Federal Practitioner

Normative ranges of testosterone in young men have been identified on the basis of a nationally representative data in a new study, and these data are expected to provide guidance when evaluating younger individuals presenting with signs and symptoms of potential testosterone deficiency, according to the investigators.

It has long been known that the ranges of normal testosterone differ by age, but the authors of this study contend that this is the first large-scale, population-based analysis conducted in the United States of testosterone levels among in men aged 20-44 years.

“These findings will provide valuable information that clinicians can use in the evaluation and management of young men presenting with concerns about testosterone deficiency,” reported a team of investigators led by Alex Zhu, MD, a urology resident at the University of Michigan, Ann Arbor, in the Journal of Urology.

Outside experts, however, disagree, one saying that the conclusions are “far off and irrational.”

A normative range of testosterone is particularly important for the evaluation of hypogonadism because values vary markedly between individuals and within individuals on repeat measurements over a 24-hour period. At least partially because of this variability, many guidelines, including those issued in by the Endocrine Society and the American Urological Association, recommend testosterone assays only in symptomatic individuals in order to reduce risk of detecting low relative levels that are not clinically relevant.
 

NHANES data provide norms

The data for this study were drawn from the National Health and Nutrition Examination Surveys (NHANES), which sample representative United States residents. The analytic cohort included 1,486 men stratified in 5-year age intervals (20-24, 25-29, 30-34, 35-39, and 40-44).

Because of the known diurnal variation in endocrine levels, only morning total testosterone levels were considered, for consistency. Individuals at risk of disturbed testosterone levels, such as those on hormonal therapy or with a history of testicular cancer, were excluded. Unlike previous analyses that have limited measurements to nonobese individuals without major comorbidities, no such restrictions were imposed in this analysis, which included a sample balanced by race.

After dividing the testosterone levels collected in the NHANES data by tertiles, the cutoff for reduced testosterone were defined as the lowest tertile for each of the five age groups studied.

Consistent with previous reports that testosterone levels decline with age, the cutoff for low testosterone declined for each increase in 5-year age interval after the age of 29 years.

Specifically, these cutoffs were, in order of advancing age, 409 ng/dL (middle tertile range, 409-558), 413 ng/dL (range, 413-575), 359 ng/dL (range, 359-498), 352 ng/dL (range, 352-478), and 350 ng/dL (range, 350-473).

As in the AUA guidelines, which define a total testosterone level below 300 ng/dL “as a reasonable cutoff in support of the diagnosis of low testosterone,” these cutoffs were established without correlation with symptoms. In younger men, like older men, testosterone levels must be within a clinical context.

“Per the AUA guidelines, clinician should consider measuring testosterone levels in patients with certain medical conditions or signs or symptoms of testosterone deficiency, such as depression, reduced motivation, infertility, reduced sex drive, and changes in erectile function,” Dr. Zhu said in an interview, adding that it is appropriate to follow the AUA guidelines “regardless of age.”
 

Hormone levels and symptoms not correlated

These recommendations are based on the fact that the correlation between symptomatic hypogonadism and testosterone levels is poor, meaning that other factors should be considered when considering whether symptoms relate to deficiency. However, Dr. Zhu contended that objective evidence of a low level of testosterone is useful in considering the role of hormone deficiency.

“Even if one were to choose a different cutoff, our age-specific normative testosterone ranges still provide young men and their physicians a framework for counseling,” according to Dr. Zhu. Because of the risk of nonspecific symptoms, such as fatigue and diminished physical performance, he called for “a high index of suspicion for testosterone deficiency even when evaluating younger men.”

Considering the diurnal fluctuations, the single measurement employed to calculate normative ranges is a limitation of this study, the authors acknowledged. They cited data suggested that up to 35% of men classified as hypogonadal on the basis of a single testosterone assay will not meet the same criterion even if evaluated in the subsequent 24 hours. It is for this reason that guidelines typically recommend measuring testosterone at least twice or with more than one type of assay.

Up until now, decisions about testosterone deficiency have been with a one-size-fits-all approach, but it has long been known that patient age is a variable in determining average levels of this hormone, Dr. Zhu reported. For this reason, he predicted that these data will have clinical utility.

“We believe that our new cutoffs play an important role in evaluating younger men presenting with symptoms [of testosterone deficiency],” Dr. Zhu said. “However, clinicians should still remember that these symptoms have causes other than low testosterone, so we cannot only focus only on testing testosterone.”

However, given the lack of correlation between symptoms and testosterone levels, this area remains controversial.
 

Value of tertile cutoffs questioned

Two independent experts challenged the methodology and conclusions of this study.

Victor Adlin, MD, an associate professor emeritus at Temple University, Philadelphia, questioned tertile levels as an approach to defining normal.

“The authors propose unusually high cut-points for a definition of low testosterone in young men,” said Dr. Adlin, whose published a comment on age-related low testosterone in response to 2020 guidelines issued by the American College of Physicians. He is concerned that these data could lead to overtreatment.

The authors “imply that [these data] would justify treatment with testosterone in many young men with symptoms such as fatigue, depression, and lack of vigor, whose relation to low testosterone is controversial,” he said in an interview. “Trials in older men have failed to show a clear response of such symptoms to testosterone therapy.”

The first author of the 2018 Endocrine Society guidelines, Shalender Bhasin, MB, BS, director of a research program in aging and metabolism at the Brigham and Women’s Hospital in Boston, was even more skeptical.

“The whole premise of generating cutoffs for a disease or condition based on the middle tertile is just so far off and irrational,” he said. A coauthor of a 2017 study designed to define harmonized testosterone reference ranges by decade of age (that he described as providing “a much larger sample size and a wider age range” than this current study), Dr. Bhasin did not see any value in the NHANES-based analysis.

Rather, he called for an effort “to dispel this ill-conceived idea that could mislead young men to think they need testosterone treatment when they are healthy.”

Dr. Zhu and Dr. Adlin reported no potential conflicts of interest. Dr. Bhasin reported financial relationships with AbbVie, Eli Lilly, Novartis, Regeneron, and Takeda.
 

Normative ranges of testosterone in young men have been identified on the basis of a nationally representative data in a new study, and these data are expected to provide guidance when evaluating younger individuals presenting with signs and symptoms of potential testosterone deficiency, according to the investigators.

It has long been known that the ranges of normal testosterone differ by age, but the authors of this study contend that this is the first large-scale, population-based analysis conducted in the United States of testosterone levels among in men aged 20-44 years.

“These findings will provide valuable information that clinicians can use in the evaluation and management of young men presenting with concerns about testosterone deficiency,” reported a team of investigators led by Alex Zhu, MD, a urology resident at the University of Michigan, Ann Arbor, in the Journal of Urology.

Outside experts, however, disagree, one saying that the conclusions are “far off and irrational.”

A normative range of testosterone is particularly important for the evaluation of hypogonadism because values vary markedly between individuals and within individuals on repeat measurements over a 24-hour period. At least partially because of this variability, many guidelines, including those issued in by the Endocrine Society and the American Urological Association, recommend testosterone assays only in symptomatic individuals in order to reduce risk of detecting low relative levels that are not clinically relevant.
 

NHANES data provide norms

The data for this study were drawn from the National Health and Nutrition Examination Surveys (NHANES), which sample representative United States residents. The analytic cohort included 1,486 men stratified in 5-year age intervals (20-24, 25-29, 30-34, 35-39, and 40-44).

Because of the known diurnal variation in endocrine levels, only morning total testosterone levels were considered, for consistency. Individuals at risk of disturbed testosterone levels, such as those on hormonal therapy or with a history of testicular cancer, were excluded. Unlike previous analyses that have limited measurements to nonobese individuals without major comorbidities, no such restrictions were imposed in this analysis, which included a sample balanced by race.

After dividing the testosterone levels collected in the NHANES data by tertiles, the cutoff for reduced testosterone were defined as the lowest tertile for each of the five age groups studied.

Consistent with previous reports that testosterone levels decline with age, the cutoff for low testosterone declined for each increase in 5-year age interval after the age of 29 years.

Specifically, these cutoffs were, in order of advancing age, 409 ng/dL (middle tertile range, 409-558), 413 ng/dL (range, 413-575), 359 ng/dL (range, 359-498), 352 ng/dL (range, 352-478), and 350 ng/dL (range, 350-473).

As in the AUA guidelines, which define a total testosterone level below 300 ng/dL “as a reasonable cutoff in support of the diagnosis of low testosterone,” these cutoffs were established without correlation with symptoms. In younger men, like older men, testosterone levels must be within a clinical context.

“Per the AUA guidelines, clinician should consider measuring testosterone levels in patients with certain medical conditions or signs or symptoms of testosterone deficiency, such as depression, reduced motivation, infertility, reduced sex drive, and changes in erectile function,” Dr. Zhu said in an interview, adding that it is appropriate to follow the AUA guidelines “regardless of age.”
 

Hormone levels and symptoms not correlated

These recommendations are based on the fact that the correlation between symptomatic hypogonadism and testosterone levels is poor, meaning that other factors should be considered when considering whether symptoms relate to deficiency. However, Dr. Zhu contended that objective evidence of a low level of testosterone is useful in considering the role of hormone deficiency.

“Even if one were to choose a different cutoff, our age-specific normative testosterone ranges still provide young men and their physicians a framework for counseling,” according to Dr. Zhu. Because of the risk of nonspecific symptoms, such as fatigue and diminished physical performance, he called for “a high index of suspicion for testosterone deficiency even when evaluating younger men.”

Considering the diurnal fluctuations, the single measurement employed to calculate normative ranges is a limitation of this study, the authors acknowledged. They cited data suggested that up to 35% of men classified as hypogonadal on the basis of a single testosterone assay will not meet the same criterion even if evaluated in the subsequent 24 hours. It is for this reason that guidelines typically recommend measuring testosterone at least twice or with more than one type of assay.

Up until now, decisions about testosterone deficiency have been with a one-size-fits-all approach, but it has long been known that patient age is a variable in determining average levels of this hormone, Dr. Zhu reported. For this reason, he predicted that these data will have clinical utility.

“We believe that our new cutoffs play an important role in evaluating younger men presenting with symptoms [of testosterone deficiency],” Dr. Zhu said. “However, clinicians should still remember that these symptoms have causes other than low testosterone, so we cannot only focus only on testing testosterone.”

However, given the lack of correlation between symptoms and testosterone levels, this area remains controversial.
 

Value of tertile cutoffs questioned

Two independent experts challenged the methodology and conclusions of this study.

Victor Adlin, MD, an associate professor emeritus at Temple University, Philadelphia, questioned tertile levels as an approach to defining normal.

“The authors propose unusually high cut-points for a definition of low testosterone in young men,” said Dr. Adlin, whose published a comment on age-related low testosterone in response to 2020 guidelines issued by the American College of Physicians. He is concerned that these data could lead to overtreatment.

The authors “imply that [these data] would justify treatment with testosterone in many young men with symptoms such as fatigue, depression, and lack of vigor, whose relation to low testosterone is controversial,” he said in an interview. “Trials in older men have failed to show a clear response of such symptoms to testosterone therapy.”

The first author of the 2018 Endocrine Society guidelines, Shalender Bhasin, MB, BS, director of a research program in aging and metabolism at the Brigham and Women’s Hospital in Boston, was even more skeptical.

“The whole premise of generating cutoffs for a disease or condition based on the middle tertile is just so far off and irrational,” he said. A coauthor of a 2017 study designed to define harmonized testosterone reference ranges by decade of age (that he described as providing “a much larger sample size and a wider age range” than this current study), Dr. Bhasin did not see any value in the NHANES-based analysis.

Rather, he called for an effort “to dispel this ill-conceived idea that could mislead young men to think they need testosterone treatment when they are healthy.”

Dr. Zhu and Dr. Adlin reported no potential conflicts of interest. Dr. Bhasin reported financial relationships with AbbVie, Eli Lilly, Novartis, Regeneron, and Takeda.
 

Normative ranges of testosterone in young men have been identified on the basis of a nationally representative data in a new study, and these data are expected to provide guidance when evaluating younger individuals presenting with signs and symptoms of potential testosterone deficiency, according to the investigators.

It has long been known that the ranges of normal testosterone differ by age, but the authors of this study contend that this is the first large-scale, population-based analysis conducted in the United States of testosterone levels among in men aged 20-44 years.

“These findings will provide valuable information that clinicians can use in the evaluation and management of young men presenting with concerns about testosterone deficiency,” reported a team of investigators led by Alex Zhu, MD, a urology resident at the University of Michigan, Ann Arbor, in the Journal of Urology.

Outside experts, however, disagree, one saying that the conclusions are “far off and irrational.”

A normative range of testosterone is particularly important for the evaluation of hypogonadism because values vary markedly between individuals and within individuals on repeat measurements over a 24-hour period. At least partially because of this variability, many guidelines, including those issued in by the Endocrine Society and the American Urological Association, recommend testosterone assays only in symptomatic individuals in order to reduce risk of detecting low relative levels that are not clinically relevant.
 

NHANES data provide norms

The data for this study were drawn from the National Health and Nutrition Examination Surveys (NHANES), which sample representative United States residents. The analytic cohort included 1,486 men stratified in 5-year age intervals (20-24, 25-29, 30-34, 35-39, and 40-44).

Because of the known diurnal variation in endocrine levels, only morning total testosterone levels were considered, for consistency. Individuals at risk of disturbed testosterone levels, such as those on hormonal therapy or with a history of testicular cancer, were excluded. Unlike previous analyses that have limited measurements to nonobese individuals without major comorbidities, no such restrictions were imposed in this analysis, which included a sample balanced by race.

After dividing the testosterone levels collected in the NHANES data by tertiles, the cutoff for reduced testosterone were defined as the lowest tertile for each of the five age groups studied.

Consistent with previous reports that testosterone levels decline with age, the cutoff for low testosterone declined for each increase in 5-year age interval after the age of 29 years.

Specifically, these cutoffs were, in order of advancing age, 409 ng/dL (middle tertile range, 409-558), 413 ng/dL (range, 413-575), 359 ng/dL (range, 359-498), 352 ng/dL (range, 352-478), and 350 ng/dL (range, 350-473).

As in the AUA guidelines, which define a total testosterone level below 300 ng/dL “as a reasonable cutoff in support of the diagnosis of low testosterone,” these cutoffs were established without correlation with symptoms. In younger men, like older men, testosterone levels must be within a clinical context.

“Per the AUA guidelines, clinician should consider measuring testosterone levels in patients with certain medical conditions or signs or symptoms of testosterone deficiency, such as depression, reduced motivation, infertility, reduced sex drive, and changes in erectile function,” Dr. Zhu said in an interview, adding that it is appropriate to follow the AUA guidelines “regardless of age.”
 

Hormone levels and symptoms not correlated

These recommendations are based on the fact that the correlation between symptomatic hypogonadism and testosterone levels is poor, meaning that other factors should be considered when considering whether symptoms relate to deficiency. However, Dr. Zhu contended that objective evidence of a low level of testosterone is useful in considering the role of hormone deficiency.

“Even if one were to choose a different cutoff, our age-specific normative testosterone ranges still provide young men and their physicians a framework for counseling,” according to Dr. Zhu. Because of the risk of nonspecific symptoms, such as fatigue and diminished physical performance, he called for “a high index of suspicion for testosterone deficiency even when evaluating younger men.”

Considering the diurnal fluctuations, the single measurement employed to calculate normative ranges is a limitation of this study, the authors acknowledged. They cited data suggested that up to 35% of men classified as hypogonadal on the basis of a single testosterone assay will not meet the same criterion even if evaluated in the subsequent 24 hours. It is for this reason that guidelines typically recommend measuring testosterone at least twice or with more than one type of assay.

Up until now, decisions about testosterone deficiency have been with a one-size-fits-all approach, but it has long been known that patient age is a variable in determining average levels of this hormone, Dr. Zhu reported. For this reason, he predicted that these data will have clinical utility.

“We believe that our new cutoffs play an important role in evaluating younger men presenting with symptoms [of testosterone deficiency],” Dr. Zhu said. “However, clinicians should still remember that these symptoms have causes other than low testosterone, so we cannot only focus only on testing testosterone.”

However, given the lack of correlation between symptoms and testosterone levels, this area remains controversial.
 

Value of tertile cutoffs questioned

Two independent experts challenged the methodology and conclusions of this study.

Victor Adlin, MD, an associate professor emeritus at Temple University, Philadelphia, questioned tertile levels as an approach to defining normal.

“The authors propose unusually high cut-points for a definition of low testosterone in young men,” said Dr. Adlin, whose published a comment on age-related low testosterone in response to 2020 guidelines issued by the American College of Physicians. He is concerned that these data could lead to overtreatment.

The authors “imply that [these data] would justify treatment with testosterone in many young men with symptoms such as fatigue, depression, and lack of vigor, whose relation to low testosterone is controversial,” he said in an interview. “Trials in older men have failed to show a clear response of such symptoms to testosterone therapy.”

The first author of the 2018 Endocrine Society guidelines, Shalender Bhasin, MB, BS, director of a research program in aging and metabolism at the Brigham and Women’s Hospital in Boston, was even more skeptical.

“The whole premise of generating cutoffs for a disease or condition based on the middle tertile is just so far off and irrational,” he said. A coauthor of a 2017 study designed to define harmonized testosterone reference ranges by decade of age (that he described as providing “a much larger sample size and a wider age range” than this current study), Dr. Bhasin did not see any value in the NHANES-based analysis.

