Clinical Endocrinology News

TOPLINE:

Naturally occurring glucose fluctuations affect cognitive function in people with type 1 diabetes, according to a new study. It matters less whether glucose is considerably higher or lower than the patient’s usual glucose level. Rather, cognition is slower when the glucose was atypical for that particular individual, with variations between different individuals.

METHODOLOGY:

• The investigators used continuous glucose monitoring (CGM) digital sensors and smartphone-based cognitive tests (cognitive ecological momentary assessment [EMA]) to collect repeated, high-frequency glucose and cognitive data. Glucose data were collected every 5 minutes; cognitive data were collected three times daily for 15 days as participants went about their daily lives.
• The study included 200 participants (mean [standard deviation] age, 47.5 [15.6] years; 53.5% female; 86% White; mean A1c, 7.5 mmol/mol [1.3]).
• Using CGM and EMA, the researchers obtained “intensive” longitudinal measurements of glucose as well as cognition (processing speed and sustained attention).
• Hierarchical Bayesian modeling estimated dynamic, within-person associations between glucose and cognition, and data-driven lasso regression identified identify clinical characteristics that predicted differences from person to person in cognitive vulnerability to glucose fluctuations.

TAKEAWAY:

• Cognitive performance was reduced both at low and high glucose levels, “reflecting vulnerability to glucose fluctuations.”
• Large glucose fluctuations were associated with slower as well as less accurate processing speed, although slight glucose elevations (relative to the individual’s own means) were associated with faster processing speed, regardless of the absolute level (eg, euglycemic vs hyperglycemic) of those means.
• By contrast, glucose fluctuations were unrelated to sustained attention.
• The researchers identified seven clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations: Older age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and larger neck circumference.

IN PRACTICE:

“Our results demonstrate that people can differ a lot from one another in how their brains are impacted by glucose,” co-senior author Laura Germine, PhD, director of the Laboratory for Brain and Cognitive Health Technology, McLean Hospital, Boston, said in a news release. “We found that minimizing glucose fluctuations in daily life is important for optimizing processing speed, and this is especially true for people who are older or have other diabetes-related health conditions.”

SOURCE:

Zoë Hawks, PhD, research investigator, McLean Hospital, Boston, was the lead and corresponding author on the study. It was published online on March 18 in Digital Medicine.

LIMITATIONS:

The researchers required 24-hour access to a smartphone with reliable Internet access, which might have biased sampling toward people of higher economic status. Moreover, the present sample was predominantly White and non-Hispanic, so findings may not be generalizable to other populations.

DISCLOSURES:

The research was supported by grants from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Alzheimer’s Association. Dr. Hawks received consulting fees from Blueprint Health. The other authors’ disclosures were listed in the original paper.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Naturally occurring glucose fluctuations affect cognitive function in people with type 1 diabetes, according to a new study. It matters less whether glucose is considerably higher or lower than the patient’s usual glucose level. Rather, cognition is slower when the glucose was atypical for that particular individual, with variations between different individuals.

METHODOLOGY:

• The investigators used continuous glucose monitoring (CGM) digital sensors and smartphone-based cognitive tests (cognitive ecological momentary assessment [EMA]) to collect repeated, high-frequency glucose and cognitive data. Glucose data were collected every 5 minutes; cognitive data were collected three times daily for 15 days as participants went about their daily lives.
• The study included 200 participants (mean [standard deviation] age, 47.5 [15.6] years; 53.5% female; 86% White; mean A1c, 7.5 mmol/mol [1.3]).
• Using CGM and EMA, the researchers obtained “intensive” longitudinal measurements of glucose as well as cognition (processing speed and sustained attention).
• Hierarchical Bayesian modeling estimated dynamic, within-person associations between glucose and cognition, and data-driven lasso regression identified identify clinical characteristics that predicted differences from person to person in cognitive vulnerability to glucose fluctuations.

TAKEAWAY:

• Cognitive performance was reduced both at low and high glucose levels, “reflecting vulnerability to glucose fluctuations.”
• Large glucose fluctuations were associated with slower as well as less accurate processing speed, although slight glucose elevations (relative to the individual’s own means) were associated with faster processing speed, regardless of the absolute level (eg, euglycemic vs hyperglycemic) of those means.
• By contrast, glucose fluctuations were unrelated to sustained attention.
• The researchers identified seven clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations: Older age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and larger neck circumference.

IN PRACTICE:

“Our results demonstrate that people can differ a lot from one another in how their brains are impacted by glucose,” co-senior author Laura Germine, PhD, director of the Laboratory for Brain and Cognitive Health Technology, McLean Hospital, Boston, said in a news release. “We found that minimizing glucose fluctuations in daily life is important for optimizing processing speed, and this is especially true for people who are older or have other diabetes-related health conditions.”

SOURCE:

Zoë Hawks, PhD, research investigator, McLean Hospital, Boston, was the lead and corresponding author on the study. It was published online on March 18 in Digital Medicine.

LIMITATIONS:

The researchers required 24-hour access to a smartphone with reliable Internet access, which might have biased sampling toward people of higher economic status. Moreover, the present sample was predominantly White and non-Hispanic, so findings may not be generalizable to other populations.

DISCLOSURES:

The research was supported by grants from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Alzheimer’s Association. Dr. Hawks received consulting fees from Blueprint Health. The other authors’ disclosures were listed in the original paper.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Naturally occurring glucose fluctuations affect cognitive function in people with type 1 diabetes, according to a new study. It matters less whether glucose is considerably higher or lower than the patient’s usual glucose level. Rather, cognition is slower when the glucose was atypical for that particular individual, with variations between different individuals.

METHODOLOGY:

• The investigators used continuous glucose monitoring (CGM) digital sensors and smartphone-based cognitive tests (cognitive ecological momentary assessment [EMA]) to collect repeated, high-frequency glucose and cognitive data. Glucose data were collected every 5 minutes; cognitive data were collected three times daily for 15 days as participants went about their daily lives.
• The study included 200 participants (mean [standard deviation] age, 47.5 [15.6] years; 53.5% female; 86% White; mean A1c, 7.5 mmol/mol [1.3]).
• Using CGM and EMA, the researchers obtained “intensive” longitudinal measurements of glucose as well as cognition (processing speed and sustained attention).
• Hierarchical Bayesian modeling estimated dynamic, within-person associations between glucose and cognition, and data-driven lasso regression identified identify clinical characteristics that predicted differences from person to person in cognitive vulnerability to glucose fluctuations.

TAKEAWAY:

• Cognitive performance was reduced both at low and high glucose levels, “reflecting vulnerability to glucose fluctuations.”
• Large glucose fluctuations were associated with slower as well as less accurate processing speed, although slight glucose elevations (relative to the individual’s own means) were associated with faster processing speed, regardless of the absolute level (eg, euglycemic vs hyperglycemic) of those means.
• By contrast, glucose fluctuations were unrelated to sustained attention.
• The researchers identified seven clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations: Older age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and larger neck circumference.

IN PRACTICE:

“Our results demonstrate that people can differ a lot from one another in how their brains are impacted by glucose,” co-senior author Laura Germine, PhD, director of the Laboratory for Brain and Cognitive Health Technology, McLean Hospital, Boston, said in a news release. “We found that minimizing glucose fluctuations in daily life is important for optimizing processing speed, and this is especially true for people who are older or have other diabetes-related health conditions.”

SOURCE:

Zoë Hawks, PhD, research investigator, McLean Hospital, Boston, was the lead and corresponding author on the study. It was published online on March 18 in Digital Medicine.

LIMITATIONS:

The researchers required 24-hour access to a smartphone with reliable Internet access, which might have biased sampling toward people of higher economic status. Moreover, the present sample was predominantly White and non-Hispanic, so findings may not be generalizable to other populations.

DISCLOSURES:

The research was supported by grants from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Alzheimer’s Association. Dr. Hawks received consulting fees from Blueprint Health. The other authors’ disclosures were listed in the original paper.
 

A version of this article appeared on Medscape.com.

PIK3CA-related overgrowth spectrum (PROS) encompasses a set of rare disorders caused by pathogenic variants in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Under normal circumstances, this pathway is activated by the stimulation of tyrosine kinase receptors that leads to tightly regulated cell growth, proliferation, and migration. However, in PROS, pathogenic variants in the PI3KCA gene lead to an abnormal accumulation of the enzyme at the cell membrane, resulting in persistent activation of the PI3K/AKT/mTOR pathway and dysregulated cell overgrowth.

Excessive cell growth and proliferation leads to the overgrowth of tissues and organs characteristically seen in PROS. Because PIK3CA pathogenic variants are not present in every cell, only certain areas of the body are affected by overgrowth; these can range from isolated digits to whole limbs, the trunk, or one or more tissues or organs.

The diagnosis of PROS is typically confirmed through genetic testing of the PIK3CA gene, which can identify the specific pathogenic variants responsible for the disorder.

Here are five things to know about PROS.

1. PROS comprises a heterogeneous group of rare congenital diseases.

PROS is a term used to describe a group of rare congenital disorders that are characterized by abnormal, segmental, or lateralized growth of various body tissues and regions. These disorders are linked by a common cause: mosaic pathogenic gain-of-function variants in the PIK3CA gene. The genetic pathogenic variants that cause these disorders are not passed down from parent to child but instead result from changes to genes during embryonic development.

PROS encompasses a range of clinical entities, each with its own set of characteristics but sharing phenotypic similarities. These clinical entities include:

• Fibroadipose hyperplasia (also called fibroadipose overgrowth)
• CLOVES syndrome (congenital lipomatosis overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal or spinal abnormalities)
• Klippel-Trenaunay syndrome
• Megalencephaly-capillary malformation (MCAP) syndrome
• Hemihyperplasia‐multiple lipomatosis syndrome
• Dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia
• Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
• Macrodactyly
• Isolated tissue dysplasia-overgrowth phenotypes: lymphatic malformations, vascular malformations, venous malformations, lipomatosis
• CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth)

The global epidemiologic characteristics of PROS are not well documented, but it is estimated that each of these conditions individually has a prevalence rate of fewer than 1 case per million population, and the collective prevalence of PROS-related syndromes is 14 cases per million population. Owing to its low prevalence and the variety of diseases it encompasses, PROS is classified as a rare disease.

2. PROS diseases have specific phenotypic features with common characteristics that result in overlapping phenomena.

The severity of clinical presentation varies in patients with PROS; some have tissue-specific distribution whereas others are more pleiotropic. In general, this condition is marked by segmental overgrowth of multiple tissues, including:

• Organs and other tissues: Excessive and asymmetric overgrowth can affect the skin, bones, muscles, and other structures, leading to disfigurement and functional impairments. The overgrowth typically follows a distal to proximal pattern, mostly unilateral and affecting the lower limbs.
• Brain: Enlargement of specific structures, including ventriculomegaly, a thick corpus callosum, or cerebellar tonsillar ectopia, can cause megalencephaly, which can lead to developmental delay, seizures, cortical dysplasia, and/or hydrocephalus.
• Vasculature: Capillary, venous, arteriovenous, and lymphatic malformations are common and occur in about 43% of patients. These abnormalities can contribute to additional complications, including swelling, pain, and increased risk for bleeding.
• Skin: Thickened epidermal nevi and pigmentary anomalies, such as hyperpigmentation or hypopigmentation, are common. These skin manifestations can be early signs of PROS and may aid in diagnosis.
• Skeletal system: Anomalies can include polydactyly, macrodactyly, macrodontia, and scoliosis or other spinal abnormalities.
• Lipomatosis overgrowth: This can occur with or without regional reduction of adipose tissue on the trunk and limbs.
• Lymphatic system: Isolated malformations may include dilated vascular channels lined by lymphatic endothelial cells, which may lead to fluid-filled cysts that usually grow proportionally with the growth of the affected person and may cause pain or significant morbidity if they are infiltrative.

3. Treatment for a PROS disorder may involve targeted options, surgical interventions, and supportive care.

Historically, treatment for overgrowth syndromes such as PROS primarily involved conservative management, focusing on addressing complications through surgical excision, orthopedic surgery, sclerotherapy, embolization, and compressive therapies. However, these strategies often proved insufficient, and patients frequently experienced relapse and progression of the condition. Indeed, PROS is a complex condition that requires a multifaceted treatment approach.

The discovery of the PIK3/AKT/mTOR activation pathway in these syndromes marked a significant therapeutic breakthrough. Targeted therapies, such as the use of mTOR inhibitors like sirolimus, have shown benefits in treating venous and lymphatic malformations in patients with PROS. More recently, a selective PIK3CA inhibitor, alpelisib, has been approved. This drug has demonstrated remarkable improvements in patients with various PROS phenotypes, including reductions in capillary malformations; cessation of chronic gastrointestinal bleeding; and improvements in scoliosis and cognitive function, particularly in patients with MCAP syndrome.

Supportive care is also a critical component of managing PROS. This includes surgical interventions for significant overgrowth, orthopedic care for scoliosis and leg-length discrepancies, and neurosurgical interventions for neurologic complications such as obstructive hydrocephalus and epilepsy. Vascular and lymphatic malformations may be treated with sclerotherapy, laser therapy, or medications such as sirolimus. Additionally, routine treatment for associated conditions such as cardiac and renal abnormalities, intellectual disabilities, polydactyly, coagulopathy, and hypothyroidism is essential. For those with pain, identifying and treating the underlying cause is crucial. In cases of severe persistent hypoglycemia, ongoing treatment, which may include cornstarch administration, is necessary. Owing to the complexity and varied manifestations of PROS, specialized multidisciplinary care for diagnosis, follow-up, and optimal management is recommended.

