Family Practice News

TOPLINE: 

Among children with traumatic injury, those of Black ethnicity are more likely than those of White ethnicity to be suspected of experiencing child abuse. Young patients and those from low socioeconomic backgrounds also face an increased likelihood of suspicion for child abuse (SCA).

METHODOLOGY:

• Researchers analyzed data on pediatric patients admitted to hospitals after sustaining a traumatic injury between 2006 and 2016 using the Kids’ Inpatient Database (KID) to investigate racial and ethnic disparities in cases in which SCA codes from the 9th and 10th editions of the International Classification of Diseases were used.
• The analysis included a weighted total of 634,309 pediatric patients with complete data, comprising 13,579 patients in the SCA subgroup and 620,730 in the non-SCA subgroup.
• Patient demographics, injury severity, and hospitalization characteristics were classified by race and ethnicity.
• The primary outcome was differences in racial and ethnic composition between the SCA and non-SCA groups, as well as compared with the overall US population using 2010 US Census data.

TAKEAWAY:

• Black patients had 75% higher odds of having a SCA code, compared with White patients; the latter ethnicity was relatively underrepresented in the SCA subgroup, compared with the distribution reported by the US Census.
• Black patients had 10% higher odds of having a SCA code (odds ratio, 1.10; P =.004) than White patients, after socioeconomic factors such as insurance type, household income based on zip code, and injury severity were controlled for.
• Black patients in the SCA subgroup experienced a 26.5% (P < .001) longer hospital stay for mild to moderate injuries and a 40.1% (P < .001) longer stay for serious injuries compared with White patients.
• Patients in the SCA subgroup were significantly younger (mean, 1.70 years vs 9.70 years), were more likely to have Medicaid insurance (76.6% vs 42.0%), and had higher mortality rates (5.6% vs 1.0%) than those in the non-SCA subgroup; they were also more likely to come from lower socioeconomic backgrounds and present with more severe injuries.

IN PRACTICE:

“However, we can identify and appropriately respond to patients with potential child abuse in an equitable way by using clinical decision support tools, seeking clinical consultation of child abuse pediatricians, practicing cultural humility, and enhancing the education and training for health care professionals on child abuse recognition, response, and prevention,” Allison M. Jackson, MD, MPH, of the Child and Adolescent Protection Center at Children’s National Hospital, Washington, DC, wrote in an accompanying editorial.

SOURCE:

The study was led by Fereshteh Salimi-Jazi, MD, of Stanford University School of Medicine in California. It was published online on December 18, 2024, in JAMA Network Open.

LIMITATIONS: 

The study relied on data from KID, which has limitations such as potential coding errors and the inability to follow patients over time. The database combines race and ethnicity in a single field as well. The study only included hospitalized patients, which may not represent all clinician suspicions of SCA cases.

DISCLOSURES:

This study was supported by a grant from the National Center for Advancing Translational Sciences of the National Institutes of Health. The authors reported no relevant conflicts of interest.

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

TOPLINE: 

Among children with traumatic injury, those of Black ethnicity are more likely than those of White ethnicity to be suspected of experiencing child abuse. Young patients and those from low socioeconomic backgrounds also face an increased likelihood of suspicion for child abuse (SCA).

METHODOLOGY:

• Researchers analyzed data on pediatric patients admitted to hospitals after sustaining a traumatic injury between 2006 and 2016 using the Kids’ Inpatient Database (KID) to investigate racial and ethnic disparities in cases in which SCA codes from the 9th and 10th editions of the International Classification of Diseases were used.
• The analysis included a weighted total of 634,309 pediatric patients with complete data, comprising 13,579 patients in the SCA subgroup and 620,730 in the non-SCA subgroup.
• Patient demographics, injury severity, and hospitalization characteristics were classified by race and ethnicity.
• The primary outcome was differences in racial and ethnic composition between the SCA and non-SCA groups, as well as compared with the overall US population using 2010 US Census data.