Rather, he called for an effort “to dispel this ill-conceived idea that could mislead young men to think they need testosterone treatment when they are healthy.”

Dr. Zhu and Dr. Adlin reported no potential conflicts of interest. Dr. Bhasin reported financial relationships with AbbVie, Eli Lilly, Novartis, Regeneron, and Takeda.
 

MONTREAL – In the treatment of thyroid nodules with radiofrequency ablation (RFA), the amount of energy delivered per unit volume of the nodule strongly correlates with the extent of nodule volume reduction after 6 and 12 months, suggesting an important indicator of treatment success.

The findings “provide an objective measure or goal energy input to achieve during the [RFA] procedure rather than relying only on the subjective judgment of sonographic changes, and in turn, produce more reliable outcomes for our patients,” first author Samantha A. Wolfe, MD, said in an interview.

Dr. Wolfe, of the department of otolaryngology – head and neck surgery at Johns Hopkins University, Baltimore, presented the findings at the American Thyroid Association annual meeting.

Commenting on the study, Insoo Suh, MD, an associate professor and associate vice chair of Surgical Innovation at New York University Langone Health, agreed that “an accounting of the total amount of energy delivered can be a useful additional data point for the operator when they are determining whether an ablation is successful.”

He noted, however, that the location of a nodule can be an important factor when deciding upon amounts of RF energy.

“Some target areas are too close for comfort to critical structures, such as the trachea or the recurrent laryngeal nerve, so sound judgment would dictate that the energy be dialed down in those areas, even if the price you pay is a slightly lower volume reduction,” he explained. 
 

Analysis of patients given RFA at Johns Hopkins

RFA utilizes RF energy for the reduction of nodule compression and aesthetic symptoms, avoiding the need for thyroid hormone replacement or surgery.

And while decisions regarding RFA treatment location and duration are commonly guided by the operator’s judgment of sonographic changes, those assessments can potentially result in inconsistent outcomes.

In observing a relationship between higher amounts of RF energy and nodule volume reduction, Dr. Wolfe and associates conducted their prospective study of nodules treated by two experienced endocrine surgeons at Johns Hopkins between June 2019 and May 2022 at 6 and 12 months in relation to the amount of total energy delivered during the treatment.

The analysis included 101 nodules, which had a median initial volume of 12.9 mL.

After 6 months, the median volume reduction ratio was 60%, and at 12 months, the median reduction was 64%.

In terms of the goal of achieving 50% or more volume reduction at 6 months, the median energy delivered was significantly higher for nodules that did reach that goal compared with those that had a volume reduction of less than 50% (2,317 vs. 1,912 J/mL, respectively; P = .01).

The figures were similar at 12 months (2,031 vs. 1254 J/mL; P < .01).

In a logistic regression analysis, the amount of energy delivered strongly increased the odds of obtaining a volume reduction ratio of at least 50% (odds ratio, 2.58; P = .048).

“Every twofold increase in energy delivered increases the odds of achieving a 50% volume ratio reduction by 2.58 times,” Dr. Wolfe explained.

Likewise, the same twofold increase in energy delivered also increased the odds of achieving a greater than 80% volume ratio reduction by 2.55 times (OR, 2.55; P = .038), she added.
 

Information may help to decide who needs multiple ablations

Of note, the effect was stronger with smaller nodules. Those with an initial volume of less than 20 mL had a significantly greater volume ratio reduction than nodules that were 20 mL or larger (61% vs. 48%, respectively; P = .05).

The initial volume of nodules that did, and did not, achieve a 50% volume ratio reduction at 6 months were 10.9 mL versus 19.1 mL, and the initial volumes of those that did, and did not, have at least a 50% reduction at 12 months were 10.5 mL and 41.5 mL.

“At 6 and 12 months, the successfully treated nodules had a significantly smaller immediate initial volume than those that did not,” Dr. Wolfe said.

“This information may aid in identifying patients with large nodules that are less likely to achieve a greater than 50% volume reduction ratio and may require multiple treatments,” she added.

Other factors – including the probe tip size and total energy delivered – did not significantly correlate with volume ratio reduction at 6 or 12 months.

There was also no significant difference in terms of thyroid-stimulating hormone levels among nodules that achieved at least a 50% volume reduction and those that did not.

Nodules that did not have a satisfactory volume reduction at 12 months had a relatively large median total energy value delivered during ablation (103,463 J, compared with 25,969 J among those achieving more than 50% volume ratio reduction), which Dr. Wolfe said likely reflects that those nodules had a large initial volume.

“This speaks to the importance of describing the energy utilized per unit of nodule volume rather than just a gross measurement,” she said during her presentation.

Dr. Wolfe added that in terms of strategies for getting more energy into the nodule, a key approach is time.

“Sometimes you will see sonographic changes very quickly in the nodule, and it could be tempting to consider that area ablated and move on if you only rely on sonographic changes,” she said in an interview. “However, our research shows that, by spending more time, and thus inputting more energy into the nodule, we had better volume reduction.”

Dr. Wolfe and Dr. Suh reported no relevant financial relationships.

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

MONTREAL – In the treatment of thyroid nodules with radiofrequency ablation (RFA), the amount of energy delivered per unit volume of the nodule strongly correlates with the extent of nodule volume reduction after 6 and 12 months, suggesting an important indicator of treatment success.

The findings “provide an objective measure or goal energy input to achieve during the [RFA] procedure rather than relying only on the subjective judgment of sonographic changes, and in turn, produce more reliable outcomes for our patients,” first author Samantha A. Wolfe, MD, said in an interview.

Dr. Wolfe, of the department of otolaryngology – head and neck surgery at Johns Hopkins University, Baltimore, presented the findings at the American Thyroid Association annual meeting.

Commenting on the study, Insoo Suh, MD, an associate professor and associate vice chair of Surgical Innovation at New York University Langone Health, agreed that “an accounting of the total amount of energy delivered can be a useful additional data point for the operator when they are determining whether an ablation is successful.”

He noted, however, that the location of a nodule can be an important factor when deciding upon amounts of RF energy.

“Some target areas are too close for comfort to critical structures, such as the trachea or the recurrent laryngeal nerve, so sound judgment would dictate that the energy be dialed down in those areas, even if the price you pay is a slightly lower volume reduction,” he explained. 
 

Analysis of patients given RFA at Johns Hopkins

RFA utilizes RF energy for the reduction of nodule compression and aesthetic symptoms, avoiding the need for thyroid hormone replacement or surgery.

And while decisions regarding RFA treatment location and duration are commonly guided by the operator’s judgment of sonographic changes, those assessments can potentially result in inconsistent outcomes.

In observing a relationship between higher amounts of RF energy and nodule volume reduction, Dr. Wolfe and associates conducted their prospective study of nodules treated by two experienced endocrine surgeons at Johns Hopkins between June 2019 and May 2022 at 6 and 12 months in relation to the amount of total energy delivered during the treatment.

The analysis included 101 nodules, which had a median initial volume of 12.9 mL.

After 6 months, the median volume reduction ratio was 60%, and at 12 months, the median reduction was 64%.

In terms of the goal of achieving 50% or more volume reduction at 6 months, the median energy delivered was significantly higher for nodules that did reach that goal compared with those that had a volume reduction of less than 50% (2,317 vs. 1,912 J/mL, respectively; P = .01).

The figures were similar at 12 months (2,031 vs. 1254 J/mL; P < .01).

In a logistic regression analysis, the amount of energy delivered strongly increased the odds of obtaining a volume reduction ratio of at least 50% (odds ratio, 2.58; P = .048).

“Every twofold increase in energy delivered increases the odds of achieving a 50% volume ratio reduction by 2.58 times,” Dr. Wolfe explained.

Likewise, the same twofold increase in energy delivered also increased the odds of achieving a greater than 80% volume ratio reduction by 2.55 times (OR, 2.55; P = .038), she added.
 

Information may help to decide who needs multiple ablations

Of note, the effect was stronger with smaller nodules. Those with an initial volume of less than 20 mL had a significantly greater volume ratio reduction than nodules that were 20 mL or larger (61% vs. 48%, respectively; P = .05).

The initial volume of nodules that did, and did not, achieve a 50% volume ratio reduction at 6 months were 10.9 mL versus 19.1 mL, and the initial volumes of those that did, and did not, have at least a 50% reduction at 12 months were 10.5 mL and 41.5 mL.

“At 6 and 12 months, the successfully treated nodules had a significantly smaller immediate initial volume than those that did not,” Dr. Wolfe said.

“This information may aid in identifying patients with large nodules that are less likely to achieve a greater than 50% volume reduction ratio and may require multiple treatments,” she added.

Other factors – including the probe tip size and total energy delivered – did not significantly correlate with volume ratio reduction at 6 or 12 months.

There was also no significant difference in terms of thyroid-stimulating hormone levels among nodules that achieved at least a 50% volume reduction and those that did not.

Nodules that did not have a satisfactory volume reduction at 12 months had a relatively large median total energy value delivered during ablation (103,463 J, compared with 25,969 J among those achieving more than 50% volume ratio reduction), which Dr. Wolfe said likely reflects that those nodules had a large initial volume.

“This speaks to the importance of describing the energy utilized per unit of nodule volume rather than just a gross measurement,” she said during her presentation.

Dr. Wolfe added that in terms of strategies for getting more energy into the nodule, a key approach is time.

“Sometimes you will see sonographic changes very quickly in the nodule, and it could be tempting to consider that area ablated and move on if you only rely on sonographic changes,” she said in an interview. “However, our research shows that, by spending more time, and thus inputting more energy into the nodule, we had better volume reduction.”

Dr. Wolfe and Dr. Suh reported no relevant financial relationships.

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

MONTREAL – In the treatment of thyroid nodules with radiofrequency ablation (RFA), the amount of energy delivered per unit volume of the nodule strongly correlates with the extent of nodule volume reduction after 6 and 12 months, suggesting an important indicator of treatment success.

The findings “provide an objective measure or goal energy input to achieve during the [RFA] procedure rather than relying only on the subjective judgment of sonographic changes, and in turn, produce more reliable outcomes for our patients,” first author Samantha A. Wolfe, MD, said in an interview.

Dr. Wolfe, of the department of otolaryngology – head and neck surgery at Johns Hopkins University, Baltimore, presented the findings at the American Thyroid Association annual meeting.

Commenting on the study, Insoo Suh, MD, an associate professor and associate vice chair of Surgical Innovation at New York University Langone Health, agreed that “an accounting of the total amount of energy delivered can be a useful additional data point for the operator when they are determining whether an ablation is successful.”

He noted, however, that the location of a nodule can be an important factor when deciding upon amounts of RF energy.

“Some target areas are too close for comfort to critical structures, such as the trachea or the recurrent laryngeal nerve, so sound judgment would dictate that the energy be dialed down in those areas, even if the price you pay is a slightly lower volume reduction,” he explained. 
 

Analysis of patients given RFA at Johns Hopkins

RFA utilizes RF energy for the reduction of nodule compression and aesthetic symptoms, avoiding the need for thyroid hormone replacement or surgery.

And while decisions regarding RFA treatment location and duration are commonly guided by the operator’s judgment of sonographic changes, those assessments can potentially result in inconsistent outcomes.

In observing a relationship between higher amounts of RF energy and nodule volume reduction, Dr. Wolfe and associates conducted their prospective study of nodules treated by two experienced endocrine surgeons at Johns Hopkins between June 2019 and May 2022 at 6 and 12 months in relation to the amount of total energy delivered during the treatment.

The analysis included 101 nodules, which had a median initial volume of 12.9 mL.

After 6 months, the median volume reduction ratio was 60%, and at 12 months, the median reduction was 64%.

In terms of the goal of achieving 50% or more volume reduction at 6 months, the median energy delivered was significantly higher for nodules that did reach that goal compared with those that had a volume reduction of less than 50% (2,317 vs. 1,912 J/mL, respectively; P = .01).

The figures were similar at 12 months (2,031 vs. 1254 J/mL; P < .01).

In a logistic regression analysis, the amount of energy delivered strongly increased the odds of obtaining a volume reduction ratio of at least 50% (odds ratio, 2.58; P = .048).

“Every twofold increase in energy delivered increases the odds of achieving a 50% volume ratio reduction by 2.58 times,” Dr. Wolfe explained.

Likewise, the same twofold increase in energy delivered also increased the odds of achieving a greater than 80% volume ratio reduction by 2.55 times (OR, 2.55; P = .038), she added.
 

Information may help to decide who needs multiple ablations

Of note, the effect was stronger with smaller nodules. Those with an initial volume of less than 20 mL had a significantly greater volume ratio reduction than nodules that were 20 mL or larger (61% vs. 48%, respectively; P = .05).

The initial volume of nodules that did, and did not, achieve a 50% volume ratio reduction at 6 months were 10.9 mL versus 19.1 mL, and the initial volumes of those that did, and did not, have at least a 50% reduction at 12 months were 10.5 mL and 41.5 mL.

“At 6 and 12 months, the successfully treated nodules had a significantly smaller immediate initial volume than those that did not,” Dr. Wolfe said.

“This information may aid in identifying patients with large nodules that are less likely to achieve a greater than 50% volume reduction ratio and may require multiple treatments,” she added.

Other factors – including the probe tip size and total energy delivered – did not significantly correlate with volume ratio reduction at 6 or 12 months.

There was also no significant difference in terms of thyroid-stimulating hormone levels among nodules that achieved at least a 50% volume reduction and those that did not.

Nodules that did not have a satisfactory volume reduction at 12 months had a relatively large median total energy value delivered during ablation (103,463 J, compared with 25,969 J among those achieving more than 50% volume ratio reduction), which Dr. Wolfe said likely reflects that those nodules had a large initial volume.

“This speaks to the importance of describing the energy utilized per unit of nodule volume rather than just a gross measurement,” she said during her presentation.

Dr. Wolfe added that in terms of strategies for getting more energy into the nodule, a key approach is time.

“Sometimes you will see sonographic changes very quickly in the nodule, and it could be tempting to consider that area ablated and move on if you only rely on sonographic changes,” she said in an interview. “However, our research shows that, by spending more time, and thus inputting more energy into the nodule, we had better volume reduction.”

Dr. Wolfe and Dr. Suh reported no relevant financial relationships.

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

A single 25-mg dose of synthetic psilocybin in combination with psychotherapy appears to effectively ease symptoms of treatment-resistant depression (TRD) – at least in the short term, new research shows.

In the largest study of psilocybin for TRD to date, results of the phase 2b randomized, double-blind trial show participants in the 25-mg dose group experienced a significant reduction in depressive symptoms for at least 3 weeks vs. patients in the 10-mg or 1-mg group, which served as the control group.

Investigators found that 29% of participants who received the 25-mg dose were in remission 3 weeks after the treatment and 37% had at least a 50% drop in depression scores. However, at the 3-month mark, only 20% of those on the 25-mg dose experienced significant improvement.

The change from baseline to week 3 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score was significantly better with a 25-mg dose than with a 1-mg dose; there was no significant difference between the 10-mg dose and the 1-mg dose, the investigators reported.

The response rate was high for those receiving the 25-mg dose, lead  investigator Guy Goodwin, MD, DPhil, told reporters attending a press briefing.

“It’s important to understand that response rates in these patients are usually somewhere between 10% and 20%, and we are seeing remission rates at three weeks of 30%,” he said.

Dr. Goodwin is chief medical officer of COMPASS Pathways, the company that funded the trial and created COMP360, the synthetic formulation of psilocybin used in the trial, and professor emeritus of psychiatry at the University of Oxford, England.

Based on the results of the trial it was announced that a phase 3 trial will launch in December.

The study was published online in the New England Journal of Medicine.
 

Further research planned

Psilocybin has been under investigation for TRD for some time, including one study that compared it with the antidepressant escitalopram (Lexapro) with promising results.

In the current study the researchers sought to find an acceptable, efficacious dose and the safety of a synthetic formulation of the drug administered in combination with psychological support.

The multicenter study was conducted at 22 sites in 10 countries and included 233 participants with TRD and evaluated the safety and efficacy of one of three doses. The study’s primary endpoint was change from baseline to 3 weeks in MADRS scores in patients with TRD. The scale runs from 0 to 60 with higher scores indicating more severe depression.

Participants were randomly assigned to receive 25 mg of psilocybin (n = 79), 10 mg (n = 75) or 1 mg (n = 79). Those taking medications discontinued them at least 2 weeks before the baseline visit. The mean MADRS score was 32 or 33 in each study group.

There was a 3- to 6-week run-up period to the study in which each participant met with a study therapist about three times to build trust and prepare for the psychedelic experience.

On the day of psilocybin administration, each participant listened to a tailored music playlist and wore eye shades while reclining in a comfortable chair to direct attention inwardly.

The psychotherapy sessions lasted 6-8 hours, and two therapists were always present. The following day, participants returned for an “integration” session with the therapists that was designed to help the participants explore insights from their session.

MADRS scores were measured at baseline, the day following psilocybin administration, and at weeks 1, 3, 6, 9, and 12.

Participants were asked to stay off standard antidepressant treatment during the first 3 weeks of the trial but could be restarted at any time if deemed necessary by a trial investigator.

Mean changes from baseline to week 3 in MADRS scores were −12.0 for 25-mg, −7.9 for 10-mg, and −5.4 for 1-mg groups. The difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P < .001 and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P = .18).

The investigators reported that in the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results.