4. PROS is a heterogeneous condition, and the clinical presentation can vary widely among affected individuals.

PROS is a complex and heterogeneous condition characterized by a wide range of clinical presentations, reflecting the diversity of affected tissues and the extent of overgrowth. Phenotypes within PROS are diverse and can range from a single lesion (ie, solitary macrodactyly) to systemic diseases (ie, Klippel-Trenaunay syndrome and CLOVES syndrome).

This heterogeneity is primarily due to the timing of the onset of the somatic causative PIK3CA pathogenic variants during embryonic and fetal development, influencing the degree of mosaicism and the combination of tissues involved (eg, neural progenitor cell pathogenic variants can lead to postnatal megalencephaly and hydrocephalus). Moreover, different gain-of-function variants in PIK3CA lead to varying levels of hyperactivation of the PI3K/AKT/mTOR pathway, resulting in diverse severity of abnormal proliferation of mesodermal and ectodermal tissues from embryogenesis onward.

This spectrum of symptoms underscores the complexity and variability of PROS, necessitating a tailored approach to diagnosis and management.

5. Regular surveillance is crucial for the effective management of PROS

Comprehensive and regular monitoring is essential to address the diverse and evolving clinical manifestations of PROS. During each medical visit, it is essential to measure growth parameters, including head circumference and the length of arms, hands, legs, and feet. This assessment helps identify any new neurologic symptoms such as seizures, changes in muscle tone, or signs of Chiari malformation.

Additionally, monitoring the patient’s developmental progress, behavior, and motor skills is vital. Clinical assessments for conditions like scoliosis and abdominal examinations for organomegaly or abdominal masses are also recommended.

Imaging plays a significant role in the ongoing evaluation of PROS. Serial head MRI is advised, with the frequency depending on the initial severity of findings and the degree of brain maturation. For patients with central nervous system overgrowth or dysplasia, brain MRI every 6 months until age 2 years, followed by annual scans until age 8 years, is recommended to monitor for progressive hydrocephalus and Chiari malformation.

Further specialized assessments may be required based on individual clinical indications. These include monitoring of vascular and lymphatic malformations, radiographs of limbs in cases of limb overgrowth, and follow-up ultrasonography or MRI for truncal overgrowth. Spinal MRI is necessary for patients with scoliosis or spinal deformities.

In cases of persistent hypoglycemia, particularly those needing ongoing treatment, blood glucose monitoring and evaluation of the hypothalamic-pituitary-adrenal axis are important.

Postsurgical patients, especially those with the CLOVES phenotype or vascular malformations, should have a hematology consultation to assess thrombosis and coagulopathy risks. The use of renal ultrasonography every 3 months until age 8 years is suggested for tumor screening, such as Wilms tumor, although this practice is somewhat controversial.

These comprehensive and tailored approaches are critical in managing the complex and varied aspects of PROS, ensuring optimal care and monitoring for affected individuals.

Dr. Keppler-Noreuil is professor of pediatrics, division of genetics and metabolism, University of Wisconsin School of Medicine and Public Health; clinical director, department of pediatrics, division of genetics and metabolism; program director, medical genetics and genomics residency, Waisman Center & UW Pediatric Specialty Clinics, University of Wisconsin. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

PIK3CA-related overgrowth spectrum (PROS) encompasses a set of rare disorders caused by pathogenic variants in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Under normal circumstances, this pathway is activated by the stimulation of tyrosine kinase receptors that leads to tightly regulated cell growth, proliferation, and migration. However, in PROS, pathogenic variants in the PI3KCA gene lead to an abnormal accumulation of the enzyme at the cell membrane, resulting in persistent activation of the PI3K/AKT/mTOR pathway and dysregulated cell overgrowth.

Excessive cell growth and proliferation leads to the overgrowth of tissues and organs characteristically seen in PROS. Because PIK3CA pathogenic variants are not present in every cell, only certain areas of the body are affected by overgrowth; these can range from isolated digits to whole limbs, the trunk, or one or more tissues or organs.

The diagnosis of PROS is typically confirmed through genetic testing of the PIK3CA gene, which can identify the specific pathogenic variants responsible for the disorder.

Here are five things to know about PROS.

1. PROS comprises a heterogeneous group of rare congenital diseases.

PROS is a term used to describe a group of rare congenital disorders that are characterized by abnormal, segmental, or lateralized growth of various body tissues and regions. These disorders are linked by a common cause: mosaic pathogenic gain-of-function variants in the PIK3CA gene. The genetic pathogenic variants that cause these disorders are not passed down from parent to child but instead result from changes to genes during embryonic development.

PROS encompasses a range of clinical entities, each with its own set of characteristics but sharing phenotypic similarities. These clinical entities include:

• Fibroadipose hyperplasia (also called fibroadipose overgrowth)
• CLOVES syndrome (congenital lipomatosis overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal or spinal abnormalities)
• Klippel-Trenaunay syndrome
• Megalencephaly-capillary malformation (MCAP) syndrome
• Hemihyperplasia‐multiple lipomatosis syndrome
• Dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia
• Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
• Macrodactyly
• Isolated tissue dysplasia-overgrowth phenotypes: lymphatic malformations, vascular malformations, venous malformations, lipomatosis
• CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth)

The global epidemiologic characteristics of PROS are not well documented, but it is estimated that each of these conditions individually has a prevalence rate of fewer than 1 case per million population, and the collective prevalence of PROS-related syndromes is 14 cases per million population. Owing to its low prevalence and the variety of diseases it encompasses, PROS is classified as a rare disease.

2. PROS diseases have specific phenotypic features with common characteristics that result in overlapping phenomena.

The severity of clinical presentation varies in patients with PROS; some have tissue-specific distribution whereas others are more pleiotropic. In general, this condition is marked by segmental overgrowth of multiple tissues, including:

• Organs and other tissues: Excessive and asymmetric overgrowth can affect the skin, bones, muscles, and other structures, leading to disfigurement and functional impairments. The overgrowth typically follows a distal to proximal pattern, mostly unilateral and affecting the lower limbs.
• Brain: Enlargement of specific structures, including ventriculomegaly, a thick corpus callosum, or cerebellar tonsillar ectopia, can cause megalencephaly, which can lead to developmental delay, seizures, cortical dysplasia, and/or hydrocephalus.
• Vasculature: Capillary, venous, arteriovenous, and lymphatic malformations are common and occur in about 43% of patients. These abnormalities can contribute to additional complications, including swelling, pain, and increased risk for bleeding.
• Skin: Thickened epidermal nevi and pigmentary anomalies, such as hyperpigmentation or hypopigmentation, are common. These skin manifestations can be early signs of PROS and may aid in diagnosis.
• Skeletal system: Anomalies can include polydactyly, macrodactyly, macrodontia, and scoliosis or other spinal abnormalities.
• Lipomatosis overgrowth: This can occur with or without regional reduction of adipose tissue on the trunk and limbs.
• Lymphatic system: Isolated malformations may include dilated vascular channels lined by lymphatic endothelial cells, which may lead to fluid-filled cysts that usually grow proportionally with the growth of the affected person and may cause pain or significant morbidity if they are infiltrative.

3. Treatment for a PROS disorder may involve targeted options, surgical interventions, and supportive care.

Historically, treatment for overgrowth syndromes such as PROS primarily involved conservative management, focusing on addressing complications through surgical excision, orthopedic surgery, sclerotherapy, embolization, and compressive therapies. However, these strategies often proved insufficient, and patients frequently experienced relapse and progression of the condition. Indeed, PROS is a complex condition that requires a multifaceted treatment approach.

The discovery of the PIK3/AKT/mTOR activation pathway in these syndromes marked a significant therapeutic breakthrough. Targeted therapies, such as the use of mTOR inhibitors like sirolimus, have shown benefits in treating venous and lymphatic malformations in patients with PROS. More recently, a selective PIK3CA inhibitor, alpelisib, has been approved. This drug has demonstrated remarkable improvements in patients with various PROS phenotypes, including reductions in capillary malformations; cessation of chronic gastrointestinal bleeding; and improvements in scoliosis and cognitive function, particularly in patients with MCAP syndrome.

Supportive care is also a critical component of managing PROS. This includes surgical interventions for significant overgrowth, orthopedic care for scoliosis and leg-length discrepancies, and neurosurgical interventions for neurologic complications such as obstructive hydrocephalus and epilepsy. Vascular and lymphatic malformations may be treated with sclerotherapy, laser therapy, or medications such as sirolimus. Additionally, routine treatment for associated conditions such as cardiac and renal abnormalities, intellectual disabilities, polydactyly, coagulopathy, and hypothyroidism is essential. For those with pain, identifying and treating the underlying cause is crucial. In cases of severe persistent hypoglycemia, ongoing treatment, which may include cornstarch administration, is necessary. Owing to the complexity and varied manifestations of PROS, specialized multidisciplinary care for diagnosis, follow-up, and optimal management is recommended.

4. PROS is a heterogeneous condition, and the clinical presentation can vary widely among affected individuals.

PROS is a complex and heterogeneous condition characterized by a wide range of clinical presentations, reflecting the diversity of affected tissues and the extent of overgrowth. Phenotypes within PROS are diverse and can range from a single lesion (ie, solitary macrodactyly) to systemic diseases (ie, Klippel-Trenaunay syndrome and CLOVES syndrome).

This heterogeneity is primarily due to the timing of the onset of the somatic causative PIK3CA pathogenic variants during embryonic and fetal development, influencing the degree of mosaicism and the combination of tissues involved (eg, neural progenitor cell pathogenic variants can lead to postnatal megalencephaly and hydrocephalus). Moreover, different gain-of-function variants in PIK3CA lead to varying levels of hyperactivation of the PI3K/AKT/mTOR pathway, resulting in diverse severity of abnormal proliferation of mesodermal and ectodermal tissues from embryogenesis onward.

This spectrum of symptoms underscores the complexity and variability of PROS, necessitating a tailored approach to diagnosis and management.

5. Regular surveillance is crucial for the effective management of PROS

Comprehensive and regular monitoring is essential to address the diverse and evolving clinical manifestations of PROS. During each medical visit, it is essential to measure growth parameters, including head circumference and the length of arms, hands, legs, and feet. This assessment helps identify any new neurologic symptoms such as seizures, changes in muscle tone, or signs of Chiari malformation.

Additionally, monitoring the patient’s developmental progress, behavior, and motor skills is vital. Clinical assessments for conditions like scoliosis and abdominal examinations for organomegaly or abdominal masses are also recommended.

Imaging plays a significant role in the ongoing evaluation of PROS. Serial head MRI is advised, with the frequency depending on the initial severity of findings and the degree of brain maturation. For patients with central nervous system overgrowth or dysplasia, brain MRI every 6 months until age 2 years, followed by annual scans until age 8 years, is recommended to monitor for progressive hydrocephalus and Chiari malformation.

Further specialized assessments may be required based on individual clinical indications. These include monitoring of vascular and lymphatic malformations, radiographs of limbs in cases of limb overgrowth, and follow-up ultrasonography or MRI for truncal overgrowth. Spinal MRI is necessary for patients with scoliosis or spinal deformities.

In cases of persistent hypoglycemia, particularly those needing ongoing treatment, blood glucose monitoring and evaluation of the hypothalamic-pituitary-adrenal axis are important.

Postsurgical patients, especially those with the CLOVES phenotype or vascular malformations, should have a hematology consultation to assess thrombosis and coagulopathy risks. The use of renal ultrasonography every 3 months until age 8 years is suggested for tumor screening, such as Wilms tumor, although this practice is somewhat controversial.

These comprehensive and tailored approaches are critical in managing the complex and varied aspects of PROS, ensuring optimal care and monitoring for affected individuals.

Dr. Keppler-Noreuil is professor of pediatrics, division of genetics and metabolism, University of Wisconsin School of Medicine and Public Health; clinical director, department of pediatrics, division of genetics and metabolism; program director, medical genetics and genomics residency, Waisman Center & UW Pediatric Specialty Clinics, University of Wisconsin. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

PIK3CA-related overgrowth spectrum (PROS) encompasses a set of rare disorders caused by pathogenic variants in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Under normal circumstances, this pathway is activated by the stimulation of tyrosine kinase receptors that leads to tightly regulated cell growth, proliferation, and migration. However, in PROS, pathogenic variants in the PI3KCA gene lead to an abnormal accumulation of the enzyme at the cell membrane, resulting in persistent activation of the PI3K/AKT/mTOR pathway and dysregulated cell overgrowth.

Excessive cell growth and proliferation leads to the overgrowth of tissues and organs characteristically seen in PROS. Because PIK3CA pathogenic variants are not present in every cell, only certain areas of the body are affected by overgrowth; these can range from isolated digits to whole limbs, the trunk, or one or more tissues or organs.

The diagnosis of PROS is typically confirmed through genetic testing of the PIK3CA gene, which can identify the specific pathogenic variants responsible for the disorder.

Here are five things to know about PROS.

1. PROS comprises a heterogeneous group of rare congenital diseases.

PROS is a term used to describe a group of rare congenital disorders that are characterized by abnormal, segmental, or lateralized growth of various body tissues and regions. These disorders are linked by a common cause: mosaic pathogenic gain-of-function variants in the PIK3CA gene. The genetic pathogenic variants that cause these disorders are not passed down from parent to child but instead result from changes to genes during embryonic development.

