TOPLINE:

The recommended 10-year interval between screening colonoscopies may be safely extended to 15 years in adults with no family history of colorectal cancer (CRC) whose first colonoscopy is negative for CRC, a population-based study suggests.

METHODOLOGY:

• Using Swedish nationwide registry data, researchers compared 110,074 individuals who had a first colonoscopy with negative findings for CRC at age 45-69 years (exposed group) with more than 1.9 million matched controls who either did not have a colonoscopy during the study period or underwent colonoscopy that led to a CRC diagnosis.
• They calculated 10-year standardized incidence ratio (SIR) and standardized mortality ratio (SMR) to compare risks for CRC and CRC-specific death in the exposed and control groups based on different follow-up screening intervals.

TAKEAWAY:

• During up to 29 years of follow-up, 484 incident CRCs and 112 CRC deaths occurred in the group with a negative initial colonoscopy.
• Up to 15 years after negative colonoscopy, the 10-year cumulative risk for CRC and CRC mortality was lower than in the control group, with an SIR of 0.72 and SMR of 0.55, respectively.
• Extending the screening interval from 10 to 15 years would miss early detection of only two CRC cases and prevention of only one CRC death per 1000 individuals, while potentially avoiding 1000 colonoscopies.

IN PRACTICE:

“This study provides evidence for recommending a longer colonoscopy screening interval than what is currently recommended in most guidelines for populations with no familial risk of CRC,” the authors wrote. “A longer interval between colonoscopy screenings could be beneficial in avoiding unnecessary invasive examinations.”

SOURCE:

The study, with first author Qunfeng Liang, MSc, with the German Cancer Research Center, Heidelberg, Germany, was published online on May 2 in JAMA Oncology.

LIMITATIONS:

The study population primarily included White individuals, particularly ethnic Swedish individuals, so external validation would be necessary to generalize the recommendation to other populations. The researchers lacked data on non-endoscopic tests, such as fecal occult blood tests, which could have been performed as a substitution for colonoscopy during the interval between colonoscopy screenings.

DISCLOSURES:

The study had no specific funding. The authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

The recommended 10-year interval between screening colonoscopies may be safely extended to 15 years in adults with no family history of colorectal cancer (CRC) whose first colonoscopy is negative for CRC, a population-based study suggests.

METHODOLOGY:

• Using Swedish nationwide registry data, researchers compared 110,074 individuals who had a first colonoscopy with negative findings for CRC at age 45-69 years (exposed group) with more than 1.9 million matched controls who either did not have a colonoscopy during the study period or underwent colonoscopy that led to a CRC diagnosis.
• They calculated 10-year standardized incidence ratio (SIR) and standardized mortality ratio (SMR) to compare risks for CRC and CRC-specific death in the exposed and control groups based on different follow-up screening intervals.

TAKEAWAY:

• During up to 29 years of follow-up, 484 incident CRCs and 112 CRC deaths occurred in the group with a negative initial colonoscopy.
• Up to 15 years after negative colonoscopy, the 10-year cumulative risk for CRC and CRC mortality was lower than in the control group, with an SIR of 0.72 and SMR of 0.55, respectively.
• Extending the screening interval from 10 to 15 years would miss early detection of only two CRC cases and prevention of only one CRC death per 1000 individuals, while potentially avoiding 1000 colonoscopies.

IN PRACTICE:

“This study provides evidence for recommending a longer colonoscopy screening interval than what is currently recommended in most guidelines for populations with no familial risk of CRC,” the authors wrote. “A longer interval between colonoscopy screenings could be beneficial in avoiding unnecessary invasive examinations.”

SOURCE:

The study, with first author Qunfeng Liang, MSc, with the German Cancer Research Center, Heidelberg, Germany, was published online on May 2 in JAMA Oncology.

LIMITATIONS:

The study population primarily included White individuals, particularly ethnic Swedish individuals, so external validation would be necessary to generalize the recommendation to other populations. The researchers lacked data on non-endoscopic tests, such as fecal occult blood tests, which could have been performed as a substitution for colonoscopy during the interval between colonoscopy screenings.

DISCLOSURES:

The study had no specific funding. The authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

The recommended 10-year interval between screening colonoscopies may be safely extended to 15 years in adults with no family history of colorectal cancer (CRC) whose first colonoscopy is negative for CRC, a population-based study suggests.

METHODOLOGY:

• Using Swedish nationwide registry data, researchers compared 110,074 individuals who had a first colonoscopy with negative findings for CRC at age 45-69 years (exposed group) with more than 1.9 million matched controls who either did not have a colonoscopy during the study period or underwent colonoscopy that led to a CRC diagnosis.
• They calculated 10-year standardized incidence ratio (SIR) and standardized mortality ratio (SMR) to compare risks for CRC and CRC-specific death in the exposed and control groups based on different follow-up screening intervals.

TAKEAWAY:

• During up to 29 years of follow-up, 484 incident CRCs and 112 CRC deaths occurred in the group with a negative initial colonoscopy.
• Up to 15 years after negative colonoscopy, the 10-year cumulative risk for CRC and CRC mortality was lower than in the control group, with an SIR of 0.72 and SMR of 0.55, respectively.
• Extending the screening interval from 10 to 15 years would miss early detection of only two CRC cases and prevention of only one CRC death per 1000 individuals, while potentially avoiding 1000 colonoscopies.

IN PRACTICE:

“This study provides evidence for recommending a longer colonoscopy screening interval than what is currently recommended in most guidelines for populations with no familial risk of CRC,” the authors wrote. “A longer interval between colonoscopy screenings could be beneficial in avoiding unnecessary invasive examinations.”

SOURCE:

The study, with first author Qunfeng Liang, MSc, with the German Cancer Research Center, Heidelberg, Germany, was published online on May 2 in JAMA Oncology.

LIMITATIONS:

The study population primarily included White individuals, particularly ethnic Swedish individuals, so external validation would be necessary to generalize the recommendation to other populations. The researchers lacked data on non-endoscopic tests, such as fecal occult blood tests, which could have been performed as a substitution for colonoscopy during the interval between colonoscopy screenings.

DISCLOSURES:

The study had no specific funding. The authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Clinical guidelines on age-related hearing loss (ARHL), published in Otolaryngology–Head and Neck Surgery, highlight referral recommendations for all clinicians, including primary care doctors, who often are the first clinicians to screen for and address the condition.

Betty S. Tsai Do, MD, with the department of head & neck surgery at Kaiser Permanente in Walnut Creek, California, is the first author for the guidelines, which recommend screening patients 50 years or older at the time of a healthcare encounter. They also detail when to test and refer.
 

Three ‘Strong Recommendations’

Three of the action points are labeled “strong recommendations.” They are:

• If screening suggests hearing loss, clinicians should conduct an audiogram or refer to a clinician who can conduct one.
• Clinicians should offer, or refer to a specialist who can offer, appropriately fit amplification, such as hearing aids.
• If patients have appropriately fit amplification and still have trouble with hearing and understanding speech, clinicians should refer patients to see if they are good candidates for a cochlear implant.

The authors note that ARHL is the most common sensory deficit seen in older patients, but it is underdiagnosed and undertreated. “Between ages 65 and 74, one in three adults experience hearing loss and almost 50% of those 75 years of age or older will report hearing loss according to the National Institute on Deafness and Other Communication Disorders.” Consequences of the untreated deficit, in addition to limiting ability to communicate, include higher risk of dementia, cardiovascular disease, depression, falls, and workplace marginalization.

Until now, there have been no evidence-based clinical guidelines on when to screen, test, and refer. Though previously proposed quality improvement measures have defined ARHL as starting at age 60, these guidelines include those 50 and older to promote earlier detection.
 

Guidelines Only Part of the Solution

While the guidelines are a step in the right direction, they won’t address some persistent barriers to changing practice, said Michael McKee, MD, MPH, a family medicine physician and co-director of the Center for Disability Health and Wellness at the University of Michigan in Ann Arbor, who was not part of the guideline team.

“I think [the guidelines] will raise the awareness on why it’s important to address hearing loss,” he says. “Many primary care providers don’t elevate hearing loss as a priority topic. The problem is that we’re struggling with getting things in place to have a more supportive system to carry out those recommendations.”
 

Lack of Training and Support

The problems include lack of training on hearing loss for physicians, starting with medical school. Another complication is time: A conversation about hearing loss adds to the multitude of conversations a primary care provider is expected to have with their patients in a short visit.

Additionally, when hearing loss is suspected, an audiologist may be hard to find to perform the audiogram, Dr. McKee says. If patients agree to see an audiologist and that specialist finds hearing loss, patients may not want to wear a device due to stigma or may not be able to afford a device that will fit properly and truly benefit them because Medicare does not cover hearing aids.

“Only about 20-plus percent of those eligible for hearing aids get them,” he said. Hearing aids available over the counter help some people, but may be difficult to fit properly and may be hard for some to use correctly, he added.

“That comes back to the primary care provider, so it’s unfortunately a very unsatisfying course,” he said.
 

‘Primary Care Providers Do Value Guidelines’

However, “Primary care providers do value guidelines. They do value strong recommendations,” he said. We are trying to figure out how we can support people with unaddressed hearing loss in the primary care setting, Dr. McKee said. “Once we get there, we need to advocate for an expansion of coverage,” he said.

The authors note that the messages in the guidelines are important for all clinicians.

“The impact of hearing loss and screening should not be the sole responsibility of an audiologist, an otolaryngologist, nor primary care provider. Any time and place that a patient interacts with the healthcare system is an opportunity for preventive healthcare, such as hearing screening, to occur,” they write.

Funding for this research was provided by the American Academy of Otolaryngology–Head and Neck Surgery Foundation. Dr. Do and Dr. McKee report no relevant financial relationships. Full disclosures of the co-authors are listed with the full text of the paper.
 

Clinical guidelines on age-related hearing loss (ARHL), published in Otolaryngology–Head and Neck Surgery, highlight referral recommendations for all clinicians, including primary care doctors, who often are the first clinicians to screen for and address the condition.

Betty S. Tsai Do, MD, with the department of head & neck surgery at Kaiser Permanente in Walnut Creek, California, is the first author for the guidelines, which recommend screening patients 50 years or older at the time of a healthcare encounter. They also detail when to test and refer.
 

Three ‘Strong Recommendations’

Three of the action points are labeled “strong recommendations.” They are:

• If screening suggests hearing loss, clinicians should conduct an audiogram or refer to a clinician who can conduct one.
• Clinicians should offer, or refer to a specialist who can offer, appropriately fit amplification, such as hearing aids.
• If patients have appropriately fit amplification and still have trouble with hearing and understanding speech, clinicians should refer patients to see if they are good candidates for a cochlear implant.

The authors note that ARHL is the most common sensory deficit seen in older patients, but it is underdiagnosed and undertreated. “Between ages 65 and 74, one in three adults experience hearing loss and almost 50% of those 75 years of age or older will report hearing loss according to the National Institute on Deafness and Other Communication Disorders.” Consequences of the untreated deficit, in addition to limiting ability to communicate, include higher risk of dementia, cardiovascular disease, depression, falls, and workplace marginalization.

Until now, there have been no evidence-based clinical guidelines on when to screen, test, and refer. Though previously proposed quality improvement measures have defined ARHL as starting at age 60, these guidelines include those 50 and older to promote earlier detection.
 

Guidelines Only Part of the Solution

While the guidelines are a step in the right direction, they won’t address some persistent barriers to changing practice, said Michael McKee, MD, MPH, a family medicine physician and co-director of the Center for Disability Health and Wellness at the University of Michigan in Ann Arbor, who was not part of the guideline team.

“I think [the guidelines] will raise the awareness on why it’s important to address hearing loss,” he says. “Many primary care providers don’t elevate hearing loss as a priority topic. The problem is that we’re struggling with getting things in place to have a more supportive system to carry out those recommendations.”
 

Lack of Training and Support

The problems include lack of training on hearing loss for physicians, starting with medical school. Another complication is time: A conversation about hearing loss adds to the multitude of conversations a primary care provider is expected to have with their patients in a short visit.

Additionally, when hearing loss is suspected, an audiologist may be hard to find to perform the audiogram, Dr. McKee says. If patients agree to see an audiologist and that specialist finds hearing loss, patients may not want to wear a device due to stigma or may not be able to afford a device that will fit properly and truly benefit them because Medicare does not cover hearing aids.

“Only about 20-plus percent of those eligible for hearing aids get them,” he said. Hearing aids available over the counter help some people, but may be difficult to fit properly and may be hard for some to use correctly, he added.

“That comes back to the primary care provider, so it’s unfortunately a very unsatisfying course,” he said.
 

‘Primary Care Providers Do Value Guidelines’

However, “Primary care providers do value guidelines. They do value strong recommendations,” he said. We are trying to figure out how we can support people with unaddressed hearing loss in the primary care setting, Dr. McKee said. “Once we get there, we need to advocate for an expansion of coverage,” he said.

The authors note that the messages in the guidelines are important for all clinicians.

“The impact of hearing loss and screening should not be the sole responsibility of an audiologist, an otolaryngologist, nor primary care provider. Any time and place that a patient interacts with the healthcare system is an opportunity for preventive healthcare, such as hearing screening, to occur,” they write.

Funding for this research was provided by the American Academy of Otolaryngology–Head and Neck Surgery Foundation. Dr. Do and Dr. McKee report no relevant financial relationships. Full disclosures of the co-authors are listed with the full text of the paper.
 

Clinical guidelines on age-related hearing loss (ARHL), published in Otolaryngology–Head and Neck Surgery, highlight referral recommendations for all clinicians, including primary care doctors, who often are the first clinicians to screen for and address the condition.