Up to 84% of those who received the 25-mg dosage reported adverse events, with the occurrence dropping slightly with each dosage group. The most frequent adverse events included headache, nausea, dizziness, and fatigue, and occurred only on administration day.

Among those who received the 25-mg dose of psilocybin, two participants reported suicidal thoughts during the 3 weeks following treatment, and 3 months post treatment, three patients exhibited suicidal behavior.

Dr. Goodwin noted that these participants had a prior history of suicidal behavior. Two participants in the 10-mg group also had suicidal thoughts. However, the investigators also noted that suicidal ideation, behavior, or self-injury occurred in all dose groups.

The researchers noted that longer and larger trials, including comparisons with existing depression treatments, are needed to determine the safety and efficacy of psilocybin for TRD.
 

Intriguing, sobering

In an accompanying editorial, Bertha Madras, PhD, McLean Hospital, Belmont, Mass., and Harvard Medical School, Boston, noted “the findings are both intriguing and sobering. The highest dose (25 mg), but not the intermediate dose (10 mg), resulted in significantly lower levels of depressive symptoms after 3 weeks than the lowest dose (1 mg, which served as a control), but the 37% incidence of response with the 25-mg dose was numerically lower than that in large trials of conventional antidepressants and less robust than in a trial showing similar efficacies of psilocybin and a selective serotonin reuptake inhibitor.”

Also sobering, she noted, were the high percentages of adverse events in the 25-mg group and suicidal ideation and behavior. Dr. Madras also wondered if “legalization and commercialization [of psychedelics] are allied with the medical movement, psychedelic shops and ‘clinics’ could proliferate even for vulnerable populations, and rigorously designed medical protocols will be compromised.

“Nevertheless,” she concluded, “it is provocative that these agents show some short-term benefit for depression in selected populations.”

Dr. Goodwin is CMO of Compass Pathways, which funded the study. He and several coauthors disclosed relationships with industry. Dr. Madras reports no relevant financial relationships.

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

A single 25-mg dose of synthetic psilocybin in combination with psychotherapy appears to effectively ease symptoms of treatment-resistant depression (TRD) – at least in the short term, new research shows.

In the largest study of psilocybin for TRD to date, results of the phase 2b randomized, double-blind trial show participants in the 25-mg dose group experienced a significant reduction in depressive symptoms for at least 3 weeks vs. patients in the 10-mg or 1-mg group, which served as the control group.

Investigators found that 29% of participants who received the 25-mg dose were in remission 3 weeks after the treatment and 37% had at least a 50% drop in depression scores. However, at the 3-month mark, only 20% of those on the 25-mg dose experienced significant improvement.

The change from baseline to week 3 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score was significantly better with a 25-mg dose than with a 1-mg dose; there was no significant difference between the 10-mg dose and the 1-mg dose, the investigators reported.

The response rate was high for those receiving the 25-mg dose, lead  investigator Guy Goodwin, MD, DPhil, told reporters attending a press briefing.

“It’s important to understand that response rates in these patients are usually somewhere between 10% and 20%, and we are seeing remission rates at three weeks of 30%,” he said.

Dr. Goodwin is chief medical officer of COMPASS Pathways, the company that funded the trial and created COMP360, the synthetic formulation of psilocybin used in the trial, and professor emeritus of psychiatry at the University of Oxford, England.

Based on the results of the trial it was announced that a phase 3 trial will launch in December.

The study was published online in the New England Journal of Medicine.
 

Further research planned

Psilocybin has been under investigation for TRD for some time, including one study that compared it with the antidepressant escitalopram (Lexapro) with promising results.

In the current study the researchers sought to find an acceptable, efficacious dose and the safety of a synthetic formulation of the drug administered in combination with psychological support.

The multicenter study was conducted at 22 sites in 10 countries and included 233 participants with TRD and evaluated the safety and efficacy of one of three doses. The study’s primary endpoint was change from baseline to 3 weeks in MADRS scores in patients with TRD. The scale runs from 0 to 60 with higher scores indicating more severe depression.

Participants were randomly assigned to receive 25 mg of psilocybin (n = 79), 10 mg (n = 75) or 1 mg (n = 79). Those taking medications discontinued them at least 2 weeks before the baseline visit. The mean MADRS score was 32 or 33 in each study group.

There was a 3- to 6-week run-up period to the study in which each participant met with a study therapist about three times to build trust and prepare for the psychedelic experience.

On the day of psilocybin administration, each participant listened to a tailored music playlist and wore eye shades while reclining in a comfortable chair to direct attention inwardly.

The psychotherapy sessions lasted 6-8 hours, and two therapists were always present. The following day, participants returned for an “integration” session with the therapists that was designed to help the participants explore insights from their session.

MADRS scores were measured at baseline, the day following psilocybin administration, and at weeks 1, 3, 6, 9, and 12.

Participants were asked to stay off standard antidepressant treatment during the first 3 weeks of the trial but could be restarted at any time if deemed necessary by a trial investigator.

Mean changes from baseline to week 3 in MADRS scores were −12.0 for 25-mg, −7.9 for 10-mg, and −5.4 for 1-mg groups. The difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P < .001 and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P = .18).

The investigators reported that in the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results.

Up to 84% of those who received the 25-mg dosage reported adverse events, with the occurrence dropping slightly with each dosage group. The most frequent adverse events included headache, nausea, dizziness, and fatigue, and occurred only on administration day.

Among those who received the 25-mg dose of psilocybin, two participants reported suicidal thoughts during the 3 weeks following treatment, and 3 months post treatment, three patients exhibited suicidal behavior.

Dr. Goodwin noted that these participants had a prior history of suicidal behavior. Two participants in the 10-mg group also had suicidal thoughts. However, the investigators also noted that suicidal ideation, behavior, or self-injury occurred in all dose groups.

The researchers noted that longer and larger trials, including comparisons with existing depression treatments, are needed to determine the safety and efficacy of psilocybin for TRD.
 

Intriguing, sobering

In an accompanying editorial, Bertha Madras, PhD, McLean Hospital, Belmont, Mass., and Harvard Medical School, Boston, noted “the findings are both intriguing and sobering. The highest dose (25 mg), but not the intermediate dose (10 mg), resulted in significantly lower levels of depressive symptoms after 3 weeks than the lowest dose (1 mg, which served as a control), but the 37% incidence of response with the 25-mg dose was numerically lower than that in large trials of conventional antidepressants and less robust than in a trial showing similar efficacies of psilocybin and a selective serotonin reuptake inhibitor.”

Also sobering, she noted, were the high percentages of adverse events in the 25-mg group and suicidal ideation and behavior. Dr. Madras also wondered if “legalization and commercialization [of psychedelics] are allied with the medical movement, psychedelic shops and ‘clinics’ could proliferate even for vulnerable populations, and rigorously designed medical protocols will be compromised.

“Nevertheless,” she concluded, “it is provocative that these agents show some short-term benefit for depression in selected populations.”

Dr. Goodwin is CMO of Compass Pathways, which funded the study. He and several coauthors disclosed relationships with industry. Dr. Madras reports no relevant financial relationships.

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

A single 25-mg dose of synthetic psilocybin in combination with psychotherapy appears to effectively ease symptoms of treatment-resistant depression (TRD) – at least in the short term, new research shows.

In the largest study of psilocybin for TRD to date, results of the phase 2b randomized, double-blind trial show participants in the 25-mg dose group experienced a significant reduction in depressive symptoms for at least 3 weeks vs. patients in the 10-mg or 1-mg group, which served as the control group.

Investigators found that 29% of participants who received the 25-mg dose were in remission 3 weeks after the treatment and 37% had at least a 50% drop in depression scores. However, at the 3-month mark, only 20% of those on the 25-mg dose experienced significant improvement.

The change from baseline to week 3 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score was significantly better with a 25-mg dose than with a 1-mg dose; there was no significant difference between the 10-mg dose and the 1-mg dose, the investigators reported.

The response rate was high for those receiving the 25-mg dose, lead  investigator Guy Goodwin, MD, DPhil, told reporters attending a press briefing.

“It’s important to understand that response rates in these patients are usually somewhere between 10% and 20%, and we are seeing remission rates at three weeks of 30%,” he said.

Dr. Goodwin is chief medical officer of COMPASS Pathways, the company that funded the trial and created COMP360, the synthetic formulation of psilocybin used in the trial, and professor emeritus of psychiatry at the University of Oxford, England.

Based on the results of the trial it was announced that a phase 3 trial will launch in December.

The study was published online in the New England Journal of Medicine.
 

Further research planned

Psilocybin has been under investigation for TRD for some time, including one study that compared it with the antidepressant escitalopram (Lexapro) with promising results.

In the current study the researchers sought to find an acceptable, efficacious dose and the safety of a synthetic formulation of the drug administered in combination with psychological support.

The multicenter study was conducted at 22 sites in 10 countries and included 233 participants with TRD and evaluated the safety and efficacy of one of three doses. The study’s primary endpoint was change from baseline to 3 weeks in MADRS scores in patients with TRD. The scale runs from 0 to 60 with higher scores indicating more severe depression.

Participants were randomly assigned to receive 25 mg of psilocybin (n = 79), 10 mg (n = 75) or 1 mg (n = 79). Those taking medications discontinued them at least 2 weeks before the baseline visit. The mean MADRS score was 32 or 33 in each study group.

There was a 3- to 6-week run-up period to the study in which each participant met with a study therapist about three times to build trust and prepare for the psychedelic experience.

On the day of psilocybin administration, each participant listened to a tailored music playlist and wore eye shades while reclining in a comfortable chair to direct attention inwardly.

The psychotherapy sessions lasted 6-8 hours, and two therapists were always present. The following day, participants returned for an “integration” session with the therapists that was designed to help the participants explore insights from their session.

MADRS scores were measured at baseline, the day following psilocybin administration, and at weeks 1, 3, 6, 9, and 12.

Participants were asked to stay off standard antidepressant treatment during the first 3 weeks of the trial but could be restarted at any time if deemed necessary by a trial investigator.

Mean changes from baseline to week 3 in MADRS scores were −12.0 for 25-mg, −7.9 for 10-mg, and −5.4 for 1-mg groups. The difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P < .001 and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P = .18).

The investigators reported that in the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results.

Up to 84% of those who received the 25-mg dosage reported adverse events, with the occurrence dropping slightly with each dosage group. The most frequent adverse events included headache, nausea, dizziness, and fatigue, and occurred only on administration day.

Among those who received the 25-mg dose of psilocybin, two participants reported suicidal thoughts during the 3 weeks following treatment, and 3 months post treatment, three patients exhibited suicidal behavior.

Dr. Goodwin noted that these participants had a prior history of suicidal behavior. Two participants in the 10-mg group also had suicidal thoughts. However, the investigators also noted that suicidal ideation, behavior, or self-injury occurred in all dose groups.

The researchers noted that longer and larger trials, including comparisons with existing depression treatments, are needed to determine the safety and efficacy of psilocybin for TRD.
 

Intriguing, sobering

In an accompanying editorial, Bertha Madras, PhD, McLean Hospital, Belmont, Mass., and Harvard Medical School, Boston, noted “the findings are both intriguing and sobering. The highest dose (25 mg), but not the intermediate dose (10 mg), resulted in significantly lower levels of depressive symptoms after 3 weeks than the lowest dose (1 mg, which served as a control), but the 37% incidence of response with the 25-mg dose was numerically lower than that in large trials of conventional antidepressants and less robust than in a trial showing similar efficacies of psilocybin and a selective serotonin reuptake inhibitor.”

Also sobering, she noted, were the high percentages of adverse events in the 25-mg group and suicidal ideation and behavior. Dr. Madras also wondered if “legalization and commercialization [of psychedelics] are allied with the medical movement, psychedelic shops and ‘clinics’ could proliferate even for vulnerable populations, and rigorously designed medical protocols will be compromised.

“Nevertheless,” she concluded, “it is provocative that these agents show some short-term benefit for depression in selected populations.”

Dr. Goodwin is CMO of Compass Pathways, which funded the study. He and several coauthors disclosed relationships with industry. Dr. Madras reports no relevant financial relationships.

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

You eat a credit card’s worth of plastic in a week. That may bother you. But does it harm you?

The answer depends on who you ask. Awareness of microplastics in general is certainly increasing; the most recent news is the detection of microplastics in human breast milk. Other research has suggested that we may be consuming up to 5 grams of plastic each week from our food, water, and certain consumer products.

The World Health Organization has been releasing reports on microplastics and human health since 2019. Their most recent report was released in late August 2022.

“Although the limited data provide little evidence that nano- and microplastic particles have adverse effects in humans, there is increasing public awareness and an overwhelming consensus among all stakeholders that plastics do not belong in the environment, and measures should be taken to mitigate exposure,” the WHO said at the time.

The WHO can’t go beyond what the data shows, of course. If microplastics are wreaking long-term havoc in our bodies as we speak, science hasn’t connected the dots enough to definitively say “this is the problem.”

But some researchers are willing to speculate – and, at the very least, the risks are becoming impossible to ignore. Dick Vethaak, PhD, a microplastics researcher and emeritus professor of ecotoxicology at Vrije Universiteit, Amsterdam, is blunt, calling them “a plastic time bomb.”
 

The plastic problem

Every piece of plastic that has ever been created is still on our planet today, apart from what has been burned. Past estimates show we only recycle about 9% of all plastic, leaving 9 billion tons in our landfills, oceans, and ecosystems. For context, that amount is 1,500 times heavier than the Great Pyramid of Khufu.

New data is even more dire. A 2022 report from Greenpeace showed a 5% U.S. recycling rate in 2021, with a large portion of what consumers think of as “recycled” still winding up in garbage piles or bodies of water.

And this plastic doesn’t disappear. Instead, it breaks down into smaller and smaller pieces known as microplastics and nanoplastics.

Microplastics have been confirmed in human blood, lung tissue, colons, placentas, stool, and breast milk. But how they impact our health is still unknown.

To assess risk, we must ask: “How hazardous is the material?” said Flemming Cassee, PhD, professor of inhalation toxicology at Utrecht (the Netherlands) University and coauthor of the WHO’s recent microplastics report.

There are three potential hazards of microplastics: their physical presence in our bodies, what they’re made of, and what they carry. To determine the extent of these risks, we need to know how much we’re exposed to, said Dr. Cassee.

The first initiative to research the impact of microplastics on human health came from the European Union in 2018. Although microplastics were around before then, we were unable to detect them, said Dr. Cassee.

That’s the real problem: Since the evidence is so new – and there hasn’t been enough of it – it’s not yet possible to draw definite conclusions.

“But looking into the future, I believe that we are likely facing a public health emergency,” warned Dr. Vethaak.
 

What, exactly, are microplastics?

Microplastics are plastic particles between 5 mm and 100 nm in diameter, or the width of a pencil eraser and something 10 times thinner than a human hair. Anything smaller than that is known as a nanoplastic.

“Microplastics include a wide range of different materials, different sizes, different shapes, different densities, and different colors,” said Evangelos Danopoulos, PhD, a microplastics researcher at Hull York (England) Medical School.

“Primary” microplastics are manufactured to be small and used in things like cosmetics and paints. “Secondary” microplastics result from the breaking down of larger plastic materials, like water bottles and plastic bags.

Secondary microplastics are more diverse than primary microplastics and can take forms ranging from fibers shed from synthetic clothing (like polyester) to pieces of a plastic spoon left in our rivers, lakes, and oceans. Any plastic in the environment will eventually become a secondary microplastic as natural forces such as wind, water currents, and UV radiation break it down into smaller and smaller pieces.

Plastic is a diverse material. Heather Leslie, PhD, senior researcher in Vrije Universiteit’s department of environment and health, likens it to spaghetti with sauce. The noodles are the long polymer backbone that all plastic shares. The sauces are “the pigments, the antioxidants, the flame retardants, etc., that make it functional,” she said.
 

What makes microplastics dangerous?

There are more than 10,000 different chemicals, or “sauces,” used to alter a plastic’s physical characteristics – making it softer, more rigid, or more flexible, said Hanna Dusza, PhD, of the Institute for Risk Assessment Sciences at Utrecht University.

As plastics degrade and become microplastics, these chemicals likely remain. Recent research has shown that microplastics leach these chemicals locally in human tissues, or other areas of accumulation, said Dr. Dusza. Some 2,400 of the 10,000 chemical additives were classified as substances of potential concern, meeting the European Union’s criteria for persistence, bioaccumulation, or toxicity.

Many of these chemicals also act as endocrine-disrupting compounds, or toxicants that imitate hormones when they enter the body. Hormones are active at very low concentrations in your bloodstream, explained Dr. Leslie. To your body, some chemical additives in plastic resemble hormones, so the body responds.

“Sometimes even a low dose of some of these additives can cause unwanted effects,” said Dr. Leslie.

Bisphenol A (BPA), for example, is one of the more infamous endocrine disruptors. It is used as an additive to make plastics more rigid and can be found in any number of plastic products, though areas of concern have been plastic water bottles, baby bottles, and the protective coatings in canned foods.

BPA may mimic estrogen, the female sex hormone essential for reproduction, neurodevelopment, and bone density. In men, estrogen regulates sperm count, sex drive, and erectile function. BPA exposure has been linked with – but not proven to cause – multiple cancer types, ADHD, obesity, and low sperm count. Most everyone has some amount of BPA circulating within their blood, but microplastics may retain BPA as they degrade, potentially increasing our exposure, leading to its unwanted consequences, said Dr. Dusza.

And BPA is just one of those 2,400 substances of “potential concern.”
 