PROS encompasses a range of clinical entities, each with its own set of characteristics but sharing phenotypic similarities. These clinical entities include:

• Fibroadipose hyperplasia (also called fibroadipose overgrowth)
• CLOVES syndrome (congenital lipomatosis overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal or spinal abnormalities)
• Klippel-Trenaunay syndrome
• Megalencephaly-capillary malformation (MCAP) syndrome
• Hemihyperplasia‐multiple lipomatosis syndrome
• Dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia
• Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)
• Macrodactyly
• Isolated tissue dysplasia-overgrowth phenotypes: lymphatic malformations, vascular malformations, venous malformations, lipomatosis
• CLAPO syndrome (capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth)

The global epidemiologic characteristics of PROS are not well documented, but it is estimated that each of these conditions individually has a prevalence rate of fewer than 1 case per million population, and the collective prevalence of PROS-related syndromes is 14 cases per million population. Owing to its low prevalence and the variety of diseases it encompasses, PROS is classified as a rare disease.

2. PROS diseases have specific phenotypic features with common characteristics that result in overlapping phenomena.

The severity of clinical presentation varies in patients with PROS; some have tissue-specific distribution whereas others are more pleiotropic. In general, this condition is marked by segmental overgrowth of multiple tissues, including:

• Organs and other tissues: Excessive and asymmetric overgrowth can affect the skin, bones, muscles, and other structures, leading to disfigurement and functional impairments. The overgrowth typically follows a distal to proximal pattern, mostly unilateral and affecting the lower limbs.
• Brain: Enlargement of specific structures, including ventriculomegaly, a thick corpus callosum, or cerebellar tonsillar ectopia, can cause megalencephaly, which can lead to developmental delay, seizures, cortical dysplasia, and/or hydrocephalus.
• Vasculature: Capillary, venous, arteriovenous, and lymphatic malformations are common and occur in about 43% of patients. These abnormalities can contribute to additional complications, including swelling, pain, and increased risk for bleeding.
• Skin: Thickened epidermal nevi and pigmentary anomalies, such as hyperpigmentation or hypopigmentation, are common. These skin manifestations can be early signs of PROS and may aid in diagnosis.
• Skeletal system: Anomalies can include polydactyly, macrodactyly, macrodontia, and scoliosis or other spinal abnormalities.
• Lipomatosis overgrowth: This can occur with or without regional reduction of adipose tissue on the trunk and limbs.
• Lymphatic system: Isolated malformations may include dilated vascular channels lined by lymphatic endothelial cells, which may lead to fluid-filled cysts that usually grow proportionally with the growth of the affected person and may cause pain or significant morbidity if they are infiltrative.

3. Treatment for a PROS disorder may involve targeted options, surgical interventions, and supportive care.

Historically, treatment for overgrowth syndromes such as PROS primarily involved conservative management, focusing on addressing complications through surgical excision, orthopedic surgery, sclerotherapy, embolization, and compressive therapies. However, these strategies often proved insufficient, and patients frequently experienced relapse and progression of the condition. Indeed, PROS is a complex condition that requires a multifaceted treatment approach.

The discovery of the PIK3/AKT/mTOR activation pathway in these syndromes marked a significant therapeutic breakthrough. Targeted therapies, such as the use of mTOR inhibitors like sirolimus, have shown benefits in treating venous and lymphatic malformations in patients with PROS. More recently, a selective PIK3CA inhibitor, alpelisib, has been approved. This drug has demonstrated remarkable improvements in patients with various PROS phenotypes, including reductions in capillary malformations; cessation of chronic gastrointestinal bleeding; and improvements in scoliosis and cognitive function, particularly in patients with MCAP syndrome.

Supportive care is also a critical component of managing PROS. This includes surgical interventions for significant overgrowth, orthopedic care for scoliosis and leg-length discrepancies, and neurosurgical interventions for neurologic complications such as obstructive hydrocephalus and epilepsy. Vascular and lymphatic malformations may be treated with sclerotherapy, laser therapy, or medications such as sirolimus. Additionally, routine treatment for associated conditions such as cardiac and renal abnormalities, intellectual disabilities, polydactyly, coagulopathy, and hypothyroidism is essential. For those with pain, identifying and treating the underlying cause is crucial. In cases of severe persistent hypoglycemia, ongoing treatment, which may include cornstarch administration, is necessary. Owing to the complexity and varied manifestations of PROS, specialized multidisciplinary care for diagnosis, follow-up, and optimal management is recommended.

4. PROS is a heterogeneous condition, and the clinical presentation can vary widely among affected individuals.

PROS is a complex and heterogeneous condition characterized by a wide range of clinical presentations, reflecting the diversity of affected tissues and the extent of overgrowth. Phenotypes within PROS are diverse and can range from a single lesion (ie, solitary macrodactyly) to systemic diseases (ie, Klippel-Trenaunay syndrome and CLOVES syndrome).

This heterogeneity is primarily due to the timing of the onset of the somatic causative PIK3CA pathogenic variants during embryonic and fetal development, influencing the degree of mosaicism and the combination of tissues involved (eg, neural progenitor cell pathogenic variants can lead to postnatal megalencephaly and hydrocephalus). Moreover, different gain-of-function variants in PIK3CA lead to varying levels of hyperactivation of the PI3K/AKT/mTOR pathway, resulting in diverse severity of abnormal proliferation of mesodermal and ectodermal tissues from embryogenesis onward.

This spectrum of symptoms underscores the complexity and variability of PROS, necessitating a tailored approach to diagnosis and management.

5. Regular surveillance is crucial for the effective management of PROS

Comprehensive and regular monitoring is essential to address the diverse and evolving clinical manifestations of PROS. During each medical visit, it is essential to measure growth parameters, including head circumference and the length of arms, hands, legs, and feet. This assessment helps identify any new neurologic symptoms such as seizures, changes in muscle tone, or signs of Chiari malformation.

Additionally, monitoring the patient’s developmental progress, behavior, and motor skills is vital. Clinical assessments for conditions like scoliosis and abdominal examinations for organomegaly or abdominal masses are also recommended.

Imaging plays a significant role in the ongoing evaluation of PROS. Serial head MRI is advised, with the frequency depending on the initial severity of findings and the degree of brain maturation. For patients with central nervous system overgrowth or dysplasia, brain MRI every 6 months until age 2 years, followed by annual scans until age 8 years, is recommended to monitor for progressive hydrocephalus and Chiari malformation.

Further specialized assessments may be required based on individual clinical indications. These include monitoring of vascular and lymphatic malformations, radiographs of limbs in cases of limb overgrowth, and follow-up ultrasonography or MRI for truncal overgrowth. Spinal MRI is necessary for patients with scoliosis or spinal deformities.

In cases of persistent hypoglycemia, particularly those needing ongoing treatment, blood glucose monitoring and evaluation of the hypothalamic-pituitary-adrenal axis are important.

Postsurgical patients, especially those with the CLOVES phenotype or vascular malformations, should have a hematology consultation to assess thrombosis and coagulopathy risks. The use of renal ultrasonography every 3 months until age 8 years is suggested for tumor screening, such as Wilms tumor, although this practice is somewhat controversial.

These comprehensive and tailored approaches are critical in managing the complex and varied aspects of PROS, ensuring optimal care and monitoring for affected individuals.

Dr. Keppler-Noreuil is professor of pediatrics, division of genetics and metabolism, University of Wisconsin School of Medicine and Public Health; clinical director, department of pediatrics, division of genetics and metabolism; program director, medical genetics and genomics residency, Waisman Center & UW Pediatric Specialty Clinics, University of Wisconsin. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Vitamin D deficiency is independently linked to the risk for diabetic peripheral neuropathy (DPN) by potentially affecting large nerve fibers in older patients with type 2 diabetes (T2D).

METHODOLOGY:

• Although previous research has shown that vitamin D deficiency is common in patients with diabetes and may increase the risk for peripheral neuropathy, its effects on large and small nerve fiber lesions have not been well explored yet.
• Researchers conducted a cross-sectional study to understand the association between vitamin D deficiency and DPN development in 230 older patients (mean age, 67 years) with T2D for about 15 years who were recruited from Beijing Hospital between 2020 and 2023.
• All patients were evaluated for DPN based on poor blood sugar control or symptoms such as pain and sensory abnormalities, of which 175 patients diagnosed with DPN were propensity-matched with 55 patients without DPN.
• Vitamin D deficiency, defined as serum 25-hydroxyvitamin D circulating levels below 20 ng/mL, was reported in 169 patients.
• Large nerve fiber lesions were evaluated using electromyography, and small nerve fiber lesions were assessed by measuring skin conductance.

TAKEAWAY:

• Vitamin D deficiency was more likely to affect large fiber lesions, suggested by longer median sensory nerve latency, minimum latency of the F-wave, and median nerve motor evoked potential latency than those in the vitamin D–sufficient group.
• Furthermore, vitamin D deficiency was linked to large fiber neuropathy with increased odds of prolongation of motor nerve latency (odds ratio, 1.362; P = .038).
• The electrochemical skin conductance, which indicates damage to small nerve fibers, was comparable between patients with and without vitamin D deficiency.

IN PRACTICE:

This study is too preliminary to have practice application.

SOURCE:

This study was led by Sijia Fei, Department of Endocrinology, Beijing Hospital, Beijing, People’s Republic of China, and was published online in Diabetes Research and Clinical Practice.

LIMITATIONS:

Skin biopsy, the “gold-standard” for quantifying intraepidermal nerve fiber density, was not used to assess small nerve fiber lesions. Additionally, a causal link between vitamin D deficiency and diabetic nerve damage was not established owing to the cross-sectional nature of the study. Some patients with T2D may have been receiving insulin therapy, which may have affected vitamin D levels.

DISCLOSURES:

The study was supported by grants from the National Natural Science Foundation of China and China National Key R&D Program. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Vitamin D deficiency is independently linked to the risk for diabetic peripheral neuropathy (DPN) by potentially affecting large nerve fibers in older patients with type 2 diabetes (T2D).

METHODOLOGY:

• Although previous research has shown that vitamin D deficiency is common in patients with diabetes and may increase the risk for peripheral neuropathy, its effects on large and small nerve fiber lesions have not been well explored yet.
• Researchers conducted a cross-sectional study to understand the association between vitamin D deficiency and DPN development in 230 older patients (mean age, 67 years) with T2D for about 15 years who were recruited from Beijing Hospital between 2020 and 2023.
• All patients were evaluated for DPN based on poor blood sugar control or symptoms such as pain and sensory abnormalities, of which 175 patients diagnosed with DPN were propensity-matched with 55 patients without DPN.
• Vitamin D deficiency, defined as serum 25-hydroxyvitamin D circulating levels below 20 ng/mL, was reported in 169 patients.
• Large nerve fiber lesions were evaluated using electromyography, and small nerve fiber lesions were assessed by measuring skin conductance.

TAKEAWAY:

• Vitamin D deficiency was more likely to affect large fiber lesions, suggested by longer median sensory nerve latency, minimum latency of the F-wave, and median nerve motor evoked potential latency than those in the vitamin D–sufficient group.
• Furthermore, vitamin D deficiency was linked to large fiber neuropathy with increased odds of prolongation of motor nerve latency (odds ratio, 1.362; P = .038).
• The electrochemical skin conductance, which indicates damage to small nerve fibers, was comparable between patients with and without vitamin D deficiency.

IN PRACTICE:

This study is too preliminary to have practice application.

SOURCE:

This study was led by Sijia Fei, Department of Endocrinology, Beijing Hospital, Beijing, People’s Republic of China, and was published online in Diabetes Research and Clinical Practice.

LIMITATIONS:

Skin biopsy, the “gold-standard” for quantifying intraepidermal nerve fiber density, was not used to assess small nerve fiber lesions. Additionally, a causal link between vitamin D deficiency and diabetic nerve damage was not established owing to the cross-sectional nature of the study. Some patients with T2D may have been receiving insulin therapy, which may have affected vitamin D levels.

DISCLOSURES:

The study was supported by grants from the National Natural Science Foundation of China and China National Key R&D Program. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Vitamin D deficiency is independently linked to the risk for diabetic peripheral neuropathy (DPN) by potentially affecting large nerve fibers in older patients with type 2 diabetes (T2D).

METHODOLOGY:

• Although previous research has shown that vitamin D deficiency is common in patients with diabetes and may increase the risk for peripheral neuropathy, its effects on large and small nerve fiber lesions have not been well explored yet.
• Researchers conducted a cross-sectional study to understand the association between vitamin D deficiency and DPN development in 230 older patients (mean age, 67 years) with T2D for about 15 years who were recruited from Beijing Hospital between 2020 and 2023.
• All patients were evaluated for DPN based on poor blood sugar control or symptoms such as pain and sensory abnormalities, of which 175 patients diagnosed with DPN were propensity-matched with 55 patients without DPN.
• Vitamin D deficiency, defined as serum 25-hydroxyvitamin D circulating levels below 20 ng/mL, was reported in 169 patients.
• Large nerve fiber lesions were evaluated using electromyography, and small nerve fiber lesions were assessed by measuring skin conductance.

TAKEAWAY:

• Vitamin D deficiency was more likely to affect large fiber lesions, suggested by longer median sensory nerve latency, minimum latency of the F-wave, and median nerve motor evoked potential latency than those in the vitamin D–sufficient group.
• Furthermore, vitamin D deficiency was linked to large fiber neuropathy with increased odds of prolongation of motor nerve latency (odds ratio, 1.362; P = .038).
• The electrochemical skin conductance, which indicates damage to small nerve fibers, was comparable between patients with and without vitamin D deficiency.

IN PRACTICE:

This study is too preliminary to have practice application.

SOURCE:

This study was led by Sijia Fei, Department of Endocrinology, Beijing Hospital, Beijing, People’s Republic of China, and was published online in Diabetes Research and Clinical Practice.

LIMITATIONS:

Skin biopsy, the “gold-standard” for quantifying intraepidermal nerve fiber density, was not used to assess small nerve fiber lesions. Additionally, a causal link between vitamin D deficiency and diabetic nerve damage was not established owing to the cross-sectional nature of the study. Some patients with T2D may have been receiving insulin therapy, which may have affected vitamin D levels.