Betty S. Tsai Do, MD, with the department of head & neck surgery at Kaiser Permanente in Walnut Creek, California, is the first author for the guidelines, which recommend screening patients 50 years or older at the time of a healthcare encounter. They also detail when to test and refer.
 

Three ‘Strong Recommendations’

Three of the action points are labeled “strong recommendations.” They are:

• If screening suggests hearing loss, clinicians should conduct an audiogram or refer to a clinician who can conduct one.
• Clinicians should offer, or refer to a specialist who can offer, appropriately fit amplification, such as hearing aids.
• If patients have appropriately fit amplification and still have trouble with hearing and understanding speech, clinicians should refer patients to see if they are good candidates for a cochlear implant.

The authors note that ARHL is the most common sensory deficit seen in older patients, but it is underdiagnosed and undertreated. “Between ages 65 and 74, one in three adults experience hearing loss and almost 50% of those 75 years of age or older will report hearing loss according to the National Institute on Deafness and Other Communication Disorders.” Consequences of the untreated deficit, in addition to limiting ability to communicate, include higher risk of dementia, cardiovascular disease, depression, falls, and workplace marginalization.

Until now, there have been no evidence-based clinical guidelines on when to screen, test, and refer. Though previously proposed quality improvement measures have defined ARHL as starting at age 60, these guidelines include those 50 and older to promote earlier detection.
 

Guidelines Only Part of the Solution

While the guidelines are a step in the right direction, they won’t address some persistent barriers to changing practice, said Michael McKee, MD, MPH, a family medicine physician and co-director of the Center for Disability Health and Wellness at the University of Michigan in Ann Arbor, who was not part of the guideline team.

“I think [the guidelines] will raise the awareness on why it’s important to address hearing loss,” he says. “Many primary care providers don’t elevate hearing loss as a priority topic. The problem is that we’re struggling with getting things in place to have a more supportive system to carry out those recommendations.”
 

Lack of Training and Support

The problems include lack of training on hearing loss for physicians, starting with medical school. Another complication is time: A conversation about hearing loss adds to the multitude of conversations a primary care provider is expected to have with their patients in a short visit.

Additionally, when hearing loss is suspected, an audiologist may be hard to find to perform the audiogram, Dr. McKee says. If patients agree to see an audiologist and that specialist finds hearing loss, patients may not want to wear a device due to stigma or may not be able to afford a device that will fit properly and truly benefit them because Medicare does not cover hearing aids.

“Only about 20-plus percent of those eligible for hearing aids get them,” he said. Hearing aids available over the counter help some people, but may be difficult to fit properly and may be hard for some to use correctly, he added.

“That comes back to the primary care provider, so it’s unfortunately a very unsatisfying course,” he said.
 

‘Primary Care Providers Do Value Guidelines’

However, “Primary care providers do value guidelines. They do value strong recommendations,” he said. We are trying to figure out how we can support people with unaddressed hearing loss in the primary care setting, Dr. McKee said. “Once we get there, we need to advocate for an expansion of coverage,” he said.

The authors note that the messages in the guidelines are important for all clinicians.

“The impact of hearing loss and screening should not be the sole responsibility of an audiologist, an otolaryngologist, nor primary care provider. Any time and place that a patient interacts with the healthcare system is an opportunity for preventive healthcare, such as hearing screening, to occur,” they write.

Funding for this research was provided by the American Academy of Otolaryngology–Head and Neck Surgery Foundation. Dr. Do and Dr. McKee report no relevant financial relationships. Full disclosures of the co-authors are listed with the full text of the paper.
 

TORONTO — Misinformation in pediatric medicine, like other areas of medicine, is widely regarded as a major public health threat, but the good news is that a new survey reveals that pediatricians still believe their counsel is respected by patients and families.

Despite acknowledging that health misinformation is on the rise, “nearly all the pediatricians we surveyed agreed or strongly agreed that their patients consider them a trusted information source,” reported Elizabeth A. Gottschlich, MA, a senior research associate with the American Academy of Pediatrics, Itasca, Illinois.

These data were generated by an ongoing cohort analysis called the Pediatricians Life and Career Experience Study (PLACES). Each year, two surveys are conducted with three groups of pediatricians in this cohort. They are defined by years in which they graduated from residency (2002-2004, 2009-2011, or 2016-2018).

While the longer survey of the two captures an array of issues regarding life and practice, the shorter “checkpoint” survey addresses a high-priority topic. In 2023, it was health misinformation. The data from this survey were presented at the Pediatric Academic Societies annual meeting.

About 40% of the 2706 pediatricians who completed this particular survey (just over 65% of the participants in PLACES) were general pediatricians, 50% were pediatric subspecialists, and 10% were hospitalists.

Almost all of the survey questions were answered on a five-point Likert scale.
 

A Matter of Trust

According to Ms. Gottschlich, approximately 80% of pediatricians agreed or strongly agreed that misinformation is a clinical issue for them. About one third of these strongly agreed, and only 6% disagreed.

There was also strong consensus that the problem has grown worse since the start of the COVID-19 epidemic. To this statement, 70% agreed or strongly agreed and 24% did not agree or disagree. Only 4% disagreed.

However, relatively few respondents appeared to be concerned about the ability of pediatricians to address the problem of misinformation, Ms. Gottschlich reported.

When asked to respond to the statement that the “community recognizes and uses pediatricians as trusted source for health information,” 87% agreed or strongly agreed. Of the remaining, 9% did not agree or disagree, leaving just 4% that disagreed or strongly disagreed.

For a similar but slightly different question, the consensus was even greater. To the statement “patients/families in your practice seek your input as a trusted source for health information,” 94% agreed or strongly agreed.
 

Encountering Misinformation

The survey went on to ask pediatricians about encounters with misinformation for seven specific issues. On the five-point Likert scale, the choices ranged from a few times per year to every day.

For reproductive health, gender-affirming care, and firearm injury prevention, about 80% of respondents answered at the very low end of the scale, meaning no more than about once per month. Encounters with misinformation was slightly greater with autism; nearly one third responded that they encountered misinformation once a week or more frequently.

For all three questions regarding vaccines, the proportions climbed substantially. Of these, the COVID-19 vaccine was the most common topic of misinformation, with more than half reporting that they addressed incorrect information once a week or more. Seven percent reported this occurs daily.

Nearly 40% of pediatricians responded that they dealt with misinformation about the HPV vaccine once per week or more, while 35% reported that they encountered misinformation this frequently about routine childhood vaccines. There was a small but not necessarily trivial proportion for each of these categories of vaccine who reported that they encountered misinformation on a daily basis.

When stratified by clinical focus, the encounters varied. For the COVID-19 vaccine, general pediatricians (67%) were far more likely to report addressing misinformation on a weekly or more frequent basis than hospitalists (39%) or subspecialists (46%). They were more than twice as likely to encounter misinformation about the HPV vaccine than hospitalists or pediatric subspecialists (46%, 17%, and 19%, respectively).

When stratified by urban, suburban, or rural practice areas, differences were relatively modest. Pediatricians in urban practices were less likely to face misinformation about HPV vaccine (29% vs 44% and 48% for suburban and rural areas, respectively), while pediatricians in rural practice were more likely to face misinformation about routine childhood vaccines (60% vs 33% and 35% for urban and suburban practices, respectively).

Differences were even narrower when misinformation encounters were compared among the West, Midwest, South, and Northeast. For the threshold of once per week or more commonly, misinformation about the COVID-19 vaccine was less common in the South (50% vs 55%-58% in the other areas), while misinformation about routine childhood vaccines was more commonly encountered in the West (41% vs 32%-35% in the other areas).
 

A Growing Problem

The confidence among pediatricians that their knowledge is valued is reassuring, according to Ms. Gottschlich, who noted that the U.S. Surgeon General declared health misinformation a serious threat to public health in 2021, but the problem of misinformation is growing, according to several sources.

One of these sources, at least in regard to adolescent health, appears to be social media, according to a recently published review article in JAMA Pediatrics. The lead author of that article, Monica L. Wang, DSc, has dual academic appointments at the Boston University School of Public Health and Harvard University’s T.H. Chan School of Public Health, Boston. Asked for a comment on this issue, she suggested that it might not be enough to just respond to misinformation but rather might be better to develop a dialogue that will reveal misconceptions.

“Just as they screen for preventive issues like seat belt use, sunscreen, and safe sex practices, [pediatricians should integrate] questions about health misinformation into visits, which can be a natural and effective way to encourage dialogue, proactively share accurate information, and promote well-being,” she said.

Agreeing with the premise that pediatricians are a credible source of information for parents and children, Dr. Wang very much endorses the principle that “pediatricians can play a critical role in addressing health misinformation.”

Ms. Gottschlich and Dr. Wang report no potential conflicts of interest.
 

TORONTO — Misinformation in pediatric medicine, like other areas of medicine, is widely regarded as a major public health threat, but the good news is that a new survey reveals that pediatricians still believe their counsel is respected by patients and families.

Despite acknowledging that health misinformation is on the rise, “nearly all the pediatricians we surveyed agreed or strongly agreed that their patients consider them a trusted information source,” reported Elizabeth A. Gottschlich, MA, a senior research associate with the American Academy of Pediatrics, Itasca, Illinois.

These data were generated by an ongoing cohort analysis called the Pediatricians Life and Career Experience Study (PLACES). Each year, two surveys are conducted with three groups of pediatricians in this cohort. They are defined by years in which they graduated from residency (2002-2004, 2009-2011, or 2016-2018).

While the longer survey of the two captures an array of issues regarding life and practice, the shorter “checkpoint” survey addresses a high-priority topic. In 2023, it was health misinformation. The data from this survey were presented at the Pediatric Academic Societies annual meeting.

About 40% of the 2706 pediatricians who completed this particular survey (just over 65% of the participants in PLACES) were general pediatricians, 50% were pediatric subspecialists, and 10% were hospitalists.

Almost all of the survey questions were answered on a five-point Likert scale.
 

A Matter of Trust

According to Ms. Gottschlich, approximately 80% of pediatricians agreed or strongly agreed that misinformation is a clinical issue for them. About one third of these strongly agreed, and only 6% disagreed.

There was also strong consensus that the problem has grown worse since the start of the COVID-19 epidemic. To this statement, 70% agreed or strongly agreed and 24% did not agree or disagree. Only 4% disagreed.

However, relatively few respondents appeared to be concerned about the ability of pediatricians to address the problem of misinformation, Ms. Gottschlich reported.

When asked to respond to the statement that the “community recognizes and uses pediatricians as trusted source for health information,” 87% agreed or strongly agreed. Of the remaining, 9% did not agree or disagree, leaving just 4% that disagreed or strongly disagreed.

For a similar but slightly different question, the consensus was even greater. To the statement “patients/families in your practice seek your input as a trusted source for health information,” 94% agreed or strongly agreed.
 

Encountering Misinformation

The survey went on to ask pediatricians about encounters with misinformation for seven specific issues. On the five-point Likert scale, the choices ranged from a few times per year to every day.

For reproductive health, gender-affirming care, and firearm injury prevention, about 80% of respondents answered at the very low end of the scale, meaning no more than about once per month. Encounters with misinformation was slightly greater with autism; nearly one third responded that they encountered misinformation once a week or more frequently.

For all three questions regarding vaccines, the proportions climbed substantially. Of these, the COVID-19 vaccine was the most common topic of misinformation, with more than half reporting that they addressed incorrect information once a week or more. Seven percent reported this occurs daily.

Nearly 40% of pediatricians responded that they dealt with misinformation about the HPV vaccine once per week or more, while 35% reported that they encountered misinformation this frequently about routine childhood vaccines. There was a small but not necessarily trivial proportion for each of these categories of vaccine who reported that they encountered misinformation on a daily basis.

When stratified by clinical focus, the encounters varied. For the COVID-19 vaccine, general pediatricians (67%) were far more likely to report addressing misinformation on a weekly or more frequent basis than hospitalists (39%) or subspecialists (46%). They were more than twice as likely to encounter misinformation about the HPV vaccine than hospitalists or pediatric subspecialists (46%, 17%, and 19%, respectively).

When stratified by urban, suburban, or rural practice areas, differences were relatively modest. Pediatricians in urban practices were less likely to face misinformation about HPV vaccine (29% vs 44% and 48% for suburban and rural areas, respectively), while pediatricians in rural practice were more likely to face misinformation about routine childhood vaccines (60% vs 33% and 35% for urban and suburban practices, respectively).

Differences were even narrower when misinformation encounters were compared among the West, Midwest, South, and Northeast. For the threshold of once per week or more commonly, misinformation about the COVID-19 vaccine was less common in the South (50% vs 55%-58% in the other areas), while misinformation about routine childhood vaccines was more commonly encountered in the West (41% vs 32%-35% in the other areas).
 

A Growing Problem

The confidence among pediatricians that their knowledge is valued is reassuring, according to Ms. Gottschlich, who noted that the U.S. Surgeon General declared health misinformation a serious threat to public health in 2021, but the problem of misinformation is growing, according to several sources.

One of these sources, at least in regard to adolescent health, appears to be social media, according to a recently published review article in JAMA Pediatrics. The lead author of that article, Monica L. Wang, DSc, has dual academic appointments at the Boston University School of Public Health and Harvard University’s T.H. Chan School of Public Health, Boston. Asked for a comment on this issue, she suggested that it might not be enough to just respond to misinformation but rather might be better to develop a dialogue that will reveal misconceptions.

“Just as they screen for preventive issues like seat belt use, sunscreen, and safe sex practices, [pediatricians should integrate] questions about health misinformation into visits, which can be a natural and effective way to encourage dialogue, proactively share accurate information, and promote well-being,” she said.

Agreeing with the premise that pediatricians are a credible source of information for parents and children, Dr. Wang very much endorses the principle that “pediatricians can play a critical role in addressing health misinformation.”

Ms. Gottschlich and Dr. Wang report no potential conflicts of interest.
 