The inflammation problem

A potentially larger health issue emerges from our bodies yet again doing what they are supposed to do when encountering microplastics. Particles can trigger an immune response when they enter your bloodstream, explains Nienke Vrisekoop, PhD, assistant professor at UMC Utrecht.

White blood cells have no issue breaking down things like bacteria, but microplastics cannot be degraded. When a white blood cell engulfs a certain mass of microplastics – either many small particles or a singular large one – it dies, releasing its enzymes and causing local inflammation.

Meanwhile, the plastic particle remains. So more white blood cells attack.

“This triggers continual activation that can result in various adverse effects, including oxidative stress and the release of cytokines that trigger inflammatory reactions, said Dr. Vethaak.

And “chronic inflammation is the prelude to chronic diseases,” said Dr. Leslie. “Every chronic disease, like cancer, heart disease, and even neuropsychiatric diseases like Parkinson’s or major depression, begins with inflammation.”

Meanwhile, inhaling microplastic particles can lead to respiratory diseases and cancer.

“The smallest particles – less than one-tenth of a micrometer – penetrate deep into the lungs and even into the bloodstream, causing damage to the heart, blood vessels and brain,” said Dr. Vetaak. “The only direct evidence comes from workers in the textile and plastic industries that had been exposed to very high amounts of plastic fibrous dust.”
 

Microplastics as carriers

Microplastics can also pick up harmful substances and deliver them into your body.

“When they’re in an environment, they basically can suck up [chemicals] like a sponge,” said Dr. Dusza. “These chemicals are known environmental pollutants, like pesticides, fluorinated compounds, flame retardants, and so on.”

Once in the body, these chemicals can be released, potentially leading to cancer, chronic inflammation, or other unknown effects.

Particles can also act as a vector for microbes, bacteria, and viruses. A September 2022 study found that infectious viruses can survive for 3 days in fresh water by “hitchhiking” on microplastics. Their porous nature provides microbes with a perfect environment in which to live and reproduce, said Dr. Dusza. If you ingest the plastics, you ingest the microbes.
 

How to minimize exposure

There is no way to avoid microplastics. They’re in the air we breathe, the products we use, the water we drink, and the food we eat.

Dr. Danopoulos reviewed 72 studies to quantify our consumption of microplastics in drinking water, salt, and seafood.

“We are exposed to millions of microplastics every year, and I was only looking at three food sources, so there are really a lot more,” he said. “Once plastic waste is mismanaged and it enters the environment, there is very little we can do to extract it.”

That said, we can take steps to lower our exposure and keep the problem from getting worse.

Water filtration is one option, though it is not perfect. Research has shown that municipal water treatment can be effective. An October 2021 study found that two methods – electrocoagulation-electroflotation and membrane filtration – can be 100% effective in removing microplastics from treated water. The problem? Not all municipal water treatment uses these methods – and you would have to investigate to find out if your locality does.

As for at-home filtration methods, they can be effective but can also be dicey. Some consumer brands claim they remove microplastics, but how well depends on not just the type of filter but the size of the particles in the water. Meanwhile, how do you know if a filter is working on your water without testing it, something few people will do? Best not to take a brand’s claims on face-value, but look for independent testing on at-home brands.

A longer-term project: Reduce our risk by reusing and recycling plastic waste. Limiting our consumption of plastic, especially single use plastic, decreases the amount available to become micro- and nanoplastics.

We must all learn to not treat plastic as waste, but rather as a renewable material, said Dr. Cassee. But if that seems like a tall order, it’s because it is.

“You’re a human being and you have a voice and there are a lot of other humans out there with voices,” said Dr. Leslie.

“You sign a petition in your community. You talk about it with your friends at the pub. If you’re a teacher, you discuss it in your class. You call your elected representatives and tell them what you think and how you want them to vote on bills.”

When people start working together, you can really amplify that voice, said Dr. Leslie.
 

What’s the bottom line right now, today?

Numerous sources have declared microplastics do not impact human health. But that’s largely because no direct evidence of this exists yet.

Even the WHO in its report suggests that progress must happen if we’re to fully understand the scope of the problem.

“Strengthening of the evidence necessary for reliable characterization and quantification of the risks to human health posed by [nano- and microplastics] will require active participation by all stakeholders,” it said.

All researchers interviewed for this article agree we don’t have enough evidence to draw any definite conclusions. But “if you look at the wrong endpoints, things will look safe, until you look at the endpoint where it’s really causing the problem,” said Dr. Leslie.

We must research our blind spots and continually ask: Where could we be wrong?

“It is a problem; it’s not going to go away,” said Dr. Danopoulos. “It’s going to get worse, and will continue to get worse, not by something that we are doing now but by something we did 5 years ago.”

Perhaps the question to be asked, then, is the hardest to answer: Are we willing to wait for the science?

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

You eat a credit card’s worth of plastic in a week. That may bother you. But does it harm you?

The answer depends on who you ask. Awareness of microplastics in general is certainly increasing; the most recent news is the detection of microplastics in human breast milk. Other research has suggested that we may be consuming up to 5 grams of plastic each week from our food, water, and certain consumer products.

The World Health Organization has been releasing reports on microplastics and human health since 2019. Their most recent report was released in late August 2022.

“Although the limited data provide little evidence that nano- and microplastic particles have adverse effects in humans, there is increasing public awareness and an overwhelming consensus among all stakeholders that plastics do not belong in the environment, and measures should be taken to mitigate exposure,” the WHO said at the time.

The WHO can’t go beyond what the data shows, of course. If microplastics are wreaking long-term havoc in our bodies as we speak, science hasn’t connected the dots enough to definitively say “this is the problem.”

But some researchers are willing to speculate – and, at the very least, the risks are becoming impossible to ignore. Dick Vethaak, PhD, a microplastics researcher and emeritus professor of ecotoxicology at Vrije Universiteit, Amsterdam, is blunt, calling them “a plastic time bomb.”
 

The plastic problem

Every piece of plastic that has ever been created is still on our planet today, apart from what has been burned. Past estimates show we only recycle about 9% of all plastic, leaving 9 billion tons in our landfills, oceans, and ecosystems. For context, that amount is 1,500 times heavier than the Great Pyramid of Khufu.

New data is even more dire. A 2022 report from Greenpeace showed a 5% U.S. recycling rate in 2021, with a large portion of what consumers think of as “recycled” still winding up in garbage piles or bodies of water.

And this plastic doesn’t disappear. Instead, it breaks down into smaller and smaller pieces known as microplastics and nanoplastics.

Microplastics have been confirmed in human blood, lung tissue, colons, placentas, stool, and breast milk. But how they impact our health is still unknown.

To assess risk, we must ask: “How hazardous is the material?” said Flemming Cassee, PhD, professor of inhalation toxicology at Utrecht (the Netherlands) University and coauthor of the WHO’s recent microplastics report.

There are three potential hazards of microplastics: their physical presence in our bodies, what they’re made of, and what they carry. To determine the extent of these risks, we need to know how much we’re exposed to, said Dr. Cassee.

The first initiative to research the impact of microplastics on human health came from the European Union in 2018. Although microplastics were around before then, we were unable to detect them, said Dr. Cassee.

That’s the real problem: Since the evidence is so new – and there hasn’t been enough of it – it’s not yet possible to draw definite conclusions.

“But looking into the future, I believe that we are likely facing a public health emergency,” warned Dr. Vethaak.
 

What, exactly, are microplastics?

Microplastics are plastic particles between 5 mm and 100 nm in diameter, or the width of a pencil eraser and something 10 times thinner than a human hair. Anything smaller than that is known as a nanoplastic.

“Microplastics include a wide range of different materials, different sizes, different shapes, different densities, and different colors,” said Evangelos Danopoulos, PhD, a microplastics researcher at Hull York (England) Medical School.

“Primary” microplastics are manufactured to be small and used in things like cosmetics and paints. “Secondary” microplastics result from the breaking down of larger plastic materials, like water bottles and plastic bags.

Secondary microplastics are more diverse than primary microplastics and can take forms ranging from fibers shed from synthetic clothing (like polyester) to pieces of a plastic spoon left in our rivers, lakes, and oceans. Any plastic in the environment will eventually become a secondary microplastic as natural forces such as wind, water currents, and UV radiation break it down into smaller and smaller pieces.

Plastic is a diverse material. Heather Leslie, PhD, senior researcher in Vrije Universiteit’s department of environment and health, likens it to spaghetti with sauce. The noodles are the long polymer backbone that all plastic shares. The sauces are “the pigments, the antioxidants, the flame retardants, etc., that make it functional,” she said.
 

What makes microplastics dangerous?

There are more than 10,000 different chemicals, or “sauces,” used to alter a plastic’s physical characteristics – making it softer, more rigid, or more flexible, said Hanna Dusza, PhD, of the Institute for Risk Assessment Sciences at Utrecht University.

As plastics degrade and become microplastics, these chemicals likely remain. Recent research has shown that microplastics leach these chemicals locally in human tissues, or other areas of accumulation, said Dr. Dusza. Some 2,400 of the 10,000 chemical additives were classified as substances of potential concern, meeting the European Union’s criteria for persistence, bioaccumulation, or toxicity.

Many of these chemicals also act as endocrine-disrupting compounds, or toxicants that imitate hormones when they enter the body. Hormones are active at very low concentrations in your bloodstream, explained Dr. Leslie. To your body, some chemical additives in plastic resemble hormones, so the body responds.

“Sometimes even a low dose of some of these additives can cause unwanted effects,” said Dr. Leslie.

Bisphenol A (BPA), for example, is one of the more infamous endocrine disruptors. It is used as an additive to make plastics more rigid and can be found in any number of plastic products, though areas of concern have been plastic water bottles, baby bottles, and the protective coatings in canned foods.

BPA may mimic estrogen, the female sex hormone essential for reproduction, neurodevelopment, and bone density. In men, estrogen regulates sperm count, sex drive, and erectile function. BPA exposure has been linked with – but not proven to cause – multiple cancer types, ADHD, obesity, and low sperm count. Most everyone has some amount of BPA circulating within their blood, but microplastics may retain BPA as they degrade, potentially increasing our exposure, leading to its unwanted consequences, said Dr. Dusza.

And BPA is just one of those 2,400 substances of “potential concern.”
 

The inflammation problem

A potentially larger health issue emerges from our bodies yet again doing what they are supposed to do when encountering microplastics. Particles can trigger an immune response when they enter your bloodstream, explains Nienke Vrisekoop, PhD, assistant professor at UMC Utrecht.

White blood cells have no issue breaking down things like bacteria, but microplastics cannot be degraded. When a white blood cell engulfs a certain mass of microplastics – either many small particles or a singular large one – it dies, releasing its enzymes and causing local inflammation.

Meanwhile, the plastic particle remains. So more white blood cells attack.

“This triggers continual activation that can result in various adverse effects, including oxidative stress and the release of cytokines that trigger inflammatory reactions, said Dr. Vethaak.

And “chronic inflammation is the prelude to chronic diseases,” said Dr. Leslie. “Every chronic disease, like cancer, heart disease, and even neuropsychiatric diseases like Parkinson’s or major depression, begins with inflammation.”

Meanwhile, inhaling microplastic particles can lead to respiratory diseases and cancer.

“The smallest particles – less than one-tenth of a micrometer – penetrate deep into the lungs and even into the bloodstream, causing damage to the heart, blood vessels and brain,” said Dr. Vetaak. “The only direct evidence comes from workers in the textile and plastic industries that had been exposed to very high amounts of plastic fibrous dust.”
 

Microplastics as carriers

Microplastics can also pick up harmful substances and deliver them into your body.

“When they’re in an environment, they basically can suck up [chemicals] like a sponge,” said Dr. Dusza. “These chemicals are known environmental pollutants, like pesticides, fluorinated compounds, flame retardants, and so on.”

Once in the body, these chemicals can be released, potentially leading to cancer, chronic inflammation, or other unknown effects.

Particles can also act as a vector for microbes, bacteria, and viruses. A September 2022 study found that infectious viruses can survive for 3 days in fresh water by “hitchhiking” on microplastics. Their porous nature provides microbes with a perfect environment in which to live and reproduce, said Dr. Dusza. If you ingest the plastics, you ingest the microbes.
 

How to minimize exposure

There is no way to avoid microplastics. They’re in the air we breathe, the products we use, the water we drink, and the food we eat.

Dr. Danopoulos reviewed 72 studies to quantify our consumption of microplastics in drinking water, salt, and seafood.

“We are exposed to millions of microplastics every year, and I was only looking at three food sources, so there are really a lot more,” he said. “Once plastic waste is mismanaged and it enters the environment, there is very little we can do to extract it.”

That said, we can take steps to lower our exposure and keep the problem from getting worse.

Water filtration is one option, though it is not perfect. Research has shown that municipal water treatment can be effective. An October 2021 study found that two methods – electrocoagulation-electroflotation and membrane filtration – can be 100% effective in removing microplastics from treated water. The problem? Not all municipal water treatment uses these methods – and you would have to investigate to find out if your locality does.

As for at-home filtration methods, they can be effective but can also be dicey. Some consumer brands claim they remove microplastics, but how well depends on not just the type of filter but the size of the particles in the water. Meanwhile, how do you know if a filter is working on your water without testing it, something few people will do? Best not to take a brand’s claims on face-value, but look for independent testing on at-home brands.

A longer-term project: Reduce our risk by reusing and recycling plastic waste. Limiting our consumption of plastic, especially single use plastic, decreases the amount available to become micro- and nanoplastics.

We must all learn to not treat plastic as waste, but rather as a renewable material, said Dr. Cassee. But if that seems like a tall order, it’s because it is.

“You’re a human being and you have a voice and there are a lot of other humans out there with voices,” said Dr. Leslie.

“You sign a petition in your community. You talk about it with your friends at the pub. If you’re a teacher, you discuss it in your class. You call your elected representatives and tell them what you think and how you want them to vote on bills.”

When people start working together, you can really amplify that voice, said Dr. Leslie.
 

What’s the bottom line right now, today?

Numerous sources have declared microplastics do not impact human health. But that’s largely because no direct evidence of this exists yet.

Even the WHO in its report suggests that progress must happen if we’re to fully understand the scope of the problem.

“Strengthening of the evidence necessary for reliable characterization and quantification of the risks to human health posed by [nano- and microplastics] will require active participation by all stakeholders,” it said.

All researchers interviewed for this article agree we don’t have enough evidence to draw any definite conclusions. But “if you look at the wrong endpoints, things will look safe, until you look at the endpoint where it’s really causing the problem,” said Dr. Leslie.

We must research our blind spots and continually ask: Where could we be wrong?

“It is a problem; it’s not going to go away,” said Dr. Danopoulos. “It’s going to get worse, and will continue to get worse, not by something that we are doing now but by something we did 5 years ago.”

Perhaps the question to be asked, then, is the hardest to answer: Are we willing to wait for the science?

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

You eat a credit card’s worth of plastic in a week. That may bother you. But does it harm you?

The answer depends on who you ask. Awareness of microplastics in general is certainly increasing; the most recent news is the detection of microplastics in human breast milk. Other research has suggested that we may be consuming up to 5 grams of plastic each week from our food, water, and certain consumer products.

The World Health Organization has been releasing reports on microplastics and human health since 2019. Their most recent report was released in late August 2022.

“Although the limited data provide little evidence that nano- and microplastic particles have adverse effects in humans, there is increasing public awareness and an overwhelming consensus among all stakeholders that plastics do not belong in the environment, and measures should be taken to mitigate exposure,” the WHO said at the time.

The WHO can’t go beyond what the data shows, of course. If microplastics are wreaking long-term havoc in our bodies as we speak, science hasn’t connected the dots enough to definitively say “this is the problem.”

But some researchers are willing to speculate – and, at the very least, the risks are becoming impossible to ignore. Dick Vethaak, PhD, a microplastics researcher and emeritus professor of ecotoxicology at Vrije Universiteit, Amsterdam, is blunt, calling them “a plastic time bomb.”
 

The plastic problem

Every piece of plastic that has ever been created is still on our planet today, apart from what has been burned. Past estimates show we only recycle about 9% of all plastic, leaving 9 billion tons in our landfills, oceans, and ecosystems. For context, that amount is 1,500 times heavier than the Great Pyramid of Khufu.

New data is even more dire. A 2022 report from Greenpeace showed a 5% U.S. recycling rate in 2021, with a large portion of what consumers think of as “recycled” still winding up in garbage piles or bodies of water.

And this plastic doesn’t disappear. Instead, it breaks down into smaller and smaller pieces known as microplastics and nanoplastics.

Microplastics have been confirmed in human blood, lung tissue, colons, placentas, stool, and breast milk. But how they impact our health is still unknown.

To assess risk, we must ask: “How hazardous is the material?” said Flemming Cassee, PhD, professor of inhalation toxicology at Utrecht (the Netherlands) University and coauthor of the WHO’s recent microplastics report.

There are three potential hazards of microplastics: their physical presence in our bodies, what they’re made of, and what they carry. To determine the extent of these risks, we need to know how much we’re exposed to, said Dr. Cassee.

The first initiative to research the impact of microplastics on human health came from the European Union in 2018. Although microplastics were around before then, we were unable to detect them, said Dr. Cassee.

That’s the real problem: Since the evidence is so new – and there hasn’t been enough of it – it’s not yet possible to draw definite conclusions.

“But looking into the future, I believe that we are likely facing a public health emergency,” warned Dr. Vethaak.
 