TAKEAWAY:

• Black patients had 75% higher odds of having a SCA code, compared with White patients; the latter ethnicity was relatively underrepresented in the SCA subgroup, compared with the distribution reported by the US Census.
• Black patients had 10% higher odds of having a SCA code (odds ratio, 1.10; P =.004) than White patients, after socioeconomic factors such as insurance type, household income based on zip code, and injury severity were controlled for.
• Black patients in the SCA subgroup experienced a 26.5% (P < .001) longer hospital stay for mild to moderate injuries and a 40.1% (P < .001) longer stay for serious injuries compared with White patients.
• Patients in the SCA subgroup were significantly younger (mean, 1.70 years vs 9.70 years), were more likely to have Medicaid insurance (76.6% vs 42.0%), and had higher mortality rates (5.6% vs 1.0%) than those in the non-SCA subgroup; they were also more likely to come from lower socioeconomic backgrounds and present with more severe injuries.

IN PRACTICE:

“However, we can identify and appropriately respond to patients with potential child abuse in an equitable way by using clinical decision support tools, seeking clinical consultation of child abuse pediatricians, practicing cultural humility, and enhancing the education and training for health care professionals on child abuse recognition, response, and prevention,” Allison M. Jackson, MD, MPH, of the Child and Adolescent Protection Center at Children’s National Hospital, Washington, DC, wrote in an accompanying editorial.

SOURCE:

The study was led by Fereshteh Salimi-Jazi, MD, of Stanford University School of Medicine in California. It was published online on December 18, 2024, in JAMA Network Open.

LIMITATIONS: 

The study relied on data from KID, which has limitations such as potential coding errors and the inability to follow patients over time. The database combines race and ethnicity in a single field as well. The study only included hospitalized patients, which may not represent all clinician suspicions of SCA cases.

DISCLOSURES:

This study was supported by a grant from the National Center for Advancing Translational Sciences of the National Institutes of Health. The authors reported no relevant conflicts of interest.

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

TOPLINE: 

Among children with traumatic injury, those of Black ethnicity are more likely than those of White ethnicity to be suspected of experiencing child abuse. Young patients and those from low socioeconomic backgrounds also face an increased likelihood of suspicion for child abuse (SCA).

METHODOLOGY:

• Researchers analyzed data on pediatric patients admitted to hospitals after sustaining a traumatic injury between 2006 and 2016 using the Kids’ Inpatient Database (KID) to investigate racial and ethnic disparities in cases in which SCA codes from the 9th and 10th editions of the International Classification of Diseases were used.
• The analysis included a weighted total of 634,309 pediatric patients with complete data, comprising 13,579 patients in the SCA subgroup and 620,730 in the non-SCA subgroup.
• Patient demographics, injury severity, and hospitalization characteristics were classified by race and ethnicity.
• The primary outcome was differences in racial and ethnic composition between the SCA and non-SCA groups, as well as compared with the overall US population using 2010 US Census data.

TAKEAWAY:

• Black patients had 75% higher odds of having a SCA code, compared with White patients; the latter ethnicity was relatively underrepresented in the SCA subgroup, compared with the distribution reported by the US Census.
• Black patients had 10% higher odds of having a SCA code (odds ratio, 1.10; P =.004) than White patients, after socioeconomic factors such as insurance type, household income based on zip code, and injury severity were controlled for.
• Black patients in the SCA subgroup experienced a 26.5% (P < .001) longer hospital stay for mild to moderate injuries and a 40.1% (P < .001) longer stay for serious injuries compared with White patients.
• Patients in the SCA subgroup were significantly younger (mean, 1.70 years vs 9.70 years), were more likely to have Medicaid insurance (76.6% vs 42.0%), and had higher mortality rates (5.6% vs 1.0%) than those in the non-SCA subgroup; they were also more likely to come from lower socioeconomic backgrounds and present with more severe injuries.