TORONTO — Misinformation in pediatric medicine, like other areas of medicine, is widely regarded as a major public health threat, but the good news is that a new survey reveals that pediatricians still believe their counsel is respected by patients and families.

Despite acknowledging that health misinformation is on the rise, “nearly all the pediatricians we surveyed agreed or strongly agreed that their patients consider them a trusted information source,” reported Elizabeth A. Gottschlich, MA, a senior research associate with the American Academy of Pediatrics, Itasca, Illinois.

These data were generated by an ongoing cohort analysis called the Pediatricians Life and Career Experience Study (PLACES). Each year, two surveys are conducted with three groups of pediatricians in this cohort. They are defined by years in which they graduated from residency (2002-2004, 2009-2011, or 2016-2018).

While the longer survey of the two captures an array of issues regarding life and practice, the shorter “checkpoint” survey addresses a high-priority topic. In 2023, it was health misinformation. The data from this survey were presented at the Pediatric Academic Societies annual meeting.

About 40% of the 2706 pediatricians who completed this particular survey (just over 65% of the participants in PLACES) were general pediatricians, 50% were pediatric subspecialists, and 10% were hospitalists.

Almost all of the survey questions were answered on a five-point Likert scale.
 

A Matter of Trust

According to Ms. Gottschlich, approximately 80% of pediatricians agreed or strongly agreed that misinformation is a clinical issue for them. About one third of these strongly agreed, and only 6% disagreed.

There was also strong consensus that the problem has grown worse since the start of the COVID-19 epidemic. To this statement, 70% agreed or strongly agreed and 24% did not agree or disagree. Only 4% disagreed.

However, relatively few respondents appeared to be concerned about the ability of pediatricians to address the problem of misinformation, Ms. Gottschlich reported.

When asked to respond to the statement that the “community recognizes and uses pediatricians as trusted source for health information,” 87% agreed or strongly agreed. Of the remaining, 9% did not agree or disagree, leaving just 4% that disagreed or strongly disagreed.

For a similar but slightly different question, the consensus was even greater. To the statement “patients/families in your practice seek your input as a trusted source for health information,” 94% agreed or strongly agreed.
 

Encountering Misinformation

The survey went on to ask pediatricians about encounters with misinformation for seven specific issues. On the five-point Likert scale, the choices ranged from a few times per year to every day.

For reproductive health, gender-affirming care, and firearm injury prevention, about 80% of respondents answered at the very low end of the scale, meaning no more than about once per month. Encounters with misinformation was slightly greater with autism; nearly one third responded that they encountered misinformation once a week or more frequently.

For all three questions regarding vaccines, the proportions climbed substantially. Of these, the COVID-19 vaccine was the most common topic of misinformation, with more than half reporting that they addressed incorrect information once a week or more. Seven percent reported this occurs daily.

Nearly 40% of pediatricians responded that they dealt with misinformation about the HPV vaccine once per week or more, while 35% reported that they encountered misinformation this frequently about routine childhood vaccines. There was a small but not necessarily trivial proportion for each of these categories of vaccine who reported that they encountered misinformation on a daily basis.

When stratified by clinical focus, the encounters varied. For the COVID-19 vaccine, general pediatricians (67%) were far more likely to report addressing misinformation on a weekly or more frequent basis than hospitalists (39%) or subspecialists (46%). They were more than twice as likely to encounter misinformation about the HPV vaccine than hospitalists or pediatric subspecialists (46%, 17%, and 19%, respectively).

When stratified by urban, suburban, or rural practice areas, differences were relatively modest. Pediatricians in urban practices were less likely to face misinformation about HPV vaccine (29% vs 44% and 48% for suburban and rural areas, respectively), while pediatricians in rural practice were more likely to face misinformation about routine childhood vaccines (60% vs 33% and 35% for urban and suburban practices, respectively).

Differences were even narrower when misinformation encounters were compared among the West, Midwest, South, and Northeast. For the threshold of once per week or more commonly, misinformation about the COVID-19 vaccine was less common in the South (50% vs 55%-58% in the other areas), while misinformation about routine childhood vaccines was more commonly encountered in the West (41% vs 32%-35% in the other areas).
 

A Growing Problem

The confidence among pediatricians that their knowledge is valued is reassuring, according to Ms. Gottschlich, who noted that the U.S. Surgeon General declared health misinformation a serious threat to public health in 2021, but the problem of misinformation is growing, according to several sources.

One of these sources, at least in regard to adolescent health, appears to be social media, according to a recently published review article in JAMA Pediatrics. The lead author of that article, Monica L. Wang, DSc, has dual academic appointments at the Boston University School of Public Health and Harvard University’s T.H. Chan School of Public Health, Boston. Asked for a comment on this issue, she suggested that it might not be enough to just respond to misinformation but rather might be better to develop a dialogue that will reveal misconceptions.

“Just as they screen for preventive issues like seat belt use, sunscreen, and safe sex practices, [pediatricians should integrate] questions about health misinformation into visits, which can be a natural and effective way to encourage dialogue, proactively share accurate information, and promote well-being,” she said.

Agreeing with the premise that pediatricians are a credible source of information for parents and children, Dr. Wang very much endorses the principle that “pediatricians can play a critical role in addressing health misinformation.”

Ms. Gottschlich and Dr. Wang report no potential conflicts of interest.
 

Recent newspaper headlines have focused almost exclusively on gender-affirming medical interventions for transgender youth (eg, puberty blockers and gender-affirming hormones like estrogen and testosterone). It is true that these are important treatments that are consistently tied to improvements in mental health. However, an additional powerful predictor of good mental health outcomes for transgender youth is parental support and acceptance.

It is essential that clinicians consider this when creating treatment plans for transgender youth. While transgender young people are struggling with gender dysphoria, their parents are often struggling as well. Sadly, they are often afraid to share their own struggles, despite working through these being essential for their children’s thriving and well-being. I have a few key tips for combating this issue. My upcoming book Free to Be: Understanding Kids & Gender Identity provides much more context for parents and providers, but I will highlight a few big takeaways here.

Stanford Lucille Packard Children's Hospital.

Give Parents Their Own Space

Many parents have never encountered a transgender person in their life and have a lot of questions. At times, they may be “thinking out loud” and say things in passing that aren’t their final thoughts or opinions on a matter. This can, unfortunately, be damaging to their children. I often speak with adult transgender people whose parents said something they no longer believe (eg, “being trans is just a mental illness – you need therapy to fix it”), but these comments stick in the person’s mind and drive shame and self-esteem challenges later in life, sometimes for decades. Parents need to have a safe space, with a trained professional with expertise in gender, to work through their concerns and questions away from their children, so that when they talk to their kids about gender, they are presenting their fully formed thoughts.

Validate Parents’ Difficult Experiences

As pediatric providers, we are often focused on the difficult experiences of our transgender pediatric patients. However, their parents tend to be struggling as well, and that struggling predicts adverse mental health outcomes for their children.

The most common reaction a parent has upon learning their child is transgender is fear. It’s important to validate this fear (and other feelings that come out), so that parents know they can share with you what’s really going on in their minds.

There are some common themes we see for parents. Some are big fears: fear that their child will be victimized or fear that their child will later regret taking gender-affirming hormones and blame the parents for giving permission to take them. Parents often say they had a gendered vision for what their child’s future would be like, and their child coming out as transgender changes that (it can be helpful to gently remind parents that children almost never grow up exactly how we predict).

Some themes are more mundane but nonetheless distressing for parents, such as not wanting to throw away meaningful souvenirs from past vacations that have their child’s birth name on them. Clinicians can and should validate these thoughts and feelings, while also providing additional context and education. I often recommend the book Found in Transition by Pariah Hassouri, a pediatrician who goes through many of these common struggles after her daughter comes out as transgender.

 

Take a Three-Stage Approach When Adolescents Are Considering Gender-Affirming Medical Interventions

We recently outlined our process for conducting a biopsychosocial assessment for adolescents considering pubertal suppression for adolescent gender dysphoria in The Journal of the American Academy of Child & Adolescent Psychiatry, for those who want more detail on how to conduct these assessments. On the theme of supporting parents, I would highlight the value of taking a three-stage approach. In the first stage, a clinician meets with an adolescent alone to collect their gender history and discuss important considerations regarding the medical intervention. In stage two, the same information about the medical intervention is shared with parents, along with a summary of what the adolescent shared with the clinician (with the adolescent’s consent, of course). Often there will be some areas of disconnect. We make a list of these areas of disconnect that are addressed in stage three, in which the full family is brought together to get everyone on the same page and understanding each other’s perspectives.

Common disconnects include gender dysphoria seeming to “come out of nowhere” from the parents’ perspective, necessitating the young person to recount an early life experience in which they were harassed for expressing gender nonconformity, leading them to act stereotypically in line with their sex assigned at birth for years to avoid being “outed” and harassed more. Conversations around fertility preservation can be particularly complex. Young people and their parents also sometimes have different conceptualizations of gender identity and require a shared framework for talking about gender identity (which I offer in my forthcoming book). This list of family therapy topics can be diverse and highly dependent on the family. An additional resource for this phase of the family therapy is The Family Acceptance Project, which has created culturally tailored materials to help parents understand their sexual and gender minority children.

In summary, fostering healthy family functioning is essential for the care of transgender and gender diverse youth, and parents require support in addition to their children needing support. I encourage all gender providers to incorporate the vital element of family therapy into their practice.

 

Dr. Turban is director of the Gender Psychiatry Program at the University of California, San Francisco, where he is an assistant professor of child & adolescent psychiatry and affiliate faculty at the Philip R. Lee Institute for Health Policy Studies. He is on X @jack_turban.

Recent newspaper headlines have focused almost exclusively on gender-affirming medical interventions for transgender youth (eg, puberty blockers and gender-affirming hormones like estrogen and testosterone). It is true that these are important treatments that are consistently tied to improvements in mental health. However, an additional powerful predictor of good mental health outcomes for transgender youth is parental support and acceptance.

It is essential that clinicians consider this when creating treatment plans for transgender youth. While transgender young people are struggling with gender dysphoria, their parents are often struggling as well. Sadly, they are often afraid to share their own struggles, despite working through these being essential for their children’s thriving and well-being. I have a few key tips for combating this issue. My upcoming book Free to Be: Understanding Kids & Gender Identity provides much more context for parents and providers, but I will highlight a few big takeaways here.

Stanford Lucille Packard Children's Hospital.

Give Parents Their Own Space

Many parents have never encountered a transgender person in their life and have a lot of questions. At times, they may be “thinking out loud” and say things in passing that aren’t their final thoughts or opinions on a matter. This can, unfortunately, be damaging to their children. I often speak with adult transgender people whose parents said something they no longer believe (eg, “being trans is just a mental illness – you need therapy to fix it”), but these comments stick in the person’s mind and drive shame and self-esteem challenges later in life, sometimes for decades. Parents need to have a safe space, with a trained professional with expertise in gender, to work through their concerns and questions away from their children, so that when they talk to their kids about gender, they are presenting their fully formed thoughts.

Validate Parents’ Difficult Experiences

As pediatric providers, we are often focused on the difficult experiences of our transgender pediatric patients. However, their parents tend to be struggling as well, and that struggling predicts adverse mental health outcomes for their children.

The most common reaction a parent has upon learning their child is transgender is fear. It’s important to validate this fear (and other feelings that come out), so that parents know they can share with you what’s really going on in their minds.

There are some common themes we see for parents. Some are big fears: fear that their child will be victimized or fear that their child will later regret taking gender-affirming hormones and blame the parents for giving permission to take them. Parents often say they had a gendered vision for what their child’s future would be like, and their child coming out as transgender changes that (it can be helpful to gently remind parents that children almost never grow up exactly how we predict).

Some themes are more mundane but nonetheless distressing for parents, such as not wanting to throw away meaningful souvenirs from past vacations that have their child’s birth name on them. Clinicians can and should validate these thoughts and feelings, while also providing additional context and education. I often recommend the book Found in Transition by Pariah Hassouri, a pediatrician who goes through many of these common struggles after her daughter comes out as transgender.

 

Take a Three-Stage Approach When Adolescents Are Considering Gender-Affirming Medical Interventions

We recently outlined our process for conducting a biopsychosocial assessment for adolescents considering pubertal suppression for adolescent gender dysphoria in The Journal of the American Academy of Child & Adolescent Psychiatry, for those who want more detail on how to conduct these assessments. On the theme of supporting parents, I would highlight the value of taking a three-stage approach. In the first stage, a clinician meets with an adolescent alone to collect their gender history and discuss important considerations regarding the medical intervention. In stage two, the same information about the medical intervention is shared with parents, along with a summary of what the adolescent shared with the clinician (with the adolescent’s consent, of course). Often there will be some areas of disconnect. We make a list of these areas of disconnect that are addressed in stage three, in which the full family is brought together to get everyone on the same page and understanding each other’s perspectives.

Common disconnects include gender dysphoria seeming to “come out of nowhere” from the parents’ perspective, necessitating the young person to recount an early life experience in which they were harassed for expressing gender nonconformity, leading them to act stereotypically in line with their sex assigned at birth for years to avoid being “outed” and harassed more. Conversations around fertility preservation can be particularly complex. Young people and their parents also sometimes have different conceptualizations of gender identity and require a shared framework for talking about gender identity (which I offer in my forthcoming book). This list of family therapy topics can be diverse and highly dependent on the family. An additional resource for this phase of the family therapy is The Family Acceptance Project, which has created culturally tailored materials to help parents understand their sexual and gender minority children.

In summary, fostering healthy family functioning is essential for the care of transgender and gender diverse youth, and parents require support in addition to their children needing support. I encourage all gender providers to incorporate the vital element of family therapy into their practice.