What, exactly, are microplastics?

Microplastics are plastic particles between 5 mm and 100 nm in diameter, or the width of a pencil eraser and something 10 times thinner than a human hair. Anything smaller than that is known as a nanoplastic.

“Microplastics include a wide range of different materials, different sizes, different shapes, different densities, and different colors,” said Evangelos Danopoulos, PhD, a microplastics researcher at Hull York (England) Medical School.

“Primary” microplastics are manufactured to be small and used in things like cosmetics and paints. “Secondary” microplastics result from the breaking down of larger plastic materials, like water bottles and plastic bags.

Secondary microplastics are more diverse than primary microplastics and can take forms ranging from fibers shed from synthetic clothing (like polyester) to pieces of a plastic spoon left in our rivers, lakes, and oceans. Any plastic in the environment will eventually become a secondary microplastic as natural forces such as wind, water currents, and UV radiation break it down into smaller and smaller pieces.

Plastic is a diverse material. Heather Leslie, PhD, senior researcher in Vrije Universiteit’s department of environment and health, likens it to spaghetti with sauce. The noodles are the long polymer backbone that all plastic shares. The sauces are “the pigments, the antioxidants, the flame retardants, etc., that make it functional,” she said.
 

What makes microplastics dangerous?

There are more than 10,000 different chemicals, or “sauces,” used to alter a plastic’s physical characteristics – making it softer, more rigid, or more flexible, said Hanna Dusza, PhD, of the Institute for Risk Assessment Sciences at Utrecht University.

As plastics degrade and become microplastics, these chemicals likely remain. Recent research has shown that microplastics leach these chemicals locally in human tissues, or other areas of accumulation, said Dr. Dusza. Some 2,400 of the 10,000 chemical additives were classified as substances of potential concern, meeting the European Union’s criteria for persistence, bioaccumulation, or toxicity.

Many of these chemicals also act as endocrine-disrupting compounds, or toxicants that imitate hormones when they enter the body. Hormones are active at very low concentrations in your bloodstream, explained Dr. Leslie. To your body, some chemical additives in plastic resemble hormones, so the body responds.

“Sometimes even a low dose of some of these additives can cause unwanted effects,” said Dr. Leslie.

Bisphenol A (BPA), for example, is one of the more infamous endocrine disruptors. It is used as an additive to make plastics more rigid and can be found in any number of plastic products, though areas of concern have been plastic water bottles, baby bottles, and the protective coatings in canned foods.

BPA may mimic estrogen, the female sex hormone essential for reproduction, neurodevelopment, and bone density. In men, estrogen regulates sperm count, sex drive, and erectile function. BPA exposure has been linked with – but not proven to cause – multiple cancer types, ADHD, obesity, and low sperm count. Most everyone has some amount of BPA circulating within their blood, but microplastics may retain BPA as they degrade, potentially increasing our exposure, leading to its unwanted consequences, said Dr. Dusza.

And BPA is just one of those 2,400 substances of “potential concern.”
 

The inflammation problem

A potentially larger health issue emerges from our bodies yet again doing what they are supposed to do when encountering microplastics. Particles can trigger an immune response when they enter your bloodstream, explains Nienke Vrisekoop, PhD, assistant professor at UMC Utrecht.

White blood cells have no issue breaking down things like bacteria, but microplastics cannot be degraded. When a white blood cell engulfs a certain mass of microplastics – either many small particles or a singular large one – it dies, releasing its enzymes and causing local inflammation.

Meanwhile, the plastic particle remains. So more white blood cells attack.

“This triggers continual activation that can result in various adverse effects, including oxidative stress and the release of cytokines that trigger inflammatory reactions, said Dr. Vethaak.

And “chronic inflammation is the prelude to chronic diseases,” said Dr. Leslie. “Every chronic disease, like cancer, heart disease, and even neuropsychiatric diseases like Parkinson’s or major depression, begins with inflammation.”

Meanwhile, inhaling microplastic particles can lead to respiratory diseases and cancer.

“The smallest particles – less than one-tenth of a micrometer – penetrate deep into the lungs and even into the bloodstream, causing damage to the heart, blood vessels and brain,” said Dr. Vetaak. “The only direct evidence comes from workers in the textile and plastic industries that had been exposed to very high amounts of plastic fibrous dust.”
 

Microplastics as carriers

Microplastics can also pick up harmful substances and deliver them into your body.

“When they’re in an environment, they basically can suck up [chemicals] like a sponge,” said Dr. Dusza. “These chemicals are known environmental pollutants, like pesticides, fluorinated compounds, flame retardants, and so on.”

Once in the body, these chemicals can be released, potentially leading to cancer, chronic inflammation, or other unknown effects.

Particles can also act as a vector for microbes, bacteria, and viruses. A September 2022 study found that infectious viruses can survive for 3 days in fresh water by “hitchhiking” on microplastics. Their porous nature provides microbes with a perfect environment in which to live and reproduce, said Dr. Dusza. If you ingest the plastics, you ingest the microbes.
 

How to minimize exposure

There is no way to avoid microplastics. They’re in the air we breathe, the products we use, the water we drink, and the food we eat.

Dr. Danopoulos reviewed 72 studies to quantify our consumption of microplastics in drinking water, salt, and seafood.

“We are exposed to millions of microplastics every year, and I was only looking at three food sources, so there are really a lot more,” he said. “Once plastic waste is mismanaged and it enters the environment, there is very little we can do to extract it.”

That said, we can take steps to lower our exposure and keep the problem from getting worse.

Water filtration is one option, though it is not perfect. Research has shown that municipal water treatment can be effective. An October 2021 study found that two methods – electrocoagulation-electroflotation and membrane filtration – can be 100% effective in removing microplastics from treated water. The problem? Not all municipal water treatment uses these methods – and you would have to investigate to find out if your locality does.

As for at-home filtration methods, they can be effective but can also be dicey. Some consumer brands claim they remove microplastics, but how well depends on not just the type of filter but the size of the particles in the water. Meanwhile, how do you know if a filter is working on your water without testing it, something few people will do? Best not to take a brand’s claims on face-value, but look for independent testing on at-home brands.

A longer-term project: Reduce our risk by reusing and recycling plastic waste. Limiting our consumption of plastic, especially single use plastic, decreases the amount available to become micro- and nanoplastics.

We must all learn to not treat plastic as waste, but rather as a renewable material, said Dr. Cassee. But if that seems like a tall order, it’s because it is.

“You’re a human being and you have a voice and there are a lot of other humans out there with voices,” said Dr. Leslie.

“You sign a petition in your community. You talk about it with your friends at the pub. If you’re a teacher, you discuss it in your class. You call your elected representatives and tell them what you think and how you want them to vote on bills.”

When people start working together, you can really amplify that voice, said Dr. Leslie.
 

What’s the bottom line right now, today?

Numerous sources have declared microplastics do not impact human health. But that’s largely because no direct evidence of this exists yet.

Even the WHO in its report suggests that progress must happen if we’re to fully understand the scope of the problem.

“Strengthening of the evidence necessary for reliable characterization and quantification of the risks to human health posed by [nano- and microplastics] will require active participation by all stakeholders,” it said.

All researchers interviewed for this article agree we don’t have enough evidence to draw any definite conclusions. But “if you look at the wrong endpoints, things will look safe, until you look at the endpoint where it’s really causing the problem,” said Dr. Leslie.

We must research our blind spots and continually ask: Where could we be wrong?

“It is a problem; it’s not going to go away,” said Dr. Danopoulos. “It’s going to get worse, and will continue to get worse, not by something that we are doing now but by something we did 5 years ago.”

Perhaps the question to be asked, then, is the hardest to answer: Are we willing to wait for the science?

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

Black veterans hospitalized with COVID-19 were less likely to be treated with evidence-based treatments, in a study conducted in 130 US Department of Veterans Affairs (VA) medical centers between March 1, 2020, and February 28, 2022.

The study involved 12,135 Black veterans and 40,717 White veterans. Most patients hospitalized during period 1 (March-September 2020) were Black veterans and the proportion of White patients increased over time. The latter 3 periods, which included the Delta- and Omicron-predominant periods, saw the most admissions.

Controlling for the site of treatment, Black patients were equally likely to be admitted to the intensive care unit (40% vs 43%). However, they were less likely to receive steroids, remdesivir, or immunomodulatory drugs.

The researchers say their data confirm other findings from 41 US health care systems participating in the National Patient-Centered Clinical Research Network (PCORNet), which found lower use of monoclonal antibody treatment for COVID infection for patients who identified as Asian, Black, Hispanic, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, or multiple races.

The researchers did not observe consistent differences in clinical outcomes between Black and White patients. After adjusting for demographics, chronic health conditions, severity of acute illness, and receipt of COVID-19–specific treatments, there was no association of Black race with hospital mortality or 30-day readmission. Black and White patients had a similar burden of preexisting health conditions. Of 38,782 patients discharged, 14% were readmitted within 30 days; the median time to readmission for both groups was 9 days.

Differences in care were partially explained by within- and between-hospital differences, the researchers say. They also cite research that demonstrated a poorer quality of care for hospitals with higher monthly COVID-19 discharges and hospital size.

The study results contradict the assumptions that differences in inpatient treatment by race and ethnicity may be due to differences in clinical indications for medication use based on age and comorbidities, such as chronic kidney or liver disease, the researchers say. For one thing, the VA issued a systemwide COVID-19 response plan that included specific treatment guidelines and distribution plans. But they also point to recent reports that have suggested that occult hypoxemia not detected by pulse oximetry occurs “far more often in Black patients than White patients,” which could result in delayed or missed opportunities to treat patients with COVID-19.

Black veterans hospitalized with COVID-19 were less likely to be treated with evidence-based treatments, in a study conducted in 130 US Department of Veterans Affairs (VA) medical centers between March 1, 2020, and February 28, 2022.

The study involved 12,135 Black veterans and 40,717 White veterans. Most patients hospitalized during period 1 (March-September 2020) were Black veterans and the proportion of White patients increased over time. The latter 3 periods, which included the Delta- and Omicron-predominant periods, saw the most admissions.

Controlling for the site of treatment, Black patients were equally likely to be admitted to the intensive care unit (40% vs 43%). However, they were less likely to receive steroids, remdesivir, or immunomodulatory drugs.

The researchers say their data confirm other findings from 41 US health care systems participating in the National Patient-Centered Clinical Research Network (PCORNet), which found lower use of monoclonal antibody treatment for COVID infection for patients who identified as Asian, Black, Hispanic, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, or multiple races.

The researchers did not observe consistent differences in clinical outcomes between Black and White patients. After adjusting for demographics, chronic health conditions, severity of acute illness, and receipt of COVID-19–specific treatments, there was no association of Black race with hospital mortality or 30-day readmission. Black and White patients had a similar burden of preexisting health conditions. Of 38,782 patients discharged, 14% were readmitted within 30 days; the median time to readmission for both groups was 9 days.

Differences in care were partially explained by within- and between-hospital differences, the researchers say. They also cite research that demonstrated a poorer quality of care for hospitals with higher monthly COVID-19 discharges and hospital size.

The study results contradict the assumptions that differences in inpatient treatment by race and ethnicity may be due to differences in clinical indications for medication use based on age and comorbidities, such as chronic kidney or liver disease, the researchers say. For one thing, the VA issued a systemwide COVID-19 response plan that included specific treatment guidelines and distribution plans. But they also point to recent reports that have suggested that occult hypoxemia not detected by pulse oximetry occurs “far more often in Black patients than White patients,” which could result in delayed or missed opportunities to treat patients with COVID-19.

Black veterans hospitalized with COVID-19 were less likely to be treated with evidence-based treatments, in a study conducted in 130 US Department of Veterans Affairs (VA) medical centers between March 1, 2020, and February 28, 2022.

The study involved 12,135 Black veterans and 40,717 White veterans. Most patients hospitalized during period 1 (March-September 2020) were Black veterans and the proportion of White patients increased over time. The latter 3 periods, which included the Delta- and Omicron-predominant periods, saw the most admissions.

Controlling for the site of treatment, Black patients were equally likely to be admitted to the intensive care unit (40% vs 43%). However, they were less likely to receive steroids, remdesivir, or immunomodulatory drugs.

The researchers say their data confirm other findings from 41 US health care systems participating in the National Patient-Centered Clinical Research Network (PCORNet), which found lower use of monoclonal antibody treatment for COVID infection for patients who identified as Asian, Black, Hispanic, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, or multiple races.

The researchers did not observe consistent differences in clinical outcomes between Black and White patients. After adjusting for demographics, chronic health conditions, severity of acute illness, and receipt of COVID-19–specific treatments, there was no association of Black race with hospital mortality or 30-day readmission. Black and White patients had a similar burden of preexisting health conditions. Of 38,782 patients discharged, 14% were readmitted within 30 days; the median time to readmission for both groups was 9 days.

Differences in care were partially explained by within- and between-hospital differences, the researchers say. They also cite research that demonstrated a poorer quality of care for hospitals with higher monthly COVID-19 discharges and hospital size.

The study results contradict the assumptions that differences in inpatient treatment by race and ethnicity may be due to differences in clinical indications for medication use based on age and comorbidities, such as chronic kidney or liver disease, the researchers say. For one thing, the VA issued a systemwide COVID-19 response plan that included specific treatment guidelines and distribution plans. But they also point to recent reports that have suggested that occult hypoxemia not detected by pulse oximetry occurs “far more often in Black patients than White patients,” which could result in delayed or missed opportunities to treat patients with COVID-19.

A study evaluating a new approach using a combination of two thrombolytics designed to reduce bleeding risk in patients with acute ischemic stroke has not shown any benefit on the primary outcome of all intracranial hemorrhage (ICH).

However, there were some encouraging findings including a trend towards a reduction in symptomatic ICH, researchers report, and the combination approach did not show any depletion of fibrinogen levels, which suggests a potential lower bleeding risk.

“Although the main results of this study are neutral, we are encouraged that the combination approach with a low dose of alteplase followed by the new mutant pro-urokinase product looked as effective as full-dose alteplase alone, and there were some promising signs signaling a potential lower bleeding risk,” senior investigator, Diederik Dippel, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, told this news organization.  

The DUMAS study (Dual Thrombolytic Therapy With Mutant Pro-Urokinase and Low Dose Alteplase for Ischemic Stroke) was presented at the World Stroke Congress in Singapore by study coauthor Nadinda van der Ende, MD, also from Erasmus University Medical Center. 

She pointed out that thrombolysis with intravenous alteplase increases the likelihood of a good outcome in acute ischemic stroke but can cause symptomatic intracranial hemorrhage, which can be associated with death and major disability.

Mutant pro-urokinase is a new thrombolytic agent, in development by Thrombolytic Science, Cambridge, Mass., formed by changing one amino acid in pro-urokinase to make it more stable. It is more fibrin specific than alteplase and therefore believed to have a lower risk of intracranial hemorrhage.

Fibrin is formed as the last step in the clotting process, and the precursor of fibrin in the blood is fibrinogen, Dr. van der Ende noted. Alteplase depletes fibrinogen, contributing to its increased bleeding risk, but mutant pro-urokinase is not believed to affect fibrinogen.

“Mutant pro-urokinase does not bind to intact fibrin. It only binds to fibrin that has already been primed by alteplase,” she explained.

The hypothesis behind the current study is that giving a small dose of alteplase will break down fibrin in the clot enough to expose the binding sites for mutant pro-urokinase, which can then be given to continue to lyse the clot.  

As alteplase has a short half-life, it disappears quickly, and new fibrin is not affected. As mutant pro-urokinase can only lyse fibrin that is primed with alteplase, new hemostatic clots should stay intact. Animal studies have shown less bleeding from distant sites with this approach, Dr. van der Ende said.

The primary analysis of the phase 2 DUMAS study included 238 patients with mild ischemic stroke (median National Institutes of Health Stroke Scale [NIHSS] score 3) who met the standard criteria for IV alteplase.

They were randomized to alteplase alone at the regular dose of 0.9 mg/kg (max 90 mg) with a 10% bolus and the remaining given over 60 minutes; or to a combination of a 5-mg bolus of IV alteplase followed by mutant pro-urokinase at a dose of 40 mg given over 60 minutes.

The primary outcome was the rate of all intracranial hemorrhage (symptomatic and asymptomatic) detected by neuroimaging.  

This occurred in 14% of patients in the full-dose alteplase group vs. 13% of patients in the combined alteplase/mutant pro-urokinase group, a nonsignificant difference: adjusted odds ratio, 0.99 (95% confidence interval, 0.46-2.14).

Secondary outcomes showed no significant differences in NIHSS scores at 24 hours or 5-7 days; functional outcome as measured by a shift analysis of the Modified Rankin Scale (mRS); final infarct volume; or perfusion deficit.

However, blood fibrinogen levels were not depleted and significantly higher in the alteplase/mutant pro-urokinase group than in the full-dose alteplase alone group.

In terms of safety, symptomatic ICH occurred in three patients in the alteplase group (3%) and in none (0%) in the combined alteplase/mutant pro-urokinase group; death occurred in 4% vs. 2% patients respectively; and major extracranial hemorrhage occurred in 1% in both groups.

Dr. Van der Ende concluded that the study showed an overall low rate of ICH; a combination of alteplase and mutant pro-urokinase was not superior to alteplase alone in reducing ICH rates in this population of patients with minor stroke; and mutant pro-urokinase appeared to be safe and, unlike alteplase, did not show any reduction in fibrinogen levels.