DISCLOSURES:

The study was supported by grants from the National Natural Science Foundation of China and China National Key R&D Program. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

A novel vibrating capsule that signals a postprandial feeling of fullness reduced both food and energy intake and lowered weight gain in animal studies, said researchers who are developing it as a more affordable treatment for obesity.

The capsule, called the Vibrating Ingestible BioElectronic Stimulator (VIBES), is the size of a large adult multivitamin pill and is meant to be swallowed before a meal. The VIBES capsule works by stimulating gastric stretch receptors that signal the brain through the vagal nerve and stimulate a sense of satiety.

“Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders,” wrote Shriya S. Srinivasan, PhD, at Harvard University, Boston, and her coauthors. Srinivasan, founder and director of the Biohybrid Organs and Neuroprosthetics (BIONIC) Lab, led the team that designed and prototyped the VIBES capsule.

In a pig model, the VIBES activated mechanoreceptors and triggered gastric mucosal receptors, the researchers reported. Across 108 meals, swine treated with VIBES had nearly 40% reduced food intake compared to controls given a sham pill, with no apparent neural adaptation observed.

The research was published online in Science Advances.
 

Satiety Signaling in Obesity Treatment

Caroline M. Apovian, MD, codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, who was not involved in the study, said the concept of creating the illusion of satiety is not a new one.

She was part of team that showed medically meaningful weight loss at 2 years with a surgically implanted device that intermittently blocked the vagus nerves near the junction of the stomach and esophagus. “So we’ve been aware of the potential of things like this to produce a sense of satiety and weight loss,” she said.

However, Dr. Apovian believed that a capsule such as VIBES faces a number of hurdles before it is widely used in the clinic, even if it is successfully tested on humans.

She pointed to a superabsorbent hydrogel device, Plenity (Gelesis), delivered as three oral capsules that expand with water in the stomach to create a feeling of satiety. While approved by the US Food and Drug Administration (FDA), it is not widely used, she said, as there are “hurdles” for patients to overcome, particularly in obtaining it from the pharmacy.

The VIBES capsule would in theory be acceptable to patients, Apovian said, but they are “overwhelmed by the media attention” on medications such as glucagon-like peptide 1 (GLP-1) receptor agonists, which promise dramatic weight loss, far higher than the sorts of figures VIBES could achieve.

Nevertheless, the capsule could form a part of the obesity treatment armamentarium, with the idea that it could be combined with “an agent that would act more centrally to change the body weight setpoint,” she said.

Allan Geliebter, PhD, professor, department of psychiatry, Icahn School of Medicine at Mount Sinai, New York City, said that the thinking behind the capsule is a “clever, original approach,” but he is personally skeptical that people will take them.

“It’s the largest possible capsule that’s on the market today that is approved by the FDA for swallowing,” he said, and people “have to assume it’s going to come out the other end.”

“I think it will,” Dr. Geliebter added, “but if you’re taking at least two of these a day, what’s the guarantee one won’t get stuck along the ride?”

And when it does come out, “maybe it will be visible, maybe not,” but either way, “I can see people being anxious.”

He agreed with Dr. Apovian that the arrival of GLP-1 agonists has made obesity “a tough market to compete in right now,” although he noted that the drugs “do have side effects, and not everybody tolerates them.”

The VIBES Approach

The authors noted that another approved satiety device, intragastic balloons, also were designed to induce early satiety through distension of the stomach, but they do not lead to sustained changes in hunger or eating behavior due to neural adaptation to the continuing distension.

Moreover, some balloons have been withdrawn due to safety concerns, including several deaths.

The team reasoned a mechanism or device “capable of selective mechanoreceptor activation would pose great clinical value.”

Dr. Srinivasan explained: “While vibration has been known to create proprioceptive illusions in muscles, to our knowledge, no one has tried this in the stomach.”

“Given my penchant for mechanoreceptor physiology, I was curious to see if stretch receptors in the smooth muscle could be manipulated by mechanostimulation.”

The team designed an orally ingestible 3D-printed capsule in three sections, one of which allows entry of gastric fluid to dissolve a glucose layer. This causes the release of a spring-loaded pogo pin that completes a circuit to activate the vibrating motor.

Initial testing demonstrated that the capsule, which is the size of a triple zero pill, vibrated for an average of 38.3 minutes, which was deemed acceptable as “meals are generally consumed in a 20- to 30-min window and gastric contents undergo primary mixing in approximately an hour,” the authors wrote.

Immersing the capsule in simulated gastric fluid for 24 hours and simulated intestinal fluid for 10 days at 37 °C didn’t lead to changes in the capsule; thus, it “would not damage the gastrointestinal tract even if it were to reside in the stomach for a full day or in the intestines for over a week,” the authors wrote.

Testing VIBES Satiety in Swine

To test the capsule’s performance as a potential obesity treatment, the researchers turned to a model of Yorkshire pigs ages 4-6 months. Their “gastric anatomy is similar to that of humans,” the authors wrote, and they have been widely used to evaluate biomedical devices.

The researchers found that the vibration from the capsule not only induced the afferent neural activation of gastric mechanoreceptors sensitive to stomach distention but also triggered gastric secretory activity via by what the authors call “stroking” of the gastric mucosa.

To examine the impact of the capsule on hunger and feeding behavior, they monitored the food intake of four pigs in each of three conditions:

• No treatment (control)
• Treated with a sham capsule tethered via a percutaneous endoscopic gastrostomy (PEG) tube (PEG-control)
• Treated with a VIBES capsule tethered via a PEG tube

After 2 weeks, VIBES-treated pigs consumed an average of 58.1% of their meals (n = 108 meals), PEG-control pigs consumed 84.1% (n = 100 meals), and the control group consumed 78.4% (n = 96) meals among PEG-only swine.

Per animal on average, the capsule reduced intake by 31% (P < .001), and the energy consumed per meal for each treated animal was significantly lower than that in the control period (P < .001), with no significant difference between the control and PEG-only groups (P < .1).

In a cross-over experiment, treating the swine for three meals, leaving them untreated for three meals, then treating them for another three revealed that intake increased by 38% during the untreated window.

The crossover results suggest the capsule “functions through temporal vagal activation, with little neural adaptation or long-term effect,” the team wrote.

Weight gain in VIBES-treated pigs was also significantly lower than that in the control and in the PEG-control groups (P < .05).

“Together, these data suggest that the VIBES pill significantly decreases food intake and slows the rate of weight gain in a large animal model,” the team wrote.

The VIBES capsule passed out of the treated pigs after an average of 4.4 days vs 8.3 days for a sham pill. As the “pigs generally take 7-9 days to excrete a given meal,” Dr. Srinivasan noted, “4 days is actually quite fast.”

“In humans, we expect this to pass on the same timescale as a regular meal,” she said, or approximately 24 hours. With no safety concerns identified in the study, Dr. Srinivasan did not expect there to be any significant concern over having multiple devices in the intestines from ingesting one with every meal.

The study was supported in part by grants from the National Institutes of Health, Novo Nordisk, and MIT Department of Mechanical Engineering, alongside support to individual authors via a Schmidt Science Fellowship and a National Science Foundation grant to the Computing Research Association for the CIFellows Project.

Dr. Srinivasan and two coauthors were coinventors on a patent application (application filed by the Massachusetts Institute of Technology describing the developments discussed here). Another author declared a consulting relationship with Novo Nordisk.

No other relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

A novel vibrating capsule that signals a postprandial feeling of fullness reduced both food and energy intake and lowered weight gain in animal studies, said researchers who are developing it as a more affordable treatment for obesity.

The capsule, called the Vibrating Ingestible BioElectronic Stimulator (VIBES), is the size of a large adult multivitamin pill and is meant to be swallowed before a meal. The VIBES capsule works by stimulating gastric stretch receptors that signal the brain through the vagal nerve and stimulate a sense of satiety.

“Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders,” wrote Shriya S. Srinivasan, PhD, at Harvard University, Boston, and her coauthors. Srinivasan, founder and director of the Biohybrid Organs and Neuroprosthetics (BIONIC) Lab, led the team that designed and prototyped the VIBES capsule.

In a pig model, the VIBES activated mechanoreceptors and triggered gastric mucosal receptors, the researchers reported. Across 108 meals, swine treated with VIBES had nearly 40% reduced food intake compared to controls given a sham pill, with no apparent neural adaptation observed.

The research was published online in Science Advances.
 

Satiety Signaling in Obesity Treatment

Caroline M. Apovian, MD, codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, who was not involved in the study, said the concept of creating the illusion of satiety is not a new one.

She was part of team that showed medically meaningful weight loss at 2 years with a surgically implanted device that intermittently blocked the vagus nerves near the junction of the stomach and esophagus. “So we’ve been aware of the potential of things like this to produce a sense of satiety and weight loss,” she said.

However, Dr. Apovian believed that a capsule such as VIBES faces a number of hurdles before it is widely used in the clinic, even if it is successfully tested on humans.

She pointed to a superabsorbent hydrogel device, Plenity (Gelesis), delivered as three oral capsules that expand with water in the stomach to create a feeling of satiety. While approved by the US Food and Drug Administration (FDA), it is not widely used, she said, as there are “hurdles” for patients to overcome, particularly in obtaining it from the pharmacy.

The VIBES capsule would in theory be acceptable to patients, Apovian said, but they are “overwhelmed by the media attention” on medications such as glucagon-like peptide 1 (GLP-1) receptor agonists, which promise dramatic weight loss, far higher than the sorts of figures VIBES could achieve.

Nevertheless, the capsule could form a part of the obesity treatment armamentarium, with the idea that it could be combined with “an agent that would act more centrally to change the body weight setpoint,” she said.

Allan Geliebter, PhD, professor, department of psychiatry, Icahn School of Medicine at Mount Sinai, New York City, said that the thinking behind the capsule is a “clever, original approach,” but he is personally skeptical that people will take them.

“It’s the largest possible capsule that’s on the market today that is approved by the FDA for swallowing,” he said, and people “have to assume it’s going to come out the other end.”

“I think it will,” Dr. Geliebter added, “but if you’re taking at least two of these a day, what’s the guarantee one won’t get stuck along the ride?”

And when it does come out, “maybe it will be visible, maybe not,” but either way, “I can see people being anxious.”

He agreed with Dr. Apovian that the arrival of GLP-1 agonists has made obesity “a tough market to compete in right now,” although he noted that the drugs “do have side effects, and not everybody tolerates them.”

The VIBES Approach

The authors noted that another approved satiety device, intragastic balloons, also were designed to induce early satiety through distension of the stomach, but they do not lead to sustained changes in hunger or eating behavior due to neural adaptation to the continuing distension.

Moreover, some balloons have been withdrawn due to safety concerns, including several deaths.

The team reasoned a mechanism or device “capable of selective mechanoreceptor activation would pose great clinical value.”

Dr. Srinivasan explained: “While vibration has been known to create proprioceptive illusions in muscles, to our knowledge, no one has tried this in the stomach.”

“Given my penchant for mechanoreceptor physiology, I was curious to see if stretch receptors in the smooth muscle could be manipulated by mechanostimulation.”

The team designed an orally ingestible 3D-printed capsule in three sections, one of which allows entry of gastric fluid to dissolve a glucose layer. This causes the release of a spring-loaded pogo pin that completes a circuit to activate the vibrating motor.

Initial testing demonstrated that the capsule, which is the size of a triple zero pill, vibrated for an average of 38.3 minutes, which was deemed acceptable as “meals are generally consumed in a 20- to 30-min window and gastric contents undergo primary mixing in approximately an hour,” the authors wrote.

Immersing the capsule in simulated gastric fluid for 24 hours and simulated intestinal fluid for 10 days at 37 °C didn’t lead to changes in the capsule; thus, it “would not damage the gastrointestinal tract even if it were to reside in the stomach for a full day or in the intestines for over a week,” the authors wrote.

Testing VIBES Satiety in Swine

To test the capsule’s performance as a potential obesity treatment, the researchers turned to a model of Yorkshire pigs ages 4-6 months. Their “gastric anatomy is similar to that of humans,” the authors wrote, and they have been widely used to evaluate biomedical devices.

The researchers found that the vibration from the capsule not only induced the afferent neural activation of gastric mechanoreceptors sensitive to stomach distention but also triggered gastric secretory activity via by what the authors call “stroking” of the gastric mucosa.

To examine the impact of the capsule on hunger and feeding behavior, they monitored the food intake of four pigs in each of three conditions:

• No treatment (control)
• Treated with a sham capsule tethered via a percutaneous endoscopic gastrostomy (PEG) tube (PEG-control)
• Treated with a VIBES capsule tethered via a PEG tube

After 2 weeks, VIBES-treated pigs consumed an average of 58.1% of their meals (n = 108 meals), PEG-control pigs consumed 84.1% (n = 100 meals), and the control group consumed 78.4% (n = 96) meals among PEG-only swine.

Per animal on average, the capsule reduced intake by 31% (P < .001), and the energy consumed per meal for each treated animal was significantly lower than that in the control period (P < .001), with no significant difference between the control and PEG-only groups (P < .1).

In a cross-over experiment, treating the swine for three meals, leaving them untreated for three meals, then treating them for another three revealed that intake increased by 38% during the untreated window.

The crossover results suggest the capsule “functions through temporal vagal activation, with little neural adaptation or long-term effect,” the team wrote.

Weight gain in VIBES-treated pigs was also significantly lower than that in the control and in the PEG-control groups (P < .05).

“Together, these data suggest that the VIBES pill significantly decreases food intake and slows the rate of weight gain in a large animal model,” the team wrote.