 

Dr. Turban is director of the Gender Psychiatry Program at the University of California, San Francisco, where he is an assistant professor of child & adolescent psychiatry and affiliate faculty at the Philip R. Lee Institute for Health Policy Studies. He is on X @jack_turban.

Recent newspaper headlines have focused almost exclusively on gender-affirming medical interventions for transgender youth (eg, puberty blockers and gender-affirming hormones like estrogen and testosterone). It is true that these are important treatments that are consistently tied to improvements in mental health. However, an additional powerful predictor of good mental health outcomes for transgender youth is parental support and acceptance.

It is essential that clinicians consider this when creating treatment plans for transgender youth. While transgender young people are struggling with gender dysphoria, their parents are often struggling as well. Sadly, they are often afraid to share their own struggles, despite working through these being essential for their children’s thriving and well-being. I have a few key tips for combating this issue. My upcoming book Free to Be: Understanding Kids & Gender Identity provides much more context for parents and providers, but I will highlight a few big takeaways here.

Stanford Lucille Packard Children's Hospital.

Give Parents Their Own Space

Many parents have never encountered a transgender person in their life and have a lot of questions. At times, they may be “thinking out loud” and say things in passing that aren’t their final thoughts or opinions on a matter. This can, unfortunately, be damaging to their children. I often speak with adult transgender people whose parents said something they no longer believe (eg, “being trans is just a mental illness – you need therapy to fix it”), but these comments stick in the person’s mind and drive shame and self-esteem challenges later in life, sometimes for decades. Parents need to have a safe space, with a trained professional with expertise in gender, to work through their concerns and questions away from their children, so that when they talk to their kids about gender, they are presenting their fully formed thoughts.

Validate Parents’ Difficult Experiences

As pediatric providers, we are often focused on the difficult experiences of our transgender pediatric patients. However, their parents tend to be struggling as well, and that struggling predicts adverse mental health outcomes for their children.

The most common reaction a parent has upon learning their child is transgender is fear. It’s important to validate this fear (and other feelings that come out), so that parents know they can share with you what’s really going on in their minds.

There are some common themes we see for parents. Some are big fears: fear that their child will be victimized or fear that their child will later regret taking gender-affirming hormones and blame the parents for giving permission to take them. Parents often say they had a gendered vision for what their child’s future would be like, and their child coming out as transgender changes that (it can be helpful to gently remind parents that children almost never grow up exactly how we predict).

Some themes are more mundane but nonetheless distressing for parents, such as not wanting to throw away meaningful souvenirs from past vacations that have their child’s birth name on them. Clinicians can and should validate these thoughts and feelings, while also providing additional context and education. I often recommend the book Found in Transition by Pariah Hassouri, a pediatrician who goes through many of these common struggles after her daughter comes out as transgender.

 

Take a Three-Stage Approach When Adolescents Are Considering Gender-Affirming Medical Interventions

We recently outlined our process for conducting a biopsychosocial assessment for adolescents considering pubertal suppression for adolescent gender dysphoria in The Journal of the American Academy of Child & Adolescent Psychiatry, for those who want more detail on how to conduct these assessments. On the theme of supporting parents, I would highlight the value of taking a three-stage approach. In the first stage, a clinician meets with an adolescent alone to collect their gender history and discuss important considerations regarding the medical intervention. In stage two, the same information about the medical intervention is shared with parents, along with a summary of what the adolescent shared with the clinician (with the adolescent’s consent, of course). Often there will be some areas of disconnect. We make a list of these areas of disconnect that are addressed in stage three, in which the full family is brought together to get everyone on the same page and understanding each other’s perspectives.

Common disconnects include gender dysphoria seeming to “come out of nowhere” from the parents’ perspective, necessitating the young person to recount an early life experience in which they were harassed for expressing gender nonconformity, leading them to act stereotypically in line with their sex assigned at birth for years to avoid being “outed” and harassed more. Conversations around fertility preservation can be particularly complex. Young people and their parents also sometimes have different conceptualizations of gender identity and require a shared framework for talking about gender identity (which I offer in my forthcoming book). This list of family therapy topics can be diverse and highly dependent on the family. An additional resource for this phase of the family therapy is The Family Acceptance Project, which has created culturally tailored materials to help parents understand their sexual and gender minority children.

In summary, fostering healthy family functioning is essential for the care of transgender and gender diverse youth, and parents require support in addition to their children needing support. I encourage all gender providers to incorporate the vital element of family therapy into their practice.

 

Dr. Turban is director of the Gender Psychiatry Program at the University of California, San Francisco, where he is an assistant professor of child & adolescent psychiatry and affiliate faculty at the Philip R. Lee Institute for Health Policy Studies. He is on X @jack_turban.

TOPLINE:

Nearly 90% of adults were at risk of developing cardiovascular-kidney-metabolic (CKM) syndrome between 2011 and 2020, according to new research published in JAMA.

METHODOLOGY:

• In 2023, the American Heart Association defined  to acknowledge how heart and kidney diseases, diabetes, and obesity interact and are increasingly co-occurring conditions.
• Researchers used data from the National Health and Nutrition Examination Survey between 2011 and 2020.
• More than 10,000 adults over age 20 years were included; all of them received a physical and fasting laboratory measurements and self-reported their cardiovascular disease (CVD) status.
• Researchers created categories for risk, ranging from 0 (no risk factors) to 4, using factors such as kidney disease, obesity, and hypertension.

TAKEAWAY:

• Nearly 90% of participants met the criteria for having a stage of the CKM syndrome, with rates remaining steady throughout the study period.Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.
• Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
   
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
   
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.

IN PRACTICE:

“Equitable health care approaches prioritizing CKM health are urgently needed,” the study authors wrote.

SOURCE:

The study was led by Muthiah Vaduganathan, MD, MPH, cardiologist and researcher at Brigham and Women’s Hospital, Harvard Medical School, Boston.

LIMITATIONS: 

Established CVD statuses were self-reported. Some data that would indicate advanced CKM stages were not available (eg, cardiac biomarkers, echocardiography, and coronary angiography), which may have led to an underestimation of rates.

DISCLOSURES:

One author received grants from Bristol Myers Squibb–Pfizer outside the submitted work. Dr. Vaduganathan received grants from and was an adviser and committee trial member for various pharmaceutical companies outside the submitted work. The authors reported no other disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Nearly 90% of adults were at risk of developing cardiovascular-kidney-metabolic (CKM) syndrome between 2011 and 2020, according to new research published in JAMA.

METHODOLOGY:

• In 2023, the American Heart Association defined  to acknowledge how heart and kidney diseases, diabetes, and obesity interact and are increasingly co-occurring conditions.
• Researchers used data from the National Health and Nutrition Examination Survey between 2011 and 2020.
• More than 10,000 adults over age 20 years were included; all of them received a physical and fasting laboratory measurements and self-reported their cardiovascular disease (CVD) status.
• Researchers created categories for risk, ranging from 0 (no risk factors) to 4, using factors such as kidney disease, obesity, and hypertension.

TAKEAWAY:

• Nearly 90% of participants met the criteria for having a stage of the CKM syndrome, with rates remaining steady throughout the study period.Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.
• Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
   
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
   
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.

IN PRACTICE:

“Equitable health care approaches prioritizing CKM health are urgently needed,” the study authors wrote.

SOURCE:

The study was led by Muthiah Vaduganathan, MD, MPH, cardiologist and researcher at Brigham and Women’s Hospital, Harvard Medical School, Boston.

LIMITATIONS: 

Established CVD statuses were self-reported. Some data that would indicate advanced CKM stages were not available (eg, cardiac biomarkers, echocardiography, and coronary angiography), which may have led to an underestimation of rates.

DISCLOSURES:

One author received grants from Bristol Myers Squibb–Pfizer outside the submitted work. Dr. Vaduganathan received grants from and was an adviser and committee trial member for various pharmaceutical companies outside the submitted work. The authors reported no other disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Nearly 90% of adults were at risk of developing cardiovascular-kidney-metabolic (CKM) syndrome between 2011 and 2020, according to new research published in JAMA.

METHODOLOGY:

• In 2023, the American Heart Association defined  to acknowledge how heart and kidney diseases, diabetes, and obesity interact and are increasingly co-occurring conditions.
• Researchers used data from the National Health and Nutrition Examination Survey between 2011 and 2020.
• More than 10,000 adults over age 20 years were included; all of them received a physical and fasting laboratory measurements and self-reported their cardiovascular disease (CVD) status.
• Researchers created categories for risk, ranging from 0 (no risk factors) to 4, using factors such as kidney disease, obesity, and hypertension.

TAKEAWAY:

• Nearly 90% of participants met the criteria for having a stage of the CKM syndrome, with rates remaining steady throughout the study period.Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.
• Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
   
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
   
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.

IN PRACTICE:

“Equitable health care approaches prioritizing CKM health are urgently needed,” the study authors wrote.

SOURCE:

The study was led by Muthiah Vaduganathan, MD, MPH, cardiologist and researcher at Brigham and Women’s Hospital, Harvard Medical School, Boston.

LIMITATIONS: 

Established CVD statuses were self-reported. Some data that would indicate advanced CKM stages were not available (eg, cardiac biomarkers, echocardiography, and coronary angiography), which may have led to an underestimation of rates.

DISCLOSURES:

One author received grants from Bristol Myers Squibb–Pfizer outside the submitted work. Dr. Vaduganathan received grants from and was an adviser and committee trial member for various pharmaceutical companies outside the submitted work. The authors reported no other disclosures.

A version of this article appeared on Medscape.com.

DENVER — A retrospective analysis of pediatric patients with Lennox-Gastaut syndrome (LGS) suggests that the antiseizure medication cenobamate (SK Life Sciences) in combination with existing lines of therapy may be associated with fewer hospital in-patient days and emergency room visits. The conclusions were reached by comparing outcomes to patient historical data, though they were not analyzed statistically.

A Proof-of-Concept Study

In an interview, Karen Keough, MD, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology, conceded the key limitation was that the researchers were not able to perform statistical analysis due to the nature of the data. “It’s just showing trends. It’s proof of concept that cenobamate can be effective in one of the most refractory forms of epilepsy, which always includes focal seizures. That’s what led to the initial FDA indication, but we also know that this medication has a lot of promise and is probably going to be effective in other forms of epilepsy and probably in other seizure types,” said Dr. Keough, who is a neurologist at Pediatrix Child Neurology Consultants of Austin, Texas.

Although she has seen significant improvements in many patients, Dr. Keough reported that most patients become refractory again. “Unfortunately, honeymoons are probably real in cenobamate. Continuing to follow those patients as I do, since they’re my own patients, I have quite a few who had more than a year of seizure freedom, [but] their seizures are back, though not as bad as they were before cenobamate. I just can’t get them back to that 100% control category. I do have a few that are still in the 100% control category, but not very many,” she said.

She also presented a retrospective chart review of 36 LGS patients between the ages of 1 and 27 years at the American Epilepsy Society in December 2023, which showed that addition of cenobamate was associated with a reduction in seizure frequency in 85% of patients. “It was a profound number of patients who had long periods of seizure freedom,” she said.
 

A Promising Treatment Option

Dr. Keough is considering moving cenobamate up in the treatment sequence of new LGS patients. “I don’t use cenobamate first line in anyone because we have good first-line agents for simple epilepsy in Lennox-Gastaut, but I’m bringing out cenobamate pretty early in the course, because I do think it has superior efficacy compared with most other drugs that we have available. Most of my patients are very established and they’ve seen lots of other drugs. For many patients, there are only a couple of drugs left on the list that [they] have never tried, but we’re going to put cenobamate at the top of that. For my newer diagnoses, I’m going to bring it out much earlier,” she said, though other drugs such as clobazam (Onfi) would still rank ahead of cenobamate.

The study was drawn from records of the HealthVerity Marketplace Database, which includes more than 150 commercial, Medicare, and Medicaid payers. It included 76 patients aged 17 or under who took at least one antiseizure medication between May 2020 and December 2022, and who had filled at least two prescriptions of cenobamate and had 180 or more days of medical and pharmacy enrollment. The mean age was 13.4 years (5.3% 0-5 years, 15.8% 6-11 years, 78.9% 12-17 years), and 40.8% were female. Seizure types included absence (17.1%), focal (75.0%), and generalized tonic-clonic (86.8%). All patients had a history of intractable seizures, 80.3% had a history of status epilepticus, and 28.9% had a history of infantile seizures. A little more than one fourth (27.6%) of patients had commercial insurance. In the previous 90 days, 21.1% had had an emergency room visit or in-patient hospital stay.

Common antiseizure medications taken with cenobamate included cannabidiol (n = 14), clobazam (n = 8), and levetiracetam (n = 18).

During the cenobamate treatment period, patients had a lower incidence of epilepsy-related inpatient days per year (3.36 vs 3.94), epilepsy-related ER visits per year (0.66 vs 1.19), and likelihood of requiring a new line of epilepsy therapy (35.5% vs 100%).
 

‘Promising’ Results, but More Research Is Needed

The fact that cenobamate was used in combination with other therapies, plus the lack of a control group, makes it difficult to determine if cenobamate was actually responsible for the improvements, according to Nassim Zecavati, MD, who was asked for comment on the study. “I think the results are promising, but there’s obviously a need for a randomized, controlled trial to understand whether it was this medication or the combination of cenobamate with [other medications]. How do we know that this isn’t a compound effect, that it’s multifactorial, and a combination of multiple medications versus the cenobamate?” she said.

Still, she noted that LGS patients are highly vulnerable to hospital admissions and status epilepticus, making the parameters examined in the study valid and important. “I think that this drug likely has a role in the treatment of patients with LGS, particularly pediatric patients. I think we just need more data,” said Dr. Zecavati, who is director of Epilepsy at the Children’s Hospital of Richmond in Virginia and associate professor of Neurology at Virginia Commonwealth University.