IN PRACTICE:

“However, we can identify and appropriately respond to patients with potential child abuse in an equitable way by using clinical decision support tools, seeking clinical consultation of child abuse pediatricians, practicing cultural humility, and enhancing the education and training for health care professionals on child abuse recognition, response, and prevention,” Allison M. Jackson, MD, MPH, of the Child and Adolescent Protection Center at Children’s National Hospital, Washington, DC, wrote in an accompanying editorial.

SOURCE:

The study was led by Fereshteh Salimi-Jazi, MD, of Stanford University School of Medicine in California. It was published online on December 18, 2024, in JAMA Network Open.

LIMITATIONS: 

The study relied on data from KID, which has limitations such as potential coding errors and the inability to follow patients over time. The database combines race and ethnicity in a single field as well. The study only included hospitalized patients, which may not represent all clinician suspicions of SCA cases.

DISCLOSURES:

This study was supported by a grant from the National Center for Advancing Translational Sciences of the National Institutes of Health. The authors reported no relevant conflicts of interest.

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

Clinicians frequently reach out to Catherine Varney, DO, asking if it’s safe to prescribe glucagon-like peptide 1 receptor agonists (GLP-1 RAs) to patients with thyroid disorders, such as hypothyroidism, goiter, hyperthyroidism, and nodules.

The concerns often stem from prior animal studies that revealed a link between the medications and abnormal alterations in thyroid C cells.

“What physicians need to understand is that the increased risk of thyroid cancers is specifically in those with a personal or family history of multiple endocrine neoplasia 2 (MEN2) syndrome or medullary thyroid carcinoma [MTC],” said Varney, an assistant professor of family medicine at the University of Virginia (UVA) and obesity medicine director for UVA Health, both in Charlottesville.

MTC is a common manifestation of the MEN2 syndrome, a genetic disorder that affects the endocrine glands and can cause tumors in the thyroid gland. However, MTC is very rare, making up only 3%-5% of all thyroid cancers, Varney said.

More common types of thyroid cancers, such as papillary thyroid cancer, are not contraindications to GLP-1 RAs, said Laura Davisson, MD, MPH, a professor of medicine and director of Medical Weight Management at West Virginia University, Morgantown. Papillary thyroid cancer makes up about 80% of all thyroid cancers.

If physicians are thinking about prescribing GLP-1 RAs, it’s important to learn the specific types of thyroid disorders in a patient or in their family history, Davisson said. A history of thyroid conditions, such as Graves disease, Hashimoto thyroiditis, or disorders requiring a patient to take thyroid medicine, such as levothyroxine, does not preclude a person from taking GLP-1 RAs.

If a patient does not know their family history, then a discussion about whether GLP-1 RAs are right for them should take place, Davisson said.

“They should take into consideration the risks and benefits of the medicine, and the fact that medullary thyroid cancer and MEN2 syndrome are rare, making the chances of them running in their family low,” she said. “If the patient understands the risks, they may decide the potential benefits may outweigh the risks.”

Keep in mind that the elevated risk for medullary thyroid carcinoma has not been clearly demonstrated in humans during clinical trials, only in rodents, Varney added. Rodents are more likely to develop thyroid cancer after exposure to a GLP-1 RA because rodents have higher numbers of GLP-1 receptors in their thyroid cells.

The risk for thyroid cancer is also dose dependent, and the amount of GLP-1 RA that induced thyroid tumors in the rodents was 8-60 times higher than that given to humans, Varney said.

“Nonetheless, there have been case reports of MTC in humans after taking GLP-1 RA,” she said.

 

What About GLP-1 RAs and Pancreatitis?

Pancreatitis is another condition that requires consideration when it comes to prescribing GLP-1 RAs.

While some studies show that GLP-1 RA analogs can increase the risk for pancreatitis, it’s important to know the reason behind pancreatitis before making a prescription decision, said Anila Chadha, MD, a family physician and obesity medicine physician at Dignity Health in Bakersfield, California.

