The American College of Obstetricians and Gynecologists (ACOG) has updated its breast cancer screening guidelines, recommending that individuals at an average risk for breast cancer initiate mammography screening at age 40. This change reflects evolving evidence that starting earlier screening yields greater net benefits in reducing breast cancer mortality, particularly for certain racial groups with higher risk factors.

Breast cancer is the second leading cause of cancer deaths in American women overall and the leading cause of cancer deaths among Black and Hispanic women. Although mammography has long been recognized as a life-saving tool by detecting cancer early, there has been debate on when screening should begin due to concerns about overdiagnosis, false positives, and potential harms such as unnecessary biopsies.

Recent evidence has prompted ACOG to revise its recommendation for individuals assigned female at birth, including cisgender women, transgender men, and nonbinary individuals. This updated guidance includes individuals with dense breast tissue or a family history of breast cancer but excludes those with higher risk factors, such as a personal history of breast cancer or previous high-risk lesion on a breast biopsy, genetic mutations linked to higher cancer risk, or a history of high-dose radiation therapy to their chest at a young age.

Under the new guidelines, routine screening mammography should start at age 40 and can be performed annually or every 2 years, based on an informed, shared decision-making process that considers the benefits and potential harms of frequent screening.

Previously, ACOG recommended initiating screening between ages 40 and 50, depending on individual risk factors and preferences, with screening required by age 50 at the latest. However, several factors, including an increasing incidence of breast cancer in younger women, have influenced the decision to lower the recommended starting age.
 

Increasing Incidence Among Younger Women

Between 2015 and 2019, the incidence of invasive breast cancer in women aged 40-49 years increased by approximately 2% per year.

“There has been a concerning trend of increasing breast cancer diagnoses among women in their 40s, and new data shows that earlier screening could make a significant difference in decreasing breast cancer deaths,” said Eve Zaritsky, MD, FACOG, coauthor of the clinical practice update. “While screening can sometimes cause anxiety for people and even unnecessary follow-up, the benefits of diagnosing breast cancer earlier outweigh those risks enough to warrant starting to get mammograms at age 40.”

Studies commissioned by the US Preventive Services Task Force (USPSTF) show that starting mammography at age 40 provides a greater overall benefit than beginning at age 50. Early screening reduces the number of breast cancer deaths and increases life years gained when weighed against the harms of false positives, overdiagnosis, and benign biopsies.
 

Addressing Health Inequities

The benefits of earlier screening are expected to be particularly significant for Black women, who have disproportionately high mortality rates from breast cancer. Even though Black women have a lower overall incidence of breast cancer than White women, they have a 40% higher 5-year age-adjusted mortality rate from the disease and a 45% increased incidence of invasive breast cancer before age 50. Black women are also more likely to be diagnosed with aggressive subtypes, such as triple-negative breast cancer, which is harder to detect and treat and occurs at younger ages.

Racial disparities in breast cancer outcomes are deeply rooted in inequities in social determinants of health, such as access to care, housing, and environmental conditions. Black women are also less likely to receive timely or comprehensive treatment than White women, which contributes to worse survival rates even after adjusting for socioeconomic factors and insurance status.

“Our updated recommendation addresses important inequities in breast cancer diagnosis, treatment, and death, and we hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” added coauthor Cherie C. Hill, MD, FACOG.

ACOG’s updated recommendation aligns with that of other leading organizations, including the USPSTF, the National Comprehensive Cancer Network, the American College of Radiology, and the Society of Breast Imaging. This growing consensus among experts is expected to reduce confusion among clinicians and patients regarding when to begin screening, thus improving screening rates in individuals in the 40- to 49-year age group.

Zaritsky and Hill reported no conflicts of interest.
 

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

The American College of Obstetricians and Gynecologists (ACOG) has updated its breast cancer screening guidelines, recommending that individuals at an average risk for breast cancer initiate mammography screening at age 40. This change reflects evolving evidence that starting earlier screening yields greater net benefits in reducing breast cancer mortality, particularly for certain racial groups with higher risk factors.

Breast cancer is the second leading cause of cancer deaths in American women overall and the leading cause of cancer deaths among Black and Hispanic women. Although mammography has long been recognized as a life-saving tool by detecting cancer early, there has been debate on when screening should begin due to concerns about overdiagnosis, false positives, and potential harms such as unnecessary biopsies.

Recent evidence has prompted ACOG to revise its recommendation for individuals assigned female at birth, including cisgender women, transgender men, and nonbinary individuals. This updated guidance includes individuals with dense breast tissue or a family history of breast cancer but excludes those with higher risk factors, such as a personal history of breast cancer or previous high-risk lesion on a breast biopsy, genetic mutations linked to higher cancer risk, or a history of high-dose radiation therapy to their chest at a young age.

Under the new guidelines, routine screening mammography should start at age 40 and can be performed annually or every 2 years, based on an informed, shared decision-making process that considers the benefits and potential harms of frequent screening.

Previously, ACOG recommended initiating screening between ages 40 and 50, depending on individual risk factors and preferences, with screening required by age 50 at the latest. However, several factors, including an increasing incidence of breast cancer in younger women, have influenced the decision to lower the recommended starting age.
 

Increasing Incidence Among Younger Women

Between 2015 and 2019, the incidence of invasive breast cancer in women aged 40-49 years increased by approximately 2% per year.

“There has been a concerning trend of increasing breast cancer diagnoses among women in their 40s, and new data shows that earlier screening could make a significant difference in decreasing breast cancer deaths,” said Eve Zaritsky, MD, FACOG, coauthor of the clinical practice update. “While screening can sometimes cause anxiety for people and even unnecessary follow-up, the benefits of diagnosing breast cancer earlier outweigh those risks enough to warrant starting to get mammograms at age 40.”

Studies commissioned by the US Preventive Services Task Force (USPSTF) show that starting mammography at age 40 provides a greater overall benefit than beginning at age 50. Early screening reduces the number of breast cancer deaths and increases life years gained when weighed against the harms of false positives, overdiagnosis, and benign biopsies.
 

Addressing Health Inequities

The benefits of earlier screening are expected to be particularly significant for Black women, who have disproportionately high mortality rates from breast cancer. Even though Black women have a lower overall incidence of breast cancer than White women, they have a 40% higher 5-year age-adjusted mortality rate from the disease and a 45% increased incidence of invasive breast cancer before age 50. Black women are also more likely to be diagnosed with aggressive subtypes, such as triple-negative breast cancer, which is harder to detect and treat and occurs at younger ages.

Racial disparities in breast cancer outcomes are deeply rooted in inequities in social determinants of health, such as access to care, housing, and environmental conditions. Black women are also less likely to receive timely or comprehensive treatment than White women, which contributes to worse survival rates even after adjusting for socioeconomic factors and insurance status.

“Our updated recommendation addresses important inequities in breast cancer diagnosis, treatment, and death, and we hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” added coauthor Cherie C. Hill, MD, FACOG.

ACOG’s updated recommendation aligns with that of other leading organizations, including the USPSTF, the National Comprehensive Cancer Network, the American College of Radiology, and the Society of Breast Imaging. This growing consensus among experts is expected to reduce confusion among clinicians and patients regarding when to begin screening, thus improving screening rates in individuals in the 40- to 49-year age group.

Zaritsky and Hill reported no conflicts of interest.
 

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

The American College of Obstetricians and Gynecologists (ACOG) has updated its breast cancer screening guidelines, recommending that individuals at an average risk for breast cancer initiate mammography screening at age 40. This change reflects evolving evidence that starting earlier screening yields greater net benefits in reducing breast cancer mortality, particularly for certain racial groups with higher risk factors.

Breast cancer is the second leading cause of cancer deaths in American women overall and the leading cause of cancer deaths among Black and Hispanic women. Although mammography has long been recognized as a life-saving tool by detecting cancer early, there has been debate on when screening should begin due to concerns about overdiagnosis, false positives, and potential harms such as unnecessary biopsies.

Recent evidence has prompted ACOG to revise its recommendation for individuals assigned female at birth, including cisgender women, transgender men, and nonbinary individuals. This updated guidance includes individuals with dense breast tissue or a family history of breast cancer but excludes those with higher risk factors, such as a personal history of breast cancer or previous high-risk lesion on a breast biopsy, genetic mutations linked to higher cancer risk, or a history of high-dose radiation therapy to their chest at a young age.

Under the new guidelines, routine screening mammography should start at age 40 and can be performed annually or every 2 years, based on an informed, shared decision-making process that considers the benefits and potential harms of frequent screening.

Previously, ACOG recommended initiating screening between ages 40 and 50, depending on individual risk factors and preferences, with screening required by age 50 at the latest. However, several factors, including an increasing incidence of breast cancer in younger women, have influenced the decision to lower the recommended starting age.
 

Increasing Incidence Among Younger Women

Between 2015 and 2019, the incidence of invasive breast cancer in women aged 40-49 years increased by approximately 2% per year.

“There has been a concerning trend of increasing breast cancer diagnoses among women in their 40s, and new data shows that earlier screening could make a significant difference in decreasing breast cancer deaths,” said Eve Zaritsky, MD, FACOG, coauthor of the clinical practice update. “While screening can sometimes cause anxiety for people and even unnecessary follow-up, the benefits of diagnosing breast cancer earlier outweigh those risks enough to warrant starting to get mammograms at age 40.”

Studies commissioned by the US Preventive Services Task Force (USPSTF) show that starting mammography at age 40 provides a greater overall benefit than beginning at age 50. Early screening reduces the number of breast cancer deaths and increases life years gained when weighed against the harms of false positives, overdiagnosis, and benign biopsies.
 

Addressing Health Inequities

The benefits of earlier screening are expected to be particularly significant for Black women, who have disproportionately high mortality rates from breast cancer. Even though Black women have a lower overall incidence of breast cancer than White women, they have a 40% higher 5-year age-adjusted mortality rate from the disease and a 45% increased incidence of invasive breast cancer before age 50. Black women are also more likely to be diagnosed with aggressive subtypes, such as triple-negative breast cancer, which is harder to detect and treat and occurs at younger ages.

Racial disparities in breast cancer outcomes are deeply rooted in inequities in social determinants of health, such as access to care, housing, and environmental conditions. Black women are also less likely to receive timely or comprehensive treatment than White women, which contributes to worse survival rates even after adjusting for socioeconomic factors and insurance status.

“Our updated recommendation addresses important inequities in breast cancer diagnosis, treatment, and death, and we hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” added coauthor Cherie C. Hill, MD, FACOG.

ACOG’s updated recommendation aligns with that of other leading organizations, including the USPSTF, the National Comprehensive Cancer Network, the American College of Radiology, and the Society of Breast Imaging. This growing consensus among experts is expected to reduce confusion among clinicians and patients regarding when to begin screening, thus improving screening rates in individuals in the 40- to 49-year age group.

Zaritsky and Hill reported no conflicts of interest.
 

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

VIENNA, AUSTRIA — The appropriate dose of pancreatic enzyme replacement therapy (PERT) for exocrine pancreatic insufficiency (EPI) depends on the root cause of the insufficiency, according to results of a prospective study using European registry data. 

Specifically, patients with EPI caused by pancreatic cancer or pancreatectomy need significantly more enzyme replacement than patients with insufficiency caused by chronic pancreatitis and acute pancreatitis. The need to add a proton pump inhibitor (PPI) to achieve the therapeutic goal also varies by condition, the study showed. 

World Pancreatic Cancer Coalition

One of the main symptoms of EPI is malnutrition, and successful PERT is defined as the resolution of nutritional deficiencies and relief of symptoms and signs associated with insufficiency, said study lead Enrique Domínguez Muñoz, MD, director of the department of gastroenterology and hepatology at University Hospital of Santiago de Compostela, Spain. 

Our findings show that, “in order to achieve this, enzyme dose escalation and sometimes additional treatment with a [PPI] should be applied as required by the individual”, he reported in a presentation at the United European Gastroenterology (UEG) Week 2024.

Therefore, having dose recommendations for PERT for different causes of EPI is very helpful, said Domínguez Muñoz.

Pancreatic enzyme preparations, specifically pancreatin, are the recommended first-line treatment for EPI, but the initial doses of PERT vary depending on the patient’s age (whether adult or child), the severity of the insufficiency, and the fat content of the meal eaten. 

Domínguez Muñoz and colleagues wanted to explore whether — and how — the severity of EPI varied with different diseases, therefore varying the optimal dose of PERT. 
 

Optimal Dosing to Achieve Therapeutic Goal 

The prospective study drew on data from a European multicenter registry of patients diagnosed with EPI being treated with PERT in expert centers. 

The researchers evaluated the dose of PERT required to achieve symptom relief and normalization of the nutritional status in adult patients with EPI secondary to different pancreatic diseases and conditions. The percentage of patients who required the addition of a PPI to PERT to achieve the therapeutic goal was also determined. 

Decisions on the initial enzyme dose (including the addition of a PPI) and any necessary adjustments during follow-up to achieve the therapeutic goal were made by the participants’ clinicians.

A total of 678 patients (mean age, 61.2 ± 13.8 years; 63.6% male) were stratified according to disease: 50% had chronic pancreatitis, 10% had acute pancreatitis, 17% had undergone pancreaticoduodenectomy, 15% had pancreatic cancer, and 8% had another pancreatic condition. 

To achieve the therapeutic goal, the median optimal enzyme doses with the main meal for patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer, and pancreaticoduodenectomy, were 40,000, 50,000, 70,000, and 75,000 Ph.U, respectively. The respective optimal daily enzyme doses were 100,000, 150,000, 210,000, and 225,000 Ph.U. 

The highest enzyme doses required with the main meal to achieve the therapeutic goal for patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer, and pancreaticoduodenectomy were 125,000, 210,000, 175,000, and 210,000 Ph.U, respectively. The respective highest daily enzyme doses were 400,000, 625,000, 675,000, and 750,000 Ph.U. 

The need for additional therapy with twice-daily PPI to achieve the therapeutic goal also varied according to the underlying disease. It was administered to 44.1% of patients with acute pancreatitis, 37.2% of patients with chronic pancreatitis, 78.8% of patients with pancreatic cancer, and 74.1% of patients who had undergone pancreaticoduodenectomy. 

“This shows us that sometimes we really do need to significantly increase the dose of pancreatic enzyme replacement therapy,” reported Domínguez Muñoz. 
 

Clear Direction on Where to Start

Comoderator Kasper Overbeek, MD, from the department of gastroenterology and hepatology, Erasmus MC Cancer Institute, University Medical Center, the Netherlands, commented: “It’s a useful study because it gives us practical advice on what to do in specific cases.”

Dr. Overbeek

Until now, we’ve done the same thing for everyone, he said, “but these data clearly show that this is not optimal.” 

In addition, “it is often the case with enzyme replacement therapy that doctors under-dose so it is necessary to increase the dose,” he said.

“This work gives us a clearer direction on where to start,” Overbeek said. “For example, with patients who have cancer, because they do not have time to start low and titrate up, they need a higher dose than patients with chronic pancreatitis.”

This pragmatic and novel guidance will “help us in our clinical practice,” he added.