Dr. Keough is a speaker for SK Life Sciences. Dr. Zecavati has no relevant financial disclosures.

DENVER — A retrospective analysis of pediatric patients with Lennox-Gastaut syndrome (LGS) suggests that the antiseizure medication cenobamate (SK Life Sciences) in combination with existing lines of therapy may be associated with fewer hospital in-patient days and emergency room visits. The conclusions were reached by comparing outcomes to patient historical data, though they were not analyzed statistically.

A Proof-of-Concept Study

In an interview, Karen Keough, MD, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology, conceded the key limitation was that the researchers were not able to perform statistical analysis due to the nature of the data. “It’s just showing trends. It’s proof of concept that cenobamate can be effective in one of the most refractory forms of epilepsy, which always includes focal seizures. That’s what led to the initial FDA indication, but we also know that this medication has a lot of promise and is probably going to be effective in other forms of epilepsy and probably in other seizure types,” said Dr. Keough, who is a neurologist at Pediatrix Child Neurology Consultants of Austin, Texas.

Although she has seen significant improvements in many patients, Dr. Keough reported that most patients become refractory again. “Unfortunately, honeymoons are probably real in cenobamate. Continuing to follow those patients as I do, since they’re my own patients, I have quite a few who had more than a year of seizure freedom, [but] their seizures are back, though not as bad as they were before cenobamate. I just can’t get them back to that 100% control category. I do have a few that are still in the 100% control category, but not very many,” she said.

She also presented a retrospective chart review of 36 LGS patients between the ages of 1 and 27 years at the American Epilepsy Society in December 2023, which showed that addition of cenobamate was associated with a reduction in seizure frequency in 85% of patients. “It was a profound number of patients who had long periods of seizure freedom,” she said.
 

A Promising Treatment Option

Dr. Keough is considering moving cenobamate up in the treatment sequence of new LGS patients. “I don’t use cenobamate first line in anyone because we have good first-line agents for simple epilepsy in Lennox-Gastaut, but I’m bringing out cenobamate pretty early in the course, because I do think it has superior efficacy compared with most other drugs that we have available. Most of my patients are very established and they’ve seen lots of other drugs. For many patients, there are only a couple of drugs left on the list that [they] have never tried, but we’re going to put cenobamate at the top of that. For my newer diagnoses, I’m going to bring it out much earlier,” she said, though other drugs such as clobazam (Onfi) would still rank ahead of cenobamate.

The study was drawn from records of the HealthVerity Marketplace Database, which includes more than 150 commercial, Medicare, and Medicaid payers. It included 76 patients aged 17 or under who took at least one antiseizure medication between May 2020 and December 2022, and who had filled at least two prescriptions of cenobamate and had 180 or more days of medical and pharmacy enrollment. The mean age was 13.4 years (5.3% 0-5 years, 15.8% 6-11 years, 78.9% 12-17 years), and 40.8% were female. Seizure types included absence (17.1%), focal (75.0%), and generalized tonic-clonic (86.8%). All patients had a history of intractable seizures, 80.3% had a history of status epilepticus, and 28.9% had a history of infantile seizures. A little more than one fourth (27.6%) of patients had commercial insurance. In the previous 90 days, 21.1% had had an emergency room visit or in-patient hospital stay.

Common antiseizure medications taken with cenobamate included cannabidiol (n = 14), clobazam (n = 8), and levetiracetam (n = 18).

During the cenobamate treatment period, patients had a lower incidence of epilepsy-related inpatient days per year (3.36 vs 3.94), epilepsy-related ER visits per year (0.66 vs 1.19), and likelihood of requiring a new line of epilepsy therapy (35.5% vs 100%).
 

‘Promising’ Results, but More Research Is Needed

The fact that cenobamate was used in combination with other therapies, plus the lack of a control group, makes it difficult to determine if cenobamate was actually responsible for the improvements, according to Nassim Zecavati, MD, who was asked for comment on the study. “I think the results are promising, but there’s obviously a need for a randomized, controlled trial to understand whether it was this medication or the combination of cenobamate with [other medications]. How do we know that this isn’t a compound effect, that it’s multifactorial, and a combination of multiple medications versus the cenobamate?” she said.

Still, she noted that LGS patients are highly vulnerable to hospital admissions and status epilepticus, making the parameters examined in the study valid and important. “I think that this drug likely has a role in the treatment of patients with LGS, particularly pediatric patients. I think we just need more data,” said Dr. Zecavati, who is director of Epilepsy at the Children’s Hospital of Richmond in Virginia and associate professor of Neurology at Virginia Commonwealth University.

Dr. Keough is a speaker for SK Life Sciences. Dr. Zecavati has no relevant financial disclosures.

DENVER — A retrospective analysis of pediatric patients with Lennox-Gastaut syndrome (LGS) suggests that the antiseizure medication cenobamate (SK Life Sciences) in combination with existing lines of therapy may be associated with fewer hospital in-patient days and emergency room visits. The conclusions were reached by comparing outcomes to patient historical data, though they were not analyzed statistically.

A Proof-of-Concept Study

In an interview, Karen Keough, MD, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology, conceded the key limitation was that the researchers were not able to perform statistical analysis due to the nature of the data. “It’s just showing trends. It’s proof of concept that cenobamate can be effective in one of the most refractory forms of epilepsy, which always includes focal seizures. That’s what led to the initial FDA indication, but we also know that this medication has a lot of promise and is probably going to be effective in other forms of epilepsy and probably in other seizure types,” said Dr. Keough, who is a neurologist at Pediatrix Child Neurology Consultants of Austin, Texas.

Although she has seen significant improvements in many patients, Dr. Keough reported that most patients become refractory again. “Unfortunately, honeymoons are probably real in cenobamate. Continuing to follow those patients as I do, since they’re my own patients, I have quite a few who had more than a year of seizure freedom, [but] their seizures are back, though not as bad as they were before cenobamate. I just can’t get them back to that 100% control category. I do have a few that are still in the 100% control category, but not very many,” she said.

She also presented a retrospective chart review of 36 LGS patients between the ages of 1 and 27 years at the American Epilepsy Society in December 2023, which showed that addition of cenobamate was associated with a reduction in seizure frequency in 85% of patients. “It was a profound number of patients who had long periods of seizure freedom,” she said.
 

A Promising Treatment Option

Dr. Keough is considering moving cenobamate up in the treatment sequence of new LGS patients. “I don’t use cenobamate first line in anyone because we have good first-line agents for simple epilepsy in Lennox-Gastaut, but I’m bringing out cenobamate pretty early in the course, because I do think it has superior efficacy compared with most other drugs that we have available. Most of my patients are very established and they’ve seen lots of other drugs. For many patients, there are only a couple of drugs left on the list that [they] have never tried, but we’re going to put cenobamate at the top of that. For my newer diagnoses, I’m going to bring it out much earlier,” she said, though other drugs such as clobazam (Onfi) would still rank ahead of cenobamate.

The study was drawn from records of the HealthVerity Marketplace Database, which includes more than 150 commercial, Medicare, and Medicaid payers. It included 76 patients aged 17 or under who took at least one antiseizure medication between May 2020 and December 2022, and who had filled at least two prescriptions of cenobamate and had 180 or more days of medical and pharmacy enrollment. The mean age was 13.4 years (5.3% 0-5 years, 15.8% 6-11 years, 78.9% 12-17 years), and 40.8% were female. Seizure types included absence (17.1%), focal (75.0%), and generalized tonic-clonic (86.8%). All patients had a history of intractable seizures, 80.3% had a history of status epilepticus, and 28.9% had a history of infantile seizures. A little more than one fourth (27.6%) of patients had commercial insurance. In the previous 90 days, 21.1% had had an emergency room visit or in-patient hospital stay.

Common antiseizure medications taken with cenobamate included cannabidiol (n = 14), clobazam (n = 8), and levetiracetam (n = 18).

During the cenobamate treatment period, patients had a lower incidence of epilepsy-related inpatient days per year (3.36 vs 3.94), epilepsy-related ER visits per year (0.66 vs 1.19), and likelihood of requiring a new line of epilepsy therapy (35.5% vs 100%).
 

‘Promising’ Results, but More Research Is Needed

The fact that cenobamate was used in combination with other therapies, plus the lack of a control group, makes it difficult to determine if cenobamate was actually responsible for the improvements, according to Nassim Zecavati, MD, who was asked for comment on the study. “I think the results are promising, but there’s obviously a need for a randomized, controlled trial to understand whether it was this medication or the combination of cenobamate with [other medications]. How do we know that this isn’t a compound effect, that it’s multifactorial, and a combination of multiple medications versus the cenobamate?” she said.

Still, she noted that LGS patients are highly vulnerable to hospital admissions and status epilepticus, making the parameters examined in the study valid and important. “I think that this drug likely has a role in the treatment of patients with LGS, particularly pediatric patients. I think we just need more data,” said Dr. Zecavati, who is director of Epilepsy at the Children’s Hospital of Richmond in Virginia and associate professor of Neurology at Virginia Commonwealth University.

Dr. Keough is a speaker for SK Life Sciences. Dr. Zecavati has no relevant financial disclosures.

The Diagnosis: Purpuric Drug Eruption

Histopathology revealed interface dermatitis, spongiosis, and a perivascular lymphocytic infiltrate with extravasated red blood cells consistent with a purpuric drug eruption. Our patient achieved remission of hairy cell leukemia after receiving only 2 of 5 expected doses of cladribine. The rash resolved completely in 3 weeks following a prednisone taper (Figure).

Hairy cell leukemia is a rare indolent lymphoproliferative disorder of B cells that accounts for approximately 2% of adult leukemias in the United States. Cladribine, a purine nucleoside analog that impairs DNA synthesis and repair, has become the mainstay of therapy, demonstrating a 95% complete response rate.¹ Although few reports have addressed the cutaneous reactions seen with cladribine therapy, they can occur in more than 50% of patients.^1,2 The most common skin manifestation associated with cladribine therapy is a morbilliform rash, but Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) have been reported.¹

Few cases of purpuric eruption secondary to cladribine treatment have been described, and nearly all reports involve concomitant medications such as allopurinol, which our patient was taking, and antibiotics including trimethoprim-sulfamethoxazole and penicillins.^1,3,4 In a cohort of 35 patients receiving cladribine,1 only concomitant treatment with cladribine and allopurinol caused cutaneous reactions, further supporting the hypothesis of cladribine-induced drug sensitivity. Allopurinol often is prescribed during induction therapy for prophylaxis against tumor lysis syndrome; similarly, antibiotics frequently are given prophylactically and therapeutically for neutropenic fever. It is believed that T-cell imbalance and profound lymphopenia induced by cladribine increase susceptibility to drug hypersensitivity reactions.^1,3

The typical purpuric eruption develops within 2 days of starting cladribine therapy. Diascopy will reveal petechiae, and biopsy should be performed to rule out other serious drug-induced reactions, such as erythema multiforme, Stevens-Johnson syndrome, and TEN. A cladribine-induced purpuric eruption typically is self-resolving and carries a favorable prognosis, though high-dose corticosteroids often are prescribed to hasten recovery. The rare reports of serious cutaneous reactions secondary to cladribine therapy have been with maculopapular, not purpuric eruptions.² Based on limited available data, cladribine-induced purpura should not be a limitation to continued treatment in patients who need it.¹ Careful consideration of concomitant drug use is necessary, as the current literature demonstrates resolution of rash with withdrawal of other therapies, namely allopurinol.^2-4 Future studies are needed to examine the safety of withholding offending medications and to further elucidate the mechanisms contributing to drug hypersensitivity due to cladribine.

Widespread purpura and petechiae can pose a wide differential; the patient’s recent history of cladribine administration pointed to a classic purpuric eruption. Other diagnoses such as toxic erythema of chemotherapy (TEC) and TEN are not purpuric, though plaques can be violaceous. Lack of bullae, blisters, and facial or mucosal surface involvement suggest TEN.⁵ Thrombotic thrombocytopenic purpura and disseminated intravascular coagulation do manifest with petechiae and purpura, though such a robust eruption in the context of recent cladribine therapy is less likely. The classic retiform purpura and necrosis were not present to suggest purpura fulminans from disseminated intravascular coagulation.

Several of the proposed diagnoses as well as a purpuric drug eruption would demonstrate extravasated red blood cells on histopathology, but the presence of interface dermatitis narrows the differential to a purpuric drug eruption. Necrotic keratinocytes and full-thickness necrosis were not present on biopsy to support a diagnosis of TEN in our patient. Characteristic features of TEC—including eccrine squamous syringometaplasia, dermal edema, and keratinocyte atypia—were not present on biopsy.⁶ Finally, although TEN should resolve with steroid treatment, TEC is self-limited and thrombotic thrombocytopenic purpura and disseminated intravascular coagulation would not resolve with use of steroids alone. 

The Diagnosis: Purpuric Drug Eruption

Histopathology revealed interface dermatitis, spongiosis, and a perivascular lymphocytic infiltrate with extravasated red blood cells consistent with a purpuric drug eruption. Our patient achieved remission of hairy cell leukemia after receiving only 2 of 5 expected doses of cladribine. The rash resolved completely in 3 weeks following a prednisone taper (Figure).