The VIBES capsule passed out of the treated pigs after an average of 4.4 days vs 8.3 days for a sham pill. As the “pigs generally take 7-9 days to excrete a given meal,” Dr. Srinivasan noted, “4 days is actually quite fast.”

“In humans, we expect this to pass on the same timescale as a regular meal,” she said, or approximately 24 hours. With no safety concerns identified in the study, Dr. Srinivasan did not expect there to be any significant concern over having multiple devices in the intestines from ingesting one with every meal.

The study was supported in part by grants from the National Institutes of Health, Novo Nordisk, and MIT Department of Mechanical Engineering, alongside support to individual authors via a Schmidt Science Fellowship and a National Science Foundation grant to the Computing Research Association for the CIFellows Project.

Dr. Srinivasan and two coauthors were coinventors on a patent application (application filed by the Massachusetts Institute of Technology describing the developments discussed here). Another author declared a consulting relationship with Novo Nordisk.

No other relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

A novel vibrating capsule that signals a postprandial feeling of fullness reduced both food and energy intake and lowered weight gain in animal studies, said researchers who are developing it as a more affordable treatment for obesity.

The capsule, called the Vibrating Ingestible BioElectronic Stimulator (VIBES), is the size of a large adult multivitamin pill and is meant to be swallowed before a meal. The VIBES capsule works by stimulating gastric stretch receptors that signal the brain through the vagal nerve and stimulate a sense of satiety.

“Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders,” wrote Shriya S. Srinivasan, PhD, at Harvard University, Boston, and her coauthors. Srinivasan, founder and director of the Biohybrid Organs and Neuroprosthetics (BIONIC) Lab, led the team that designed and prototyped the VIBES capsule.

In a pig model, the VIBES activated mechanoreceptors and triggered gastric mucosal receptors, the researchers reported. Across 108 meals, swine treated with VIBES had nearly 40% reduced food intake compared to controls given a sham pill, with no apparent neural adaptation observed.

The research was published online in Science Advances.
 

Satiety Signaling in Obesity Treatment

Caroline M. Apovian, MD, codirector, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, who was not involved in the study, said the concept of creating the illusion of satiety is not a new one.

She was part of team that showed medically meaningful weight loss at 2 years with a surgically implanted device that intermittently blocked the vagus nerves near the junction of the stomach and esophagus. “So we’ve been aware of the potential of things like this to produce a sense of satiety and weight loss,” she said.

However, Dr. Apovian believed that a capsule such as VIBES faces a number of hurdles before it is widely used in the clinic, even if it is successfully tested on humans.

She pointed to a superabsorbent hydrogel device, Plenity (Gelesis), delivered as three oral capsules that expand with water in the stomach to create a feeling of satiety. While approved by the US Food and Drug Administration (FDA), it is not widely used, she said, as there are “hurdles” for patients to overcome, particularly in obtaining it from the pharmacy.

The VIBES capsule would in theory be acceptable to patients, Apovian said, but they are “overwhelmed by the media attention” on medications such as glucagon-like peptide 1 (GLP-1) receptor agonists, which promise dramatic weight loss, far higher than the sorts of figures VIBES could achieve.

Nevertheless, the capsule could form a part of the obesity treatment armamentarium, with the idea that it could be combined with “an agent that would act more centrally to change the body weight setpoint,” she said.

Allan Geliebter, PhD, professor, department of psychiatry, Icahn School of Medicine at Mount Sinai, New York City, said that the thinking behind the capsule is a “clever, original approach,” but he is personally skeptical that people will take them.

“It’s the largest possible capsule that’s on the market today that is approved by the FDA for swallowing,” he said, and people “have to assume it’s going to come out the other end.”

“I think it will,” Dr. Geliebter added, “but if you’re taking at least two of these a day, what’s the guarantee one won’t get stuck along the ride?”

And when it does come out, “maybe it will be visible, maybe not,” but either way, “I can see people being anxious.”

He agreed with Dr. Apovian that the arrival of GLP-1 agonists has made obesity “a tough market to compete in right now,” although he noted that the drugs “do have side effects, and not everybody tolerates them.”

The VIBES Approach

The authors noted that another approved satiety device, intragastic balloons, also were designed to induce early satiety through distension of the stomach, but they do not lead to sustained changes in hunger or eating behavior due to neural adaptation to the continuing distension.

Moreover, some balloons have been withdrawn due to safety concerns, including several deaths.

The team reasoned a mechanism or device “capable of selective mechanoreceptor activation would pose great clinical value.”

Dr. Srinivasan explained: “While vibration has been known to create proprioceptive illusions in muscles, to our knowledge, no one has tried this in the stomach.”

“Given my penchant for mechanoreceptor physiology, I was curious to see if stretch receptors in the smooth muscle could be manipulated by mechanostimulation.”

The team designed an orally ingestible 3D-printed capsule in three sections, one of which allows entry of gastric fluid to dissolve a glucose layer. This causes the release of a spring-loaded pogo pin that completes a circuit to activate the vibrating motor.

Initial testing demonstrated that the capsule, which is the size of a triple zero pill, vibrated for an average of 38.3 minutes, which was deemed acceptable as “meals are generally consumed in a 20- to 30-min window and gastric contents undergo primary mixing in approximately an hour,” the authors wrote.

Immersing the capsule in simulated gastric fluid for 24 hours and simulated intestinal fluid for 10 days at 37 °C didn’t lead to changes in the capsule; thus, it “would not damage the gastrointestinal tract even if it were to reside in the stomach for a full day or in the intestines for over a week,” the authors wrote.

Testing VIBES Satiety in Swine

To test the capsule’s performance as a potential obesity treatment, the researchers turned to a model of Yorkshire pigs ages 4-6 months. Their “gastric anatomy is similar to that of humans,” the authors wrote, and they have been widely used to evaluate biomedical devices.

The researchers found that the vibration from the capsule not only induced the afferent neural activation of gastric mechanoreceptors sensitive to stomach distention but also triggered gastric secretory activity via by what the authors call “stroking” of the gastric mucosa.

To examine the impact of the capsule on hunger and feeding behavior, they monitored the food intake of four pigs in each of three conditions:

• No treatment (control)
• Treated with a sham capsule tethered via a percutaneous endoscopic gastrostomy (PEG) tube (PEG-control)
• Treated with a VIBES capsule tethered via a PEG tube

After 2 weeks, VIBES-treated pigs consumed an average of 58.1% of their meals (n = 108 meals), PEG-control pigs consumed 84.1% (n = 100 meals), and the control group consumed 78.4% (n = 96) meals among PEG-only swine.

Per animal on average, the capsule reduced intake by 31% (P < .001), and the energy consumed per meal for each treated animal was significantly lower than that in the control period (P < .001), with no significant difference between the control and PEG-only groups (P < .1).

In a cross-over experiment, treating the swine for three meals, leaving them untreated for three meals, then treating them for another three revealed that intake increased by 38% during the untreated window.

The crossover results suggest the capsule “functions through temporal vagal activation, with little neural adaptation or long-term effect,” the team wrote.

Weight gain in VIBES-treated pigs was also significantly lower than that in the control and in the PEG-control groups (P < .05).

“Together, these data suggest that the VIBES pill significantly decreases food intake and slows the rate of weight gain in a large animal model,” the team wrote.

The VIBES capsule passed out of the treated pigs after an average of 4.4 days vs 8.3 days for a sham pill. As the “pigs generally take 7-9 days to excrete a given meal,” Dr. Srinivasan noted, “4 days is actually quite fast.”

“In humans, we expect this to pass on the same timescale as a regular meal,” she said, or approximately 24 hours. With no safety concerns identified in the study, Dr. Srinivasan did not expect there to be any significant concern over having multiple devices in the intestines from ingesting one with every meal.

The study was supported in part by grants from the National Institutes of Health, Novo Nordisk, and MIT Department of Mechanical Engineering, alongside support to individual authors via a Schmidt Science Fellowship and a National Science Foundation grant to the Computing Research Association for the CIFellows Project.

Dr. Srinivasan and two coauthors were coinventors on a patent application (application filed by the Massachusetts Institute of Technology describing the developments discussed here). Another author declared a consulting relationship with Novo Nordisk.

No other relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

Among the potential uses envisioned for artificial intelligence (AI) in healthcare is decreasing provider burden by using the technology to help respond to patients’ questions submitted through portals.

Easing the burden on providers of responding to each question is a target ripe for solutions as during the COVID pandemic, such messages increased 157% from prepandemic levels, say authors of a paper published online in JAMA Network Open. Each additional message added 2.3 minutes to time spent on the electronic health record (EHR) per day.

Researchers at Stanford Health Care, led by Patricia Garcia, MD, with the department of medicine, conducted a 5-week, prospective, single-group quality improvement study from July 10 through August 13, 2023, at Stanford to test an AI response system.
 

Large Language Model Used

All attending physicians, advanced practice providers, clinic nurses, and clinical pharmacists from the divisions of primary care and gastroenterology and hepatology were enrolled in a pilot program that offered the option to answer patients’ questions with drafts that were generated by a Health Insurance Portability and Accountability Act–compliant large language model integrated into EHRs. Drafts were then reviewed by the provider.

The study primarily tested whether providers (162 were included) would use the AI-generated drafts. Secondary outcomes included whether using such a system saved time or improved the clinician experience.

Participants received survey emails before and after the pilot period and answered questions on areas including task load, EHR burden, usability, work exhaustion, burnout, and satisfaction.

Researchers found that the overall average utilization rate per clinician was 20% but there were significant between-group differences. For example, in gastroenterology and hepatology, nurses used the AI tool the most at 29% and physicians/APPs had a 24% usage rate, whereas clinical pharmacists had the highest use rate for primary care at 44% compared with physician use at 15%.
 

Burden Improved, But Didn’t Save Time

AI did not appear to save time but did improve task load scores and work exhaustion scores. The report states that there was no change in reply action time, write time, or read time between the prepilot and pilot periods. However, there were significant reductions in the physician task load score derivative (mean [SD], 61.31 [17.23] pre survey vs 47.26 [17.11] post survey; paired difference, −13.87; 95% CI, −17.38 to −9.50; P < .001) and work exhaustion scores decreased by a third (mean [SD], 1.95 [0.79] pre survey vs 1.62 [0.68] post survey; paired difference, −0.33; 95% CI, −0.50 to −0.17; P < .001)

The authors wrote that improvements in task load and emotional exhaustion scores suggest that generated replies have the potential to lessen cognitive burden and burnout. Though the AI tool didn’t save time, editing responses may be less cognitively taxing than writing responses for providers, the authors suggest.
 

Quality of AI Responses

Comments about AI response message voice and/or tone were the most common and had the highest absolute number of negative comments (10 positive, 2 neutral, and 14 negative). The most negative comments were about length (too long or too short) of the draft message (1 positive, 2 neutral, and 8 negative).

Comments on accuracy of the draft response were fairly even ­— 4 positive and 5 negative — but there were no adverse safety signals, the authors report.

The providers had high expectations about use and quality of the tool that “were either met or exceeded at the end of the pilot,” Dr. Garcia and coauthors write. “Given the evidence that burnout is associated with turnover, reductions in clinical activity, and quality, even a modest improvement may have a substantial impact.”

One coauthor reported grants from Google, Omada Health, and PredictaMed outside the submitted work. Another coauthor reported having a patent for Well-being Index Instruments and Mayo Leadership Impact Index, with royalties paid from Mayo Clinic, and receiving honoraria for presenting grand rounds, keynote lectures, and advising health care organizations on clinician well-being. No other disclosures were reported. 

Among the potential uses envisioned for artificial intelligence (AI) in healthcare is decreasing provider burden by using the technology to help respond to patients’ questions submitted through portals.

Easing the burden on providers of responding to each question is a target ripe for solutions as during the COVID pandemic, such messages increased 157% from prepandemic levels, say authors of a paper published online in JAMA Network Open. Each additional message added 2.3 minutes to time spent on the electronic health record (EHR) per day.

Researchers at Stanford Health Care, led by Patricia Garcia, MD, with the department of medicine, conducted a 5-week, prospective, single-group quality improvement study from July 10 through August 13, 2023, at Stanford to test an AI response system.
 

Large Language Model Used

All attending physicians, advanced practice providers, clinic nurses, and clinical pharmacists from the divisions of primary care and gastroenterology and hepatology were enrolled in a pilot program that offered the option to answer patients’ questions with drafts that were generated by a Health Insurance Portability and Accountability Act–compliant large language model integrated into EHRs. Drafts were then reviewed by the provider.

The study primarily tested whether providers (162 were included) would use the AI-generated drafts. Secondary outcomes included whether using such a system saved time or improved the clinician experience.

Participants received survey emails before and after the pilot period and answered questions on areas including task load, EHR burden, usability, work exhaustion, burnout, and satisfaction.

Researchers found that the overall average utilization rate per clinician was 20% but there were significant between-group differences. For example, in gastroenterology and hepatology, nurses used the AI tool the most at 29% and physicians/APPs had a 24% usage rate, whereas clinical pharmacists had the highest use rate for primary care at 44% compared with physician use at 15%.
 

Burden Improved, But Didn’t Save Time

AI did not appear to save time but did improve task load scores and work exhaustion scores. The report states that there was no change in reply action time, write time, or read time between the prepilot and pilot periods. However, there were significant reductions in the physician task load score derivative (mean [SD], 61.31 [17.23] pre survey vs 47.26 [17.11] post survey; paired difference, −13.87; 95% CI, −17.38 to −9.50; P < .001) and work exhaustion scores decreased by a third (mean [SD], 1.95 [0.79] pre survey vs 1.62 [0.68] post survey; paired difference, −0.33; 95% CI, −0.50 to −0.17; P < .001)

The authors wrote that improvements in task load and emotional exhaustion scores suggest that generated replies have the potential to lessen cognitive burden and burnout. Though the AI tool didn’t save time, editing responses may be less cognitively taxing than writing responses for providers, the authors suggest.
 