Domínguez Muñoz reports receiving speaking and consultancy fees from Viatris, Abbott Pharmaceuticals, and Boston Scientific. Overbeek reports no relevant disclosures.

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

VIENNA, AUSTRIA — The appropriate dose of pancreatic enzyme replacement therapy (PERT) for exocrine pancreatic insufficiency (EPI) depends on the root cause of the insufficiency, according to results of a prospective study using European registry data. 

Specifically, patients with EPI caused by pancreatic cancer or pancreatectomy need significantly more enzyme replacement than patients with insufficiency caused by chronic pancreatitis and acute pancreatitis. The need to add a proton pump inhibitor (PPI) to achieve the therapeutic goal also varies by condition, the study showed. 

World Pancreatic Cancer Coalition

One of the main symptoms of EPI is malnutrition, and successful PERT is defined as the resolution of nutritional deficiencies and relief of symptoms and signs associated with insufficiency, said study lead Enrique Domínguez Muñoz, MD, director of the department of gastroenterology and hepatology at University Hospital of Santiago de Compostela, Spain. 

Our findings show that, “in order to achieve this, enzyme dose escalation and sometimes additional treatment with a [PPI] should be applied as required by the individual”, he reported in a presentation at the United European Gastroenterology (UEG) Week 2024.

Therefore, having dose recommendations for PERT for different causes of EPI is very helpful, said Domínguez Muñoz.

Pancreatic enzyme preparations, specifically pancreatin, are the recommended first-line treatment for EPI, but the initial doses of PERT vary depending on the patient’s age (whether adult or child), the severity of the insufficiency, and the fat content of the meal eaten. 

Domínguez Muñoz and colleagues wanted to explore whether — and how — the severity of EPI varied with different diseases, therefore varying the optimal dose of PERT. 
 

Optimal Dosing to Achieve Therapeutic Goal 

The prospective study drew on data from a European multicenter registry of patients diagnosed with EPI being treated with PERT in expert centers. 

The researchers evaluated the dose of PERT required to achieve symptom relief and normalization of the nutritional status in adult patients with EPI secondary to different pancreatic diseases and conditions. The percentage of patients who required the addition of a PPI to PERT to achieve the therapeutic goal was also determined. 

Decisions on the initial enzyme dose (including the addition of a PPI) and any necessary adjustments during follow-up to achieve the therapeutic goal were made by the participants’ clinicians.

A total of 678 patients (mean age, 61.2 ± 13.8 years; 63.6% male) were stratified according to disease: 50% had chronic pancreatitis, 10% had acute pancreatitis, 17% had undergone pancreaticoduodenectomy, 15% had pancreatic cancer, and 8% had another pancreatic condition. 

To achieve the therapeutic goal, the median optimal enzyme doses with the main meal for patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer, and pancreaticoduodenectomy, were 40,000, 50,000, 70,000, and 75,000 Ph.U, respectively. The respective optimal daily enzyme doses were 100,000, 150,000, 210,000, and 225,000 Ph.U. 

The highest enzyme doses required with the main meal to achieve the therapeutic goal for patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer, and pancreaticoduodenectomy were 125,000, 210,000, 175,000, and 210,000 Ph.U, respectively. The respective highest daily enzyme doses were 400,000, 625,000, 675,000, and 750,000 Ph.U. 

The need for additional therapy with twice-daily PPI to achieve the therapeutic goal also varied according to the underlying disease. It was administered to 44.1% of patients with acute pancreatitis, 37.2% of patients with chronic pancreatitis, 78.8% of patients with pancreatic cancer, and 74.1% of patients who had undergone pancreaticoduodenectomy. 

“This shows us that sometimes we really do need to significantly increase the dose of pancreatic enzyme replacement therapy,” reported Domínguez Muñoz. 
 

Clear Direction on Where to Start

Comoderator Kasper Overbeek, MD, from the department of gastroenterology and hepatology, Erasmus MC Cancer Institute, University Medical Center, the Netherlands, commented: “It’s a useful study because it gives us practical advice on what to do in specific cases.”

Dr. Overbeek

Until now, we’ve done the same thing for everyone, he said, “but these data clearly show that this is not optimal.” 

In addition, “it is often the case with enzyme replacement therapy that doctors under-dose so it is necessary to increase the dose,” he said.

“This work gives us a clearer direction on where to start,” Overbeek said. “For example, with patients who have cancer, because they do not have time to start low and titrate up, they need a higher dose than patients with chronic pancreatitis.”

This pragmatic and novel guidance will “help us in our clinical practice,” he added.

Domínguez Muñoz reports receiving speaking and consultancy fees from Viatris, Abbott Pharmaceuticals, and Boston Scientific. Overbeek reports no relevant disclosures.

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

VIENNA, AUSTRIA — The appropriate dose of pancreatic enzyme replacement therapy (PERT) for exocrine pancreatic insufficiency (EPI) depends on the root cause of the insufficiency, according to results of a prospective study using European registry data. 

Specifically, patients with EPI caused by pancreatic cancer or pancreatectomy need significantly more enzyme replacement than patients with insufficiency caused by chronic pancreatitis and acute pancreatitis. The need to add a proton pump inhibitor (PPI) to achieve the therapeutic goal also varies by condition, the study showed. 

World Pancreatic Cancer Coalition

One of the main symptoms of EPI is malnutrition, and successful PERT is defined as the resolution of nutritional deficiencies and relief of symptoms and signs associated with insufficiency, said study lead Enrique Domínguez Muñoz, MD, director of the department of gastroenterology and hepatology at University Hospital of Santiago de Compostela, Spain. 

Our findings show that, “in order to achieve this, enzyme dose escalation and sometimes additional treatment with a [PPI] should be applied as required by the individual”, he reported in a presentation at the United European Gastroenterology (UEG) Week 2024.

Therefore, having dose recommendations for PERT for different causes of EPI is very helpful, said Domínguez Muñoz.

Pancreatic enzyme preparations, specifically pancreatin, are the recommended first-line treatment for EPI, but the initial doses of PERT vary depending on the patient’s age (whether adult or child), the severity of the insufficiency, and the fat content of the meal eaten. 

Domínguez Muñoz and colleagues wanted to explore whether — and how — the severity of EPI varied with different diseases, therefore varying the optimal dose of PERT. 
 

Optimal Dosing to Achieve Therapeutic Goal 

The prospective study drew on data from a European multicenter registry of patients diagnosed with EPI being treated with PERT in expert centers. 

The researchers evaluated the dose of PERT required to achieve symptom relief and normalization of the nutritional status in adult patients with EPI secondary to different pancreatic diseases and conditions. The percentage of patients who required the addition of a PPI to PERT to achieve the therapeutic goal was also determined. 

Decisions on the initial enzyme dose (including the addition of a PPI) and any necessary adjustments during follow-up to achieve the therapeutic goal were made by the participants’ clinicians.

A total of 678 patients (mean age, 61.2 ± 13.8 years; 63.6% male) were stratified according to disease: 50% had chronic pancreatitis, 10% had acute pancreatitis, 17% had undergone pancreaticoduodenectomy, 15% had pancreatic cancer, and 8% had another pancreatic condition. 

To achieve the therapeutic goal, the median optimal enzyme doses with the main meal for patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer, and pancreaticoduodenectomy, were 40,000, 50,000, 70,000, and 75,000 Ph.U, respectively. The respective optimal daily enzyme doses were 100,000, 150,000, 210,000, and 225,000 Ph.U. 

The highest enzyme doses required with the main meal to achieve the therapeutic goal for patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer, and pancreaticoduodenectomy were 125,000, 210,000, 175,000, and 210,000 Ph.U, respectively. The respective highest daily enzyme doses were 400,000, 625,000, 675,000, and 750,000 Ph.U. 

The need for additional therapy with twice-daily PPI to achieve the therapeutic goal also varied according to the underlying disease. It was administered to 44.1% of patients with acute pancreatitis, 37.2% of patients with chronic pancreatitis, 78.8% of patients with pancreatic cancer, and 74.1% of patients who had undergone pancreaticoduodenectomy. 

“This shows us that sometimes we really do need to significantly increase the dose of pancreatic enzyme replacement therapy,” reported Domínguez Muñoz. 
 

Clear Direction on Where to Start

Comoderator Kasper Overbeek, MD, from the department of gastroenterology and hepatology, Erasmus MC Cancer Institute, University Medical Center, the Netherlands, commented: “It’s a useful study because it gives us practical advice on what to do in specific cases.”

Dr. Overbeek

Until now, we’ve done the same thing for everyone, he said, “but these data clearly show that this is not optimal.” 

In addition, “it is often the case with enzyme replacement therapy that doctors under-dose so it is necessary to increase the dose,” he said.

“This work gives us a clearer direction on where to start,” Overbeek said. “For example, with patients who have cancer, because they do not have time to start low and titrate up, they need a higher dose than patients with chronic pancreatitis.”

This pragmatic and novel guidance will “help us in our clinical practice,” he added.

Domínguez Muñoz reports receiving speaking and consultancy fees from Viatris, Abbott Pharmaceuticals, and Boston Scientific. Overbeek reports no relevant disclosures.

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

SAVANNAH, GEORGIA — There’s no medical treatment for Charcot-Marie-Tooth (CMT) disease, a debilitating neurologic disorder that’s both progressive and incurable. But now, nerve specialists learned, new potential treatments are moving closer to clinical trials.

Genetic-based therapies for CMT are currently in preclinical research phases, and an experimental small-molecule drug has reached phase 3 in humans, neurologists told an audience at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. But the neurologists also noted challenges, such as determining the best way to track disease progression — which can be slow — and the need to recruit high numbers of patients for trials.
 

A Common Genetic Neuromuscular Disorder

As Mario Saporta, MD, PhD, MBA, of the University of Miami, Coral Gables, Florida, explained, CMT is the most common genetic neuromuscular disorder, affecting 1 in 2500 people or about 130,000-150,000 in the United States. “Typically, it’s a length-dependent neuropathy, where your longest nerves would be affected earlier and more severely. That’s why we see foot deformities, inverted champagne bottle legs, and hand atrophy.”

Most patients with CMT in the United States have type 1A, which is linked to duplication of the PMP22 gene. All types lead to axonal degeneration, which appears to be the main cause of functional disability, Saporta said. “Patients become weaker and then progress with time, following the degree of axonal generation that they have.”

As many as 150 genes may eventually be deemed to cause CMT. The high number of genetically different forms makes diagnosis and genetic therapy difficult, he said, but that’s just part of the picture. Variations among mutations mean there’s “probably actually over 1000 different diseases” within CMT from a biologic perspective.
 

Genetic Therapy

In regard to genetic treatment, Bipasha Mukherjee-Clavin, MD, PhD, of Johns Hopkins University School of Medicine, Baltimore, Maryland, said a key factor is whether the patient’s form of CMT is passed on in an autosomal dominant or autosomal recessive manner.

“Autosomal dominant conditions are typically caused by gain of function mutations. So that means the goal of our genetic therapeutic would be to reduce expression of the mutated gene,” she said. “In contrast, autosomal recessive conditions are caused by loss-of-function mutations, which means the goal of our genetic therapeutic would be to replace the mutated gene with a normal, wild-type copy.”

A tool like CRISPR could be used to directly edit the part of the genome with a CMT-causing mutation or a viral vector could deliver a healthy, wild-type copy of a gene, she said. These approaches are both being tested.

Another approach is to reduce expression at the RNA level. “RNA therapeutics are FDA [Food and Drug Administration]–approved for other neuromuscular indications, and you may well be using some of these in your own clinical practice,” she said.

Currently, about seven different projects are in the works on the RNA therapeutics front in CMT, she said, including six focusing on type 1A. Mukherjee-Clavin believes that this subtype is a “great” target because it’s so common, affecting an estimated 1 in 5000 people.

“You actually have enough patients to power a clinical trial,” she said. Also, “it’s a homogeneous population, both in terms of the genetics and in terms of the clinical presentation.”
 

Preclinical Treatment Approaches

However, there are challenges. Drug delivery to Schwann cells, which insulate axons, is difficult, she said. “The other problem is that we want to avoid overly silencing PMP22 because that runs the theoretical risk of causing a different condition, HNPP [hereditary neuropathy with liability to pressure palsies]. HNPP is caused by deletions of PMP22, so we want to avoid that situation.”

Mukherjee-Clavin highlighted two RNA therapeutic products that she expects to move from preclinical to clinical research soon.

One is TVR110 by Armatus Bio, a microRNA intrathecal injection product, which aims to reduce PMP22 overexpression. “It targets basically reduces PMP22 mRNA expression and then normalizes the amount of PMP22 protein that is ultimately generated,” she said.

The other therapy, a small interfering RNA intravenous product delivered to Schwann cells, is being developed by DTx Pharma/Novartis.

Outside of the RNA arena, “there are a number of other programs that are in the preclinical phases that I think will be moving through this pipeline,” Mukherjee-Clavin said. “We’ll see if some of these enter first-in-human clinical trials.”

Meanwhile, Saporta highlighted small-molecule strategies that target a subtype of CMT called sorbitol dehydrogenase (SORD) deficiency that’s caused by mutations in the SORD gene. He noted that Applied Therapeutics is testing an investigational drug called govorestat (AT-007) in 56 patients in a double-blind, randomized, placebo-controlled phase 3 registrational study. The company recently reported that interim 12-month results are promising.

Saporta disclosed consulting for DTx Pharma/Novartis, Applied Therapeutics, and Pharnext. Mukherjee-Clavin had no disclosures.

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

SAVANNAH, GEORGIA — There’s no medical treatment for Charcot-Marie-Tooth (CMT) disease, a debilitating neurologic disorder that’s both progressive and incurable. But now, nerve specialists learned, new potential treatments are moving closer to clinical trials.

Genetic-based therapies for CMT are currently in preclinical research phases, and an experimental small-molecule drug has reached phase 3 in humans, neurologists told an audience at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. But the neurologists also noted challenges, such as determining the best way to track disease progression — which can be slow — and the need to recruit high numbers of patients for trials.
 

A Common Genetic Neuromuscular Disorder

As Mario Saporta, MD, PhD, MBA, of the University of Miami, Coral Gables, Florida, explained, CMT is the most common genetic neuromuscular disorder, affecting 1 in 2500 people or about 130,000-150,000 in the United States. “Typically, it’s a length-dependent neuropathy, where your longest nerves would be affected earlier and more severely. That’s why we see foot deformities, inverted champagne bottle legs, and hand atrophy.”

Most patients with CMT in the United States have type 1A, which is linked to duplication of the PMP22 gene. All types lead to axonal degeneration, which appears to be the main cause of functional disability, Saporta said. “Patients become weaker and then progress with time, following the degree of axonal generation that they have.”

As many as 150 genes may eventually be deemed to cause CMT. The high number of genetically different forms makes diagnosis and genetic therapy difficult, he said, but that’s just part of the picture. Variations among mutations mean there’s “probably actually over 1000 different diseases” within CMT from a biologic perspective.
 

Genetic Therapy

In regard to genetic treatment, Bipasha Mukherjee-Clavin, MD, PhD, of Johns Hopkins University School of Medicine, Baltimore, Maryland, said a key factor is whether the patient’s form of CMT is passed on in an autosomal dominant or autosomal recessive manner.