Hairy cell leukemia is a rare indolent lymphoproliferative disorder of B cells that accounts for approximately 2% of adult leukemias in the United States. Cladribine, a purine nucleoside analog that impairs DNA synthesis and repair, has become the mainstay of therapy, demonstrating a 95% complete response rate.¹ Although few reports have addressed the cutaneous reactions seen with cladribine therapy, they can occur in more than 50% of patients.^1,2 The most common skin manifestation associated with cladribine therapy is a morbilliform rash, but Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) have been reported.¹

Few cases of purpuric eruption secondary to cladribine treatment have been described, and nearly all reports involve concomitant medications such as allopurinol, which our patient was taking, and antibiotics including trimethoprim-sulfamethoxazole and penicillins.^1,3,4 In a cohort of 35 patients receiving cladribine,1 only concomitant treatment with cladribine and allopurinol caused cutaneous reactions, further supporting the hypothesis of cladribine-induced drug sensitivity. Allopurinol often is prescribed during induction therapy for prophylaxis against tumor lysis syndrome; similarly, antibiotics frequently are given prophylactically and therapeutically for neutropenic fever. It is believed that T-cell imbalance and profound lymphopenia induced by cladribine increase susceptibility to drug hypersensitivity reactions.^1,3

The typical purpuric eruption develops within 2 days of starting cladribine therapy. Diascopy will reveal petechiae, and biopsy should be performed to rule out other serious drug-induced reactions, such as erythema multiforme, Stevens-Johnson syndrome, and TEN. A cladribine-induced purpuric eruption typically is self-resolving and carries a favorable prognosis, though high-dose corticosteroids often are prescribed to hasten recovery. The rare reports of serious cutaneous reactions secondary to cladribine therapy have been with maculopapular, not purpuric eruptions.² Based on limited available data, cladribine-induced purpura should not be a limitation to continued treatment in patients who need it.¹ Careful consideration of concomitant drug use is necessary, as the current literature demonstrates resolution of rash with withdrawal of other therapies, namely allopurinol.^2-4 Future studies are needed to examine the safety of withholding offending medications and to further elucidate the mechanisms contributing to drug hypersensitivity due to cladribine.

Widespread purpura and petechiae can pose a wide differential; the patient’s recent history of cladribine administration pointed to a classic purpuric eruption. Other diagnoses such as toxic erythema of chemotherapy (TEC) and TEN are not purpuric, though plaques can be violaceous. Lack of bullae, blisters, and facial or mucosal surface involvement suggest TEN.⁵ Thrombotic thrombocytopenic purpura and disseminated intravascular coagulation do manifest with petechiae and purpura, though such a robust eruption in the context of recent cladribine therapy is less likely. The classic retiform purpura and necrosis were not present to suggest purpura fulminans from disseminated intravascular coagulation.

Several of the proposed diagnoses as well as a purpuric drug eruption would demonstrate extravasated red blood cells on histopathology, but the presence of interface dermatitis narrows the differential to a purpuric drug eruption. Necrotic keratinocytes and full-thickness necrosis were not present on biopsy to support a diagnosis of TEN in our patient. Characteristic features of TEC—including eccrine squamous syringometaplasia, dermal edema, and keratinocyte atypia—were not present on biopsy.⁶ Finally, although TEN should resolve with steroid treatment, TEC is self-limited and thrombotic thrombocytopenic purpura and disseminated intravascular coagulation would not resolve with use of steroids alone. 

The Diagnosis: Purpuric Drug Eruption

Histopathology revealed interface dermatitis, spongiosis, and a perivascular lymphocytic infiltrate with extravasated red blood cells consistent with a purpuric drug eruption. Our patient achieved remission of hairy cell leukemia after receiving only 2 of 5 expected doses of cladribine. The rash resolved completely in 3 weeks following a prednisone taper (Figure).

Hairy cell leukemia is a rare indolent lymphoproliferative disorder of B cells that accounts for approximately 2% of adult leukemias in the United States. Cladribine, a purine nucleoside analog that impairs DNA synthesis and repair, has become the mainstay of therapy, demonstrating a 95% complete response rate.¹ Although few reports have addressed the cutaneous reactions seen with cladribine therapy, they can occur in more than 50% of patients.^1,2 The most common skin manifestation associated with cladribine therapy is a morbilliform rash, but Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) have been reported.¹

Few cases of purpuric eruption secondary to cladribine treatment have been described, and nearly all reports involve concomitant medications such as allopurinol, which our patient was taking, and antibiotics including trimethoprim-sulfamethoxazole and penicillins.^1,3,4 In a cohort of 35 patients receiving cladribine,1 only concomitant treatment with cladribine and allopurinol caused cutaneous reactions, further supporting the hypothesis of cladribine-induced drug sensitivity. Allopurinol often is prescribed during induction therapy for prophylaxis against tumor lysis syndrome; similarly, antibiotics frequently are given prophylactically and therapeutically for neutropenic fever. It is believed that T-cell imbalance and profound lymphopenia induced by cladribine increase susceptibility to drug hypersensitivity reactions.^1,3

The typical purpuric eruption develops within 2 days of starting cladribine therapy. Diascopy will reveal petechiae, and biopsy should be performed to rule out other serious drug-induced reactions, such as erythema multiforme, Stevens-Johnson syndrome, and TEN. A cladribine-induced purpuric eruption typically is self-resolving and carries a favorable prognosis, though high-dose corticosteroids often are prescribed to hasten recovery. The rare reports of serious cutaneous reactions secondary to cladribine therapy have been with maculopapular, not purpuric eruptions.² Based on limited available data, cladribine-induced purpura should not be a limitation to continued treatment in patients who need it.¹ Careful consideration of concomitant drug use is necessary, as the current literature demonstrates resolution of rash with withdrawal of other therapies, namely allopurinol.^2-4 Future studies are needed to examine the safety of withholding offending medications and to further elucidate the mechanisms contributing to drug hypersensitivity due to cladribine.

Widespread purpura and petechiae can pose a wide differential; the patient’s recent history of cladribine administration pointed to a classic purpuric eruption. Other diagnoses such as toxic erythema of chemotherapy (TEC) and TEN are not purpuric, though plaques can be violaceous. Lack of bullae, blisters, and facial or mucosal surface involvement suggest TEN.⁵ Thrombotic thrombocytopenic purpura and disseminated intravascular coagulation do manifest with petechiae and purpura, though such a robust eruption in the context of recent cladribine therapy is less likely. The classic retiform purpura and necrosis were not present to suggest purpura fulminans from disseminated intravascular coagulation.

Several of the proposed diagnoses as well as a purpuric drug eruption would demonstrate extravasated red blood cells on histopathology, but the presence of interface dermatitis narrows the differential to a purpuric drug eruption. Necrotic keratinocytes and full-thickness necrosis were not present on biopsy to support a diagnosis of TEN in our patient. Characteristic features of TEC—including eccrine squamous syringometaplasia, dermal edema, and keratinocyte atypia—were not present on biopsy.⁶ Finally, although TEN should resolve with steroid treatment, TEC is self-limited and thrombotic thrombocytopenic purpura and disseminated intravascular coagulation would not resolve with use of steroids alone. 

A plastic surgeon broke federal law when he restricted patients from posting negative reviews by requiring them to sign nondisclosure agreements before they received care, a district judge has ruled.

Seattle-based surgeon Javad Sajan, MD, ran afoul of the Consumer Review Fairness Act (CRFA) by requiring more than 10,000 patients to sign the agreements, according to a recent decision by US District Judge Ricardo S. Martinez. The law protects consumers’ rights to post truthful reviews about businesses. 

Judge Martinez wrote that the terms of Dr. Sajan’s nondisclosure agreements “clearly include language prohibiting or restricting patients from posting negative reviews,” in violation of CRFA. Penalties for the offense will be determined at a September trial. 

This news organization contacted Dr. Sajan’s office and his attorney for comment but did not get a response. 

The decision is the latest development in an ongoing legal dispute between Dr. Sajan and the State of Washington over whether the surgeon’s efforts to limit negative online reviews were illegal. 

Beginning in 2017, Dr. Sajan and his practice, Allure Esthetic, introduced agreements that “forced” patients to contact the business directly if they had concerns rather than post a negative review, according to a 2022 lawsuit against Dr. Sajan filed by Washington Attorney General Robert Ferguson. 

“Online reviews are often the first stop when consumers are determining who to trust,” Mr. Ferguson said in a statement. “That’s especially critical when those services deal with a patient’s health and safety. We will take action against those who illegally stop Washingtonians from sharing reviews with the public.”

If patients posted negative reviews, the clinic, in some cases, threatened litigation, according to the complaint. In other cases, patients were allegedly offered money and free services in exchange for taking the reviews down. Patients who accepted cash or services were required to sign a second agreement forbidding them from posting future negative reviews and imposing a $250,000 penalty for failure to comply, according to court documents. 

In court documents, Dr. Sajan’s attorneys argued the agreements did not violate CRFA because patients had the opportunity to modify the language or decline signing them, which hundreds did. The CRFA requires Mr. Ferguson to prove that consumers lacked a meaningful opportunity to negotiate the terms, attorneys for Dr. Sajan argued in court records. 

But Judge Martinez wrote that the patients who declined to sign the agreements or changed the terms represented only a “tiny fraction” of the affected patients.

The agreement language restricts patients from speaking out by forcing dissatisfied patients to work with Allure until a resolution is reached, Judge Martinez noted in his decision. “At the very least, this would delay patients from posting such reviews and force patients to interact in some way with Allure, and it certainly appears to prohibit posting reviews until Allure agrees to some kind of favorable resolution.”
 

Surgeon Posted Fake Positive Reviews to Counteract Bad Reviews, AG Says

Employee accounts in court documents describe a physician fixated on reviews who went to great lengths to ensure positive reviews about his work outweighed the negative. 

Former employees said they were instructed to track down patients who left negative reviews and either “threaten” them to take the posts down or offer them “money” or other things, according to Mr. Ferguson’s lawsuit. If patients could not be identified, the practice would file a defamation lawsuit against the anonymous person who posted the review and use litigation to subpoena the website for the reviewer’s IP address in order to identify them, according to court documents. 

Employees testified they had regular meetings to review current negative reviews and discuss what steps they were taking to get them removed. At team meetings, in-house counsel would regularly present an Excel spreadsheet with updates on progress in getting patients to remove negative reviews, according to court documents. 

In addition to restricting negative reviews, Mr. Ferguson accuses Dr. Sajan of posting fake positive reviews and “buying” thousands of fake followers on social media. 

At Dr. Sajan’s direction, employees created Gmail accounts using stock photos for their profile pictures and used the accounts to post fake reviews of Allure Esthetic and Dr. Sajan, according to the complaint. The practice also used members of an online forum called BlackHatWorld.com to create fake email accounts and to post fake reviews, the attorney general alleges. Many of the fake positive reviews, including the fake Google reviews, still appear on online review sites today, the attorney general contends. 

Dr. Sajan and his practice also allegedly manipulated social media to appear more popular. Mr. Ferguson claims that Dr. Sajan instructed his former web designer to purchase 60,000 followers through a vendor on BlackHatWorld.com. Most of Dr. Sajan’s current Instagram followers are not real, according to Mr. Ferguson. 

The practice also used a social media bot tool to buy thousands of fake likes on Instagram, YouTube, and other social media, according to court documents. 

In addition, Dr. Sajan and his practice are accused of significantly altering “before and after” photos of patients and using fake email accounts to allow the clinic to take skincare rebates intended for patients.

All of these practices violated HIPAA, the state Consumer Protection Act (CPA) and the federal CRFA, according to Mr. Ferguson. 
 

Surgeon Claims Competitor Behind Allegations 

Attorneys for Dr. Sajan argue a competitor is behind the accusations and that other regulatory entities determined the practice did nothing wrong. 

The competitor, a Seattle-based plastic surgeon, filed numerous complaints about Dr. Sajan to the Washington Medical Commission (WMC), according to court documents. The medical commission reviewed the third agreement and closed its investigation, finding that if the allegations were true, “no violation of law occurred,” court records show. 

“Defendants relied upon this closing code from the WMC that the (non-disclosure) forms were lawful,” Dr. Sajan’s attorneys wrote in court documents.

The US Department of Health & Human Services Office for Civil Rights (OCR) also reviewed and audited Dr. Sajan’s use of the agreements, his attorneys noted. In a notice from OCR included in court exhibits, the agency wrote that all matters at issue have now been resolved through the practice’s voluntary compliance actions and that it was closing its investigation. 

Attorneys for Dr. Sajan accuse Mr. Ferguson and state investigators of withholding the full extent of the competitor’s involvement in their investigation and failing to identify the competitor in written discovery or any of its initial disclosures. Dr. Sajan and his team discovered that the competitor was a source of key information through public records requests, according to court documents. 

The remaining claims against Dr. Sajan will be addressed at trial, set for September 9, 2024. 
 

A version of this article appeared on Medscape.com.

A plastic surgeon broke federal law when he restricted patients from posting negative reviews by requiring them to sign nondisclosure agreements before they received care, a district judge has ruled.

Seattle-based surgeon Javad Sajan, MD, ran afoul of the Consumer Review Fairness Act (CRFA) by requiring more than 10,000 patients to sign the agreements, according to a recent decision by US District Judge Ricardo S. Martinez. The law protects consumers’ rights to post truthful reviews about businesses. 

Judge Martinez wrote that the terms of Dr. Sajan’s nondisclosure agreements “clearly include language prohibiting or restricting patients from posting negative reviews,” in violation of CRFA. Penalties for the offense will be determined at a September trial. 

This news organization contacted Dr. Sajan’s office and his attorney for comment but did not get a response. 

The decision is the latest development in an ongoing legal dispute between Dr. Sajan and the State of Washington over whether the surgeon’s efforts to limit negative online reviews were illegal. 

Beginning in 2017, Dr. Sajan and his practice, Allure Esthetic, introduced agreements that “forced” patients to contact the business directly if they had concerns rather than post a negative review, according to a 2022 lawsuit against Dr. Sajan filed by Washington Attorney General Robert Ferguson. 

“Online reviews are often the first stop when consumers are determining who to trust,” Mr. Ferguson said in a statement. “That’s especially critical when those services deal with a patient’s health and safety. We will take action against those who illegally stop Washingtonians from sharing reviews with the public.”

