWGUC work group that formulated the new recommendations consisted of eight pediatric rheumatologists and eight ophthalmologists with expertise in pediatric uveitis.

One major shift from the previous guidelines is the lack of distinction between JIAU and CAU, said lead author Ivan Foeldvari, MD, head of the Hamburg (Germany) Center for Pediatric and Adolescent Rheumatology.

“We are considering these two conditions equivalent regarding the ophthalmological presentation,” Dr. Foeldvari said in an interview.

These guidelines have also expanded possible treatment options for these conditions in light of data from clinical trials that have pointed to new options, Dr. Foeldvari noted.

The guidelines also present new options, compared with the 2019 American College of Rheumatology/Arthritis Foundation JIA-associated uveitis guideline. The data cutoff for that guideline was 2014. “Many key papers were published since 2014,” Dr. Foeldvari said.

Another major change is in the escalation of therapy, he noted.

“We view glucocorticoids as a bridging agent, which is very important to emphasize,” Dr. Foeldvari said. “We do not want oral glucocorticoids used as a monotherapy. If you consider a child who has severe uveitis and you want to give an oral glucocorticoid treatment, then it should be considered only for bridging. We suggest to start a DMARD [disease-modifying antirheumatic drug].”

The specific recommendation is that methotrexate be the first DMARD that clinicians choose after using glucocorticoids as a bridging therapy; adalimumab is recommended as the next treatment choice for patients who do not respond to methotrexate.

The working group also calls for limited use of topical glucocorticoids in the affected eye, he said.

“We recommend no more than two or three drops long term in the eye, because there are studies that show continuous local therapy is the main reason that children may develop blindness,” Dr. Foeldvari said. “With respect to oral corticosteroids, they have a lot of systemic effects. Those effects include a high risk of infection, weight gain, and growth disturbance.”

The new recommendations can guide treatment decisions for rheumatologists and ophthalmologists alike, according to Daniel J. Lovell, MD, MPH, the Joseph E. Levinson Endowed Chair of Pediatric Rheumatology and professor of pediatrics at the University of Cincinnati and Cincinnati Children’s Hospital Medical Center. He was one of the authors of the 2019 ACR/Arthritis Foundation guideline.

“We [rheumatologists] comanage these patients with ophthalmologists,” Dr. Lovell said in an interview. “Ophthalmologists are oftentimes not as experienced in using biologics or methotrexate in terms of monitoring for safety and dosing.”

Dr. Lovell pointed out that the key message from this set of recommendations is to curb the use of topical steroids.

“Topical steroids should be used sparingly and as monotherapy for a very short period of time,” Dr. Lovell said. “Any guidelines agree that if eye inflammation is still present at 3 months, we need to move beyond topical steroid monotherapy.”

These new recommendations from MIWGUC are fairly consistent with the 2019 ACR/Arthritis Foundation guideline, he noted.

“The differences are very minor,” Dr. Lovell said. “In both instances, systemic corticosteroids should be bridging therapy. If you have a patient who needs systemic corticosteroids in addition to topical at the same time, you should be talking about adding other anti-inflammatory treatments, such as traditional and/or biologic DMARDs. Both MIWGUC and the ACR guidelines agree on that.”

The 2019 ACR/Arthritis Foundation guideline did not mention rituximab as an option, nor Janus kinase (JAK) inhibitors, Dr. Lovell said, noting there was no literature on JAK inhibitors as a possible option for JIAU when the guideline was being formulated.

Both sets of guidelines point out that there is a dearth of literature with respect to determining the safe dose of maintenance topical corticosteroids, Dr. Lovell said.

“The ACR 2019 guidelines state you should add systemic therapy if there is persistent eye inflammation despite use of up to two drops per day of topical corticosteroids, while the European [MIWGUC] guideline states you can allow up to three drops,” he said. “In both instances, they are quoting the same two sources. Both guidelines indicate that the literature is very scant as to defining a true, safe dose of topical ocular corticosteroids. They differ by one drop allowed per day. In both instances, in the presence of active uveitis, at 3 months on topical steroid monotherapy, both [guidelines] strongly recommend adding systemic therapy.”

Marinka Twilt, MD, MSCE, PhD, associate professor in the department of pediatrics at the University of Calgary (Alta.), noted in an interview that these latest recommendations from MIWGUC have included consensus views on what to do if certain medications fail to lead to remission, which is not addressed in the 2019 ACR/Arthritis Foundation guideline.

“The new manuscript provides consensus on the use of abatacept, JAK inhibitors, and rituximab if patients are refractory to adalimumab and tocilizumab, which is not discussed in the 2019 recommendations,” Dr. Twilt said.

She also pointed out that these recommendations suggest adalimumab as treatment before infliximab, whereas the 2019 guideline did not recommend using one or the other first.

In compiling the recommendations, the authors received no outside financial support. Dr. Foeldvari is a member of advisory boards for Lilly, Pfizer, Novartis, and Medac. Dr. Lovell and Dr. Twilt disclosed no relevant financial relationships.

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