“We think the lack of an effect on fibrinogen with this new combination of a small alteplase bolus followed by mutant pro-urokinase infusion is promising,” Dr. Dippel commented. “The fact that there was no symptomatic ICH with the combination treatment is also encouraging. Although the primary endpoint of this trial was neutral, we still believe this is a very interesting approach, with the potential for reduced bleeding, compared with alteplase alone, but we need larger numbers to see an effect on outcomes.”

Dr. Dippel also pointed out that the study included only patients with minor stroke who were not eligible for endovascular therapy, and these patients have a low risk of a poor outcome and a low bleeding risk. 

They are hoping to do another study in patients with more severe stroke, who have a higher bleeding risk and would have more to gain from this combination approach.

Because many patients with severe stroke now have immediate thrombectomy if they present to a comprehensive stroke center, a trial in severe stroke patients would have to be done in primary stroke centers, so if the patents are referred to thrombectomy, the thrombolytic would have a chance to work, Dr. Dippel added.

Commenting on the study for this news organization, Stefan Kiechl, MD, Medical University of Innsbruck (Austria), who is cochair of the World Stroke Congress scientific committee, said, “Alteplase is not fibrin specific, and also causes a degeneration of fibrinogen, which results in ‘fibrinogen depletion coagulopathy.’ It is assumed that 20%-40% of intracerebral bleeding after thrombolysis with alteplase is caused by this problem. DUMAS tests the combination of a substantially reduced alteplase [5 mg] dose plus mutant pro-urokinase to avoid this problem.”

The new thrombolysis protocol, however, did not result in a lower bleeding risk, compared to the comparator alteplase,” he added. “The main limitation of this study is that mainly patients with minor strokes were included. Patients with moderate and severe strokes, who have a substantial risk of bleeding, were not adequately addressed.”

The DUMAS trial was funded by an unrestricted grant from Thrombolytic Science, paid to the institution. Dr. Van der Ende and Dr. Dippel report no relevant disclosures.
 

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

A study evaluating a new approach using a combination of two thrombolytics designed to reduce bleeding risk in patients with acute ischemic stroke has not shown any benefit on the primary outcome of all intracranial hemorrhage (ICH).

However, there were some encouraging findings including a trend towards a reduction in symptomatic ICH, researchers report, and the combination approach did not show any depletion of fibrinogen levels, which suggests a potential lower bleeding risk.

“Although the main results of this study are neutral, we are encouraged that the combination approach with a low dose of alteplase followed by the new mutant pro-urokinase product looked as effective as full-dose alteplase alone, and there were some promising signs signaling a potential lower bleeding risk,” senior investigator, Diederik Dippel, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, told this news organization.  

The DUMAS study (Dual Thrombolytic Therapy With Mutant Pro-Urokinase and Low Dose Alteplase for Ischemic Stroke) was presented at the World Stroke Congress in Singapore by study coauthor Nadinda van der Ende, MD, also from Erasmus University Medical Center. 

She pointed out that thrombolysis with intravenous alteplase increases the likelihood of a good outcome in acute ischemic stroke but can cause symptomatic intracranial hemorrhage, which can be associated with death and major disability.

Mutant pro-urokinase is a new thrombolytic agent, in development by Thrombolytic Science, Cambridge, Mass., formed by changing one amino acid in pro-urokinase to make it more stable. It is more fibrin specific than alteplase and therefore believed to have a lower risk of intracranial hemorrhage.

Fibrin is formed as the last step in the clotting process, and the precursor of fibrin in the blood is fibrinogen, Dr. van der Ende noted. Alteplase depletes fibrinogen, contributing to its increased bleeding risk, but mutant pro-urokinase is not believed to affect fibrinogen.

“Mutant pro-urokinase does not bind to intact fibrin. It only binds to fibrin that has already been primed by alteplase,” she explained.

The hypothesis behind the current study is that giving a small dose of alteplase will break down fibrin in the clot enough to expose the binding sites for mutant pro-urokinase, which can then be given to continue to lyse the clot.  

As alteplase has a short half-life, it disappears quickly, and new fibrin is not affected. As mutant pro-urokinase can only lyse fibrin that is primed with alteplase, new hemostatic clots should stay intact. Animal studies have shown less bleeding from distant sites with this approach, Dr. van der Ende said.

The primary analysis of the phase 2 DUMAS study included 238 patients with mild ischemic stroke (median National Institutes of Health Stroke Scale [NIHSS] score 3) who met the standard criteria for IV alteplase.

They were randomized to alteplase alone at the regular dose of 0.9 mg/kg (max 90 mg) with a 10% bolus and the remaining given over 60 minutes; or to a combination of a 5-mg bolus of IV alteplase followed by mutant pro-urokinase at a dose of 40 mg given over 60 minutes.

The primary outcome was the rate of all intracranial hemorrhage (symptomatic and asymptomatic) detected by neuroimaging.  

This occurred in 14% of patients in the full-dose alteplase group vs. 13% of patients in the combined alteplase/mutant pro-urokinase group, a nonsignificant difference: adjusted odds ratio, 0.99 (95% confidence interval, 0.46-2.14).

Secondary outcomes showed no significant differences in NIHSS scores at 24 hours or 5-7 days; functional outcome as measured by a shift analysis of the Modified Rankin Scale (mRS); final infarct volume; or perfusion deficit.

However, blood fibrinogen levels were not depleted and significantly higher in the alteplase/mutant pro-urokinase group than in the full-dose alteplase alone group.

In terms of safety, symptomatic ICH occurred in three patients in the alteplase group (3%) and in none (0%) in the combined alteplase/mutant pro-urokinase group; death occurred in 4% vs. 2% patients respectively; and major extracranial hemorrhage occurred in 1% in both groups.

Dr. Van der Ende concluded that the study showed an overall low rate of ICH; a combination of alteplase and mutant pro-urokinase was not superior to alteplase alone in reducing ICH rates in this population of patients with minor stroke; and mutant pro-urokinase appeared to be safe and, unlike alteplase, did not show any reduction in fibrinogen levels.

“We think the lack of an effect on fibrinogen with this new combination of a small alteplase bolus followed by mutant pro-urokinase infusion is promising,” Dr. Dippel commented. “The fact that there was no symptomatic ICH with the combination treatment is also encouraging. Although the primary endpoint of this trial was neutral, we still believe this is a very interesting approach, with the potential for reduced bleeding, compared with alteplase alone, but we need larger numbers to see an effect on outcomes.”

Dr. Dippel also pointed out that the study included only patients with minor stroke who were not eligible for endovascular therapy, and these patients have a low risk of a poor outcome and a low bleeding risk. 

They are hoping to do another study in patients with more severe stroke, who have a higher bleeding risk and would have more to gain from this combination approach.

Because many patients with severe stroke now have immediate thrombectomy if they present to a comprehensive stroke center, a trial in severe stroke patients would have to be done in primary stroke centers, so if the patents are referred to thrombectomy, the thrombolytic would have a chance to work, Dr. Dippel added.

Commenting on the study for this news organization, Stefan Kiechl, MD, Medical University of Innsbruck (Austria), who is cochair of the World Stroke Congress scientific committee, said, “Alteplase is not fibrin specific, and also causes a degeneration of fibrinogen, which results in ‘fibrinogen depletion coagulopathy.’ It is assumed that 20%-40% of intracerebral bleeding after thrombolysis with alteplase is caused by this problem. DUMAS tests the combination of a substantially reduced alteplase [5 mg] dose plus mutant pro-urokinase to avoid this problem.”

The new thrombolysis protocol, however, did not result in a lower bleeding risk, compared to the comparator alteplase,” he added. “The main limitation of this study is that mainly patients with minor strokes were included. Patients with moderate and severe strokes, who have a substantial risk of bleeding, were not adequately addressed.”

The DUMAS trial was funded by an unrestricted grant from Thrombolytic Science, paid to the institution. Dr. Van der Ende and Dr. Dippel report no relevant disclosures.
 

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

A study evaluating a new approach using a combination of two thrombolytics designed to reduce bleeding risk in patients with acute ischemic stroke has not shown any benefit on the primary outcome of all intracranial hemorrhage (ICH).

However, there were some encouraging findings including a trend towards a reduction in symptomatic ICH, researchers report, and the combination approach did not show any depletion of fibrinogen levels, which suggests a potential lower bleeding risk.

“Although the main results of this study are neutral, we are encouraged that the combination approach with a low dose of alteplase followed by the new mutant pro-urokinase product looked as effective as full-dose alteplase alone, and there were some promising signs signaling a potential lower bleeding risk,” senior investigator, Diederik Dippel, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, told this news organization.  

The DUMAS study (Dual Thrombolytic Therapy With Mutant Pro-Urokinase and Low Dose Alteplase for Ischemic Stroke) was presented at the World Stroke Congress in Singapore by study coauthor Nadinda van der Ende, MD, also from Erasmus University Medical Center. 

She pointed out that thrombolysis with intravenous alteplase increases the likelihood of a good outcome in acute ischemic stroke but can cause symptomatic intracranial hemorrhage, which can be associated with death and major disability.

Mutant pro-urokinase is a new thrombolytic agent, in development by Thrombolytic Science, Cambridge, Mass., formed by changing one amino acid in pro-urokinase to make it more stable. It is more fibrin specific than alteplase and therefore believed to have a lower risk of intracranial hemorrhage.

Fibrin is formed as the last step in the clotting process, and the precursor of fibrin in the blood is fibrinogen, Dr. van der Ende noted. Alteplase depletes fibrinogen, contributing to its increased bleeding risk, but mutant pro-urokinase is not believed to affect fibrinogen.

“Mutant pro-urokinase does not bind to intact fibrin. It only binds to fibrin that has already been primed by alteplase,” she explained.

The hypothesis behind the current study is that giving a small dose of alteplase will break down fibrin in the clot enough to expose the binding sites for mutant pro-urokinase, which can then be given to continue to lyse the clot.  

As alteplase has a short half-life, it disappears quickly, and new fibrin is not affected. As mutant pro-urokinase can only lyse fibrin that is primed with alteplase, new hemostatic clots should stay intact. Animal studies have shown less bleeding from distant sites with this approach, Dr. van der Ende said.

The primary analysis of the phase 2 DUMAS study included 238 patients with mild ischemic stroke (median National Institutes of Health Stroke Scale [NIHSS] score 3) who met the standard criteria for IV alteplase.

They were randomized to alteplase alone at the regular dose of 0.9 mg/kg (max 90 mg) with a 10% bolus and the remaining given over 60 minutes; or to a combination of a 5-mg bolus of IV alteplase followed by mutant pro-urokinase at a dose of 40 mg given over 60 minutes.

The primary outcome was the rate of all intracranial hemorrhage (symptomatic and asymptomatic) detected by neuroimaging.  

This occurred in 14% of patients in the full-dose alteplase group vs. 13% of patients in the combined alteplase/mutant pro-urokinase group, a nonsignificant difference: adjusted odds ratio, 0.99 (95% confidence interval, 0.46-2.14).

Secondary outcomes showed no significant differences in NIHSS scores at 24 hours or 5-7 days; functional outcome as measured by a shift analysis of the Modified Rankin Scale (mRS); final infarct volume; or perfusion deficit.

However, blood fibrinogen levels were not depleted and significantly higher in the alteplase/mutant pro-urokinase group than in the full-dose alteplase alone group.

In terms of safety, symptomatic ICH occurred in three patients in the alteplase group (3%) and in none (0%) in the combined alteplase/mutant pro-urokinase group; death occurred in 4% vs. 2% patients respectively; and major extracranial hemorrhage occurred in 1% in both groups.

Dr. Van der Ende concluded that the study showed an overall low rate of ICH; a combination of alteplase and mutant pro-urokinase was not superior to alteplase alone in reducing ICH rates in this population of patients with minor stroke; and mutant pro-urokinase appeared to be safe and, unlike alteplase, did not show any reduction in fibrinogen levels.

“We think the lack of an effect on fibrinogen with this new combination of a small alteplase bolus followed by mutant pro-urokinase infusion is promising,” Dr. Dippel commented. “The fact that there was no symptomatic ICH with the combination treatment is also encouraging. Although the primary endpoint of this trial was neutral, we still believe this is a very interesting approach, with the potential for reduced bleeding, compared with alteplase alone, but we need larger numbers to see an effect on outcomes.”

Dr. Dippel also pointed out that the study included only patients with minor stroke who were not eligible for endovascular therapy, and these patients have a low risk of a poor outcome and a low bleeding risk. 

They are hoping to do another study in patients with more severe stroke, who have a higher bleeding risk and would have more to gain from this combination approach.

Because many patients with severe stroke now have immediate thrombectomy if they present to a comprehensive stroke center, a trial in severe stroke patients would have to be done in primary stroke centers, so if the patents are referred to thrombectomy, the thrombolytic would have a chance to work, Dr. Dippel added.

Commenting on the study for this news organization, Stefan Kiechl, MD, Medical University of Innsbruck (Austria), who is cochair of the World Stroke Congress scientific committee, said, “Alteplase is not fibrin specific, and also causes a degeneration of fibrinogen, which results in ‘fibrinogen depletion coagulopathy.’ It is assumed that 20%-40% of intracerebral bleeding after thrombolysis with alteplase is caused by this problem. DUMAS tests the combination of a substantially reduced alteplase [5 mg] dose plus mutant pro-urokinase to avoid this problem.”

The new thrombolysis protocol, however, did not result in a lower bleeding risk, compared to the comparator alteplase,” he added. “The main limitation of this study is that mainly patients with minor strokes were included. Patients with moderate and severe strokes, who have a substantial risk of bleeding, were not adequately addressed.”

The DUMAS trial was funded by an unrestricted grant from Thrombolytic Science, paid to the institution. Dr. Van der Ende and Dr. Dippel report no relevant disclosures.
 

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

The US Department of Veterans Affairs (VA) is pushing further deployments of the system to June 2023 “to address challenges” and make sure it’s functioning optimally.

Among the challenges: Safety concerns “voluminous enough and prevalent enough” to prompt the VA to disclose to 41,500 veterans enrolled in Washington, Idaho, Oregon, Montana, and Ohio that their care “may have been impacted as a result of the system’s deployment as it is currently configured,” VA Undersecretary for Health Shereef Elnahal said in a news conference.

The plan was to launch in the first quarter of 2023 in Western Washington, Michigan, and Ohio. But in a recent release, the VA said an investigation had found several technical and system issues, such as latency and slowness, and problems with patient scheduling, referrals, medication management, and other types of medical orders. During this “assess and address” period, the VA says, it will correct outstanding issues—especially those that may have patient safety implications—before restarting deployments at other VA medical centers.

“Right now, the Oracle Cerner [EHR] system is not delivering for veterans or VA health care providers—and we are holding Oracle Cerner and ourselves accountable to get this right,” said VA Deputy Secretary Donald Remy, who has oversight over the EHR program. “We are delaying all future deployments of the new EHR while we fully assess performance and address every concern. Veterans and clinicians deserve a seamless, modernized health record system, and we will not rest until they get it.”

The modernized EHR, intended to replace the Veterans Health Information Systems and Technology Architecture (VistA), has been plagued by problems from the very first launch in October 2020 at Mann-Grandstaff VA Medical Center and associated clinics in the Northwest. Deputy Inspector David Case, of the Office of Inspector General (OIG), reported to the House Committee on Veterans’ Affairs on oversight between 2020 and July 2021. Among other things, the OIG identified problems with the infrastructure and with users’ experiences. Clinical and administrative staff at Mann-Grandstaff and a Columbus clinic shared their frustration with OIG personnel about the “significant system and process limitations that raised concerns about the continuity of and prompt access to quality patient care.”

For example, according to an OIG report from July 2022, the new EHR sent thousands of orders for medical care to an “undetectable location, or unknown queue” instead of the intended location. The mis-delivery caused 149 patient harm events.

On October 11, the VA confirmed to The Spokesman-Review, a Spokane-based newspaper, that a patient had died at the VA clinic in Columbus. The death was attributed to the patient not receiving medication due to incorrect information. The incident is being treated as a potential “sentinel event.”

Elnahal, who met with employees in September at the Columbus clinic where the Oracle Cerner system was launched in April, said he found that the highly complex system made it hard for clinicians to perform routine tasks, such as ordering tests or follow-up appointments. Delays in follow-ups—including a yearlong delay in treatment for a veteran ultimately diagnosed with terminal cancer—were the main cause of the cases of harm cited in the July OIG report.

The veterans who received the letter about the potential impact on their health care “got caught up in this phenomenon of commands not getting where they need to go,” Elnahal said in a news conference in September.

Senator Patty Murray (D-WA), a senior member of the Veterans Affairs Committee, has been consistently pressing the VA to do something about the EHR system’s flaws. “It’s painfully clear,” she said in a statement, “we need to stop this program until the VA can fix these serious issues before they hurt anyone else.”

After finding more than 200 orders in the unknown queue in May 2022, the OIG said, it “has concerns with the effectiveness of Cerner’s plan to mitigate the safety risk.” While executing its “assess and address” plan, the VA will continue to focus on the 5 facilities where the new system has been deployed. “Sometimes, you’re not presented with options to immediately resolve the safety concerns that are in front of you,” Elnahal told reporters. “It is simply the case that the best option in front of us to resolve these patient safety concerns is to work with Oracle Cerner over the next several months to resolve the Cerner system issues at the sites where it exists. We know that this is possible, because other health systems have gone through this journey before, and I think we can do it.”