Quality of AI Responses

Comments about AI response message voice and/or tone were the most common and had the highest absolute number of negative comments (10 positive, 2 neutral, and 14 negative). The most negative comments were about length (too long or too short) of the draft message (1 positive, 2 neutral, and 8 negative).

Comments on accuracy of the draft response were fairly even ­— 4 positive and 5 negative — but there were no adverse safety signals, the authors report.

The providers had high expectations about use and quality of the tool that “were either met or exceeded at the end of the pilot,” Dr. Garcia and coauthors write. “Given the evidence that burnout is associated with turnover, reductions in clinical activity, and quality, even a modest improvement may have a substantial impact.”

One coauthor reported grants from Google, Omada Health, and PredictaMed outside the submitted work. Another coauthor reported having a patent for Well-being Index Instruments and Mayo Leadership Impact Index, with royalties paid from Mayo Clinic, and receiving honoraria for presenting grand rounds, keynote lectures, and advising health care organizations on clinician well-being. No other disclosures were reported. 

Among the potential uses envisioned for artificial intelligence (AI) in healthcare is decreasing provider burden by using the technology to help respond to patients’ questions submitted through portals.

Easing the burden on providers of responding to each question is a target ripe for solutions as during the COVID pandemic, such messages increased 157% from prepandemic levels, say authors of a paper published online in JAMA Network Open. Each additional message added 2.3 minutes to time spent on the electronic health record (EHR) per day.

Researchers at Stanford Health Care, led by Patricia Garcia, MD, with the department of medicine, conducted a 5-week, prospective, single-group quality improvement study from July 10 through August 13, 2023, at Stanford to test an AI response system.
 

Large Language Model Used

All attending physicians, advanced practice providers, clinic nurses, and clinical pharmacists from the divisions of primary care and gastroenterology and hepatology were enrolled in a pilot program that offered the option to answer patients’ questions with drafts that were generated by a Health Insurance Portability and Accountability Act–compliant large language model integrated into EHRs. Drafts were then reviewed by the provider.

The study primarily tested whether providers (162 were included) would use the AI-generated drafts. Secondary outcomes included whether using such a system saved time or improved the clinician experience.

Participants received survey emails before and after the pilot period and answered questions on areas including task load, EHR burden, usability, work exhaustion, burnout, and satisfaction.

Researchers found that the overall average utilization rate per clinician was 20% but there were significant between-group differences. For example, in gastroenterology and hepatology, nurses used the AI tool the most at 29% and physicians/APPs had a 24% usage rate, whereas clinical pharmacists had the highest use rate for primary care at 44% compared with physician use at 15%.
 

Burden Improved, But Didn’t Save Time

AI did not appear to save time but did improve task load scores and work exhaustion scores. The report states that there was no change in reply action time, write time, or read time between the prepilot and pilot periods. However, there were significant reductions in the physician task load score derivative (mean [SD], 61.31 [17.23] pre survey vs 47.26 [17.11] post survey; paired difference, −13.87; 95% CI, −17.38 to −9.50; P < .001) and work exhaustion scores decreased by a third (mean [SD], 1.95 [0.79] pre survey vs 1.62 [0.68] post survey; paired difference, −0.33; 95% CI, −0.50 to −0.17; P < .001)

The authors wrote that improvements in task load and emotional exhaustion scores suggest that generated replies have the potential to lessen cognitive burden and burnout. Though the AI tool didn’t save time, editing responses may be less cognitively taxing than writing responses for providers, the authors suggest.
 

Quality of AI Responses

Comments about AI response message voice and/or tone were the most common and had the highest absolute number of negative comments (10 positive, 2 neutral, and 14 negative). The most negative comments were about length (too long or too short) of the draft message (1 positive, 2 neutral, and 8 negative).

Comments on accuracy of the draft response were fairly even ­— 4 positive and 5 negative — but there were no adverse safety signals, the authors report.

The providers had high expectations about use and quality of the tool that “were either met or exceeded at the end of the pilot,” Dr. Garcia and coauthors write. “Given the evidence that burnout is associated with turnover, reductions in clinical activity, and quality, even a modest improvement may have a substantial impact.”

One coauthor reported grants from Google, Omada Health, and PredictaMed outside the submitted work. Another coauthor reported having a patent for Well-being Index Instruments and Mayo Leadership Impact Index, with royalties paid from Mayo Clinic, and receiving honoraria for presenting grand rounds, keynote lectures, and advising health care organizations on clinician well-being. No other disclosures were reported. 

Most major cancer trial centers in the United States are located closer to populations with higher proportions of White, affluent individuals, a new study finds.

This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.

“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”

Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.

“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.

To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.

These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).

The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.

“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.

The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.

In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.

“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”

A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.

Most major cancer trial centers in the United States are located closer to populations with higher proportions of White, affluent individuals, a new study finds.

This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.

“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”

Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.

“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.

To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.

These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).

The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.

“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.

The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.

In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.

“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”

A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.

Most major cancer trial centers in the United States are located closer to populations with higher proportions of White, affluent individuals, a new study finds.

This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.

“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”

Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.

“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.

To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.

These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).

The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.

“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.

The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.

In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.

“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”

A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.

TOPLINE:

Sodium-glucose cotransporter 2 inhibitor (SGLT2i)-associated diabetes ketoacidosis (DKA) in people with type 2 diabetes (T2D) is associated with lower degrees of hyperglycemia over the first 24 hours of treatment than seen in type 1 diabetes (T1D)-associated DKA, potentially leading to hypo- or hyperglycemia if the same insulin infusion protocols are used.

METHODOLOGY:

• Retrospective cohort study comparing natural history and response to treatment for 37 episodes of SGLT2i-associated DKA (n = 27) or ketosis (n = 10) in people with T2D vs 19 episodes of T1D-associated DKA in people of the same age range as the T2D group, identified from endocrine consultation requests in two South Australian tertiary hospitals.

TAKEAWAY:

• Patients with T2D and SGLT2i-associated DKA had milder DKA than T1D-associated DKA (median ketone peak, 5.3 vs 6.5 mmol/L; P = .02).
• The SGLT2i group had delayed resolution compared with the T1D group (median time, 36 vs 18 h; P = .002).
• Weight was higher in the T2D SGLT2i group than the T1D group (81.8 vs 67.7 kg; P = .04) yet patients with SGLT2i DKA received significantly less insulin (intravenous and subcutaneous) in the first 24 hours of treatment compared with the T1D DKA group (median dose, 44.0 vs 87.0 units; P = .01).
• In SGLT2i DKA, changes in ketone levels over the first 24 hours were significantly associated with baseline insulin therapy (P = .002), lower bicarbonate nadir (P = .02), and higher admission plasma glucose (P = .24).

IN PRACTICE:

“T1D DKA is driven by absolute insulin deficiency, leading to ketosis and hyperglycemia. In contrast, SGLT2i DKA occurs due to a reduction in plasma glucose from urinary glucose losses, which reduces insulin secretion and stimulates glucagon secretion, leading to ketosis. Accordingly, plasma glucose levels in SGLT2i DKA are often normal or mildly elevated.” “Despite these differences, the American Association of Clinical Endocrinologists and American College of Endocrinology recommend treatment with the same protocols for both types. This may result in hypoglycemia when patients receive fixed-dose insulin infusion or inadequate insulin dosing and reduced ketone clearance when patients receive dynamic insulin infusions.” “It would be reasonable, based on the evidence and the safety profile of intravenous dextrose, to increase dextrose infusion rates and concentration to allow increased insulin administration and suppression of ketosis.”

SOURCE:

Conducted by Mahesh M. Umapathysivam, DPhil, of Southern Adelaide Diabetes and Endocrine Services, Flinders Medical Centre, Adelaide, South Australia, and colleagues. The study was published online in JAMA Network Open.

LIMITATIONS:

The study was retrospective, and the sample size was small.

DISCLOSURES:

This work has been supported by a Diabetes South Australia (SA) investigator grant and support from the Hospital Research Foundation. Umapathysivam reported receiving grants from Diabetes SA during the conduct of the study and grants from the Australian Diabetes Society funded by AstraZeneca outside the submitted work.

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

TOPLINE:

Sodium-glucose cotransporter 2 inhibitor (SGLT2i)-associated diabetes ketoacidosis (DKA) in people with type 2 diabetes (T2D) is associated with lower degrees of hyperglycemia over the first 24 hours of treatment than seen in type 1 diabetes (T1D)-associated DKA, potentially leading to hypo- or hyperglycemia if the same insulin infusion protocols are used.

METHODOLOGY:

• Retrospective cohort study comparing natural history and response to treatment for 37 episodes of SGLT2i-associated DKA (n = 27) or ketosis (n = 10) in people with T2D vs 19 episodes of T1D-associated DKA in people of the same age range as the T2D group, identified from endocrine consultation requests in two South Australian tertiary hospitals.

TAKEAWAY:

• Patients with T2D and SGLT2i-associated DKA had milder DKA than T1D-associated DKA (median ketone peak, 5.3 vs 6.5 mmol/L; P = .02).
• The SGLT2i group had delayed resolution compared with the T1D group (median time, 36 vs 18 h; P = .002).
• Weight was higher in the T2D SGLT2i group than the T1D group (81.8 vs 67.7 kg; P = .04) yet patients with SGLT2i DKA received significantly less insulin (intravenous and subcutaneous) in the first 24 hours of treatment compared with the T1D DKA group (median dose, 44.0 vs 87.0 units; P = .01).
• In SGLT2i DKA, changes in ketone levels over the first 24 hours were significantly associated with baseline insulin therapy (P = .002), lower bicarbonate nadir (P = .02), and higher admission plasma glucose (P = .24).

IN PRACTICE:

“T1D DKA is driven by absolute insulin deficiency, leading to ketosis and hyperglycemia. In contrast, SGLT2i DKA occurs due to a reduction in plasma glucose from urinary glucose losses, which reduces insulin secretion and stimulates glucagon secretion, leading to ketosis. Accordingly, plasma glucose levels in SGLT2i DKA are often normal or mildly elevated.” “Despite these differences, the American Association of Clinical Endocrinologists and American College of Endocrinology recommend treatment with the same protocols for both types. This may result in hypoglycemia when patients receive fixed-dose insulin infusion or inadequate insulin dosing and reduced ketone clearance when patients receive dynamic insulin infusions.” “It would be reasonable, based on the evidence and the safety profile of intravenous dextrose, to increase dextrose infusion rates and concentration to allow increased insulin administration and suppression of ketosis.”

SOURCE:

Conducted by Mahesh M. Umapathysivam, DPhil, of Southern Adelaide Diabetes and Endocrine Services, Flinders Medical Centre, Adelaide, South Australia, and colleagues. The study was published online in JAMA Network Open.

LIMITATIONS:

The study was retrospective, and the sample size was small.

DISCLOSURES:

This work has been supported by a Diabetes South Australia (SA) investigator grant and support from the Hospital Research Foundation. Umapathysivam reported receiving grants from Diabetes SA during the conduct of the study and grants from the Australian Diabetes Society funded by AstraZeneca outside the submitted work.

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

TOPLINE:

Sodium-glucose cotransporter 2 inhibitor (SGLT2i)-associated diabetes ketoacidosis (DKA) in people with type 2 diabetes (T2D) is associated with lower degrees of hyperglycemia over the first 24 hours of treatment than seen in type 1 diabetes (T1D)-associated DKA, potentially leading to hypo- or hyperglycemia if the same insulin infusion protocols are used.

METHODOLOGY:

• Retrospective cohort study comparing natural history and response to treatment for 37 episodes of SGLT2i-associated DKA (n = 27) or ketosis (n = 10) in people with T2D vs 19 episodes of T1D-associated DKA in people of the same age range as the T2D group, identified from endocrine consultation requests in two South Australian tertiary hospitals.

TAKEAWAY:

• Patients with T2D and SGLT2i-associated DKA had milder DKA than T1D-associated DKA (median ketone peak, 5.3 vs 6.5 mmol/L; P = .02).
• The SGLT2i group had delayed resolution compared with the T1D group (median time, 36 vs 18 h; P = .002).
• Weight was higher in the T2D SGLT2i group than the T1D group (81.8 vs 67.7 kg; P = .04) yet patients with SGLT2i DKA received significantly less insulin (intravenous and subcutaneous) in the first 24 hours of treatment compared with the T1D DKA group (median dose, 44.0 vs 87.0 units; P = .01).
• In SGLT2i DKA, changes in ketone levels over the first 24 hours were significantly associated with baseline insulin therapy (P = .002), lower bicarbonate nadir (P = .02), and higher admission plasma glucose (P = .24).

IN PRACTICE:

“T1D DKA is driven by absolute insulin deficiency, leading to ketosis and hyperglycemia. In contrast, SGLT2i DKA occurs due to a reduction in plasma glucose from urinary glucose losses, which reduces insulin secretion and stimulates glucagon secretion, leading to ketosis. Accordingly, plasma glucose levels in SGLT2i DKA are often normal or mildly elevated.” “Despite these differences, the American Association of Clinical Endocrinologists and American College of Endocrinology recommend treatment with the same protocols for both types. This may result in hypoglycemia when patients receive fixed-dose insulin infusion or inadequate insulin dosing and reduced ketone clearance when patients receive dynamic insulin infusions.” “It would be reasonable, based on the evidence and the safety profile of intravenous dextrose, to increase dextrose infusion rates and concentration to allow increased insulin administration and suppression of ketosis.”