“Autosomal dominant conditions are typically caused by gain of function mutations. So that means the goal of our genetic therapeutic would be to reduce expression of the mutated gene,” she said. “In contrast, autosomal recessive conditions are caused by loss-of-function mutations, which means the goal of our genetic therapeutic would be to replace the mutated gene with a normal, wild-type copy.”

A tool like CRISPR could be used to directly edit the part of the genome with a CMT-causing mutation or a viral vector could deliver a healthy, wild-type copy of a gene, she said. These approaches are both being tested.

Another approach is to reduce expression at the RNA level. “RNA therapeutics are FDA [Food and Drug Administration]–approved for other neuromuscular indications, and you may well be using some of these in your own clinical practice,” she said.

Currently, about seven different projects are in the works on the RNA therapeutics front in CMT, she said, including six focusing on type 1A. Mukherjee-Clavin believes that this subtype is a “great” target because it’s so common, affecting an estimated 1 in 5000 people.

“You actually have enough patients to power a clinical trial,” she said. Also, “it’s a homogeneous population, both in terms of the genetics and in terms of the clinical presentation.”
 

Preclinical Treatment Approaches

However, there are challenges. Drug delivery to Schwann cells, which insulate axons, is difficult, she said. “The other problem is that we want to avoid overly silencing PMP22 because that runs the theoretical risk of causing a different condition, HNPP [hereditary neuropathy with liability to pressure palsies]. HNPP is caused by deletions of PMP22, so we want to avoid that situation.”

Mukherjee-Clavin highlighted two RNA therapeutic products that she expects to move from preclinical to clinical research soon.

One is TVR110 by Armatus Bio, a microRNA intrathecal injection product, which aims to reduce PMP22 overexpression. “It targets basically reduces PMP22 mRNA expression and then normalizes the amount of PMP22 protein that is ultimately generated,” she said.

The other therapy, a small interfering RNA intravenous product delivered to Schwann cells, is being developed by DTx Pharma/Novartis.

Outside of the RNA arena, “there are a number of other programs that are in the preclinical phases that I think will be moving through this pipeline,” Mukherjee-Clavin said. “We’ll see if some of these enter first-in-human clinical trials.”

Meanwhile, Saporta highlighted small-molecule strategies that target a subtype of CMT called sorbitol dehydrogenase (SORD) deficiency that’s caused by mutations in the SORD gene. He noted that Applied Therapeutics is testing an investigational drug called govorestat (AT-007) in 56 patients in a double-blind, randomized, placebo-controlled phase 3 registrational study. The company recently reported that interim 12-month results are promising.

Saporta disclosed consulting for DTx Pharma/Novartis, Applied Therapeutics, and Pharnext. Mukherjee-Clavin had no disclosures.

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

SAVANNAH, GEORGIA — There’s no medical treatment for Charcot-Marie-Tooth (CMT) disease, a debilitating neurologic disorder that’s both progressive and incurable. But now, nerve specialists learned, new potential treatments are moving closer to clinical trials.

Genetic-based therapies for CMT are currently in preclinical research phases, and an experimental small-molecule drug has reached phase 3 in humans, neurologists told an audience at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. But the neurologists also noted challenges, such as determining the best way to track disease progression — which can be slow — and the need to recruit high numbers of patients for trials.
 

A Common Genetic Neuromuscular Disorder

As Mario Saporta, MD, PhD, MBA, of the University of Miami, Coral Gables, Florida, explained, CMT is the most common genetic neuromuscular disorder, affecting 1 in 2500 people or about 130,000-150,000 in the United States. “Typically, it’s a length-dependent neuropathy, where your longest nerves would be affected earlier and more severely. That’s why we see foot deformities, inverted champagne bottle legs, and hand atrophy.”

Most patients with CMT in the United States have type 1A, which is linked to duplication of the PMP22 gene. All types lead to axonal degeneration, which appears to be the main cause of functional disability, Saporta said. “Patients become weaker and then progress with time, following the degree of axonal generation that they have.”

As many as 150 genes may eventually be deemed to cause CMT. The high number of genetically different forms makes diagnosis and genetic therapy difficult, he said, but that’s just part of the picture. Variations among mutations mean there’s “probably actually over 1000 different diseases” within CMT from a biologic perspective.
 

Genetic Therapy

In regard to genetic treatment, Bipasha Mukherjee-Clavin, MD, PhD, of Johns Hopkins University School of Medicine, Baltimore, Maryland, said a key factor is whether the patient’s form of CMT is passed on in an autosomal dominant or autosomal recessive manner.

“Autosomal dominant conditions are typically caused by gain of function mutations. So that means the goal of our genetic therapeutic would be to reduce expression of the mutated gene,” she said. “In contrast, autosomal recessive conditions are caused by loss-of-function mutations, which means the goal of our genetic therapeutic would be to replace the mutated gene with a normal, wild-type copy.”

A tool like CRISPR could be used to directly edit the part of the genome with a CMT-causing mutation or a viral vector could deliver a healthy, wild-type copy of a gene, she said. These approaches are both being tested.

Another approach is to reduce expression at the RNA level. “RNA therapeutics are FDA [Food and Drug Administration]–approved for other neuromuscular indications, and you may well be using some of these in your own clinical practice,” she said.

Currently, about seven different projects are in the works on the RNA therapeutics front in CMT, she said, including six focusing on type 1A. Mukherjee-Clavin believes that this subtype is a “great” target because it’s so common, affecting an estimated 1 in 5000 people.

“You actually have enough patients to power a clinical trial,” she said. Also, “it’s a homogeneous population, both in terms of the genetics and in terms of the clinical presentation.”
 

Preclinical Treatment Approaches

However, there are challenges. Drug delivery to Schwann cells, which insulate axons, is difficult, she said. “The other problem is that we want to avoid overly silencing PMP22 because that runs the theoretical risk of causing a different condition, HNPP [hereditary neuropathy with liability to pressure palsies]. HNPP is caused by deletions of PMP22, so we want to avoid that situation.”

Mukherjee-Clavin highlighted two RNA therapeutic products that she expects to move from preclinical to clinical research soon.

One is TVR110 by Armatus Bio, a microRNA intrathecal injection product, which aims to reduce PMP22 overexpression. “It targets basically reduces PMP22 mRNA expression and then normalizes the amount of PMP22 protein that is ultimately generated,” she said.

The other therapy, a small interfering RNA intravenous product delivered to Schwann cells, is being developed by DTx Pharma/Novartis.

Outside of the RNA arena, “there are a number of other programs that are in the preclinical phases that I think will be moving through this pipeline,” Mukherjee-Clavin said. “We’ll see if some of these enter first-in-human clinical trials.”

Meanwhile, Saporta highlighted small-molecule strategies that target a subtype of CMT called sorbitol dehydrogenase (SORD) deficiency that’s caused by mutations in the SORD gene. He noted that Applied Therapeutics is testing an investigational drug called govorestat (AT-007) in 56 patients in a double-blind, randomized, placebo-controlled phase 3 registrational study. The company recently reported that interim 12-month results are promising.

Saporta disclosed consulting for DTx Pharma/Novartis, Applied Therapeutics, and Pharnext. Mukherjee-Clavin had no disclosures.

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

TOPLINE:

VIENNA — Individuals with ulcerative colitis (UC) who carry the HLA-DRB1*01:03 allele are at increased risk of having a more severe disease course requiring major surgery, hospitalization, and high-dose systemic corticosteroids within 3 years of diagnosis, according to a Danish study.

METHODOLOGY:

• Reliable biomarkers are lacking to identify patients with inflammatory bowel disease at greater risk for severe disease and who therefore might require intensified monitoring and treatment.
• Researchers explored genetic variants associated with severe UC in patients from two Danish cohorts, whose DNA was extracted from dried blood spots and full blood, with genotyping then performed to assess the presence of human leukocyte antigen (HLA) alleles and single-nucleotide variants.
• Severe UC was defined as having at least one major UC-related operation, at least two UC-related hospitalizations exceeding 2 days, and/or use of at least 5000 mg of systemic corticosteroids within 3 years of diagnosis. Patients not meeting these criteria were considered to have less severe UC and included as the comparison group.
• A genome-wide association study was conducted comparing severe vs less severe UC.

TAKEAWAY:

• Researchers analyzed 4491 patients with UC (mean age at diagnosis, 23 years; 53% women; 27% with severe UC) and determined that carriers of the HLA-DRB1*01:03 allele had a significantly higher risk for severe UC (odds ratio, 3.32).
• Compared with noncarriers, those with this allele had an approximately sixfold increased risk of needing major surgery, a fivefold increased risk of requiring at least two hospitalizations, and a twofold increased risk for use of over 5000 mg of systemic corticosteroids within 3 years of diagnosis.
• Time-to-event analysis showed that the association between carriers and disease severity extended beyond 3 years after diagnosis.
• Compared with noncarriers, those with the HLA-DRB1*01:03 allele had a higher hazard ratio for time to hospitalization, major surgery, and first treatment with systemic corticosteroids.

IN PRACTICE:

“Although HLA-DRB1*01:03 is a low-frequency allele, carriers have a significantly higher risk of severe ulcerative colitis. Given the low cost of typing a single HLA allele, HLA-DRB1*01:03 could be a valuable tool for risk assessment of patients with ulcerative colitis at diagnosis,” the authors concluded.

SOURCE:

The study, with first author Marie Vibeke Vestergaard, MSc, Aalborg University, Aalborg, Denmark, was published online on October 15 in JAMA, to coincide with its presentation at United European Gastroenterology (UEG) Week 2024 in Vienna, Austria. 

LIMITATIONS:

The findings are based on a Danish population of European genetic ancestry and require validation in diverse patient cohorts with UC.

DISCLOSURES:

The study was funded by the Danish National Research Foundation, the Lundbeck Foundation, and the Novo Nordisk Foundation. The authors reported no relevant disclosures related to the study.
 

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

TOPLINE:

VIENNA — Individuals with ulcerative colitis (UC) who carry the HLA-DRB1*01:03 allele are at increased risk of having a more severe disease course requiring major surgery, hospitalization, and high-dose systemic corticosteroids within 3 years of diagnosis, according to a Danish study.

METHODOLOGY:

• Reliable biomarkers are lacking to identify patients with inflammatory bowel disease at greater risk for severe disease and who therefore might require intensified monitoring and treatment.
• Researchers explored genetic variants associated with severe UC in patients from two Danish cohorts, whose DNA was extracted from dried blood spots and full blood, with genotyping then performed to assess the presence of human leukocyte antigen (HLA) alleles and single-nucleotide variants.
• Severe UC was defined as having at least one major UC-related operation, at least two UC-related hospitalizations exceeding 2 days, and/or use of at least 5000 mg of systemic corticosteroids within 3 years of diagnosis. Patients not meeting these criteria were considered to have less severe UC and included as the comparison group.
• A genome-wide association study was conducted comparing severe vs less severe UC.

TAKEAWAY:

• Researchers analyzed 4491 patients with UC (mean age at diagnosis, 23 years; 53% women; 27% with severe UC) and determined that carriers of the HLA-DRB1*01:03 allele had a significantly higher risk for severe UC (odds ratio, 3.32).
• Compared with noncarriers, those with this allele had an approximately sixfold increased risk of needing major surgery, a fivefold increased risk of requiring at least two hospitalizations, and a twofold increased risk for use of over 5000 mg of systemic corticosteroids within 3 years of diagnosis.
• Time-to-event analysis showed that the association between carriers and disease severity extended beyond 3 years after diagnosis.
• Compared with noncarriers, those with the HLA-DRB1*01:03 allele had a higher hazard ratio for time to hospitalization, major surgery, and first treatment with systemic corticosteroids.

IN PRACTICE:

“Although HLA-DRB1*01:03 is a low-frequency allele, carriers have a significantly higher risk of severe ulcerative colitis. Given the low cost of typing a single HLA allele, HLA-DRB1*01:03 could be a valuable tool for risk assessment of patients with ulcerative colitis at diagnosis,” the authors concluded.

SOURCE:

The study, with first author Marie Vibeke Vestergaard, MSc, Aalborg University, Aalborg, Denmark, was published online on October 15 in JAMA, to coincide with its presentation at United European Gastroenterology (UEG) Week 2024 in Vienna, Austria. 

LIMITATIONS:

The findings are based on a Danish population of European genetic ancestry and require validation in diverse patient cohorts with UC.

DISCLOSURES:

The study was funded by the Danish National Research Foundation, the Lundbeck Foundation, and the Novo Nordisk Foundation. The authors reported no relevant disclosures related to the study.
 

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

TOPLINE:

VIENNA — Individuals with ulcerative colitis (UC) who carry the HLA-DRB1*01:03 allele are at increased risk of having a more severe disease course requiring major surgery, hospitalization, and high-dose systemic corticosteroids within 3 years of diagnosis, according to a Danish study.

METHODOLOGY:

• Reliable biomarkers are lacking to identify patients with inflammatory bowel disease at greater risk for severe disease and who therefore might require intensified monitoring and treatment.
• Researchers explored genetic variants associated with severe UC in patients from two Danish cohorts, whose DNA was extracted from dried blood spots and full blood, with genotyping then performed to assess the presence of human leukocyte antigen (HLA) alleles and single-nucleotide variants.
• Severe UC was defined as having at least one major UC-related operation, at least two UC-related hospitalizations exceeding 2 days, and/or use of at least 5000 mg of systemic corticosteroids within 3 years of diagnosis. Patients not meeting these criteria were considered to have less severe UC and included as the comparison group.
• A genome-wide association study was conducted comparing severe vs less severe UC.

TAKEAWAY:

• Researchers analyzed 4491 patients with UC (mean age at diagnosis, 23 years; 53% women; 27% with severe UC) and determined that carriers of the HLA-DRB1*01:03 allele had a significantly higher risk for severe UC (odds ratio, 3.32).
• Compared with noncarriers, those with this allele had an approximately sixfold increased risk of needing major surgery, a fivefold increased risk of requiring at least two hospitalizations, and a twofold increased risk for use of over 5000 mg of systemic corticosteroids within 3 years of diagnosis.
• Time-to-event analysis showed that the association between carriers and disease severity extended beyond 3 years after diagnosis.
• Compared with noncarriers, those with the HLA-DRB1*01:03 allele had a higher hazard ratio for time to hospitalization, major surgery, and first treatment with systemic corticosteroids.

IN PRACTICE:

“Although HLA-DRB1*01:03 is a low-frequency allele, carriers have a significantly higher risk of severe ulcerative colitis. Given the low cost of typing a single HLA allele, HLA-DRB1*01:03 could be a valuable tool for risk assessment of patients with ulcerative colitis at diagnosis,” the authors concluded.

SOURCE:

The study, with first author Marie Vibeke Vestergaard, MSc, Aalborg University, Aalborg, Denmark, was published online on October 15 in JAMA, to coincide with its presentation at United European Gastroenterology (UEG) Week 2024 in Vienna, Austria. 

LIMITATIONS:

The findings are based on a Danish population of European genetic ancestry and require validation in diverse patient cohorts with UC.