Veterans who believe their care may have been affected can call a dedicated call center at 800.319.9446. A VA health care team will follow up within 5 days.

The US Department of Veterans Affairs (VA) is pushing further deployments of the system to June 2023 “to address challenges” and make sure it’s functioning optimally.

Among the challenges: Safety concerns “voluminous enough and prevalent enough” to prompt the VA to disclose to 41,500 veterans enrolled in Washington, Idaho, Oregon, Montana, and Ohio that their care “may have been impacted as a result of the system’s deployment as it is currently configured,” VA Undersecretary for Health Shereef Elnahal said in a news conference.

The plan was to launch in the first quarter of 2023 in Western Washington, Michigan, and Ohio. But in a recent release, the VA said an investigation had found several technical and system issues, such as latency and slowness, and problems with patient scheduling, referrals, medication management, and other types of medical orders. During this “assess and address” period, the VA says, it will correct outstanding issues—especially those that may have patient safety implications—before restarting deployments at other VA medical centers.

“Right now, the Oracle Cerner [EHR] system is not delivering for veterans or VA health care providers—and we are holding Oracle Cerner and ourselves accountable to get this right,” said VA Deputy Secretary Donald Remy, who has oversight over the EHR program. “We are delaying all future deployments of the new EHR while we fully assess performance and address every concern. Veterans and clinicians deserve a seamless, modernized health record system, and we will not rest until they get it.”

The modernized EHR, intended to replace the Veterans Health Information Systems and Technology Architecture (VistA), has been plagued by problems from the very first launch in October 2020 at Mann-Grandstaff VA Medical Center and associated clinics in the Northwest. Deputy Inspector David Case, of the Office of Inspector General (OIG), reported to the House Committee on Veterans’ Affairs on oversight between 2020 and July 2021. Among other things, the OIG identified problems with the infrastructure and with users’ experiences. Clinical and administrative staff at Mann-Grandstaff and a Columbus clinic shared their frustration with OIG personnel about the “significant system and process limitations that raised concerns about the continuity of and prompt access to quality patient care.”

For example, according to an OIG report from July 2022, the new EHR sent thousands of orders for medical care to an “undetectable location, or unknown queue” instead of the intended location. The mis-delivery caused 149 patient harm events.

On October 11, the VA confirmed to The Spokesman-Review, a Spokane-based newspaper, that a patient had died at the VA clinic in Columbus. The death was attributed to the patient not receiving medication due to incorrect information. The incident is being treated as a potential “sentinel event.”

Elnahal, who met with employees in September at the Columbus clinic where the Oracle Cerner system was launched in April, said he found that the highly complex system made it hard for clinicians to perform routine tasks, such as ordering tests or follow-up appointments. Delays in follow-ups—including a yearlong delay in treatment for a veteran ultimately diagnosed with terminal cancer—were the main cause of the cases of harm cited in the July OIG report.

The veterans who received the letter about the potential impact on their health care “got caught up in this phenomenon of commands not getting where they need to go,” Elnahal said in a news conference in September.

Senator Patty Murray (D-WA), a senior member of the Veterans Affairs Committee, has been consistently pressing the VA to do something about the EHR system’s flaws. “It’s painfully clear,” she said in a statement, “we need to stop this program until the VA can fix these serious issues before they hurt anyone else.”

After finding more than 200 orders in the unknown queue in May 2022, the OIG said, it “has concerns with the effectiveness of Cerner’s plan to mitigate the safety risk.” While executing its “assess and address” plan, the VA will continue to focus on the 5 facilities where the new system has been deployed. “Sometimes, you’re not presented with options to immediately resolve the safety concerns that are in front of you,” Elnahal told reporters. “It is simply the case that the best option in front of us to resolve these patient safety concerns is to work with Oracle Cerner over the next several months to resolve the Cerner system issues at the sites where it exists. We know that this is possible, because other health systems have gone through this journey before, and I think we can do it.”

Veterans who believe their care may have been affected can call a dedicated call center at 800.319.9446. A VA health care team will follow up within 5 days.

The US Department of Veterans Affairs (VA) is pushing further deployments of the system to June 2023 “to address challenges” and make sure it’s functioning optimally.

Among the challenges: Safety concerns “voluminous enough and prevalent enough” to prompt the VA to disclose to 41,500 veterans enrolled in Washington, Idaho, Oregon, Montana, and Ohio that their care “may have been impacted as a result of the system’s deployment as it is currently configured,” VA Undersecretary for Health Shereef Elnahal said in a news conference.

The plan was to launch in the first quarter of 2023 in Western Washington, Michigan, and Ohio. But in a recent release, the VA said an investigation had found several technical and system issues, such as latency and slowness, and problems with patient scheduling, referrals, medication management, and other types of medical orders. During this “assess and address” period, the VA says, it will correct outstanding issues—especially those that may have patient safety implications—before restarting deployments at other VA medical centers.

“Right now, the Oracle Cerner [EHR] system is not delivering for veterans or VA health care providers—and we are holding Oracle Cerner and ourselves accountable to get this right,” said VA Deputy Secretary Donald Remy, who has oversight over the EHR program. “We are delaying all future deployments of the new EHR while we fully assess performance and address every concern. Veterans and clinicians deserve a seamless, modernized health record system, and we will not rest until they get it.”

The modernized EHR, intended to replace the Veterans Health Information Systems and Technology Architecture (VistA), has been plagued by problems from the very first launch in October 2020 at Mann-Grandstaff VA Medical Center and associated clinics in the Northwest. Deputy Inspector David Case, of the Office of Inspector General (OIG), reported to the House Committee on Veterans’ Affairs on oversight between 2020 and July 2021. Among other things, the OIG identified problems with the infrastructure and with users’ experiences. Clinical and administrative staff at Mann-Grandstaff and a Columbus clinic shared their frustration with OIG personnel about the “significant system and process limitations that raised concerns about the continuity of and prompt access to quality patient care.”

For example, according to an OIG report from July 2022, the new EHR sent thousands of orders for medical care to an “undetectable location, or unknown queue” instead of the intended location. The mis-delivery caused 149 patient harm events.

On October 11, the VA confirmed to The Spokesman-Review, a Spokane-based newspaper, that a patient had died at the VA clinic in Columbus. The death was attributed to the patient not receiving medication due to incorrect information. The incident is being treated as a potential “sentinel event.”

Elnahal, who met with employees in September at the Columbus clinic where the Oracle Cerner system was launched in April, said he found that the highly complex system made it hard for clinicians to perform routine tasks, such as ordering tests or follow-up appointments. Delays in follow-ups—including a yearlong delay in treatment for a veteran ultimately diagnosed with terminal cancer—were the main cause of the cases of harm cited in the July OIG report.

The veterans who received the letter about the potential impact on their health care “got caught up in this phenomenon of commands not getting where they need to go,” Elnahal said in a news conference in September.

Senator Patty Murray (D-WA), a senior member of the Veterans Affairs Committee, has been consistently pressing the VA to do something about the EHR system’s flaws. “It’s painfully clear,” she said in a statement, “we need to stop this program until the VA can fix these serious issues before they hurt anyone else.”

After finding more than 200 orders in the unknown queue in May 2022, the OIG said, it “has concerns with the effectiveness of Cerner’s plan to mitigate the safety risk.” While executing its “assess and address” plan, the VA will continue to focus on the 5 facilities where the new system has been deployed. “Sometimes, you’re not presented with options to immediately resolve the safety concerns that are in front of you,” Elnahal told reporters. “It is simply the case that the best option in front of us to resolve these patient safety concerns is to work with Oracle Cerner over the next several months to resolve the Cerner system issues at the sites where it exists. We know that this is possible, because other health systems have gone through this journey before, and I think we can do it.”

Veterans who believe their care may have been affected can call a dedicated call center at 800.319.9446. A VA health care team will follow up within 5 days.

Most hospitals in the United States have yet to transition from conventional to high-sensitivity cardiac troponin (hs-cTn) assays, despite their greater sensitivity for myocardial injury, a new National Cardiovascular Data Registry (NCDR) registry study indicates.

hs-cTn assays have been used in routine clinical practice in Europe, Canada, and Australia since 2010, but the first such assay did not gain approval in the United States until 2017. Although single-center studies have examined their efficacy and potential downstream consequences, few data exist on hs-cTn implementation nationally, explained study author Cian McCarthy, MB, BCh, BAO, Massachusetts General Hospital, Boston.

The results were published online in the Journal of the American College of Cardiology and will be presented Nov. 5 at the American Heart Association scientific sessions.

For the study, Dr. McCarthy and colleagues examined 550 hospitals participating in the NCDR Chest Pain-MI registry from January 2019 through September 2021.

Of the 251,000 patients included in the analysis (mean age, 64 years; 41.5% female), 155,049 had a non–ST-segment myocardial infarction (NSTEMI), 15,989 had unstable angina, and 79,962 had low-risk chest pain.

The hs-cTn assays included Roche Diagnostic’s Elecsys Gen5 STAT troponin T assay (23%); Abbott’s ARCHITECT STAT (17%); Beckman Coulter’s ACCESS (21%); and Siemens’ Atellica IM (18%), Dimension VISTA (14%), Dimension EXL (4%), and ADVIA Centaur (2%) troponin I assays.

During the study period, 11.5% of patients were evaluated with hs-cTn assays and the remainder were evaluated with conventional troponin assays. These patients were slightly older (65.0 vs. 64.0 years), more commonly White (83.1% vs. 79.9%), less likely to be of Hispanic or Latino ethnicity (8.9% vs. 10.0%), and less likely to be uninsured (6.8% vs. 8.3%; P for all < .001).

A slightly higher proportion of patients evaluated with hs-cTn assays were diagnosed with unstable angina (7.1% vs. 6.3%), a lower proportion with NSTEMI (61.1% vs. 61.9%), and a similar proportion with low-risk chest pain (31.8% vs. 31.9%) compared with those evaluated by conventional troponin assays.

Implementation, defined as at least 25% of patients evaluated by hs-cTn in each quarter, increased from 3.3% in the first quarter of 2019 to 32.6% in the third quarter of 2021 (P trend < .001).

Using higher implementation thresholds of at least 50% and 75% of patients evaluated by hs-cTn, the prevalence in 2021 was 28.9% and 24.7%, respectively.

“So still, the majority of the hospitals by the end of the third quarter 2021 were not using these assays,” Dr. McCarthy said.

Potential explanations for the slow uptake are that prospective comparative effectiveness trials of These assays have predominantly been in international populations and real-world data on U.S. implementation have been limited to integrated health networks at academic institutions.

Approval of several assays was also delayed and the study data cut off just before the October publication of the 2021 AHA/ACC Chest Pain guideline. “So, whether the chest pain guideline with the new class 1 recommendation for hs-cTn will lead to further uptake is something that will need to be looked at in the future,” he said.
 

Downstream testing

In adjusted analyses, hs-cTn use was associated with more echocardiography among patients with non-ST elevation–acute coronary syndrome (NSTE-ACS) (82.4% vs. 75.0%; odds ratio [OR], 1.43; 95% confidence interval [CI], 1.19-1.73), but not among those with low-risk chest pain (19.7% vs. 19.4%; OR, 0.93; 95% CI, 0.71-1.22) compared with conventional cTn assays.

Importantly, hs-cTn was not associated with a difference in stress testing or CT coronary angiography utilization.

Use of hs-cTn was associated with lower use of invasive coronary angiography among patients with low-risk chest pain (3.7% vs. 4.5%; OR, 0.73, 95% CI, 0.58-0.92) but similar use for NSTE-ACS (96.3% vs. 95.8%; OR, 0.99, 95% CI, 0.82-1.19).

Among patients with NSTE-ACS, there also was no difference in revascularization with percutaneous coronary intervention (PCI) (52.7% vs. 52.3%; OR, 0.99; 95% CI, 0.94-1.04) or coronary bypass graft surgery (9.4% vs. 9.1%; OR, 1.06; 95% CI, 0.94-1.18).

PCI (0.1% vs. 0.2%; P = .05) and bypass graft surgery (both 0.1%) were uncommon among patients with low-risk chest pain.

In-hospital mortality was similar among patients with low-risk chest pain evaluated using hs-cTn assays vs. conventional troponin assays (0% vs. 0.02%; P = .16) and among patients with NSTE-ACS (2.8% vs. 3.2%; OR, 0.98, 95% CI, 0.87-1.11).

Length of stay was slightly shorter with hs-cTn use for patients with low-risk chest pain (median, 5.8 vs. 6.2 hours; P < .001) and patients with NSTE-ACS (66.9 vs. 67.8 hours; P = .01).

“There was always a concern that maybe high-sensitivity cardiac troponin would dramatically increase testing and could even increase length of stay, but I think these data are reassuring, in that this study suggests high-sensitivity cardiac troponin is associated with a small reduction in length of stay and possibly more appropriate use of testing with echocardiography in STEMI and a reduction in invasive angiography in low-risk patients,” Dr. McCarthy said. “But the majority of hospitals haven’t implemented the assay.”

The authors pointed out that because registry entry of patients with low-risk chest pain and unstable angina is optional for participating sites, the percentage of patients with NSTEMI is higher than in typical chest pain analyses. This higher pretest probability for MI may thus affect post-test accuracy for a true positive result. “That stated, this is the exact scenario where higher sensitivity might be associated with favorable impact on utilization.”

Among other limitations: There was the potential for unmeasured confounders, the accuracy of diagnoses could not be confirmed, patients with type 2 MI were excluded from the registry, and post-discharge safety was not assessed.

“These data indicate further opportunities to more widely and effectively implement hs-cTn in the U.S. hospitals persist that could optimize care for patients with possible or definitive ACS,” Dr. McCarthy and colleagues concluded.

The study was funded by the American College of Cardiology’s National Cardiovascular Data Registry. Dr. McCarthy is supported by the National Heart, Lung, and Blood Institute and has received consulting income from Abbott Laboratories.

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

Most hospitals in the United States have yet to transition from conventional to high-sensitivity cardiac troponin (hs-cTn) assays, despite their greater sensitivity for myocardial injury, a new National Cardiovascular Data Registry (NCDR) registry study indicates.

hs-cTn assays have been used in routine clinical practice in Europe, Canada, and Australia since 2010, but the first such assay did not gain approval in the United States until 2017. Although single-center studies have examined their efficacy and potential downstream consequences, few data exist on hs-cTn implementation nationally, explained study author Cian McCarthy, MB, BCh, BAO, Massachusetts General Hospital, Boston.

The results were published online in the Journal of the American College of Cardiology and will be presented Nov. 5 at the American Heart Association scientific sessions.

For the study, Dr. McCarthy and colleagues examined 550 hospitals participating in the NCDR Chest Pain-MI registry from January 2019 through September 2021.

Of the 251,000 patients included in the analysis (mean age, 64 years; 41.5% female), 155,049 had a non–ST-segment myocardial infarction (NSTEMI), 15,989 had unstable angina, and 79,962 had low-risk chest pain.

The hs-cTn assays included Roche Diagnostic’s Elecsys Gen5 STAT troponin T assay (23%); Abbott’s ARCHITECT STAT (17%); Beckman Coulter’s ACCESS (21%); and Siemens’ Atellica IM (18%), Dimension VISTA (14%), Dimension EXL (4%), and ADVIA Centaur (2%) troponin I assays.

During the study period, 11.5% of patients were evaluated with hs-cTn assays and the remainder were evaluated with conventional troponin assays. These patients were slightly older (65.0 vs. 64.0 years), more commonly White (83.1% vs. 79.9%), less likely to be of Hispanic or Latino ethnicity (8.9% vs. 10.0%), and less likely to be uninsured (6.8% vs. 8.3%; P for all < .001).

A slightly higher proportion of patients evaluated with hs-cTn assays were diagnosed with unstable angina (7.1% vs. 6.3%), a lower proportion with NSTEMI (61.1% vs. 61.9%), and a similar proportion with low-risk chest pain (31.8% vs. 31.9%) compared with those evaluated by conventional troponin assays.

Implementation, defined as at least 25% of patients evaluated by hs-cTn in each quarter, increased from 3.3% in the first quarter of 2019 to 32.6% in the third quarter of 2021 (P trend < .001).

Using higher implementation thresholds of at least 50% and 75% of patients evaluated by hs-cTn, the prevalence in 2021 was 28.9% and 24.7%, respectively.

“So still, the majority of the hospitals by the end of the third quarter 2021 were not using these assays,” Dr. McCarthy said.

Potential explanations for the slow uptake are that prospective comparative effectiveness trials of These assays have predominantly been in international populations and real-world data on U.S. implementation have been limited to integrated health networks at academic institutions.

Approval of several assays was also delayed and the study data cut off just before the October publication of the 2021 AHA/ACC Chest Pain guideline. “So, whether the chest pain guideline with the new class 1 recommendation for hs-cTn will lead to further uptake is something that will need to be looked at in the future,” he said.
 

Downstream testing

In adjusted analyses, hs-cTn use was associated with more echocardiography among patients with non-ST elevation–acute coronary syndrome (NSTE-ACS) (82.4% vs. 75.0%; odds ratio [OR], 1.43; 95% confidence interval [CI], 1.19-1.73), but not among those with low-risk chest pain (19.7% vs. 19.4%; OR, 0.93; 95% CI, 0.71-1.22) compared with conventional cTn assays.

Importantly, hs-cTn was not associated with a difference in stress testing or CT coronary angiography utilization.