SOURCE:

Conducted by Mahesh M. Umapathysivam, DPhil, of Southern Adelaide Diabetes and Endocrine Services, Flinders Medical Centre, Adelaide, South Australia, and colleagues. The study was published online in JAMA Network Open.

LIMITATIONS:

The study was retrospective, and the sample size was small.

DISCLOSURES:

This work has been supported by a Diabetes South Australia (SA) investigator grant and support from the Hospital Research Foundation. Umapathysivam reported receiving grants from Diabetes SA during the conduct of the study and grants from the Australian Diabetes Society funded by AstraZeneca outside the submitted work.

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

TOPLINE: 

Despite the risk of worsening acne with progestin-only long-acting reversible contraception (LARC) in a study of adolescents and young adults, acne alone was not a common reason for discontinuation.

METHODOLOGY:

• Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
• In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
• Overall, 24% of participants had acne at the time of LARC insertion.
• Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.

TAKEAWAY: 

• During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
• Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
• Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.

IN PRACTICE:

The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”

SOURCE:

The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.

LIMITATIONS:

Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.

DISCLOSURES: 

The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.

A version of this article appeared on Medscape.com.

TOPLINE: 

Despite the risk of worsening acne with progestin-only long-acting reversible contraception (LARC) in a study of adolescents and young adults, acne alone was not a common reason for discontinuation.

METHODOLOGY:

• Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
• In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
• Overall, 24% of participants had acne at the time of LARC insertion.
• Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.

TAKEAWAY: 

• During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
• Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
• Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.

IN PRACTICE:

The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”

SOURCE:

The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.

LIMITATIONS:

Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.

DISCLOSURES: 

The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.

A version of this article appeared on Medscape.com.

TOPLINE: 

Despite the risk of worsening acne with progestin-only long-acting reversible contraception (LARC) in a study of adolescents and young adults, acne alone was not a common reason for discontinuation.

METHODOLOGY:

• Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
• In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
• Overall, 24% of participants had acne at the time of LARC insertion.
• Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.

TAKEAWAY: 

• During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
• Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
• Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.

IN PRACTICE:

The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”

SOURCE:

The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.

LIMITATIONS:

Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.

DISCLOSURES: 

The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

The risk for type 2 diabetes (T2D) was higher in individuals who followed a pro-inflammatory diet and had a high habitual salt intake than in those who followed an anti-inflammatory diet and used less salt.

METHODOLOGY:

• High scores on the dietary inflammatory index (DII) — a scoring system that measures the inflammatory potential of an individual’s diet — and high salt intake are associated with increased cardiovascular disease risk; however, studies investigating the association between DII and salt intake with incident T2D risk are scarce.
• Researchers investigated the association between a pro-inflammatory diet, habitual salt intake, and the risk for T2D among 171,094 participants from the UK Biobank (mean age, 55.98 years; 40.7% men).
• Participants were free of diabetes at baseline, had completed at least one dietary recall questionnaire, and were followed up for a median period of 13.5 years.
• The energy-adjusted DII was calculated on the basis of 28 food and nutrient parameter-specific scores, while habitual salt intake was assessed through self-reported frequency of adding salt to foods.
• Any newly diagnosed cases of T2D were considered the first occurrences of health outcomes.

TAKEAWAY:

• Incident cases of T2D were reported in 6216 individuals over the median follow-up period.
• The risk of developing T2D was 18% higher in individuals who followed a pro-inflammatory vs anti-inflammatory diet (adjusted hazard ratio [HR], 1.18; 95% CI, 1.11-1.25); the risk for T2D was elevated by 4% for each one-point increment in the energy-adjusted DII.
• Compared with participants who never or rarely added salt to foods, the risk for T2D increased gradually in those who sometimes (HR, 1.10; 95% CI, 1.04-1.16), usually (HR, 1.14; 95% CI, 1.05-1.24), and always (HR, 1.30; 95% CI, 1.15-1.47) added salt to foods.
• The risk for T2D was the highest in participants who followed a pro-inflammatory diet and always added salt to foods (HR, 1.60; 95% CI, 1.32-1.90) compared with those who followed an anti-inflammatory diet and never or rarely added salt to foods.

IN PRACTICE:

“Our findings indicate that a pro-inflammatory diet and higher habitual salt intake were associated with an increased risk of type 2 diabetes. These results support the public health promotion of an anti-inflammatory diet and reducing salt intake to prevent the onset of type 2 diabetes,” the authors wrote.

SOURCE:

This study was led by Wenqui Shen, MD, from the Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

Data from a 24-hour dietary recall questionnaire were used to calculate the energy-adjusted DII, which might have led to incidences of incorrect reporting. This study could not measure all components of the DII score. Unmeasured variables and residual confounders might also be present, which were not considered in this analysis.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, Project of Biobank from the Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, and other sources. The authors declared no conflicts of interest.

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

TOPLINE:

The risk for type 2 diabetes (T2D) was higher in individuals who followed a pro-inflammatory diet and had a high habitual salt intake than in those who followed an anti-inflammatory diet and used less salt.

METHODOLOGY:

• High scores on the dietary inflammatory index (DII) — a scoring system that measures the inflammatory potential of an individual’s diet — and high salt intake are associated with increased cardiovascular disease risk; however, studies investigating the association between DII and salt intake with incident T2D risk are scarce.
• Researchers investigated the association between a pro-inflammatory diet, habitual salt intake, and the risk for T2D among 171,094 participants from the UK Biobank (mean age, 55.98 years; 40.7% men).
• Participants were free of diabetes at baseline, had completed at least one dietary recall questionnaire, and were followed up for a median period of 13.5 years.
• The energy-adjusted DII was calculated on the basis of 28 food and nutrient parameter-specific scores, while habitual salt intake was assessed through self-reported frequency of adding salt to foods.
• Any newly diagnosed cases of T2D were considered the first occurrences of health outcomes.

TAKEAWAY:

• Incident cases of T2D were reported in 6216 individuals over the median follow-up period.
• The risk of developing T2D was 18% higher in individuals who followed a pro-inflammatory vs anti-inflammatory diet (adjusted hazard ratio [HR], 1.18; 95% CI, 1.11-1.25); the risk for T2D was elevated by 4% for each one-point increment in the energy-adjusted DII.
• Compared with participants who never or rarely added salt to foods, the risk for T2D increased gradually in those who sometimes (HR, 1.10; 95% CI, 1.04-1.16), usually (HR, 1.14; 95% CI, 1.05-1.24), and always (HR, 1.30; 95% CI, 1.15-1.47) added salt to foods.
• The risk for T2D was the highest in participants who followed a pro-inflammatory diet and always added salt to foods (HR, 1.60; 95% CI, 1.32-1.90) compared with those who followed an anti-inflammatory diet and never or rarely added salt to foods.

IN PRACTICE:

“Our findings indicate that a pro-inflammatory diet and higher habitual salt intake were associated with an increased risk of type 2 diabetes. These results support the public health promotion of an anti-inflammatory diet and reducing salt intake to prevent the onset of type 2 diabetes,” the authors wrote.

SOURCE:

This study was led by Wenqui Shen, MD, from the Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

Data from a 24-hour dietary recall questionnaire were used to calculate the energy-adjusted DII, which might have led to incidences of incorrect reporting. This study could not measure all components of the DII score. Unmeasured variables and residual confounders might also be present, which were not considered in this analysis.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, Project of Biobank from the Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, and other sources. The authors declared no conflicts of interest.

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

TOPLINE:

The risk for type 2 diabetes (T2D) was higher in individuals who followed a pro-inflammatory diet and had a high habitual salt intake than in those who followed an anti-inflammatory diet and used less salt.

METHODOLOGY:

• High scores on the dietary inflammatory index (DII) — a scoring system that measures the inflammatory potential of an individual’s diet — and high salt intake are associated with increased cardiovascular disease risk; however, studies investigating the association between DII and salt intake with incident T2D risk are scarce.
• Researchers investigated the association between a pro-inflammatory diet, habitual salt intake, and the risk for T2D among 171,094 participants from the UK Biobank (mean age, 55.98 years; 40.7% men).
• Participants were free of diabetes at baseline, had completed at least one dietary recall questionnaire, and were followed up for a median period of 13.5 years.
• The energy-adjusted DII was calculated on the basis of 28 food and nutrient parameter-specific scores, while habitual salt intake was assessed through self-reported frequency of adding salt to foods.
• Any newly diagnosed cases of T2D were considered the first occurrences of health outcomes.

TAKEAWAY:

• Incident cases of T2D were reported in 6216 individuals over the median follow-up period.
• The risk of developing T2D was 18% higher in individuals who followed a pro-inflammatory vs anti-inflammatory diet (adjusted hazard ratio [HR], 1.18; 95% CI, 1.11-1.25); the risk for T2D was elevated by 4% for each one-point increment in the energy-adjusted DII.
• Compared with participants who never or rarely added salt to foods, the risk for T2D increased gradually in those who sometimes (HR, 1.10; 95% CI, 1.04-1.16), usually (HR, 1.14; 95% CI, 1.05-1.24), and always (HR, 1.30; 95% CI, 1.15-1.47) added salt to foods.
• The risk for T2D was the highest in participants who followed a pro-inflammatory diet and always added salt to foods (HR, 1.60; 95% CI, 1.32-1.90) compared with those who followed an anti-inflammatory diet and never or rarely added salt to foods.

IN PRACTICE:

“Our findings indicate that a pro-inflammatory diet and higher habitual salt intake were associated with an increased risk of type 2 diabetes. These results support the public health promotion of an anti-inflammatory diet and reducing salt intake to prevent the onset of type 2 diabetes,” the authors wrote.

SOURCE:

This study was led by Wenqui Shen, MD, from the Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

Data from a 24-hour dietary recall questionnaire were used to calculate the energy-adjusted DII, which might have led to incidences of incorrect reporting. This study could not measure all components of the DII score. Unmeasured variables and residual confounders might also be present, which were not considered in this analysis.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, Project of Biobank from the Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, and other sources. The authors declared no conflicts of interest.

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

Informing patients of a dire diagnosis — or even one that will require significant lifestyle changes — is never easy. But what’s even more challenging is when patients don’t accept their medical condition or a future that might include a difficult treatment protocol or even new medications or surgery.

“This is a challenging space to be in because this isn’t an exact science,” said Jack Jacoub, MD, medical director of MemorialCare Cancer Institute at Orange Coast Memorial in Fountain Valley, California. “There’s no formal training to deal with this — experience is your best teacher.”

Ultimately, helping a person reconceptualize what their future looks like is at the heart of every one of these conversations, said Sourav Sengupta, MD, MPH, associate professor of psychiatry and pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York. “As physicians, we’re charged with helping our patients navigate a difficult and challenging time in their life,” he told this news organization.

“It’s not infrequent that patients are struggling to rethink what it will be like to be a person with an illness that might be chronic and how this will change their life,” he said.

And because denial is commonly the initial way a patient might cope with absorbing news that’s hard to hear, you’ll need to be extremely patient and empathetic.

“The goal is to build trust with this person, including trust in you, the hospital itself, and the entire team treating the patient,” Dr. Jacoub said.

“A diagnosis, especially in my field of oncology, can be scary. Spending time explaining their prognosis is very important. This can’t be a rushed scenario.”

More advice on helping patients who are in denial about their medical condition:
 

Make Sure They Understand What’s Going on

In cardiology, it’s common for patients to be hospitalized when they first learn that they have a disease they must manage for the rest of their life, said Stephanie Saucier, MD, a noninvasive cardiologist and codirector of the Women’s Heart Wellness Program at Hartford Healthcare’s Heart and Vascular Institute.

“Especially after someone has had a heart attack, a stroke, or they had bypass or stents placed, I like to see what their understanding of the disease is,” Dr. Saucier said. “I ask them, ‘What do you understand about what happened to you’. It can get confusing when you’re in the hospital and are told a lot of information in a short period of time.”
 

Share the Data

If a patient remains resistant to the news of a diagnosis, sharing test results can be beneficial. “I’ll often say, ‘here are the scans; this is the path report; this is the bloodwork; this is your biopsy report; these are the things we have’,” Dr. Jacoub said.

“Yes, this is clinical, but it helps to communicate the information you have and do it with data. For example, I might add, ‘Would you like to see some of the things [results, scans, tests] we’re talking about today?’ This also helps establish trust.”
 

Help Them Wrap Their Mind Around a Lifelong Condition

It’s often challenging for patients to accept that what they think is a one-time health issue will affect them for a lifetime. “I use juvenile diabetes as a way to explain this,” Dr. Saucier said. “I ask them what they would do if, say, their child was diagnosed with juvenile diabetes.”

Of course, patients agree that they wouldn’t give a child insulin for only a brief period. They understand that the condition must be treated in the long term. This kind of analogy can help patients understand that they, too, have a disorder requiring lifelong treatment.
 

Be Ready to Respond

Dr. Sengupta says that it’s important to be prepared with an answer if your patient is challenging or suggests that the diagnosis is fake or that you don’t have their best interests in mind.

“It’s understandable that patients might feel frustrated and upset,” he said. “It’s challenging when somehow a patient doesn’t assume my best intent.”

They might say something like, “You’re trying to make more money” or “you’re a shill for a pharma company.” In that case, you must listen. Patiently explain, “I’m your doctor; I work for you; I’m most interested in you feeling healthy and well.”

Occasionally, you’ll need a thick skin when it comes to inaccurate, controversial, or conspiratorial conversations with patients.
 

Acknowledge Differences

News of an illness may clash with a person’s take on the world. “A cancer diagnosis, for example, may clash with religious beliefs or faith-based ideology about the healthcare system,” said Aaron Fletcher, MD, a board-certified otolaryngologist specializing in head and neck surgery at the Georgia Center for Ear, Nose, Throat, and Facial Plastic Surgery in Atlanta, Georgia.