DISCLOSURES:

The study was funded by the Danish National Research Foundation, the Lundbeck Foundation, and the Novo Nordisk Foundation. The authors reported no relevant disclosures related to the study.
 

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

Katie Sullivan, DNP, FNP-C, is publicizing her own challenge with updating an insulin pump as part of an effort to bring an end to the biannual seasonal clock changes in the United States.

On March 10, 2024, Sullivan, who works in the Endocrinology Clinic, Michigan State University, East Lansing, Michigan, mistakenly reversed the AM and PM settings while adjusting her own insulin pump. Sullivan, who has type 1 diabetes, noticed several hours later that her blood glucose levels had become higher than usual and was surprised to see her pump showed sleep mode during the day.

She was able to address this glitch before going to sleep and thus “escaped a potential occurrence of nocturnal hypoglycemia,” Sullivan and her colleague, Saleh Aldasouqi, MD, wrote in a September commentary in the journal Clinical Diabetes.

The risk of daylight saving time (DST) changes for people with insulin pumps is well known. Aldasouqi himself raised it in a 2014 article in the Journal of Diabetes Science and Technology.

Medtronic Inc., the leading maker of insulin pumps, told this news organization in an email that it intends for future devices to automate DST changes. The company did not provide any further details on when such changes would happen.

For now, Medtronic and other makers of insulin pumps join in twice-a-year efforts to remind people they need to update their devices to adjust for DST changes. They will need to gear up these outreach campaigns, which include social media posts, again ahead of the end of DST on November 3, when clocks shift back an hour. Diabetes clinics and hospitals also send notes to patients.

Even so, people will fail to make this change or to do it correctly.

“Despite our efforts to educate our patients about DST glitches, we have detected incorrect time settings in some of our patients’ insulin pumps after the DST changes in the fall and spring and occasional cases of incorrect insulin dosing, resulting in hyperglycemia or hypoglycemia,” Sullivan and Aldasouqi wrote in their article.

The US Food and Drug Administration (FDA) database of injuries and mishaps with devices contains many reports about patients not adjusting their insulin pumps for DST.

Known as Manufacturer and User Facility Device Experience (MAUDE), this database does not provide identifying details about the patients. Instead, the reports contain only a few lines describing what happened. In many cases, people were able to easily resolve their temporary glycemic issues and then set their devices to the correct time.

But some of the MAUDE reports tell of more severe consequences, with people ending up in emergency rooms because they did not adjust their insulin pumps for DST.

Among these is a report about a November 2022 incident, where a patient suffered due to what appeared to be inaccurate continuous glucose monitor readings, combined with the effects of an insulin pump that had not been updated for a DST change.

Although that patient’s mother was available to assist and the patient consumed three dextrose candies, the patient still reportedly lost consciousness and experienced tremors. That led to hospitalization, where the patient was treated with intravenous saline, intravenous insulin, saline fluids, and insulin fluids. The patient left the hospital with “the issue resolved and no permanent damage” but then switched to another method of insulin therapy, the MAUDE report said.

It’s unclear how often DST changes lead to problems with insulin pumps, reflecting difficulties in tracking flaws and glitches in medical devices, Madris Kinard, the chief executive officer and founder of Device Events, told this news organization.

The FDA relies heavily on passive surveillance, gathering MAUDE reports submitted by companies, clinicians, and patients. That means many cases likely are missed, said Kinard who earlier worked as an analyst at the FDA, updating processes and systems to help identify risky devices.

For example, Sullivan told this news organization she had not filed a report for her incident with the insulin pump.
 

Permanent Standard Time?

Many clinicians, including Aldasouqi and Sullivan, argue a better solution to these challenges would be to end DST.

In their Clinical Diabetes article, they also cited other health risks associated with clock changes such as fatigue, headache, and loss of attention and alertness that can result in injuries.

But a permanent time change is a “politically charged issue, and it continues to be debated nationally and at the state level,” they wrote.

At least 30 states also considered measures this year related to DST, according to the National Conference of State Legislatures. A pending Senate bill intended to make DST permanent has the support of 8 Democrats and 11 Republicans, including Sen. Tommy Tuberville (R-Ala).

“It’s amazing how many phone calls we get over this one topic. People across America agree that changing our clocks back and forth twice a year really makes no sense,” Tuberville said last year on the Senate floor. “People call and say they’re just sick of it.”

These federal and state efforts have stalled to date on the key question of whether to make either standard time or DST permanent, the National Conference of State Legislatures noted. A shift to permanent DST might have benefits for some agricultural and recreational industries, but many physicians say it would be bad for people’s health.

The American Academy of Sleep Medicine (AASM) argues strongly for moving to permanent standard time. In a position statement published in the Journal of Clinical Sleep Medicine, the group said the acute transitions from standard time to DST pose harms, citing research indicating increased risks for adverse cardiovascular events, mood disorders, and motor vehicle crashes.

The solution is to end shifts in time and opt for standard time, which best aligns with the human biological clock, AASM said.

AASM noted that there already was a failed experiment in the United States with a shift to permanent DST. Congress established this in response to the 1973 OPEC oil embargo, expecting that allowing more evening hours with light would lead to energy savings. That didn’t pay off in the expected reduction in energy and the policy was highly unpopular, especially in rural areas, AASM said.

“After a single winter, the policy was reversed by an overwhelming congressional majority,” wrote Muhammad Adeel Rishi, MD, and other authors of the statement. “The unpopularity of the act was likely because despite greater evening light, the policy resulted in a greater proportion of days that required waking up on dark mornings, particularly in the winter.”

Karin G. Johnson, MD, professor of neurology at the UMass Chan School of Medicine, Worcester, Massachusetts, told this news organization that a shift to permanent DST would rob many people of the signals their bodies need for sleep.

“Sunrises and sunsets are later and that creates a desire for our body to stay up later and have more trouble getting up in the morning,” Johnson said. “You’re all but making it impossible for certain segments of the population to get enough sleep” with permanent DST.

Johnson, Sullivan, and Aldasouqi had no relevant financial disclosures.

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

Katie Sullivan, DNP, FNP-C, is publicizing her own challenge with updating an insulin pump as part of an effort to bring an end to the biannual seasonal clock changes in the United States.

On March 10, 2024, Sullivan, who works in the Endocrinology Clinic, Michigan State University, East Lansing, Michigan, mistakenly reversed the AM and PM settings while adjusting her own insulin pump. Sullivan, who has type 1 diabetes, noticed several hours later that her blood glucose levels had become higher than usual and was surprised to see her pump showed sleep mode during the day.

She was able to address this glitch before going to sleep and thus “escaped a potential occurrence of nocturnal hypoglycemia,” Sullivan and her colleague, Saleh Aldasouqi, MD, wrote in a September commentary in the journal Clinical Diabetes.

The risk of daylight saving time (DST) changes for people with insulin pumps is well known. Aldasouqi himself raised it in a 2014 article in the Journal of Diabetes Science and Technology.

Medtronic Inc., the leading maker of insulin pumps, told this news organization in an email that it intends for future devices to automate DST changes. The company did not provide any further details on when such changes would happen.

For now, Medtronic and other makers of insulin pumps join in twice-a-year efforts to remind people they need to update their devices to adjust for DST changes. They will need to gear up these outreach campaigns, which include social media posts, again ahead of the end of DST on November 3, when clocks shift back an hour. Diabetes clinics and hospitals also send notes to patients.

Even so, people will fail to make this change or to do it correctly.

“Despite our efforts to educate our patients about DST glitches, we have detected incorrect time settings in some of our patients’ insulin pumps after the DST changes in the fall and spring and occasional cases of incorrect insulin dosing, resulting in hyperglycemia or hypoglycemia,” Sullivan and Aldasouqi wrote in their article.

The US Food and Drug Administration (FDA) database of injuries and mishaps with devices contains many reports about patients not adjusting their insulin pumps for DST.

Known as Manufacturer and User Facility Device Experience (MAUDE), this database does not provide identifying details about the patients. Instead, the reports contain only a few lines describing what happened. In many cases, people were able to easily resolve their temporary glycemic issues and then set their devices to the correct time.

But some of the MAUDE reports tell of more severe consequences, with people ending up in emergency rooms because they did not adjust their insulin pumps for DST.

Among these is a report about a November 2022 incident, where a patient suffered due to what appeared to be inaccurate continuous glucose monitor readings, combined with the effects of an insulin pump that had not been updated for a DST change.

Although that patient’s mother was available to assist and the patient consumed three dextrose candies, the patient still reportedly lost consciousness and experienced tremors. That led to hospitalization, where the patient was treated with intravenous saline, intravenous insulin, saline fluids, and insulin fluids. The patient left the hospital with “the issue resolved and no permanent damage” but then switched to another method of insulin therapy, the MAUDE report said.

It’s unclear how often DST changes lead to problems with insulin pumps, reflecting difficulties in tracking flaws and glitches in medical devices, Madris Kinard, the chief executive officer and founder of Device Events, told this news organization.

The FDA relies heavily on passive surveillance, gathering MAUDE reports submitted by companies, clinicians, and patients. That means many cases likely are missed, said Kinard who earlier worked as an analyst at the FDA, updating processes and systems to help identify risky devices.

For example, Sullivan told this news organization she had not filed a report for her incident with the insulin pump.
 

Permanent Standard Time?

Many clinicians, including Aldasouqi and Sullivan, argue a better solution to these challenges would be to end DST.

In their Clinical Diabetes article, they also cited other health risks associated with clock changes such as fatigue, headache, and loss of attention and alertness that can result in injuries.

But a permanent time change is a “politically charged issue, and it continues to be debated nationally and at the state level,” they wrote.

At least 30 states also considered measures this year related to DST, according to the National Conference of State Legislatures. A pending Senate bill intended to make DST permanent has the support of 8 Democrats and 11 Republicans, including Sen. Tommy Tuberville (R-Ala).

“It’s amazing how many phone calls we get over this one topic. People across America agree that changing our clocks back and forth twice a year really makes no sense,” Tuberville said last year on the Senate floor. “People call and say they’re just sick of it.”

These federal and state efforts have stalled to date on the key question of whether to make either standard time or DST permanent, the National Conference of State Legislatures noted. A shift to permanent DST might have benefits for some agricultural and recreational industries, but many physicians say it would be bad for people’s health.

The American Academy of Sleep Medicine (AASM) argues strongly for moving to permanent standard time. In a position statement published in the Journal of Clinical Sleep Medicine, the group said the acute transitions from standard time to DST pose harms, citing research indicating increased risks for adverse cardiovascular events, mood disorders, and motor vehicle crashes.

The solution is to end shifts in time and opt for standard time, which best aligns with the human biological clock, AASM said.

AASM noted that there already was a failed experiment in the United States with a shift to permanent DST. Congress established this in response to the 1973 OPEC oil embargo, expecting that allowing more evening hours with light would lead to energy savings. That didn’t pay off in the expected reduction in energy and the policy was highly unpopular, especially in rural areas, AASM said.

“After a single winter, the policy was reversed by an overwhelming congressional majority,” wrote Muhammad Adeel Rishi, MD, and other authors of the statement. “The unpopularity of the act was likely because despite greater evening light, the policy resulted in a greater proportion of days that required waking up on dark mornings, particularly in the winter.”

Karin G. Johnson, MD, professor of neurology at the UMass Chan School of Medicine, Worcester, Massachusetts, told this news organization that a shift to permanent DST would rob many people of the signals their bodies need for sleep.

“Sunrises and sunsets are later and that creates a desire for our body to stay up later and have more trouble getting up in the morning,” Johnson said. “You’re all but making it impossible for certain segments of the population to get enough sleep” with permanent DST.

Johnson, Sullivan, and Aldasouqi had no relevant financial disclosures.

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

Katie Sullivan, DNP, FNP-C, is publicizing her own challenge with updating an insulin pump as part of an effort to bring an end to the biannual seasonal clock changes in the United States.

On March 10, 2024, Sullivan, who works in the Endocrinology Clinic, Michigan State University, East Lansing, Michigan, mistakenly reversed the AM and PM settings while adjusting her own insulin pump. Sullivan, who has type 1 diabetes, noticed several hours later that her blood glucose levels had become higher than usual and was surprised to see her pump showed sleep mode during the day.

She was able to address this glitch before going to sleep and thus “escaped a potential occurrence of nocturnal hypoglycemia,” Sullivan and her colleague, Saleh Aldasouqi, MD, wrote in a September commentary in the journal Clinical Diabetes.

The risk of daylight saving time (DST) changes for people with insulin pumps is well known. Aldasouqi himself raised it in a 2014 article in the Journal of Diabetes Science and Technology.

Medtronic Inc., the leading maker of insulin pumps, told this news organization in an email that it intends for future devices to automate DST changes. The company did not provide any further details on when such changes would happen.

For now, Medtronic and other makers of insulin pumps join in twice-a-year efforts to remind people they need to update their devices to adjust for DST changes. They will need to gear up these outreach campaigns, which include social media posts, again ahead of the end of DST on November 3, when clocks shift back an hour. Diabetes clinics and hospitals also send notes to patients.

Even so, people will fail to make this change or to do it correctly.

“Despite our efforts to educate our patients about DST glitches, we have detected incorrect time settings in some of our patients’ insulin pumps after the DST changes in the fall and spring and occasional cases of incorrect insulin dosing, resulting in hyperglycemia or hypoglycemia,” Sullivan and Aldasouqi wrote in their article.

The US Food and Drug Administration (FDA) database of injuries and mishaps with devices contains many reports about patients not adjusting their insulin pumps for DST.

Known as Manufacturer and User Facility Device Experience (MAUDE), this database does not provide identifying details about the patients. Instead, the reports contain only a few lines describing what happened. In many cases, people were able to easily resolve their temporary glycemic issues and then set their devices to the correct time.

But some of the MAUDE reports tell of more severe consequences, with people ending up in emergency rooms because they did not adjust their insulin pumps for DST.

Among these is a report about a November 2022 incident, where a patient suffered due to what appeared to be inaccurate continuous glucose monitor readings, combined with the effects of an insulin pump that had not been updated for a DST change.

Although that patient’s mother was available to assist and the patient consumed three dextrose candies, the patient still reportedly lost consciousness and experienced tremors. That led to hospitalization, where the patient was treated with intravenous saline, intravenous insulin, saline fluids, and insulin fluids. The patient left the hospital with “the issue resolved and no permanent damage” but then switched to another method of insulin therapy, the MAUDE report said.

It’s unclear how often DST changes lead to problems with insulin pumps, reflecting difficulties in tracking flaws and glitches in medical devices, Madris Kinard, the chief executive officer and founder of Device Events, told this news organization.

The FDA relies heavily on passive surveillance, gathering MAUDE reports submitted by companies, clinicians, and patients. That means many cases likely are missed, said Kinard who earlier worked as an analyst at the FDA, updating processes and systems to help identify risky devices.

For example, Sullivan told this news organization she had not filed a report for her incident with the insulin pump.
 

Permanent Standard Time?

Many clinicians, including Aldasouqi and Sullivan, argue a better solution to these challenges would be to end DST.

In their Clinical Diabetes article, they also cited other health risks associated with clock changes such as fatigue, headache, and loss of attention and alertness that can result in injuries.