Use of hs-cTn was associated with lower use of invasive coronary angiography among patients with low-risk chest pain (3.7% vs. 4.5%; OR, 0.73, 95% CI, 0.58-0.92) but similar use for NSTE-ACS (96.3% vs. 95.8%; OR, 0.99, 95% CI, 0.82-1.19).

Among patients with NSTE-ACS, there also was no difference in revascularization with percutaneous coronary intervention (PCI) (52.7% vs. 52.3%; OR, 0.99; 95% CI, 0.94-1.04) or coronary bypass graft surgery (9.4% vs. 9.1%; OR, 1.06; 95% CI, 0.94-1.18).

PCI (0.1% vs. 0.2%; P = .05) and bypass graft surgery (both 0.1%) were uncommon among patients with low-risk chest pain.

In-hospital mortality was similar among patients with low-risk chest pain evaluated using hs-cTn assays vs. conventional troponin assays (0% vs. 0.02%; P = .16) and among patients with NSTE-ACS (2.8% vs. 3.2%; OR, 0.98, 95% CI, 0.87-1.11).

Length of stay was slightly shorter with hs-cTn use for patients with low-risk chest pain (median, 5.8 vs. 6.2 hours; P < .001) and patients with NSTE-ACS (66.9 vs. 67.8 hours; P = .01).

“There was always a concern that maybe high-sensitivity cardiac troponin would dramatically increase testing and could even increase length of stay, but I think these data are reassuring, in that this study suggests high-sensitivity cardiac troponin is associated with a small reduction in length of stay and possibly more appropriate use of testing with echocardiography in STEMI and a reduction in invasive angiography in low-risk patients,” Dr. McCarthy said. “But the majority of hospitals haven’t implemented the assay.”

The authors pointed out that because registry entry of patients with low-risk chest pain and unstable angina is optional for participating sites, the percentage of patients with NSTEMI is higher than in typical chest pain analyses. This higher pretest probability for MI may thus affect post-test accuracy for a true positive result. “That stated, this is the exact scenario where higher sensitivity might be associated with favorable impact on utilization.”

Among other limitations: There was the potential for unmeasured confounders, the accuracy of diagnoses could not be confirmed, patients with type 2 MI were excluded from the registry, and post-discharge safety was not assessed.

“These data indicate further opportunities to more widely and effectively implement hs-cTn in the U.S. hospitals persist that could optimize care for patients with possible or definitive ACS,” Dr. McCarthy and colleagues concluded.

The study was funded by the American College of Cardiology’s National Cardiovascular Data Registry. Dr. McCarthy is supported by the National Heart, Lung, and Blood Institute and has received consulting income from Abbott Laboratories.

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

Most hospitals in the United States have yet to transition from conventional to high-sensitivity cardiac troponin (hs-cTn) assays, despite their greater sensitivity for myocardial injury, a new National Cardiovascular Data Registry (NCDR) registry study indicates.

hs-cTn assays have been used in routine clinical practice in Europe, Canada, and Australia since 2010, but the first such assay did not gain approval in the United States until 2017. Although single-center studies have examined their efficacy and potential downstream consequences, few data exist on hs-cTn implementation nationally, explained study author Cian McCarthy, MB, BCh, BAO, Massachusetts General Hospital, Boston.

The results were published online in the Journal of the American College of Cardiology and will be presented Nov. 5 at the American Heart Association scientific sessions.

For the study, Dr. McCarthy and colleagues examined 550 hospitals participating in the NCDR Chest Pain-MI registry from January 2019 through September 2021.

Of the 251,000 patients included in the analysis (mean age, 64 years; 41.5% female), 155,049 had a non–ST-segment myocardial infarction (NSTEMI), 15,989 had unstable angina, and 79,962 had low-risk chest pain.

The hs-cTn assays included Roche Diagnostic’s Elecsys Gen5 STAT troponin T assay (23%); Abbott’s ARCHITECT STAT (17%); Beckman Coulter’s ACCESS (21%); and Siemens’ Atellica IM (18%), Dimension VISTA (14%), Dimension EXL (4%), and ADVIA Centaur (2%) troponin I assays.

During the study period, 11.5% of patients were evaluated with hs-cTn assays and the remainder were evaluated with conventional troponin assays. These patients were slightly older (65.0 vs. 64.0 years), more commonly White (83.1% vs. 79.9%), less likely to be of Hispanic or Latino ethnicity (8.9% vs. 10.0%), and less likely to be uninsured (6.8% vs. 8.3%; P for all < .001).

A slightly higher proportion of patients evaluated with hs-cTn assays were diagnosed with unstable angina (7.1% vs. 6.3%), a lower proportion with NSTEMI (61.1% vs. 61.9%), and a similar proportion with low-risk chest pain (31.8% vs. 31.9%) compared with those evaluated by conventional troponin assays.

Implementation, defined as at least 25% of patients evaluated by hs-cTn in each quarter, increased from 3.3% in the first quarter of 2019 to 32.6% in the third quarter of 2021 (P trend < .001).

Using higher implementation thresholds of at least 50% and 75% of patients evaluated by hs-cTn, the prevalence in 2021 was 28.9% and 24.7%, respectively.

“So still, the majority of the hospitals by the end of the third quarter 2021 were not using these assays,” Dr. McCarthy said.

Potential explanations for the slow uptake are that prospective comparative effectiveness trials of These assays have predominantly been in international populations and real-world data on U.S. implementation have been limited to integrated health networks at academic institutions.

Approval of several assays was also delayed and the study data cut off just before the October publication of the 2021 AHA/ACC Chest Pain guideline. “So, whether the chest pain guideline with the new class 1 recommendation for hs-cTn will lead to further uptake is something that will need to be looked at in the future,” he said.
 

Downstream testing

In adjusted analyses, hs-cTn use was associated with more echocardiography among patients with non-ST elevation–acute coronary syndrome (NSTE-ACS) (82.4% vs. 75.0%; odds ratio [OR], 1.43; 95% confidence interval [CI], 1.19-1.73), but not among those with low-risk chest pain (19.7% vs. 19.4%; OR, 0.93; 95% CI, 0.71-1.22) compared with conventional cTn assays.

Importantly, hs-cTn was not associated with a difference in stress testing or CT coronary angiography utilization.

Use of hs-cTn was associated with lower use of invasive coronary angiography among patients with low-risk chest pain (3.7% vs. 4.5%; OR, 0.73, 95% CI, 0.58-0.92) but similar use for NSTE-ACS (96.3% vs. 95.8%; OR, 0.99, 95% CI, 0.82-1.19).

Among patients with NSTE-ACS, there also was no difference in revascularization with percutaneous coronary intervention (PCI) (52.7% vs. 52.3%; OR, 0.99; 95% CI, 0.94-1.04) or coronary bypass graft surgery (9.4% vs. 9.1%; OR, 1.06; 95% CI, 0.94-1.18).

PCI (0.1% vs. 0.2%; P = .05) and bypass graft surgery (both 0.1%) were uncommon among patients with low-risk chest pain.

In-hospital mortality was similar among patients with low-risk chest pain evaluated using hs-cTn assays vs. conventional troponin assays (0% vs. 0.02%; P = .16) and among patients with NSTE-ACS (2.8% vs. 3.2%; OR, 0.98, 95% CI, 0.87-1.11).

Length of stay was slightly shorter with hs-cTn use for patients with low-risk chest pain (median, 5.8 vs. 6.2 hours; P < .001) and patients with NSTE-ACS (66.9 vs. 67.8 hours; P = .01).

“There was always a concern that maybe high-sensitivity cardiac troponin would dramatically increase testing and could even increase length of stay, but I think these data are reassuring, in that this study suggests high-sensitivity cardiac troponin is associated with a small reduction in length of stay and possibly more appropriate use of testing with echocardiography in STEMI and a reduction in invasive angiography in low-risk patients,” Dr. McCarthy said. “But the majority of hospitals haven’t implemented the assay.”

The authors pointed out that because registry entry of patients with low-risk chest pain and unstable angina is optional for participating sites, the percentage of patients with NSTEMI is higher than in typical chest pain analyses. This higher pretest probability for MI may thus affect post-test accuracy for a true positive result. “That stated, this is the exact scenario where higher sensitivity might be associated with favorable impact on utilization.”

Among other limitations: There was the potential for unmeasured confounders, the accuracy of diagnoses could not be confirmed, patients with type 2 MI were excluded from the registry, and post-discharge safety was not assessed.

“These data indicate further opportunities to more widely and effectively implement hs-cTn in the U.S. hospitals persist that could optimize care for patients with possible or definitive ACS,” Dr. McCarthy and colleagues concluded.

The study was funded by the American College of Cardiology’s National Cardiovascular Data Registry. Dr. McCarthy is supported by the National Heart, Lung, and Blood Institute and has received consulting income from Abbott Laboratories.

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

New trial data from drugmaker Pfizer shows promising results of a vaccine given to mothers during pregnancy that later protects infants in their first months from the worst effects of respiratory syncytial virus, or RSV.

Pfizer will apply for FDA approval by the end of the year, the company said in a statement Nov. 1.

Trial results are so promising that – after talking with government regulators – the company will stop enrolling new people in the study.

Specifically, the company reported that the vaccine prevented severe illness particularly well during the first 90 days of life, with measurable protection against severe illness continuing through 6 months of age. (That period is when infants are the most fragile if they get sick with RSV.)

RSV is a respiratory illness than can affect anyone, usually resulting in no symptoms or those similar to the common cold. But it can be particularly dangerous – and even deadly – for babies and for people over the age of 65. Pfizer and another drug company, GSK, are developing promising vaccines for older adults, the Washington Post reported.

RSV is the leading cause of hospitalization for infants, the Post noted.

The Pfizer study, called MATISSE, enrolled 7,400 pregnant women in 18 countries worldwide. Those who received the vaccine were given it during the late second to third trimester of pregnancy. Women in the study were monitored for safety through the rest of their pregnancy and 6 months after their children were born. Infants were monitored for at least 1 year for safety and effectiveness; more than half of them were monitored for 2 years.

The Pfizer vaccine works by passing maternal antibodies to the infant during pregnancy, the Post reported, noting that other vaccines transmitted via maternal immunization include those for influenza, diphtheria, tetanus, and pertussis.

Annually, RSV has a devastating impact on young children, hospitalizing tens of thousands and causing up to 300 deaths, data show.

For every 100 children who get RSV under 6 months of age, one or two of them may need to be hospitalized, according to the CDC. Those hospitalized infants may need oxygen, intubation, or even mechanical ventilation to help with breathing.

“Most improve with this type of supportive care and are discharged in a few days,” the CDC said.

“I think this is a big step for protecting babies against RSV and improving overall lung health,” vaccine researcher Barney Graham, PhD, told the Post. “Overall, it’s an exciting time for RSV. It’s also a troubling time, because you see how the patterns of infection have been changed by COVID, and we’re having an earlier, bigger season this year than we have for a couple of years – and it’s causing a lot of hospitalization and misery for people.”

As many as four RSV vaccines may have applications submitted to the FDA in 2022, according to CNN. Also in development is an antibody shot given to infants just after they are born, the news outlet reported.

Pfizer’s data, announced Tuesday, has not yet been published or peer-reviewed, but the company said it is seeking peer-reviewed publication.

“We are thrilled by these data, as this is the first-ever investigational vaccine shown to help protect newborns against severe RSV-related respiratory illness immediately at birth,” Annaliesa Anderson, PhD, Pfizer chief scientific officer for vaccine research & development, said in a statement. “We look forward to working with the FDA and other regulatory agencies to bring this vaccine candidate to expectant mothers to help protect their infants against severe RSV during their most vulnerable first six months of life, which has the highest burden of RSV illness in infants.”

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

New trial data from drugmaker Pfizer shows promising results of a vaccine given to mothers during pregnancy that later protects infants in their first months from the worst effects of respiratory syncytial virus, or RSV.

Pfizer will apply for FDA approval by the end of the year, the company said in a statement Nov. 1.

Trial results are so promising that – after talking with government regulators – the company will stop enrolling new people in the study.

Specifically, the company reported that the vaccine prevented severe illness particularly well during the first 90 days of life, with measurable protection against severe illness continuing through 6 months of age. (That period is when infants are the most fragile if they get sick with RSV.)

RSV is a respiratory illness than can affect anyone, usually resulting in no symptoms or those similar to the common cold. But it can be particularly dangerous – and even deadly – for babies and for people over the age of 65. Pfizer and another drug company, GSK, are developing promising vaccines for older adults, the Washington Post reported.

RSV is the leading cause of hospitalization for infants, the Post noted.

The Pfizer study, called MATISSE, enrolled 7,400 pregnant women in 18 countries worldwide. Those who received the vaccine were given it during the late second to third trimester of pregnancy. Women in the study were monitored for safety through the rest of their pregnancy and 6 months after their children were born. Infants were monitored for at least 1 year for safety and effectiveness; more than half of them were monitored for 2 years.

The Pfizer vaccine works by passing maternal antibodies to the infant during pregnancy, the Post reported, noting that other vaccines transmitted via maternal immunization include those for influenza, diphtheria, tetanus, and pertussis.

Annually, RSV has a devastating impact on young children, hospitalizing tens of thousands and causing up to 300 deaths, data show.

For every 100 children who get RSV under 6 months of age, one or two of them may need to be hospitalized, according to the CDC. Those hospitalized infants may need oxygen, intubation, or even mechanical ventilation to help with breathing.

“Most improve with this type of supportive care and are discharged in a few days,” the CDC said.

“I think this is a big step for protecting babies against RSV and improving overall lung health,” vaccine researcher Barney Graham, PhD, told the Post. “Overall, it’s an exciting time for RSV. It’s also a troubling time, because you see how the patterns of infection have been changed by COVID, and we’re having an earlier, bigger season this year than we have for a couple of years – and it’s causing a lot of hospitalization and misery for people.”

As many as four RSV vaccines may have applications submitted to the FDA in 2022, according to CNN. Also in development is an antibody shot given to infants just after they are born, the news outlet reported.

Pfizer’s data, announced Tuesday, has not yet been published or peer-reviewed, but the company said it is seeking peer-reviewed publication.

“We are thrilled by these data, as this is the first-ever investigational vaccine shown to help protect newborns against severe RSV-related respiratory illness immediately at birth,” Annaliesa Anderson, PhD, Pfizer chief scientific officer for vaccine research & development, said in a statement. “We look forward to working with the FDA and other regulatory agencies to bring this vaccine candidate to expectant mothers to help protect their infants against severe RSV during their most vulnerable first six months of life, which has the highest burden of RSV illness in infants.”

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

New trial data from drugmaker Pfizer shows promising results of a vaccine given to mothers during pregnancy that later protects infants in their first months from the worst effects of respiratory syncytial virus, or RSV.

Pfizer will apply for FDA approval by the end of the year, the company said in a statement Nov. 1.

Trial results are so promising that – after talking with government regulators – the company will stop enrolling new people in the study.

Specifically, the company reported that the vaccine prevented severe illness particularly well during the first 90 days of life, with measurable protection against severe illness continuing through 6 months of age. (That period is when infants are the most fragile if they get sick with RSV.)

RSV is a respiratory illness than can affect anyone, usually resulting in no symptoms or those similar to the common cold. But it can be particularly dangerous – and even deadly – for babies and for people over the age of 65. Pfizer and another drug company, GSK, are developing promising vaccines for older adults, the Washington Post reported.

RSV is the leading cause of hospitalization for infants, the Post noted.

The Pfizer study, called MATISSE, enrolled 7,400 pregnant women in 18 countries worldwide. Those who received the vaccine were given it during the late second to third trimester of pregnancy. Women in the study were monitored for safety through the rest of their pregnancy and 6 months after their children were born. Infants were monitored for at least 1 year for safety and effectiveness; more than half of them were monitored for 2 years.

The Pfizer vaccine works by passing maternal antibodies to the infant during pregnancy, the Post reported, noting that other vaccines transmitted via maternal immunization include those for influenza, diphtheria, tetanus, and pertussis.

Annually, RSV has a devastating impact on young children, hospitalizing tens of thousands and causing up to 300 deaths, data show.

For every 100 children who get RSV under 6 months of age, one or two of them may need to be hospitalized, according to the CDC. Those hospitalized infants may need oxygen, intubation, or even mechanical ventilation to help with breathing.

“Most improve with this type of supportive care and are discharged in a few days,” the CDC said.

“I think this is a big step for protecting babies against RSV and improving overall lung health,” vaccine researcher Barney Graham, PhD, told the Post. “Overall, it’s an exciting time for RSV. It’s also a troubling time, because you see how the patterns of infection have been changed by COVID, and we’re having an earlier, bigger season this year than we have for a couple of years – and it’s causing a lot of hospitalization and misery for people.”

As many as four RSV vaccines may have applications submitted to the FDA in 2022, according to CNN. Also in development is an antibody shot given to infants just after they are born, the news outlet reported.

Pfizer’s data, announced Tuesday, has not yet been published or peer-reviewed, but the company said it is seeking peer-reviewed publication.

“We are thrilled by these data, as this is the first-ever investigational vaccine shown to help protect newborns against severe RSV-related respiratory illness immediately at birth,” Annaliesa Anderson, PhD, Pfizer chief scientific officer for vaccine research & development, said in a statement. “We look forward to working with the FDA and other regulatory agencies to bring this vaccine candidate to expectant mothers to help protect their infants against severe RSV during their most vulnerable first six months of life, which has the highest burden of RSV illness in infants.”

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