If patients posted negative reviews, the clinic, in some cases, threatened litigation, according to the complaint. In other cases, patients were allegedly offered money and free services in exchange for taking the reviews down. Patients who accepted cash or services were required to sign a second agreement forbidding them from posting future negative reviews and imposing a $250,000 penalty for failure to comply, according to court documents. 

In court documents, Dr. Sajan’s attorneys argued the agreements did not violate CRFA because patients had the opportunity to modify the language or decline signing them, which hundreds did. The CRFA requires Mr. Ferguson to prove that consumers lacked a meaningful opportunity to negotiate the terms, attorneys for Dr. Sajan argued in court records. 

But Judge Martinez wrote that the patients who declined to sign the agreements or changed the terms represented only a “tiny fraction” of the affected patients.

The agreement language restricts patients from speaking out by forcing dissatisfied patients to work with Allure until a resolution is reached, Judge Martinez noted in his decision. “At the very least, this would delay patients from posting such reviews and force patients to interact in some way with Allure, and it certainly appears to prohibit posting reviews until Allure agrees to some kind of favorable resolution.”
 

Surgeon Posted Fake Positive Reviews to Counteract Bad Reviews, AG Says

Employee accounts in court documents describe a physician fixated on reviews who went to great lengths to ensure positive reviews about his work outweighed the negative. 

Former employees said they were instructed to track down patients who left negative reviews and either “threaten” them to take the posts down or offer them “money” or other things, according to Mr. Ferguson’s lawsuit. If patients could not be identified, the practice would file a defamation lawsuit against the anonymous person who posted the review and use litigation to subpoena the website for the reviewer’s IP address in order to identify them, according to court documents. 

Employees testified they had regular meetings to review current negative reviews and discuss what steps they were taking to get them removed. At team meetings, in-house counsel would regularly present an Excel spreadsheet with updates on progress in getting patients to remove negative reviews, according to court documents. 

In addition to restricting negative reviews, Mr. Ferguson accuses Dr. Sajan of posting fake positive reviews and “buying” thousands of fake followers on social media. 

At Dr. Sajan’s direction, employees created Gmail accounts using stock photos for their profile pictures and used the accounts to post fake reviews of Allure Esthetic and Dr. Sajan, according to the complaint. The practice also used members of an online forum called BlackHatWorld.com to create fake email accounts and to post fake reviews, the attorney general alleges. Many of the fake positive reviews, including the fake Google reviews, still appear on online review sites today, the attorney general contends. 

Dr. Sajan and his practice also allegedly manipulated social media to appear more popular. Mr. Ferguson claims that Dr. Sajan instructed his former web designer to purchase 60,000 followers through a vendor on BlackHatWorld.com. Most of Dr. Sajan’s current Instagram followers are not real, according to Mr. Ferguson. 

The practice also used a social media bot tool to buy thousands of fake likes on Instagram, YouTube, and other social media, according to court documents. 

In addition, Dr. Sajan and his practice are accused of significantly altering “before and after” photos of patients and using fake email accounts to allow the clinic to take skincare rebates intended for patients.

All of these practices violated HIPAA, the state Consumer Protection Act (CPA) and the federal CRFA, according to Mr. Ferguson. 
 

Surgeon Claims Competitor Behind Allegations 

Attorneys for Dr. Sajan argue a competitor is behind the accusations and that other regulatory entities determined the practice did nothing wrong. 

The competitor, a Seattle-based plastic surgeon, filed numerous complaints about Dr. Sajan to the Washington Medical Commission (WMC), according to court documents. The medical commission reviewed the third agreement and closed its investigation, finding that if the allegations were true, “no violation of law occurred,” court records show. 

“Defendants relied upon this closing code from the WMC that the (non-disclosure) forms were lawful,” Dr. Sajan’s attorneys wrote in court documents.

The US Department of Health & Human Services Office for Civil Rights (OCR) also reviewed and audited Dr. Sajan’s use of the agreements, his attorneys noted. In a notice from OCR included in court exhibits, the agency wrote that all matters at issue have now been resolved through the practice’s voluntary compliance actions and that it was closing its investigation. 

Attorneys for Dr. Sajan accuse Mr. Ferguson and state investigators of withholding the full extent of the competitor’s involvement in their investigation and failing to identify the competitor in written discovery or any of its initial disclosures. Dr. Sajan and his team discovered that the competitor was a source of key information through public records requests, according to court documents. 

The remaining claims against Dr. Sajan will be addressed at trial, set for September 9, 2024. 
 

A version of this article appeared on Medscape.com.

A plastic surgeon broke federal law when he restricted patients from posting negative reviews by requiring them to sign nondisclosure agreements before they received care, a district judge has ruled.

Seattle-based surgeon Javad Sajan, MD, ran afoul of the Consumer Review Fairness Act (CRFA) by requiring more than 10,000 patients to sign the agreements, according to a recent decision by US District Judge Ricardo S. Martinez. The law protects consumers’ rights to post truthful reviews about businesses. 

Judge Martinez wrote that the terms of Dr. Sajan’s nondisclosure agreements “clearly include language prohibiting or restricting patients from posting negative reviews,” in violation of CRFA. Penalties for the offense will be determined at a September trial. 

This news organization contacted Dr. Sajan’s office and his attorney for comment but did not get a response. 

The decision is the latest development in an ongoing legal dispute between Dr. Sajan and the State of Washington over whether the surgeon’s efforts to limit negative online reviews were illegal. 

Beginning in 2017, Dr. Sajan and his practice, Allure Esthetic, introduced agreements that “forced” patients to contact the business directly if they had concerns rather than post a negative review, according to a 2022 lawsuit against Dr. Sajan filed by Washington Attorney General Robert Ferguson. 

“Online reviews are often the first stop when consumers are determining who to trust,” Mr. Ferguson said in a statement. “That’s especially critical when those services deal with a patient’s health and safety. We will take action against those who illegally stop Washingtonians from sharing reviews with the public.”

If patients posted negative reviews, the clinic, in some cases, threatened litigation, according to the complaint. In other cases, patients were allegedly offered money and free services in exchange for taking the reviews down. Patients who accepted cash or services were required to sign a second agreement forbidding them from posting future negative reviews and imposing a $250,000 penalty for failure to comply, according to court documents. 

In court documents, Dr. Sajan’s attorneys argued the agreements did not violate CRFA because patients had the opportunity to modify the language or decline signing them, which hundreds did. The CRFA requires Mr. Ferguson to prove that consumers lacked a meaningful opportunity to negotiate the terms, attorneys for Dr. Sajan argued in court records. 

But Judge Martinez wrote that the patients who declined to sign the agreements or changed the terms represented only a “tiny fraction” of the affected patients.

The agreement language restricts patients from speaking out by forcing dissatisfied patients to work with Allure until a resolution is reached, Judge Martinez noted in his decision. “At the very least, this would delay patients from posting such reviews and force patients to interact in some way with Allure, and it certainly appears to prohibit posting reviews until Allure agrees to some kind of favorable resolution.”
 

Surgeon Posted Fake Positive Reviews to Counteract Bad Reviews, AG Says

Employee accounts in court documents describe a physician fixated on reviews who went to great lengths to ensure positive reviews about his work outweighed the negative. 

Former employees said they were instructed to track down patients who left negative reviews and either “threaten” them to take the posts down or offer them “money” or other things, according to Mr. Ferguson’s lawsuit. If patients could not be identified, the practice would file a defamation lawsuit against the anonymous person who posted the review and use litigation to subpoena the website for the reviewer’s IP address in order to identify them, according to court documents. 

Employees testified they had regular meetings to review current negative reviews and discuss what steps they were taking to get them removed. At team meetings, in-house counsel would regularly present an Excel spreadsheet with updates on progress in getting patients to remove negative reviews, according to court documents. 

In addition to restricting negative reviews, Mr. Ferguson accuses Dr. Sajan of posting fake positive reviews and “buying” thousands of fake followers on social media. 

At Dr. Sajan’s direction, employees created Gmail accounts using stock photos for their profile pictures and used the accounts to post fake reviews of Allure Esthetic and Dr. Sajan, according to the complaint. The practice also used members of an online forum called BlackHatWorld.com to create fake email accounts and to post fake reviews, the attorney general alleges. Many of the fake positive reviews, including the fake Google reviews, still appear on online review sites today, the attorney general contends. 

Dr. Sajan and his practice also allegedly manipulated social media to appear more popular. Mr. Ferguson claims that Dr. Sajan instructed his former web designer to purchase 60,000 followers through a vendor on BlackHatWorld.com. Most of Dr. Sajan’s current Instagram followers are not real, according to Mr. Ferguson. 

The practice also used a social media bot tool to buy thousands of fake likes on Instagram, YouTube, and other social media, according to court documents. 

In addition, Dr. Sajan and his practice are accused of significantly altering “before and after” photos of patients and using fake email accounts to allow the clinic to take skincare rebates intended for patients.

All of these practices violated HIPAA, the state Consumer Protection Act (CPA) and the federal CRFA, according to Mr. Ferguson. 
 

Surgeon Claims Competitor Behind Allegations 

Attorneys for Dr. Sajan argue a competitor is behind the accusations and that other regulatory entities determined the practice did nothing wrong. 

The competitor, a Seattle-based plastic surgeon, filed numerous complaints about Dr. Sajan to the Washington Medical Commission (WMC), according to court documents. The medical commission reviewed the third agreement and closed its investigation, finding that if the allegations were true, “no violation of law occurred,” court records show. 

“Defendants relied upon this closing code from the WMC that the (non-disclosure) forms were lawful,” Dr. Sajan’s attorneys wrote in court documents.

The US Department of Health & Human Services Office for Civil Rights (OCR) also reviewed and audited Dr. Sajan’s use of the agreements, his attorneys noted. In a notice from OCR included in court exhibits, the agency wrote that all matters at issue have now been resolved through the practice’s voluntary compliance actions and that it was closing its investigation. 

Attorneys for Dr. Sajan accuse Mr. Ferguson and state investigators of withholding the full extent of the competitor’s involvement in their investigation and failing to identify the competitor in written discovery or any of its initial disclosures. Dr. Sajan and his team discovered that the competitor was a source of key information through public records requests, according to court documents. 

The remaining claims against Dr. Sajan will be addressed at trial, set for September 9, 2024. 
 

A version of this article appeared on Medscape.com.

A new two-measure metric seems to improve accuracy and statistical precision in assessing celiac disease (CeD) histology compared with either of two components alone, according to a study in Clinical Gastroenterology and Hepatology.

The new morphometric duodenal biopsy mucosal scale joins together villous height-to-crypt depth ratio (Vh:Cd) and intraepithelial lymphocytes (IEL) — each key CeD histological measures of the small intestine — in a scale called VCIEL.

The authors believe the VCIEL will enable a broader and more accurate measurement of mucosal health in CeD. It will be particularly useful for population analysis in clinical trials and could improve the powering of trial design. “Use of VCIEL may lead to better outcome measures for potential new therapeutic treatments benefiting patients,” wrote Jocelyn A. Silvester, MD, PhD, a pediatrician at Boston Children’s Hospital and an assistant professor at Harvard Medical School, and colleagues.

Boston Children’s Hospital

The Study

In the absence of a broadly accepted single measure of mucosal injury in CeD, the group assessed whether the composite metric could improve statistical precision for assessing histology.

Enter VCIEL, which combines the Vh:Cd and IEL for individual patients with equal weighting by converting each scale to a fraction of their standard deviation and summing the results.

The researchers applied the VCIEL formula in a reanalysis of four clinical gluten-challenge trials and compared the results for Vh:Cd and IEL separately with those for VCIEL for clinical significance (effect size) and statistical significance.

In reanalysis of the ALV003-1021 trial, for example, the researchers observed an effect size and P value (analysis of covariance) of 1.37 and .038 for a delta (difference) value of Vh:Cd 1.17 and .005 for IEL and 1.86 and .004 for VCIEL.

For the similar gluten-challenge IMGX003-NCCIH-1721 trial, the corresponding delta results were .76 and .057 for Vh:Cd, .98 and .018 for IEL, and 1.14 and .007 for VCIEL. Comparable improvements with VCIEL over individual Vh:Cd and IEL were observed for other studies, including a nontherapeutic gluten challenge study.

In NCT03409796 trial data, the computation of VCIEL values showed an improved statistical significance relative to the component values of Vh:Cd and IEL by the within-group paired 2-tailed t test P values from baseline to day 15, particularly at a 10-g gluten challenge dose: Vh:Cd, IEL, VCIEL = .0050, .0031, and .0014, respectively.

Little correlation emerged between baseline values and changes with intervention for Vh:Cd and IEL on an individual patient basis.

The greater accuracy and statistical precision of the VCIEL scale are presumably due to averaging over some of the measurement uncertainty in individual patient and timepoint Vh:Cd and IEL values and creating a composite of different histologic properties, the authors noted.

This study was funded by ImmunogenX, Inc. First author Jack A. Syage is a cofounder and shareholder in ImmunogenX Inc. Dr. Silvester has served on an advisory board for Takeda Pharmaceuticals and has received research funding from Biomedal S.L., Cour Pharmaceuticals, and Glutenostics LLC. Several coauthors disclosed various financial ties to multiple private-sector pharmaceutical and biomedical companies, including ImmunogenX.

A new two-measure metric seems to improve accuracy and statistical precision in assessing celiac disease (CeD) histology compared with either of two components alone, according to a study in Clinical Gastroenterology and Hepatology.

The new morphometric duodenal biopsy mucosal scale joins together villous height-to-crypt depth ratio (Vh:Cd) and intraepithelial lymphocytes (IEL) — each key CeD histological measures of the small intestine — in a scale called VCIEL.