But a permanent time change is a “politically charged issue, and it continues to be debated nationally and at the state level,” they wrote.

At least 30 states also considered measures this year related to DST, according to the National Conference of State Legislatures. A pending Senate bill intended to make DST permanent has the support of 8 Democrats and 11 Republicans, including Sen. Tommy Tuberville (R-Ala).

“It’s amazing how many phone calls we get over this one topic. People across America agree that changing our clocks back and forth twice a year really makes no sense,” Tuberville said last year on the Senate floor. “People call and say they’re just sick of it.”

These federal and state efforts have stalled to date on the key question of whether to make either standard time or DST permanent, the National Conference of State Legislatures noted. A shift to permanent DST might have benefits for some agricultural and recreational industries, but many physicians say it would be bad for people’s health.

The American Academy of Sleep Medicine (AASM) argues strongly for moving to permanent standard time. In a position statement published in the Journal of Clinical Sleep Medicine, the group said the acute transitions from standard time to DST pose harms, citing research indicating increased risks for adverse cardiovascular events, mood disorders, and motor vehicle crashes.

The solution is to end shifts in time and opt for standard time, which best aligns with the human biological clock, AASM said.

AASM noted that there already was a failed experiment in the United States with a shift to permanent DST. Congress established this in response to the 1973 OPEC oil embargo, expecting that allowing more evening hours with light would lead to energy savings. That didn’t pay off in the expected reduction in energy and the policy was highly unpopular, especially in rural areas, AASM said.

“After a single winter, the policy was reversed by an overwhelming congressional majority,” wrote Muhammad Adeel Rishi, MD, and other authors of the statement. “The unpopularity of the act was likely because despite greater evening light, the policy resulted in a greater proportion of days that required waking up on dark mornings, particularly in the winter.”

Karin G. Johnson, MD, professor of neurology at the UMass Chan School of Medicine, Worcester, Massachusetts, told this news organization that a shift to permanent DST would rob many people of the signals their bodies need for sleep.

“Sunrises and sunsets are later and that creates a desire for our body to stay up later and have more trouble getting up in the morning,” Johnson said. “You’re all but making it impossible for certain segments of the population to get enough sleep” with permanent DST.

Johnson, Sullivan, and Aldasouqi had no relevant financial disclosures.

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

Researchers may be on track to develop a much-needed tool for studying endometriosis: A noninvasive stool test that could replace the current gold standard of laparoscopy.

Their approach, which focuses on the link between the gut microbiome and endometriosis, also identified a bacterial metabolite they said might be developed as an oral medication for the condition, which affects at least 11% of women.

In previous research, Rama Kommagani, PhD, an associate professor in the Department of Pathology & Immunology at Baylor College of Medicine in Houston, Texas, worked with a mouse model in which endometrial tissue from donor rodents was injected into the peritoneal space of healthy rodents to induce the disorder.

Transfer of fecal microbiota from mice with endometriosis to those without the condition induced the trademark lesions, suggesting the microbiome influences the development of endometriosis. Treating the animals with the antibiotic metronidazole inhibited the progression of endometrial lesions.

Kommagani speculated the microbes release metabolites that stimulate the growth of the endometrial lesions. “Bad bacteria release metabolites, you know, which actually promote the disease,” Kommagani said. “But the good bacteria might release some protective metabolites such as short-chain fatty acids.”

In a new study, Kommagani and his colleagues sought to identify a unique profile of bacteria-derived metabolites that could reliably diagnose endometriosis. Using stool specimens from 18 women with the condition and 31 without the disease, his team conducted whole metabolic profiling of the gut microbiota.

After identifying hundreds of metabolites in the samples, further analysis revealed a subset of 12 metabolites that consistently differentiated women with and without endometriosis.

These findings led to more questions. “If a metabolite is lower in women with endometriosis, does it have any functional relevance?” Kommagani said.

One candidate was 4-hydroxyindole (4HI), which was found in lower levels in the stool of patients. This substance is a little-understood derivative of its parent compound, indole, which occurs naturally in plants and has a wide range of therapeutic uses.

Using a mouse model, Kommagani’s lab demonstrated that feeding mice 4HI before receiving an endometrial transplant prevented the development of lesions typical of endometriosis. Mice given 4HI after they had developed endometriosis showed regression of lesions and decreased response to painful stimuli.

“In a nutshell, we found a specific set of bacterial metabolites in stool, which could be used towards a noninvasive diagnostic test,” Kommagani said. “But we also found this distinct, specific metabolite that could be used as a therapeutic molecule.” 

Tatnai Burnett, MD, an assistant professor of obstetrics and gynecology at Mayo Clinic in Rochester, Minnesota, who is not associated with the study, said a noninvasive test would have several advantages over the current methods of diagnosing endometriosis. Clinicians could detect and treat women earlier in the course of their disease. Secondly, a test with sufficient negative predictive value would be helpful in deciding whether to initiate treatment with hormones or other oral medications or go straight to surgery. “I would choose not to do a surgery if I knew with enough certainty that I wasn’t going to find anything,” said Burnett.

Lastly, a test that was quantitative and showed a response to treatment could be used as a disease activity marker to monitor the course of someone’s treatment.

But Burnett said more data on the approach are necessary. “This is a fairly small study, as it goes, for developing a screening test,” he said. “We need to see what its positive predictive value, negative predictive value, sensitivity, and specificity are in a bigger group.”

The road to a cure is even longer than the path to developing a screening test. Kommagani’s lab is now conducting more studies in mice to elucidate the pharmacokinetics and toxicology of 4HI before human trials can be attempted.

And as Burnett pointed out, although mouse models are great for experimentation and generating hypotheses, “We’ve seen way too many times in the past where something’s really exciting in a mouse model or a rat model or a monkey model, and it just doesn’t pan out in humans.”

Kommagani received funding from National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society. Burnett reported no financial conflicts of interest.

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

Researchers may be on track to develop a much-needed tool for studying endometriosis: A noninvasive stool test that could replace the current gold standard of laparoscopy.

Their approach, which focuses on the link between the gut microbiome and endometriosis, also identified a bacterial metabolite they said might be developed as an oral medication for the condition, which affects at least 11% of women.

In previous research, Rama Kommagani, PhD, an associate professor in the Department of Pathology & Immunology at Baylor College of Medicine in Houston, Texas, worked with a mouse model in which endometrial tissue from donor rodents was injected into the peritoneal space of healthy rodents to induce the disorder.

Transfer of fecal microbiota from mice with endometriosis to those without the condition induced the trademark lesions, suggesting the microbiome influences the development of endometriosis. Treating the animals with the antibiotic metronidazole inhibited the progression of endometrial lesions.

Kommagani speculated the microbes release metabolites that stimulate the growth of the endometrial lesions. “Bad bacteria release metabolites, you know, which actually promote the disease,” Kommagani said. “But the good bacteria might release some protective metabolites such as short-chain fatty acids.”

In a new study, Kommagani and his colleagues sought to identify a unique profile of bacteria-derived metabolites that could reliably diagnose endometriosis. Using stool specimens from 18 women with the condition and 31 without the disease, his team conducted whole metabolic profiling of the gut microbiota.

After identifying hundreds of metabolites in the samples, further analysis revealed a subset of 12 metabolites that consistently differentiated women with and without endometriosis.

These findings led to more questions. “If a metabolite is lower in women with endometriosis, does it have any functional relevance?” Kommagani said.

One candidate was 4-hydroxyindole (4HI), which was found in lower levels in the stool of patients. This substance is a little-understood derivative of its parent compound, indole, which occurs naturally in plants and has a wide range of therapeutic uses.

Using a mouse model, Kommagani’s lab demonstrated that feeding mice 4HI before receiving an endometrial transplant prevented the development of lesions typical of endometriosis. Mice given 4HI after they had developed endometriosis showed regression of lesions and decreased response to painful stimuli.

“In a nutshell, we found a specific set of bacterial metabolites in stool, which could be used towards a noninvasive diagnostic test,” Kommagani said. “But we also found this distinct, specific metabolite that could be used as a therapeutic molecule.” 

Tatnai Burnett, MD, an assistant professor of obstetrics and gynecology at Mayo Clinic in Rochester, Minnesota, who is not associated with the study, said a noninvasive test would have several advantages over the current methods of diagnosing endometriosis. Clinicians could detect and treat women earlier in the course of their disease. Secondly, a test with sufficient negative predictive value would be helpful in deciding whether to initiate treatment with hormones or other oral medications or go straight to surgery. “I would choose not to do a surgery if I knew with enough certainty that I wasn’t going to find anything,” said Burnett.

Lastly, a test that was quantitative and showed a response to treatment could be used as a disease activity marker to monitor the course of someone’s treatment.

But Burnett said more data on the approach are necessary. “This is a fairly small study, as it goes, for developing a screening test,” he said. “We need to see what its positive predictive value, negative predictive value, sensitivity, and specificity are in a bigger group.”

The road to a cure is even longer than the path to developing a screening test. Kommagani’s lab is now conducting more studies in mice to elucidate the pharmacokinetics and toxicology of 4HI before human trials can be attempted.

And as Burnett pointed out, although mouse models are great for experimentation and generating hypotheses, “We’ve seen way too many times in the past where something’s really exciting in a mouse model or a rat model or a monkey model, and it just doesn’t pan out in humans.”

Kommagani received funding from National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society. Burnett reported no financial conflicts of interest.

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

Researchers may be on track to develop a much-needed tool for studying endometriosis: A noninvasive stool test that could replace the current gold standard of laparoscopy.

Their approach, which focuses on the link between the gut microbiome and endometriosis, also identified a bacterial metabolite they said might be developed as an oral medication for the condition, which affects at least 11% of women.

In previous research, Rama Kommagani, PhD, an associate professor in the Department of Pathology & Immunology at Baylor College of Medicine in Houston, Texas, worked with a mouse model in which endometrial tissue from donor rodents was injected into the peritoneal space of healthy rodents to induce the disorder.

Transfer of fecal microbiota from mice with endometriosis to those without the condition induced the trademark lesions, suggesting the microbiome influences the development of endometriosis. Treating the animals with the antibiotic metronidazole inhibited the progression of endometrial lesions.

Kommagani speculated the microbes release metabolites that stimulate the growth of the endometrial lesions. “Bad bacteria release metabolites, you know, which actually promote the disease,” Kommagani said. “But the good bacteria might release some protective metabolites such as short-chain fatty acids.”

In a new study, Kommagani and his colleagues sought to identify a unique profile of bacteria-derived metabolites that could reliably diagnose endometriosis. Using stool specimens from 18 women with the condition and 31 without the disease, his team conducted whole metabolic profiling of the gut microbiota.

After identifying hundreds of metabolites in the samples, further analysis revealed a subset of 12 metabolites that consistently differentiated women with and without endometriosis.

These findings led to more questions. “If a metabolite is lower in women with endometriosis, does it have any functional relevance?” Kommagani said.

One candidate was 4-hydroxyindole (4HI), which was found in lower levels in the stool of patients. This substance is a little-understood derivative of its parent compound, indole, which occurs naturally in plants and has a wide range of therapeutic uses.

Using a mouse model, Kommagani’s lab demonstrated that feeding mice 4HI before receiving an endometrial transplant prevented the development of lesions typical of endometriosis. Mice given 4HI after they had developed endometriosis showed regression of lesions and decreased response to painful stimuli.

“In a nutshell, we found a specific set of bacterial metabolites in stool, which could be used towards a noninvasive diagnostic test,” Kommagani said. “But we also found this distinct, specific metabolite that could be used as a therapeutic molecule.” 

Tatnai Burnett, MD, an assistant professor of obstetrics and gynecology at Mayo Clinic in Rochester, Minnesota, who is not associated with the study, said a noninvasive test would have several advantages over the current methods of diagnosing endometriosis. Clinicians could detect and treat women earlier in the course of their disease. Secondly, a test with sufficient negative predictive value would be helpful in deciding whether to initiate treatment with hormones or other oral medications or go straight to surgery. “I would choose not to do a surgery if I knew with enough certainty that I wasn’t going to find anything,” said Burnett.

Lastly, a test that was quantitative and showed a response to treatment could be used as a disease activity marker to monitor the course of someone’s treatment.

But Burnett said more data on the approach are necessary. “This is a fairly small study, as it goes, for developing a screening test,” he said. “We need to see what its positive predictive value, negative predictive value, sensitivity, and specificity are in a bigger group.”

The road to a cure is even longer than the path to developing a screening test. Kommagani’s lab is now conducting more studies in mice to elucidate the pharmacokinetics and toxicology of 4HI before human trials can be attempted.

And as Burnett pointed out, although mouse models are great for experimentation and generating hypotheses, “We’ve seen way too many times in the past where something’s really exciting in a mouse model or a rat model or a monkey model, and it just doesn’t pan out in humans.”

Kommagani received funding from National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society. Burnett reported no financial conflicts of interest.

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

Postoperative chronic pain (POCP) is common and is expected to become increasingly prevalent. This type of pain, however, which specifically arises following surgery, independent of any infection or surgical failure, remains poorly understood. Facilities dedicated to treating it are nearly nonexistent.

At the 2024 congress of the French Society of Anesthesia and Resuscitation, anesthesiologists specializing in pain management advocated for improved management of POCP. They put themselves forward as essential interlocutors and actors in this effort. The anesthesiologists also called for better recognition of postoperative pain by patients, general practitioners, and surgeons to enable early intervention and reduce the risk for chronicity.
 

Underrecognized, Poorly Managed

POCP is defined as persistent pain lasting more than 3 months after surgery, unrelated to preoperative pain, and not associated with surgical complications. It can manifest in various forms, but the most typical scenario involves a patient complaining of persistent pain that developed following a surgical procedure. Normal radiological and biologic assessments rule out infectious complications. The persistence of pain long after surgery contrasts with what is often considered a successful surgical outcome by the surgeon.

“Of the 10 million patients operated on each year in France, it is estimated that about 10% will develop POCP, equating to 1.2 million patients,” explained Cyril Quémeneur, a specialist in anesthesiology and pain management at Pitié-Salpêtrière Hospital in Paris, France.

Because of the increasing number of surgical interventions in recent years, POCP has become a major concern. “Currently, there are 275 facilities dedicated to chronic pain across the country, capable of accommodating between 300,000 and 400,000 patients. Given that knee replacement surgery — the incidence of which is rising sharply — results in postoperative pain for 20%-30% of operated patients, the question of managing this type of pain will become even more pressing in the future,” said Quémeneur.

Moreover, specialized facilities for transitional pain management are not widespread in France, unlike in Canada, which has been developing them for about a decade, he noted.

France’s pain treatment centers “are overwhelmed,” said Gilles Lebuffe, a specialist in anesthesiology and pain management at Lille University Hospital in Lille, France. “Thus, the time between when the patient is operated on and when we discuss chronic pain allows the painful condition to establish itself, leading to central sensitization at the neurological level.” Once established, this pain is difficult to treat. “The later a patient arrives at a pain center, the more challenging the situation is to manage,” said Lebuffe.
 

Risk Factors

It is therefore crucial to identify patients at higher risk for postoperative pain during the anesthesia consultation, thus allowing for monitoring during the postoperative period. These pains can be highly debilitating because of their intensity, chronicity, and impact on quality of life.