“If you have a patient who is coming to you with these beliefs, you need to have a lot of empathy, patience, and good communication skills. It’s up to you to break through the initial doubt and do your best to explain things in layman’s terms.”
 

Find Mutual Ground

If your patient still denies their health issues, try to find one thing you can agree on regarding a long-term game plan. “I’ll say, ‘Can we at least agree to discuss this with other family members or people who care about you’?” Dr. Jacoub said.

“I always tell patients that loved ones are welcome to call me so long as they [the patient] give permission. Sometimes, this is all that it takes to get them to accept their health situation.”
 

Seven Ways to Cope With Diagnosis  Denial

This news organization asked David Cutler, MD, a board-certified family medicine physician at Providence Saint John›s Health Center in Santa Monica, California, for tips in helping patients who are having a challenging time accepting their condition:

• Listen Actively. Allow the patient to express their feelings and concerns without judgment. Active listening can help them feel heard and understood, which may open the door to discussing their condition more openly.
• Provide Information. Offer factual information about their medical condition, treatment options, and the potential consequences of denial. Provide resources such as pamphlets, websites, or books that they can review at their own pace.
• Encourage Professional Help. You may want to suggest that your patient seek professional help from a therapist, counselor, or support group. A mental health professional can assist patients in processing their emotions and addressing their denial constructively.
• Involve Trusted Individuals. Enlist the support of trusted friends, family members, or healthcare professionals who can help reinforce the importance of facing their medical condition.
• Respect Autonomy. While it’s essential to encourage the person to accept their diagnosis, ultimately, the decision to get treatment lies with them. Respect their autonomy and avoid pushing them too hard, which could lead to resistance or further denial.
• Be Patient and Persistent. Overcoming denial is often a gradual process. Be patient and persistent in supporting the person, even if progress seems slow.
• Set Boundaries. It’s essential to set boundaries to protect your well-being. While you can offer support and encouragement, you cannot force someone to accept their medical condition. Recognize when your efforts are not being productive and take care of yourself in the process.

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

Informing patients of a dire diagnosis — or even one that will require significant lifestyle changes — is never easy. But what’s even more challenging is when patients don’t accept their medical condition or a future that might include a difficult treatment protocol or even new medications or surgery.

“This is a challenging space to be in because this isn’t an exact science,” said Jack Jacoub, MD, medical director of MemorialCare Cancer Institute at Orange Coast Memorial in Fountain Valley, California. “There’s no formal training to deal with this — experience is your best teacher.”

Ultimately, helping a person reconceptualize what their future looks like is at the heart of every one of these conversations, said Sourav Sengupta, MD, MPH, associate professor of psychiatry and pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York. “As physicians, we’re charged with helping our patients navigate a difficult and challenging time in their life,” he told this news organization.

“It’s not infrequent that patients are struggling to rethink what it will be like to be a person with an illness that might be chronic and how this will change their life,” he said.

And because denial is commonly the initial way a patient might cope with absorbing news that’s hard to hear, you’ll need to be extremely patient and empathetic.

“The goal is to build trust with this person, including trust in you, the hospital itself, and the entire team treating the patient,” Dr. Jacoub said.

“A diagnosis, especially in my field of oncology, can be scary. Spending time explaining their prognosis is very important. This can’t be a rushed scenario.”

More advice on helping patients who are in denial about their medical condition:
 

Make Sure They Understand What’s Going on

In cardiology, it’s common for patients to be hospitalized when they first learn that they have a disease they must manage for the rest of their life, said Stephanie Saucier, MD, a noninvasive cardiologist and codirector of the Women’s Heart Wellness Program at Hartford Healthcare’s Heart and Vascular Institute.

“Especially after someone has had a heart attack, a stroke, or they had bypass or stents placed, I like to see what their understanding of the disease is,” Dr. Saucier said. “I ask them, ‘What do you understand about what happened to you’. It can get confusing when you’re in the hospital and are told a lot of information in a short period of time.”
 

Share the Data

If a patient remains resistant to the news of a diagnosis, sharing test results can be beneficial. “I’ll often say, ‘here are the scans; this is the path report; this is the bloodwork; this is your biopsy report; these are the things we have’,” Dr. Jacoub said.

“Yes, this is clinical, but it helps to communicate the information you have and do it with data. For example, I might add, ‘Would you like to see some of the things [results, scans, tests] we’re talking about today?’ This also helps establish trust.”
 

Help Them Wrap Their Mind Around a Lifelong Condition

It’s often challenging for patients to accept that what they think is a one-time health issue will affect them for a lifetime. “I use juvenile diabetes as a way to explain this,” Dr. Saucier said. “I ask them what they would do if, say, their child was diagnosed with juvenile diabetes.”

Of course, patients agree that they wouldn’t give a child insulin for only a brief period. They understand that the condition must be treated in the long term. This kind of analogy can help patients understand that they, too, have a disorder requiring lifelong treatment.
 

Be Ready to Respond

Dr. Sengupta says that it’s important to be prepared with an answer if your patient is challenging or suggests that the diagnosis is fake or that you don’t have their best interests in mind.

“It’s understandable that patients might feel frustrated and upset,” he said. “It’s challenging when somehow a patient doesn’t assume my best intent.”

They might say something like, “You’re trying to make more money” or “you’re a shill for a pharma company.” In that case, you must listen. Patiently explain, “I’m your doctor; I work for you; I’m most interested in you feeling healthy and well.”

Occasionally, you’ll need a thick skin when it comes to inaccurate, controversial, or conspiratorial conversations with patients.
 

Acknowledge Differences

News of an illness may clash with a person’s take on the world. “A cancer diagnosis, for example, may clash with religious beliefs or faith-based ideology about the healthcare system,” said Aaron Fletcher, MD, a board-certified otolaryngologist specializing in head and neck surgery at the Georgia Center for Ear, Nose, Throat, and Facial Plastic Surgery in Atlanta, Georgia.

“If you have a patient who is coming to you with these beliefs, you need to have a lot of empathy, patience, and good communication skills. It’s up to you to break through the initial doubt and do your best to explain things in layman’s terms.”
 

Find Mutual Ground

If your patient still denies their health issues, try to find one thing you can agree on regarding a long-term game plan. “I’ll say, ‘Can we at least agree to discuss this with other family members or people who care about you’?” Dr. Jacoub said.

“I always tell patients that loved ones are welcome to call me so long as they [the patient] give permission. Sometimes, this is all that it takes to get them to accept their health situation.”
 

Seven Ways to Cope With Diagnosis  Denial

This news organization asked David Cutler, MD, a board-certified family medicine physician at Providence Saint John›s Health Center in Santa Monica, California, for tips in helping patients who are having a challenging time accepting their condition:

• Listen Actively. Allow the patient to express their feelings and concerns without judgment. Active listening can help them feel heard and understood, which may open the door to discussing their condition more openly.
• Provide Information. Offer factual information about their medical condition, treatment options, and the potential consequences of denial. Provide resources such as pamphlets, websites, or books that they can review at their own pace.
• Encourage Professional Help. You may want to suggest that your patient seek professional help from a therapist, counselor, or support group. A mental health professional can assist patients in processing their emotions and addressing their denial constructively.
• Involve Trusted Individuals. Enlist the support of trusted friends, family members, or healthcare professionals who can help reinforce the importance of facing their medical condition.
• Respect Autonomy. While it’s essential to encourage the person to accept their diagnosis, ultimately, the decision to get treatment lies with them. Respect their autonomy and avoid pushing them too hard, which could lead to resistance or further denial.
• Be Patient and Persistent. Overcoming denial is often a gradual process. Be patient and persistent in supporting the person, even if progress seems slow.
• Set Boundaries. It’s essential to set boundaries to protect your well-being. While you can offer support and encouragement, you cannot force someone to accept their medical condition. Recognize when your efforts are not being productive and take care of yourself in the process.

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

Informing patients of a dire diagnosis — or even one that will require significant lifestyle changes — is never easy. But what’s even more challenging is when patients don’t accept their medical condition or a future that might include a difficult treatment protocol or even new medications or surgery.

“This is a challenging space to be in because this isn’t an exact science,” said Jack Jacoub, MD, medical director of MemorialCare Cancer Institute at Orange Coast Memorial in Fountain Valley, California. “There’s no formal training to deal with this — experience is your best teacher.”

Ultimately, helping a person reconceptualize what their future looks like is at the heart of every one of these conversations, said Sourav Sengupta, MD, MPH, associate professor of psychiatry and pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York. “As physicians, we’re charged with helping our patients navigate a difficult and challenging time in their life,” he told this news organization.

“It’s not infrequent that patients are struggling to rethink what it will be like to be a person with an illness that might be chronic and how this will change their life,” he said.

And because denial is commonly the initial way a patient might cope with absorbing news that’s hard to hear, you’ll need to be extremely patient and empathetic.

“The goal is to build trust with this person, including trust in you, the hospital itself, and the entire team treating the patient,” Dr. Jacoub said.

“A diagnosis, especially in my field of oncology, can be scary. Spending time explaining their prognosis is very important. This can’t be a rushed scenario.”

More advice on helping patients who are in denial about their medical condition:
 

Make Sure They Understand What’s Going on

In cardiology, it’s common for patients to be hospitalized when they first learn that they have a disease they must manage for the rest of their life, said Stephanie Saucier, MD, a noninvasive cardiologist and codirector of the Women’s Heart Wellness Program at Hartford Healthcare’s Heart and Vascular Institute.

“Especially after someone has had a heart attack, a stroke, or they had bypass or stents placed, I like to see what their understanding of the disease is,” Dr. Saucier said. “I ask them, ‘What do you understand about what happened to you’. It can get confusing when you’re in the hospital and are told a lot of information in a short period of time.”
 

Share the Data

If a patient remains resistant to the news of a diagnosis, sharing test results can be beneficial. “I’ll often say, ‘here are the scans; this is the path report; this is the bloodwork; this is your biopsy report; these are the things we have’,” Dr. Jacoub said.

“Yes, this is clinical, but it helps to communicate the information you have and do it with data. For example, I might add, ‘Would you like to see some of the things [results, scans, tests] we’re talking about today?’ This also helps establish trust.”
 

Help Them Wrap Their Mind Around a Lifelong Condition

It’s often challenging for patients to accept that what they think is a one-time health issue will affect them for a lifetime. “I use juvenile diabetes as a way to explain this,” Dr. Saucier said. “I ask them what they would do if, say, their child was diagnosed with juvenile diabetes.”

Of course, patients agree that they wouldn’t give a child insulin for only a brief period. They understand that the condition must be treated in the long term. This kind of analogy can help patients understand that they, too, have a disorder requiring lifelong treatment.
 

Be Ready to Respond

Dr. Sengupta says that it’s important to be prepared with an answer if your patient is challenging or suggests that the diagnosis is fake or that you don’t have their best interests in mind.

“It’s understandable that patients might feel frustrated and upset,” he said. “It’s challenging when somehow a patient doesn’t assume my best intent.”

They might say something like, “You’re trying to make more money” or “you’re a shill for a pharma company.” In that case, you must listen. Patiently explain, “I’m your doctor; I work for you; I’m most interested in you feeling healthy and well.”

Occasionally, you’ll need a thick skin when it comes to inaccurate, controversial, or conspiratorial conversations with patients.
 

Acknowledge Differences

News of an illness may clash with a person’s take on the world. “A cancer diagnosis, for example, may clash with religious beliefs or faith-based ideology about the healthcare system,” said Aaron Fletcher, MD, a board-certified otolaryngologist specializing in head and neck surgery at the Georgia Center for Ear, Nose, Throat, and Facial Plastic Surgery in Atlanta, Georgia.

“If you have a patient who is coming to you with these beliefs, you need to have a lot of empathy, patience, and good communication skills. It’s up to you to break through the initial doubt and do your best to explain things in layman’s terms.”
 

Find Mutual Ground

If your patient still denies their health issues, try to find one thing you can agree on regarding a long-term game plan. “I’ll say, ‘Can we at least agree to discuss this with other family members or people who care about you’?” Dr. Jacoub said.

“I always tell patients that loved ones are welcome to call me so long as they [the patient] give permission. Sometimes, this is all that it takes to get them to accept their health situation.”
 

Seven Ways to Cope With Diagnosis  Denial

This news organization asked David Cutler, MD, a board-certified family medicine physician at Providence Saint John›s Health Center in Santa Monica, California, for tips in helping patients who are having a challenging time accepting their condition:

• Listen Actively. Allow the patient to express their feelings and concerns without judgment. Active listening can help them feel heard and understood, which may open the door to discussing their condition more openly.
• Provide Information. Offer factual information about their medical condition, treatment options, and the potential consequences of denial. Provide resources such as pamphlets, websites, or books that they can review at their own pace.
• Encourage Professional Help. You may want to suggest that your patient seek professional help from a therapist, counselor, or support group. A mental health professional can assist patients in processing their emotions and addressing their denial constructively.
• Involve Trusted Individuals. Enlist the support of trusted friends, family members, or healthcare professionals who can help reinforce the importance of facing their medical condition.
• Respect Autonomy. While it’s essential to encourage the person to accept their diagnosis, ultimately, the decision to get treatment lies with them. Respect their autonomy and avoid pushing them too hard, which could lead to resistance or further denial.
• Be Patient and Persistent. Overcoming denial is often a gradual process. Be patient and persistent in supporting the person, even if progress seems slow.
• Set Boundaries. It’s essential to set boundaries to protect your well-being. While you can offer support and encouragement, you cannot force someone to accept their medical condition. Recognize when your efforts are not being productive and take care of yourself in the process.

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