The authors believe the VCIEL will enable a broader and more accurate measurement of mucosal health in CeD. It will be particularly useful for population analysis in clinical trials and could improve the powering of trial design. “Use of VCIEL may lead to better outcome measures for potential new therapeutic treatments benefiting patients,” wrote Jocelyn A. Silvester, MD, PhD, a pediatrician at Boston Children’s Hospital and an assistant professor at Harvard Medical School, and colleagues.

Boston Children’s Hospital

The Study

In the absence of a broadly accepted single measure of mucosal injury in CeD, the group assessed whether the composite metric could improve statistical precision for assessing histology.

Enter VCIEL, which combines the Vh:Cd and IEL for individual patients with equal weighting by converting each scale to a fraction of their standard deviation and summing the results.

The researchers applied the VCIEL formula in a reanalysis of four clinical gluten-challenge trials and compared the results for Vh:Cd and IEL separately with those for VCIEL for clinical significance (effect size) and statistical significance.

In reanalysis of the ALV003-1021 trial, for example, the researchers observed an effect size and P value (analysis of covariance) of 1.37 and .038 for a delta (difference) value of Vh:Cd 1.17 and .005 for IEL and 1.86 and .004 for VCIEL.

For the similar gluten-challenge IMGX003-NCCIH-1721 trial, the corresponding delta results were .76 and .057 for Vh:Cd, .98 and .018 for IEL, and 1.14 and .007 for VCIEL. Comparable improvements with VCIEL over individual Vh:Cd and IEL were observed for other studies, including a nontherapeutic gluten challenge study.

In NCT03409796 trial data, the computation of VCIEL values showed an improved statistical significance relative to the component values of Vh:Cd and IEL by the within-group paired 2-tailed t test P values from baseline to day 15, particularly at a 10-g gluten challenge dose: Vh:Cd, IEL, VCIEL = .0050, .0031, and .0014, respectively.

Little correlation emerged between baseline values and changes with intervention for Vh:Cd and IEL on an individual patient basis.

The greater accuracy and statistical precision of the VCIEL scale are presumably due to averaging over some of the measurement uncertainty in individual patient and timepoint Vh:Cd and IEL values and creating a composite of different histologic properties, the authors noted.

This study was funded by ImmunogenX, Inc. First author Jack A. Syage is a cofounder and shareholder in ImmunogenX Inc. Dr. Silvester has served on an advisory board for Takeda Pharmaceuticals and has received research funding from Biomedal S.L., Cour Pharmaceuticals, and Glutenostics LLC. Several coauthors disclosed various financial ties to multiple private-sector pharmaceutical and biomedical companies, including ImmunogenX.

A new two-measure metric seems to improve accuracy and statistical precision in assessing celiac disease (CeD) histology compared with either of two components alone, according to a study in Clinical Gastroenterology and Hepatology.

The new morphometric duodenal biopsy mucosal scale joins together villous height-to-crypt depth ratio (Vh:Cd) and intraepithelial lymphocytes (IEL) — each key CeD histological measures of the small intestine — in a scale called VCIEL.

The authors believe the VCIEL will enable a broader and more accurate measurement of mucosal health in CeD. It will be particularly useful for population analysis in clinical trials and could improve the powering of trial design. “Use of VCIEL may lead to better outcome measures for potential new therapeutic treatments benefiting patients,” wrote Jocelyn A. Silvester, MD, PhD, a pediatrician at Boston Children’s Hospital and an assistant professor at Harvard Medical School, and colleagues.

Boston Children’s Hospital

The Study

In the absence of a broadly accepted single measure of mucosal injury in CeD, the group assessed whether the composite metric could improve statistical precision for assessing histology.

Enter VCIEL, which combines the Vh:Cd and IEL for individual patients with equal weighting by converting each scale to a fraction of their standard deviation and summing the results.

The researchers applied the VCIEL formula in a reanalysis of four clinical gluten-challenge trials and compared the results for Vh:Cd and IEL separately with those for VCIEL for clinical significance (effect size) and statistical significance.

In reanalysis of the ALV003-1021 trial, for example, the researchers observed an effect size and P value (analysis of covariance) of 1.37 and .038 for a delta (difference) value of Vh:Cd 1.17 and .005 for IEL and 1.86 and .004 for VCIEL.

For the similar gluten-challenge IMGX003-NCCIH-1721 trial, the corresponding delta results were .76 and .057 for Vh:Cd, .98 and .018 for IEL, and 1.14 and .007 for VCIEL. Comparable improvements with VCIEL over individual Vh:Cd and IEL were observed for other studies, including a nontherapeutic gluten challenge study.

In NCT03409796 trial data, the computation of VCIEL values showed an improved statistical significance relative to the component values of Vh:Cd and IEL by the within-group paired 2-tailed t test P values from baseline to day 15, particularly at a 10-g gluten challenge dose: Vh:Cd, IEL, VCIEL = .0050, .0031, and .0014, respectively.

Little correlation emerged between baseline values and changes with intervention for Vh:Cd and IEL on an individual patient basis.

The greater accuracy and statistical precision of the VCIEL scale are presumably due to averaging over some of the measurement uncertainty in individual patient and timepoint Vh:Cd and IEL values and creating a composite of different histologic properties, the authors noted.

This study was funded by ImmunogenX, Inc. First author Jack A. Syage is a cofounder and shareholder in ImmunogenX Inc. Dr. Silvester has served on an advisory board for Takeda Pharmaceuticals and has received research funding from Biomedal S.L., Cour Pharmaceuticals, and Glutenostics LLC. Several coauthors disclosed various financial ties to multiple private-sector pharmaceutical and biomedical companies, including ImmunogenX.

The relatively new antibiotic cefiderocol given in the form of eye drops may be a way to combat a type of ocular infection that broke out in the United States last year, according to research presented at the 2024 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO).

The infections, linked to contaminated bottles of artificial tears, were detected in 81 patients in 18 states. The outbreak led to loss of vision in 14 patients, surgical removal of the eyeball in four patients, and four deaths, according to health officials. 

An extensively drug-resistant strain of Pseudomonas aeruginosa that had not previously been reported in the country caused the infections. Scientists cautioned last year that the bacteria potentially could spread from person to person. 

At ARVO on May 6, Eric G. Romanowski, MS, research director of the Charles T. Campbell Ophthalmic Microbiology Laboratory at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, described studies that his lab conducted evaluating topical cefiderocol as a potential treatment option for these infections (Abstract 2095).

Investigators had found that the bacterial strain was susceptible to this medication, which was approved by the US Food and Drug Administration in 2019 as a treatment for complicated urinary tract infections. But the antibiotic had not been tested as an eye drop.

“We showed that the ‘Trojan-horse’ antibiotic, cefiderocol … was non-toxic and effective against the highly resistant outbreak strain in an experimental model of infection,” Dr. Romanowski and co–lead investigator Robert M. Q. Shanks, PhD, said in a statement about their research. “These results demonstrate that topical cefiderocol could be a new weapon in the ophthalmologist’s arsenal for the treatment of corneal infections caused by highly antibiotic-resistant Pseudomonas aeruginosa.”
 

Experimental Models

Dr. Romanowski’s group, with colleagues at the Geisel School of Medicine at Dartmouth University, Hanover, New Hampshire, used minimum inhibitory concentration testing to evaluate the effectiveness of cefiderocol against 135 isolates from eye infections. They also tested ocular toxicity and antibiotic efficacy of cefiderocol eye drops in a rabbit model of keratitis caused by the bacterial strain.

Cefiderocol was “well tolerated on rabbit corneas,” they reported. It also was effective in vitro against the isolates and in vivo in the rabbit model of keratitis.

They first published their findings as a preprint in September 2023 and then in Ophthalmology Science in December.

 

A ‘Duty to the Profession’

Their paper noted that “there is no current consensus as to the most effective antimicrobial strategy to deal with” extensively drug-resistant keratitis.

During the outbreak, clinicians tried various treatment regimens, with mixed results. In one case, a combination of intravenous cefiderocol and other topical and oral medications appeared to be successful.

Dr. Romanowski’s team decided to test cefiderocol drops with their own resources “as a duty to the profession,” he said. “Not many labs do these types of studies.”

“We would like to see further development of this antibiotic for potential use,” Dr. Romanowski added. “It would be up to any individual clinician to determine whether to use this antibiotic in an emergency situation.”

A version of this article appeared on Medscape.com.

The relatively new antibiotic cefiderocol given in the form of eye drops may be a way to combat a type of ocular infection that broke out in the United States last year, according to research presented at the 2024 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO).

The infections, linked to contaminated bottles of artificial tears, were detected in 81 patients in 18 states. The outbreak led to loss of vision in 14 patients, surgical removal of the eyeball in four patients, and four deaths, according to health officials. 

An extensively drug-resistant strain of Pseudomonas aeruginosa that had not previously been reported in the country caused the infections. Scientists cautioned last year that the bacteria potentially could spread from person to person. 

At ARVO on May 6, Eric G. Romanowski, MS, research director of the Charles T. Campbell Ophthalmic Microbiology Laboratory at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, described studies that his lab conducted evaluating topical cefiderocol as a potential treatment option for these infections (Abstract 2095).

Investigators had found that the bacterial strain was susceptible to this medication, which was approved by the US Food and Drug Administration in 2019 as a treatment for complicated urinary tract infections. But the antibiotic had not been tested as an eye drop.

“We showed that the ‘Trojan-horse’ antibiotic, cefiderocol … was non-toxic and effective against the highly resistant outbreak strain in an experimental model of infection,” Dr. Romanowski and co–lead investigator Robert M. Q. Shanks, PhD, said in a statement about their research. “These results demonstrate that topical cefiderocol could be a new weapon in the ophthalmologist’s arsenal for the treatment of corneal infections caused by highly antibiotic-resistant Pseudomonas aeruginosa.”
 

Experimental Models

Dr. Romanowski’s group, with colleagues at the Geisel School of Medicine at Dartmouth University, Hanover, New Hampshire, used minimum inhibitory concentration testing to evaluate the effectiveness of cefiderocol against 135 isolates from eye infections. They also tested ocular toxicity and antibiotic efficacy of cefiderocol eye drops in a rabbit model of keratitis caused by the bacterial strain.

Cefiderocol was “well tolerated on rabbit corneas,” they reported. It also was effective in vitro against the isolates and in vivo in the rabbit model of keratitis.

They first published their findings as a preprint in September 2023 and then in Ophthalmology Science in December.

 

A ‘Duty to the Profession’

Their paper noted that “there is no current consensus as to the most effective antimicrobial strategy to deal with” extensively drug-resistant keratitis.

During the outbreak, clinicians tried various treatment regimens, with mixed results. In one case, a combination of intravenous cefiderocol and other topical and oral medications appeared to be successful.

Dr. Romanowski’s team decided to test cefiderocol drops with their own resources “as a duty to the profession,” he said. “Not many labs do these types of studies.”

“We would like to see further development of this antibiotic for potential use,” Dr. Romanowski added. “It would be up to any individual clinician to determine whether to use this antibiotic in an emergency situation.”

A version of this article appeared on Medscape.com.

The relatively new antibiotic cefiderocol given in the form of eye drops may be a way to combat a type of ocular infection that broke out in the United States last year, according to research presented at the 2024 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO).

The infections, linked to contaminated bottles of artificial tears, were detected in 81 patients in 18 states. The outbreak led to loss of vision in 14 patients, surgical removal of the eyeball in four patients, and four deaths, according to health officials. 

An extensively drug-resistant strain of Pseudomonas aeruginosa that had not previously been reported in the country caused the infections. Scientists cautioned last year that the bacteria potentially could spread from person to person. 

At ARVO on May 6, Eric G. Romanowski, MS, research director of the Charles T. Campbell Ophthalmic Microbiology Laboratory at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, described studies that his lab conducted evaluating topical cefiderocol as a potential treatment option for these infections (Abstract 2095).

Investigators had found that the bacterial strain was susceptible to this medication, which was approved by the US Food and Drug Administration in 2019 as a treatment for complicated urinary tract infections. But the antibiotic had not been tested as an eye drop.

“We showed that the ‘Trojan-horse’ antibiotic, cefiderocol … was non-toxic and effective against the highly resistant outbreak strain in an experimental model of infection,” Dr. Romanowski and co–lead investigator Robert M. Q. Shanks, PhD, said in a statement about their research. “These results demonstrate that topical cefiderocol could be a new weapon in the ophthalmologist’s arsenal for the treatment of corneal infections caused by highly antibiotic-resistant Pseudomonas aeruginosa.”
 

Experimental Models

Dr. Romanowski’s group, with colleagues at the Geisel School of Medicine at Dartmouth University, Hanover, New Hampshire, used minimum inhibitory concentration testing to evaluate the effectiveness of cefiderocol against 135 isolates from eye infections. They also tested ocular toxicity and antibiotic efficacy of cefiderocol eye drops in a rabbit model of keratitis caused by the bacterial strain.

Cefiderocol was “well tolerated on rabbit corneas,” they reported. It also was effective in vitro against the isolates and in vivo in the rabbit model of keratitis.

They first published their findings as a preprint in September 2023 and then in Ophthalmology Science in December.

 

A ‘Duty to the Profession’

Their paper noted that “there is no current consensus as to the most effective antimicrobial strategy to deal with” extensively drug-resistant keratitis.

During the outbreak, clinicians tried various treatment regimens, with mixed results. In one case, a combination of intravenous cefiderocol and other topical and oral medications appeared to be successful.

Dr. Romanowski’s team decided to test cefiderocol drops with their own resources “as a duty to the profession,” he said. “Not many labs do these types of studies.”

“We would like to see further development of this antibiotic for potential use,” Dr. Romanowski added. “It would be up to any individual clinician to determine whether to use this antibiotic in an emergency situation.”

A version of this article appeared on Medscape.com.