To target these patients, it is essential to understand which surgeries and patient types constitute risk factors, as well as the characteristics of the pain experienced.

While all surgeries can lead to POCP, certain procedures are more likely to result in chronic pain. They include breast surgery with mastectomy, thoracic and spinal surgery, amputations, and knee replacement surgery. Notably, surgical repair of inguinal hernias, considered routine surgery, is emblematic of the risk for POCP. Its incidence after this procedure is 10% or more in the literature.

In addition, POCP often has neuropathic characteristics. Patients frequently describe their pain using terms like “burning” or “electric shock.” These pains are often associated with strange sensations such as tingling, prickling, itching, or numbness. “This describes neuropathic pain, which increases the risk of chronicity,” said Lebuffe.
 

Preoperative Opioid Use

Another warning sign for healthcare professionals is that patients with chronic pain may have factors associated with vulnerability. Women, who have a higher incidence of chronic pain syndrome, are at greater risk of developing postoperative chronic pain than men.

It has also been shown that preoperative opioid use leads to higher postoperative pain intensities for several days. This is a factor to consider, even though opioid consumption rates in France are far lower than those in the United States, where as much as 35% of patients use opioids preoperatively, said Frédéric Aubrun, head of the Anesthesia and Intensive Care Department and a pain management specialist at the Hospices Civils de Lyon in Lyon, France. Finally, significant literature indicates that psychological fragility is a risk factor for more intense acute pain and for POCP. “Patients with chronic pain frequently have depressive symptoms and anxiety,” said Lebuffe.
 

Involving General Practitioners

Because one responsibility of general practitioners is to identify patients with abnormal postoperative pain trajectories, the anesthesiologists at the press conference advocated for greater patient awareness and increased involvement of general practitioners in this identification process.

“If there is an expected duration of postoperative pain at varying intensities, since it all depends on the patient’s journey (the number of reoperations, history of opioid use, etc.), it is necessary to make patients aware that it is not normal to suffer long after a surgical intervention,” said Aubrun. In addition, it is important to “connect with primary care” and mobilize general practitioners to “detect patients sliding toward opioid overconsumption” and refer them to the appropriate care structure, he said.

Although dedicated facilities for this type of pain — like transitional pain clinics in Canada or northern Europe — do not exist in France, some hospitals, like Lille University Hospital, have established “intermediate consultations targeting patients with specific pain or chronicity characteristics. In these consultations, patients are systematically reviewed 4-6 weeks after surgery by the surgeon, who has been trained to identify neuropathic pain,” said Lebuffe. When a patient with such pain is identified, he or she is referred to an intermediate consultation and seen by a fellow anesthesiologist. The advantage of this consultation is that it is linked to a chronic pain structure. Consequently, frequent exchanges occur with the pain specialists involved in this structure, thus allowing for immediate optimization of pain treatments. The goal is to halt the process of central sensitization.

“We strongly believe in this type of transitional structure, even though it requires significant human resources,” said Lebuffe. He also called for a “societal reflection” on this issue because patients with chronic pain represent a significant cost to society, in terms of medications and work stoppages. Moreover, patients who are forced to stop working see their lives disrupted.
 

Managing POCP

When POCP with neuropathic characteristics has been diagnosed, specific treatments and techniques for chronic pain can be prescribed earlier than they currently are. “Systemic drug treatments for neuropathic POCP rely on various therapeutic classes (opioids, antidepressants, antiepileptics), which are not without side effects for the patient,” said Violaine D’ans, an anesthesiologist and pain management specialist at Polyclinique du Parc in Caen, France. Hence, the idea is to prescribe a minimal dose while providing the patient with techniques available to anesthesiologists. “We have a good range of management options that we use in perioperative pain management, and we have a role to play in radio- or CT-guided perinerve infiltrations, with continuous peripheral nerve blocks and possibly later with electrostimulation to help restore movement and avoid kinesiophobia.”

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Postoperative chronic pain (POCP) is common and is expected to become increasingly prevalent. This type of pain, however, which specifically arises following surgery, independent of any infection or surgical failure, remains poorly understood. Facilities dedicated to treating it are nearly nonexistent.

At the 2024 congress of the French Society of Anesthesia and Resuscitation, anesthesiologists specializing in pain management advocated for improved management of POCP. They put themselves forward as essential interlocutors and actors in this effort. The anesthesiologists also called for better recognition of postoperative pain by patients, general practitioners, and surgeons to enable early intervention and reduce the risk for chronicity.
 

Underrecognized, Poorly Managed

POCP is defined as persistent pain lasting more than 3 months after surgery, unrelated to preoperative pain, and not associated with surgical complications. It can manifest in various forms, but the most typical scenario involves a patient complaining of persistent pain that developed following a surgical procedure. Normal radiological and biologic assessments rule out infectious complications. The persistence of pain long after surgery contrasts with what is often considered a successful surgical outcome by the surgeon.

“Of the 10 million patients operated on each year in France, it is estimated that about 10% will develop POCP, equating to 1.2 million patients,” explained Cyril Quémeneur, a specialist in anesthesiology and pain management at Pitié-Salpêtrière Hospital in Paris, France.

Because of the increasing number of surgical interventions in recent years, POCP has become a major concern. “Currently, there are 275 facilities dedicated to chronic pain across the country, capable of accommodating between 300,000 and 400,000 patients. Given that knee replacement surgery — the incidence of which is rising sharply — results in postoperative pain for 20%-30% of operated patients, the question of managing this type of pain will become even more pressing in the future,” said Quémeneur.

Moreover, specialized facilities for transitional pain management are not widespread in France, unlike in Canada, which has been developing them for about a decade, he noted.

France’s pain treatment centers “are overwhelmed,” said Gilles Lebuffe, a specialist in anesthesiology and pain management at Lille University Hospital in Lille, France. “Thus, the time between when the patient is operated on and when we discuss chronic pain allows the painful condition to establish itself, leading to central sensitization at the neurological level.” Once established, this pain is difficult to treat. “The later a patient arrives at a pain center, the more challenging the situation is to manage,” said Lebuffe.
 

Risk Factors

It is therefore crucial to identify patients at higher risk for postoperative pain during the anesthesia consultation, thus allowing for monitoring during the postoperative period. These pains can be highly debilitating because of their intensity, chronicity, and impact on quality of life.

To target these patients, it is essential to understand which surgeries and patient types constitute risk factors, as well as the characteristics of the pain experienced.

While all surgeries can lead to POCP, certain procedures are more likely to result in chronic pain. They include breast surgery with mastectomy, thoracic and spinal surgery, amputations, and knee replacement surgery. Notably, surgical repair of inguinal hernias, considered routine surgery, is emblematic of the risk for POCP. Its incidence after this procedure is 10% or more in the literature.

In addition, POCP often has neuropathic characteristics. Patients frequently describe their pain using terms like “burning” or “electric shock.” These pains are often associated with strange sensations such as tingling, prickling, itching, or numbness. “This describes neuropathic pain, which increases the risk of chronicity,” said Lebuffe.
 

Preoperative Opioid Use

Another warning sign for healthcare professionals is that patients with chronic pain may have factors associated with vulnerability. Women, who have a higher incidence of chronic pain syndrome, are at greater risk of developing postoperative chronic pain than men.

It has also been shown that preoperative opioid use leads to higher postoperative pain intensities for several days. This is a factor to consider, even though opioid consumption rates in France are far lower than those in the United States, where as much as 35% of patients use opioids preoperatively, said Frédéric Aubrun, head of the Anesthesia and Intensive Care Department and a pain management specialist at the Hospices Civils de Lyon in Lyon, France. Finally, significant literature indicates that psychological fragility is a risk factor for more intense acute pain and for POCP. “Patients with chronic pain frequently have depressive symptoms and anxiety,” said Lebuffe.
 

Involving General Practitioners

Because one responsibility of general practitioners is to identify patients with abnormal postoperative pain trajectories, the anesthesiologists at the press conference advocated for greater patient awareness and increased involvement of general practitioners in this identification process.

“If there is an expected duration of postoperative pain at varying intensities, since it all depends on the patient’s journey (the number of reoperations, history of opioid use, etc.), it is necessary to make patients aware that it is not normal to suffer long after a surgical intervention,” said Aubrun. In addition, it is important to “connect with primary care” and mobilize general practitioners to “detect patients sliding toward opioid overconsumption” and refer them to the appropriate care structure, he said.

Although dedicated facilities for this type of pain — like transitional pain clinics in Canada or northern Europe — do not exist in France, some hospitals, like Lille University Hospital, have established “intermediate consultations targeting patients with specific pain or chronicity characteristics. In these consultations, patients are systematically reviewed 4-6 weeks after surgery by the surgeon, who has been trained to identify neuropathic pain,” said Lebuffe. When a patient with such pain is identified, he or she is referred to an intermediate consultation and seen by a fellow anesthesiologist. The advantage of this consultation is that it is linked to a chronic pain structure. Consequently, frequent exchanges occur with the pain specialists involved in this structure, thus allowing for immediate optimization of pain treatments. The goal is to halt the process of central sensitization.

“We strongly believe in this type of transitional structure, even though it requires significant human resources,” said Lebuffe. He also called for a “societal reflection” on this issue because patients with chronic pain represent a significant cost to society, in terms of medications and work stoppages. Moreover, patients who are forced to stop working see their lives disrupted.
 

Managing POCP

When POCP with neuropathic characteristics has been diagnosed, specific treatments and techniques for chronic pain can be prescribed earlier than they currently are. “Systemic drug treatments for neuropathic POCP rely on various therapeutic classes (opioids, antidepressants, antiepileptics), which are not without side effects for the patient,” said Violaine D’ans, an anesthesiologist and pain management specialist at Polyclinique du Parc in Caen, France. Hence, the idea is to prescribe a minimal dose while providing the patient with techniques available to anesthesiologists. “We have a good range of management options that we use in perioperative pain management, and we have a role to play in radio- or CT-guided perinerve infiltrations, with continuous peripheral nerve blocks and possibly later with electrostimulation to help restore movement and avoid kinesiophobia.”

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Postoperative chronic pain (POCP) is common and is expected to become increasingly prevalent. This type of pain, however, which specifically arises following surgery, independent of any infection or surgical failure, remains poorly understood. Facilities dedicated to treating it are nearly nonexistent.

At the 2024 congress of the French Society of Anesthesia and Resuscitation, anesthesiologists specializing in pain management advocated for improved management of POCP. They put themselves forward as essential interlocutors and actors in this effort. The anesthesiologists also called for better recognition of postoperative pain by patients, general practitioners, and surgeons to enable early intervention and reduce the risk for chronicity.
 

Underrecognized, Poorly Managed

POCP is defined as persistent pain lasting more than 3 months after surgery, unrelated to preoperative pain, and not associated with surgical complications. It can manifest in various forms, but the most typical scenario involves a patient complaining of persistent pain that developed following a surgical procedure. Normal radiological and biologic assessments rule out infectious complications. The persistence of pain long after surgery contrasts with what is often considered a successful surgical outcome by the surgeon.

“Of the 10 million patients operated on each year in France, it is estimated that about 10% will develop POCP, equating to 1.2 million patients,” explained Cyril Quémeneur, a specialist in anesthesiology and pain management at Pitié-Salpêtrière Hospital in Paris, France.

Because of the increasing number of surgical interventions in recent years, POCP has become a major concern. “Currently, there are 275 facilities dedicated to chronic pain across the country, capable of accommodating between 300,000 and 400,000 patients. Given that knee replacement surgery — the incidence of which is rising sharply — results in postoperative pain for 20%-30% of operated patients, the question of managing this type of pain will become even more pressing in the future,” said Quémeneur.

Moreover, specialized facilities for transitional pain management are not widespread in France, unlike in Canada, which has been developing them for about a decade, he noted.

France’s pain treatment centers “are overwhelmed,” said Gilles Lebuffe, a specialist in anesthesiology and pain management at Lille University Hospital in Lille, France. “Thus, the time between when the patient is operated on and when we discuss chronic pain allows the painful condition to establish itself, leading to central sensitization at the neurological level.” Once established, this pain is difficult to treat. “The later a patient arrives at a pain center, the more challenging the situation is to manage,” said Lebuffe.
 

Risk Factors

It is therefore crucial to identify patients at higher risk for postoperative pain during the anesthesia consultation, thus allowing for monitoring during the postoperative period. These pains can be highly debilitating because of their intensity, chronicity, and impact on quality of life.

To target these patients, it is essential to understand which surgeries and patient types constitute risk factors, as well as the characteristics of the pain experienced.

While all surgeries can lead to POCP, certain procedures are more likely to result in chronic pain. They include breast surgery with mastectomy, thoracic and spinal surgery, amputations, and knee replacement surgery. Notably, surgical repair of inguinal hernias, considered routine surgery, is emblematic of the risk for POCP. Its incidence after this procedure is 10% or more in the literature.

In addition, POCP often has neuropathic characteristics. Patients frequently describe their pain using terms like “burning” or “electric shock.” These pains are often associated with strange sensations such as tingling, prickling, itching, or numbness. “This describes neuropathic pain, which increases the risk of chronicity,” said Lebuffe.
 

Preoperative Opioid Use

Another warning sign for healthcare professionals is that patients with chronic pain may have factors associated with vulnerability. Women, who have a higher incidence of chronic pain syndrome, are at greater risk of developing postoperative chronic pain than men.

It has also been shown that preoperative opioid use leads to higher postoperative pain intensities for several days. This is a factor to consider, even though opioid consumption rates in France are far lower than those in the United States, where as much as 35% of patients use opioids preoperatively, said Frédéric Aubrun, head of the Anesthesia and Intensive Care Department and a pain management specialist at the Hospices Civils de Lyon in Lyon, France. Finally, significant literature indicates that psychological fragility is a risk factor for more intense acute pain and for POCP. “Patients with chronic pain frequently have depressive symptoms and anxiety,” said Lebuffe.
 

Involving General Practitioners

Because one responsibility of general practitioners is to identify patients with abnormal postoperative pain trajectories, the anesthesiologists at the press conference advocated for greater patient awareness and increased involvement of general practitioners in this identification process.

“If there is an expected duration of postoperative pain at varying intensities, since it all depends on the patient’s journey (the number of reoperations, history of opioid use, etc.), it is necessary to make patients aware that it is not normal to suffer long after a surgical intervention,” said Aubrun. In addition, it is important to “connect with primary care” and mobilize general practitioners to “detect patients sliding toward opioid overconsumption” and refer them to the appropriate care structure, he said.

Although dedicated facilities for this type of pain — like transitional pain clinics in Canada or northern Europe — do not exist in France, some hospitals, like Lille University Hospital, have established “intermediate consultations targeting patients with specific pain or chronicity characteristics. In these consultations, patients are systematically reviewed 4-6 weeks after surgery by the surgeon, who has been trained to identify neuropathic pain,” said Lebuffe. When a patient with such pain is identified, he or she is referred to an intermediate consultation and seen by a fellow anesthesiologist. The advantage of this consultation is that it is linked to a chronic pain structure. Consequently, frequent exchanges occur with the pain specialists involved in this structure, thus allowing for immediate optimization of pain treatments. The goal is to halt the process of central sensitization.

“We strongly believe in this type of transitional structure, even though it requires significant human resources,” said Lebuffe. He also called for a “societal reflection” on this issue because patients with chronic pain represent a significant cost to society, in terms of medications and work stoppages. Moreover, patients who are forced to stop working see their lives disrupted.
 

Managing POCP

When POCP with neuropathic characteristics has been diagnosed, specific treatments and techniques for chronic pain can be prescribed earlier than they currently are. “Systemic drug treatments for neuropathic POCP rely on various therapeutic classes (opioids, antidepressants, antiepileptics), which are not without side effects for the patient,” said Violaine D’ans, an anesthesiologist and pain management specialist at Polyclinique du Parc in Caen, France. Hence, the idea is to prescribe a minimal dose while providing the patient with techniques available to anesthesiologists. “We have a good range of management options that we use in perioperative pain management, and we have a role to play in radio- or CT-guided perinerve infiltrations, with continuous peripheral nerve blocks and possibly later with electrostimulation to help restore movement and avoid kinesiophobia.”

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In several countries, including China, Mexico, and the United States, the incidence of type 2 diabetes now exceeds that of type 1 diabetes among patients younger than 20 years.

“This is an emerging epidemic,” said Orit Pinhas-Hamiel, MD, director of the Pediatric Endocrinology and Diabetes Unit at Sheba Medical Center in Ramat Gan, Israel, at the annual meeting of the European Association for the Study of Diabetes, noting that these young patients, most with obesity, exhibit a significantly higher incidence of complications than adults with type 2 diabetes or young people with type 1 diabetes.

In 2017-2018, the incidence of type 2 diabetes among patients aged 15-19 years (19.7 per 100,000) surpassed that of type 1 diabetes (14.6 per 100,000), according to data from the United States.

“This is the first time that the incidence of type 2 diabetes has exceeded that of type 1 among youth,” said Pinhas-Hamiel. A review of 2021 published a few months ago highlighted this surge, with countries like China, India, the United States, Brazil, and Mexico leading the way.
 

SEARCH and TODAY

The SEARCH for Diabetes in Youth study, which was launched in 2000, is a multicenter observational study in the United States aimed at estimating the prevalence, incidence, and complications of types 1 and 2 diabetes among young patients. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study is an interventional study focusing on adolescents with type 2 diabetes to evaluate the effectiveness of various treatment options.

“Diabesity” — the dual global epidemic of obesity and type 2 diabetes — has visible consequences from the moment of diagnosis, including hypertension. In the TODAY study, 11.6% adolescents had hypertension at diagnosis. A study conducted in Hong Kong involving 391 children younger than 18 years revealed that 22.5% had hypertension. In SEARCH, 27% young patients diagnosed with type 2 diabetes for 1.5 years had hypertension.

In addition, the SEARCH study found that 27% young individuals had low levels of high-density lipoprotein cholesterol, while 25% had high triglyceride levels, at 1.5 years after diagnosis.

Overall, the cumulative incidence of long-term diabetic complications was assessed in 500 adolescents participating in TODAY (mean age, 26.4 ± 2.8 years; mean time since diagnosis, 13.3 ± 1.8 years). The initial prevalence was 19.2%, while the cumulative incidence rose to 67.5% after 15 years of follow-up.

For dyslipidemia, the initial prevalence was 20.8%, with a cumulative incidence of 51.6%. The incidence of diabetic nephropathy was 54.8% and neuropathies was 32.4%. The prevalence of retinopathy was 13.7% for the period 2010-2011 and 51% for 2017-2018.

At least one complication was observed in 60.1% participants and at least two in 28.4%. As expected, risk factors for developing complications included belonging to a racial or ethnic minority, hyperglycemia, hypertension, and dyslipidemia.

“Among those who developed type 2 diabetes in adolescence, the risk for complications, including microvascular complications, has continuously increased and affected most participants in young adulthood,” said Pinhas-Hamiel.

At the same time, the rate of treatment with lipid-lowering and antihypertensive medications remains low among young people with type 2 diabetes. The management of dyslipidemia is suboptimal, with only 5% young patients with diabetes and dyslipidemia receiving appropriate medications. Furthermore, treatment adherence is lacking. In the TODAY cohort, for example, only one third of participants with high levels of low-density lipoprotein cholesterol were on lipid-lowering medications, and only half of the young patients with hypertension were taking antihypertensives.
 

Focus on Diabetic Nephropathy

Diabetic kidney disease is the leading microvascular complication of type 2 diabetes in adolescents. It is associated with rapid progression and poor prognosis. The natural history begins with hyperfiltration: A consequence of obesity and impaired glucose tolerance. Structural renal changes can be detected as early as 1.5 years after diagnosis.

The second stage is characterized by a reduction in the glomerular filtration rate. At this stage, “the structural changes in the kidney are typical but often present,” said Pinhas-Hamiel, making this period critical for reducing risk factors.

In TODAY, the cumulative incidence of diabetic nephropathy was 54.8%. The prevalence at inclusion was 8%. In SEARCH, after 8 years, the prevalence of diabetic kidney disease was 19.9% among adolescents with type 2 diabetes vs 5.8% among those with type 1 diabetes. A pre-analysis revealed that the overall prevalence of macroalbuminuria among 730 children and adolescents with type 2 diabetes was 3.8%. The ages at diagnosis of type 2 diabetes ranged from 6.5 to 21 years, and the duration of the disease varied from diagnosis to 15 years after.

Diabetic retinopathy was present in 50% participants in the TODAY study at age 25 years (ie, after 12 years of disease). In SEARCH, 56% young patients had diabetic retinopathy after 12.5 years of diabetes. In addition, in the same study, the prevalence of peripheral neuropathy, assessed after 8 years, was 22% among adolescents with type 2 diabetes vs 7% among those with type 1 diabetes.
 

Cardiovascular Autonomic Neuropathy

A decrease in heart rate variability was observed in 47% young patients with type 2 diabetes after an average disease duration of only 1.7 years. In SEARCH, the prevalence of cardiovascular autonomic neuropathy, assessed after 8 years of disease, was 17% in adolescents with type 2 diabetes versus 12% in those with type 1 diabetes.

Overall, 7.1% participants had three complications: nephropathy, retinopathy, and neuropathy. The cumulative incidence of microvascular complications was 80%.

Moreover, A1c levels deteriorated progressively throughout the follow-up period. Approximately 45% participants had an A1c of at least 10%, and 20% were between 8% and 10%. Body mass index consistently remained between 35 and 37.5.

Young patients with type 2 diabetes exhibit endothelial dysfunction, increased carotid intima-media thickness, elevated arterial stiffness, left ventricular hypertrophy, diastolic dysfunction, and reduced maximal exercise capacity. All these factors predict cardiovascular morbidity and mortality.

In TODAY, 17 serious cardiovascular events were recorded, including four myocardial infarctions, six cases of congestive heart failure, three coronary events, and four strokes.

In an analysis of the TODAY and SEARCH studies, although the average duration of diabetes was similar, complications were more frequent among young patients with type 2 diabetes than among those with type 1 diabetes. Microvascular complications were 2.5 times more frequent, and macrovascular complications were four times more frequent.

In SEARCH, excessive mortality was observed among young adults for each type of diabetes. Differences in risk were associated with diabetes type, age, race/ethnicity, and sex. Mortality ratios were 1.5 and 2.3 for types 1 and 2 diabetes, respectively.

Women had higher mortality rates than men. Diabetes was the underlying cause of death in 9.1% cases, which was comparable to cardiovascular diseases or cancer (10.9%). According to a life expectancy model, young patients with type 2 diabetes lose about 15 years of life.
 

Eating Disorders and Depression

Beyond these complications, other issues are often present among adolescents with type 2 diabetes. Approximately 50% have eating disorders (compared with 21% among those with type 1 diabetes), 19.3% report depressive symptoms, and 18.9% have expressed thoughts of self-harm. In addition, 19.6% have polycystic ovary syndrome. Z-scores for bone mineral density at the femoral neck and lumbar spine were significantly lower in adolescents with type 2 diabetes than in healthy peers. The presence of metabolic dysfunction–associated fatty liver disease is also more pronounced.

“The recent approvals of new pharmacological interventions for weight loss and improved glycemic control in adolescents offer hope. We hope that, over the next decade, the prevalence of complications among these young patients with type 2 diabetes will decline. In the meantime, a proactive approach is essential to prevent complications related to type 2 diabetes in these youth,” Pinhas-Hamiel concluded.

For more information, see ISPAD Clinical Practice Consensus Guidelines 2022: Type 2 Diabetes in Children and Adolescents.

Pinhas-Hamiel reported no relevant financial relationships.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In several countries, including China, Mexico, and the United States, the incidence of type 2 diabetes now exceeds that of type 1 diabetes among patients younger than 20 years.

“This is an emerging epidemic,” said Orit Pinhas-Hamiel, MD, director of the Pediatric Endocrinology and Diabetes Unit at Sheba Medical Center in Ramat Gan, Israel, at the annual meeting of the European Association for the Study of Diabetes, noting that these young patients, most with obesity, exhibit a significantly higher incidence of complications than adults with type 2 diabetes or young people with type 1 diabetes.

In 2017-2018, the incidence of type 2 diabetes among patients aged 15-19 years (19.7 per 100,000) surpassed that of type 1 diabetes (14.6 per 100,000), according to data from the United States.

“This is the first time that the incidence of type 2 diabetes has exceeded that of type 1 among youth,” said Pinhas-Hamiel. A review of 2021 published a few months ago highlighted this surge, with countries like China, India, the United States, Brazil, and Mexico leading the way.
 

SEARCH and TODAY

The SEARCH for Diabetes in Youth study, which was launched in 2000, is a multicenter observational study in the United States aimed at estimating the prevalence, incidence, and complications of types 1 and 2 diabetes among young patients. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study is an interventional study focusing on adolescents with type 2 diabetes to evaluate the effectiveness of various treatment options.

“Diabesity” — the dual global epidemic of obesity and type 2 diabetes — has visible consequences from the moment of diagnosis, including hypertension. In the TODAY study, 11.6% adolescents had hypertension at diagnosis. A study conducted in Hong Kong involving 391 children younger than 18 years revealed that 22.5% had hypertension. In SEARCH, 27% young patients diagnosed with type 2 diabetes for 1.5 years had hypertension.

In addition, the SEARCH study found that 27% young individuals had low levels of high-density lipoprotein cholesterol, while 25% had high triglyceride levels, at 1.5 years after diagnosis.

Overall, the cumulative incidence of long-term diabetic complications was assessed in 500 adolescents participating in TODAY (mean age, 26.4 ± 2.8 years; mean time since diagnosis, 13.3 ± 1.8 years). The initial prevalence was 19.2%, while the cumulative incidence rose to 67.5% after 15 years of follow-up.

For dyslipidemia, the initial prevalence was 20.8%, with a cumulative incidence of 51.6%. The incidence of diabetic nephropathy was 54.8% and neuropathies was 32.4%. The prevalence of retinopathy was 13.7% for the period 2010-2011 and 51% for 2017-2018.

At least one complication was observed in 60.1% participants and at least two in 28.4%. As expected, risk factors for developing complications included belonging to a racial or ethnic minority, hyperglycemia, hypertension, and dyslipidemia.

“Among those who developed type 2 diabetes in adolescence, the risk for complications, including microvascular complications, has continuously increased and affected most participants in young adulthood,” said Pinhas-Hamiel.

At the same time, the rate of treatment with lipid-lowering and antihypertensive medications remains low among young people with type 2 diabetes. The management of dyslipidemia is suboptimal, with only 5% young patients with diabetes and dyslipidemia receiving appropriate medications. Furthermore, treatment adherence is lacking. In the TODAY cohort, for example, only one third of participants with high levels of low-density lipoprotein cholesterol were on lipid-lowering medications, and only half of the young patients with hypertension were taking antihypertensives.
 

Focus on Diabetic Nephropathy

Diabetic kidney disease is the leading microvascular complication of type 2 diabetes in adolescents. It is associated with rapid progression and poor prognosis. The natural history begins with hyperfiltration: A consequence of obesity and impaired glucose tolerance. Structural renal changes can be detected as early as 1.5 years after diagnosis.

The second stage is characterized by a reduction in the glomerular filtration rate. At this stage, “the structural changes in the kidney are typical but often present,” said Pinhas-Hamiel, making this period critical for reducing risk factors.

In TODAY, the cumulative incidence of diabetic nephropathy was 54.8%. The prevalence at inclusion was 8%. In SEARCH, after 8 years, the prevalence of diabetic kidney disease was 19.9% among adolescents with type 2 diabetes vs 5.8% among those with type 1 diabetes. A pre-analysis revealed that the overall prevalence of macroalbuminuria among 730 children and adolescents with type 2 diabetes was 3.8%. The ages at diagnosis of type 2 diabetes ranged from 6.5 to 21 years, and the duration of the disease varied from diagnosis to 15 years after.

Diabetic retinopathy was present in 50% participants in the TODAY study at age 25 years (ie, after 12 years of disease). In SEARCH, 56% young patients had diabetic retinopathy after 12.5 years of diabetes. In addition, in the same study, the prevalence of peripheral neuropathy, assessed after 8 years, was 22% among adolescents with type 2 diabetes vs 7% among those with type 1 diabetes.
 

Cardiovascular Autonomic Neuropathy

A decrease in heart rate variability was observed in 47% young patients with type 2 diabetes after an average disease duration of only 1.7 years. In SEARCH, the prevalence of cardiovascular autonomic neuropathy, assessed after 8 years of disease, was 17% in adolescents with type 2 diabetes versus 12% in those with type 1 diabetes.

Overall, 7.1% participants had three complications: nephropathy, retinopathy, and neuropathy. The cumulative incidence of microvascular complications was 80%.

Moreover, A1c levels deteriorated progressively throughout the follow-up period. Approximately 45% participants had an A1c of at least 10%, and 20% were between 8% and 10%. Body mass index consistently remained between 35 and 37.5.

Young patients with type 2 diabetes exhibit endothelial dysfunction, increased carotid intima-media thickness, elevated arterial stiffness, left ventricular hypertrophy, diastolic dysfunction, and reduced maximal exercise capacity. All these factors predict cardiovascular morbidity and mortality.

In TODAY, 17 serious cardiovascular events were recorded, including four myocardial infarctions, six cases of congestive heart failure, three coronary events, and four strokes.

In an analysis of the TODAY and SEARCH studies, although the average duration of diabetes was similar, complications were more frequent among young patients with type 2 diabetes than among those with type 1 diabetes. Microvascular complications were 2.5 times more frequent, and macrovascular complications were four times more frequent.

In SEARCH, excessive mortality was observed among young adults for each type of diabetes. Differences in risk were associated with diabetes type, age, race/ethnicity, and sex. Mortality ratios were 1.5 and 2.3 for types 1 and 2 diabetes, respectively.

Women had higher mortality rates than men. Diabetes was the underlying cause of death in 9.1% cases, which was comparable to cardiovascular diseases or cancer (10.9%). According to a life expectancy model, young patients with type 2 diabetes lose about 15 years of life.
 

Eating Disorders and Depression

Beyond these complications, other issues are often present among adolescents with type 2 diabetes. Approximately 50% have eating disorders (compared with 21% among those with type 1 diabetes), 19.3% report depressive symptoms, and 18.9% have expressed thoughts of self-harm. In addition, 19.6% have polycystic ovary syndrome. Z-scores for bone mineral density at the femoral neck and lumbar spine were significantly lower in adolescents with type 2 diabetes than in healthy peers. The presence of metabolic dysfunction–associated fatty liver disease is also more pronounced.

“The recent approvals of new pharmacological interventions for weight loss and improved glycemic control in adolescents offer hope. We hope that, over the next decade, the prevalence of complications among these young patients with type 2 diabetes will decline. In the meantime, a proactive approach is essential to prevent complications related to type 2 diabetes in these youth,” Pinhas-Hamiel concluded.

For more information, see ISPAD Clinical Practice Consensus Guidelines 2022: Type 2 Diabetes in Children and Adolescents.

Pinhas-Hamiel reported no relevant financial relationships.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In several countries, including China, Mexico, and the United States, the incidence of type 2 diabetes now exceeds that of type 1 diabetes among patients younger than 20 years.

“This is an emerging epidemic,” said Orit Pinhas-Hamiel, MD, director of the Pediatric Endocrinology and Diabetes Unit at Sheba Medical Center in Ramat Gan, Israel, at the annual meeting of the European Association for the Study of Diabetes, noting that these young patients, most with obesity, exhibit a significantly higher incidence of complications than adults with type 2 diabetes or young people with type 1 diabetes.

In 2017-2018, the incidence of type 2 diabetes among patients aged 15-19 years (19.7 per 100,000) surpassed that of type 1 diabetes (14.6 per 100,000), according to data from the United States.

“This is the first time that the incidence of type 2 diabetes has exceeded that of type 1 among youth,” said Pinhas-Hamiel. A review of 2021 published a few months ago highlighted this surge, with countries like China, India, the United States, Brazil, and Mexico leading the way.
 

SEARCH and TODAY

The SEARCH for Diabetes in Youth study, which was launched in 2000, is a multicenter observational study in the United States aimed at estimating the prevalence, incidence, and complications of types 1 and 2 diabetes among young patients. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study is an interventional study focusing on adolescents with type 2 diabetes to evaluate the effectiveness of various treatment options.

“Diabesity” — the dual global epidemic of obesity and type 2 diabetes — has visible consequences from the moment of diagnosis, including hypertension. In the TODAY study, 11.6% adolescents had hypertension at diagnosis. A study conducted in Hong Kong involving 391 children younger than 18 years revealed that 22.5% had hypertension. In SEARCH, 27% young patients diagnosed with type 2 diabetes for 1.5 years had hypertension.

In addition, the SEARCH study found that 27% young individuals had low levels of high-density lipoprotein cholesterol, while 25% had high triglyceride levels, at 1.5 years after diagnosis.

Overall, the cumulative incidence of long-term diabetic complications was assessed in 500 adolescents participating in TODAY (mean age, 26.4 ± 2.8 years; mean time since diagnosis, 13.3 ± 1.8 years). The initial prevalence was 19.2%, while the cumulative incidence rose to 67.5% after 15 years of follow-up.

For dyslipidemia, the initial prevalence was 20.8%, with a cumulative incidence of 51.6%. The incidence of diabetic nephropathy was 54.8% and neuropathies was 32.4%. The prevalence of retinopathy was 13.7% for the period 2010-2011 and 51% for 2017-2018.

At least one complication was observed in 60.1% participants and at least two in 28.4%. As expected, risk factors for developing complications included belonging to a racial or ethnic minority, hyperglycemia, hypertension, and dyslipidemia.

“Among those who developed type 2 diabetes in adolescence, the risk for complications, including microvascular complications, has continuously increased and affected most participants in young adulthood,” said Pinhas-Hamiel.

At the same time, the rate of treatment with lipid-lowering and antihypertensive medications remains low among young people with type 2 diabetes. The management of dyslipidemia is suboptimal, with only 5% young patients with diabetes and dyslipidemia receiving appropriate medications. Furthermore, treatment adherence is lacking. In the TODAY cohort, for example, only one third of participants with high levels of low-density lipoprotein cholesterol were on lipid-lowering medications, and only half of the young patients with hypertension were taking antihypertensives.
 

Focus on Diabetic Nephropathy

Diabetic kidney disease is the leading microvascular complication of type 2 diabetes in adolescents. It is associated with rapid progression and poor prognosis. The natural history begins with hyperfiltration: A consequence of obesity and impaired glucose tolerance. Structural renal changes can be detected as early as 1.5 years after diagnosis.

The second stage is characterized by a reduction in the glomerular filtration rate. At this stage, “the structural changes in the kidney are typical but often present,” said Pinhas-Hamiel, making this period critical for reducing risk factors.

In TODAY, the cumulative incidence of diabetic nephropathy was 54.8%. The prevalence at inclusion was 8%. In SEARCH, after 8 years, the prevalence of diabetic kidney disease was 19.9% among adolescents with type 2 diabetes vs 5.8% among those with type 1 diabetes. A pre-analysis revealed that the overall prevalence of macroalbuminuria among 730 children and adolescents with type 2 diabetes was 3.8%. The ages at diagnosis of type 2 diabetes ranged from 6.5 to 21 years, and the duration of the disease varied from diagnosis to 15 years after.

Diabetic retinopathy was present in 50% participants in the TODAY study at age 25 years (ie, after 12 years of disease). In SEARCH, 56% young patients had diabetic retinopathy after 12.5 years of diabetes. In addition, in the same study, the prevalence of peripheral neuropathy, assessed after 8 years, was 22% among adolescents with type 2 diabetes vs 7% among those with type 1 diabetes.
 

Cardiovascular Autonomic Neuropathy

A decrease in heart rate variability was observed in 47% young patients with type 2 diabetes after an average disease duration of only 1.7 years. In SEARCH, the prevalence of cardiovascular autonomic neuropathy, assessed after 8 years of disease, was 17% in adolescents with type 2 diabetes versus 12% in those with type 1 diabetes.

Overall, 7.1% participants had three complications: nephropathy, retinopathy, and neuropathy. The cumulative incidence of microvascular complications was 80%.

Moreover, A1c levels deteriorated progressively throughout the follow-up period. Approximately 45% participants had an A1c of at least 10%, and 20% were between 8% and 10%. Body mass index consistently remained between 35 and 37.5.

Young patients with type 2 diabetes exhibit endothelial dysfunction, increased carotid intima-media thickness, elevated arterial stiffness, left ventricular hypertrophy, diastolic dysfunction, and reduced maximal exercise capacity. All these factors predict cardiovascular morbidity and mortality.

In TODAY, 17 serious cardiovascular events were recorded, including four myocardial infarctions, six cases of congestive heart failure, three coronary events, and four strokes.

In an analysis of the TODAY and SEARCH studies, although the average duration of diabetes was similar, complications were more frequent among young patients with type 2 diabetes than among those with type 1 diabetes. Microvascular complications were 2.5 times more frequent, and macrovascular complications were four times more frequent.

In SEARCH, excessive mortality was observed among young adults for each type of diabetes. Differences in risk were associated with diabetes type, age, race/ethnicity, and sex. Mortality ratios were 1.5 and 2.3 for types 1 and 2 diabetes, respectively.

Women had higher mortality rates than men. Diabetes was the underlying cause of death in 9.1% cases, which was comparable to cardiovascular diseases or cancer (10.9%). According to a life expectancy model, young patients with type 2 diabetes lose about 15 years of life.
 

Eating Disorders and Depression

Beyond these complications, other issues are often present among adolescents with type 2 diabetes. Approximately 50% have eating disorders (compared with 21% among those with type 1 diabetes), 19.3% report depressive symptoms, and 18.9% have expressed thoughts of self-harm. In addition, 19.6% have polycystic ovary syndrome. Z-scores for bone mineral density at the femoral neck and lumbar spine were significantly lower in adolescents with type 2 diabetes than in healthy peers. The presence of metabolic dysfunction–associated fatty liver disease is also more pronounced.

“The recent approvals of new pharmacological interventions for weight loss and improved glycemic control in adolescents offer hope. We hope that, over the next decade, the prevalence of complications among these young patients with type 2 diabetes will decline. In the meantime, a proactive approach is essential to prevent complications related to type 2 diabetes in these youth,” Pinhas-Hamiel concluded.

For more information, see ISPAD Clinical Practice Consensus Guidelines 2022: Type 2 Diabetes in Children and Adolescents.

Pinhas-Hamiel reported no relevant financial relationships.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Editor's Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Editor's Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Editor's Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

Bright light therapy (BLT) is associated with a 41% remission rate in patients with nonseasonal depressive disorders, significantly higher than the remission rates reported with other treatments, a new meta-analysis shows.
 

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of 11 randomized clinical trials with 858 patients with nonseasonal depressive disorders.
• Included studies compared BLT alone or BLT plus antidepressant with placebo, antidepressant monotherapy, or dim red light.
• BLT was administered using a fluorescent light box producing white light at 10,000 lux for at least 30 minutes daily.
• The primary outcomes were the remission of symptoms and response to treatment, assessed using scales such as the Hamilton Rating Scale for Depression (HAM-D).

TAKEAWAY:

• The estimated remission rate was significantly higher for patients with nonseasonal depressive disorders in the BLT group than for those in the control group (41% vs 23.5%; P < .001).
• The response rate was also higher for patients in the BLT group than for those in the control group (60% vs 39%; P < .001).
• In the subgroup analysis on the basis of the duration of follow-up periods, the BLT group had better remission and response rates than the control group for both short-term (< 4 weeks; P < .001) and long-term (> 4 weeks; P = .04) follow-up periods, which suggests that patients achieved remission and responded to treatment more quickly with BLT than with antidepressants alone.
• The BLT group had a significantly greater reduction in HAM-D scores than the control group (mean difference, −1.44; P = .003).

IN PRACTICE:

“These findings suggest that BLT was an effective adjunctive treatment for nonseasonal depressive disorders, and the response time to the initial treatment may be improved with the addition of BLT,” the study authors wrote.
 

SOURCE:

The study was led by Artur Menegaz de Almeida, MS, Federal University of Mato Grosso, Sinop, Brazil. It was published online on October 2, 2024, in JAMA Psychiatry.
 

LIMITATIONS:

Slight differences were observed in the mean follow-up time between the included trials. The definitions for remission rates and response to treatment varied among the included studies, and they also involved different levels of disorder severity. Additionally, the study did not enable the separate analysis of each included depressive disorder, nor bipolar or unipolar subtypes of major depressive disorder. The moderate number of studies included may have affected the generalizability of the findings.
 

DISCLOSURES:

Study funding was not disclosed. No relevant conflicts of interest were disclosed.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Bright light therapy (BLT) is associated with a 41% remission rate in patients with nonseasonal depressive disorders, significantly higher than the remission rates reported with other treatments, a new meta-analysis shows.
 

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of 11 randomized clinical trials with 858 patients with nonseasonal depressive disorders.
• Included studies compared BLT alone or BLT plus antidepressant with placebo, antidepressant monotherapy, or dim red light.
• BLT was administered using a fluorescent light box producing white light at 10,000 lux for at least 30 minutes daily.
• The primary outcomes were the remission of symptoms and response to treatment, assessed using scales such as the Hamilton Rating Scale for Depression (HAM-D).

TAKEAWAY:

• The estimated remission rate was significantly higher for patients with nonseasonal depressive disorders in the BLT group than for those in the control group (41% vs 23.5%; P < .001).
• The response rate was also higher for patients in the BLT group than for those in the control group (60% vs 39%; P < .001).
• In the subgroup analysis on the basis of the duration of follow-up periods, the BLT group had better remission and response rates than the control group for both short-term (< 4 weeks; P < .001) and long-term (> 4 weeks; P = .04) follow-up periods, which suggests that patients achieved remission and responded to treatment more quickly with BLT than with antidepressants alone.
• The BLT group had a significantly greater reduction in HAM-D scores than the control group (mean difference, −1.44; P = .003).

IN PRACTICE:

“These findings suggest that BLT was an effective adjunctive treatment for nonseasonal depressive disorders, and the response time to the initial treatment may be improved with the addition of BLT,” the study authors wrote.
 

SOURCE:

The study was led by Artur Menegaz de Almeida, MS, Federal University of Mato Grosso, Sinop, Brazil. It was published online on October 2, 2024, in JAMA Psychiatry.
 

LIMITATIONS:

Slight differences were observed in the mean follow-up time between the included trials. The definitions for remission rates and response to treatment varied among the included studies, and they also involved different levels of disorder severity. Additionally, the study did not enable the separate analysis of each included depressive disorder, nor bipolar or unipolar subtypes of major depressive disorder. The moderate number of studies included may have affected the generalizability of the findings.
 

DISCLOSURES:

Study funding was not disclosed. No relevant conflicts of interest were disclosed.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Bright light therapy (BLT) is associated with a 41% remission rate in patients with nonseasonal depressive disorders, significantly higher than the remission rates reported with other treatments, a new meta-analysis shows.
 

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of 11 randomized clinical trials with 858 patients with nonseasonal depressive disorders.
• Included studies compared BLT alone or BLT plus antidepressant with placebo, antidepressant monotherapy, or dim red light.
• BLT was administered using a fluorescent light box producing white light at 10,000 lux for at least 30 minutes daily.
• The primary outcomes were the remission of symptoms and response to treatment, assessed using scales such as the Hamilton Rating Scale for Depression (HAM-D).

TAKEAWAY:

• The estimated remission rate was significantly higher for patients with nonseasonal depressive disorders in the BLT group than for those in the control group (41% vs 23.5%; P < .001).
• The response rate was also higher for patients in the BLT group than for those in the control group (60% vs 39%; P < .001).
• In the subgroup analysis on the basis of the duration of follow-up periods, the BLT group had better remission and response rates than the control group for both short-term (< 4 weeks; P < .001) and long-term (> 4 weeks; P = .04) follow-up periods, which suggests that patients achieved remission and responded to treatment more quickly with BLT than with antidepressants alone.
• The BLT group had a significantly greater reduction in HAM-D scores than the control group (mean difference, −1.44; P = .003).

IN PRACTICE:

“These findings suggest that BLT was an effective adjunctive treatment for nonseasonal depressive disorders, and the response time to the initial treatment may be improved with the addition of BLT,” the study authors wrote.
 

SOURCE:

The study was led by Artur Menegaz de Almeida, MS, Federal University of Mato Grosso, Sinop, Brazil. It was published online on October 2, 2024, in JAMA Psychiatry.
 

LIMITATIONS:

Slight differences were observed in the mean follow-up time between the included trials. The definitions for remission rates and response to treatment varied among the included studies, and they also involved different levels of disorder severity. Additionally, the study did not enable the separate analysis of each included depressive disorder, nor bipolar or unipolar subtypes of major depressive disorder. The moderate number of studies included may have affected the generalizability of the findings.
 

DISCLOSURES:

Study funding was not disclosed. No relevant conflicts of interest were disclosed.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.