If the pancreatitis is caused by alcohol or is medication induced, GLP-1 RAs are not recommended, Chadha said. If gallbladder stones are behind the pancreatitis, that’s different.

“If a patient has a well-documented history of gallstone-induced pancreatitis and the patient has had a cholecystectomy, it would be OK to prescribe GLP-1 [medications] after shared decision-making with the patient,” she said.

Some patients worry about taking GLP-1 RAs if they have other types of pancreatic disease beyond pancreatitis, said Davisson, but guidelines do not identify conditions such as pancreatic cysts or a family history of pancreatic cancer as contraindications to GLP-1 RAs.

However, be mindful that GLP-1 RA medications can increase gallbladder disease, Chadha said. A 2022 analysis in JAMA Internal Medicine, for example, found that the use of GLP-1 RAs was associated with an increased risk for gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss.

If a history of gallstones is present, physicians should tell patients that GLP-1 RA analogs can increase biliary colic, chances of cholecystitis, or even cholecystitis, Chadha said.

Gallbladder disease itself is not a contraindication, she said, but these patients can experience more disease complications when taking GLP-1 RAs.

Varney recently treated a middle-aged female patient who experienced biliary colic after taking a GLP-1 RA medication. The patient had a starting body mass index (BMI) of about 45 and lost 24% of her starting weight over 12 months using a combination of strengthening and cardiovascular training; a reduced-calorie, high-protein diet; and semaglutide for weight loss, Varney said.

The patient began developing upper gastrointestinal symptoms, including mild biliary colic, without concerning lab findings. An ultrasound revealed that she had new gallstones, compared with an ultrasound a few years prior. Varney started the patient on ursodeoxycholic acid, and over the course of 6 weeks, the patient’s symptoms gradually improved and eventually resolved.

“In a situation like this, many physicians might have discontinued the obesity medication, potentially deciding not to restart it due to the symptoms she was experiencing,” Varney said. “However, I believe it’s important to recognize that these medications offer far more than just weight loss benefits. The positive effects extend to cardiovascular, metabolic, and mental health, which are often overlooked when the focus is solely on the number on the scale or BMI.”

Other medical conditions that GLP-1 RAs may exacerbate include gastroparesis and diabetic retinopathy, Chadha noted. GLP-1 RA drugs can worsen these conditions and are not recommended for patients with such a history.

Nor are GLP-1 RA medications a good idea for patients struggling with severe constipation.

“It is very difficult to tolerate these medications because it can make constipation worse,” Chadha said. “In addition, if a patient struggles with severe heartburn, it can make the tolerability of these medications difficult.”

 

What Patients Should Know Before Using GLP-1 RAs

Not every overweight patient is a good candidate for GLP-1 RAs, and it’s important that doctors explain why the medications may not be right for them, Davisson said.

“If a patient only has a few pounds to lose (15-20 lb) and does not accept that these medications are intended to be a long-term treatment for the chronic diseases of diabetes or obesity, then they might not be a good candidate for the medication,” Davisson said.

Also essential is making sure patients are willing to follow appropriate healthy eating guidelines when on the medications, including getting enough protein and produce to maintain lean body mass and the necessary fiber to keep bowel habits regular.

Varney often hears concerns from physicians about the long-term effects of GLP-1 RAs. She said this class of medications has been used for nearly 20 years to treat type 2 diabetes, and the data over the past two decades have shown that the benefits of GLP-1 RAs far outweigh the risks for most patients.

Recent studies have also highlighted significant long-term benefits, including a marked reduction in cardiovascular events, heart failure, and kidney disease, she said.

“These outcomes underscore the effectiveness and safety of GLP-1 RAs not just for obesity treatment but for improving overall health, particularly in high-risk populations,” she said. “As physicians, it’s crucial to consider this extensive body of evidence when evaluating the use of these medications for patients, especially when the potential health benefits extend well beyond weight loss alone.”

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

Clinicians frequently reach out to Catherine Varney, DO, asking if it’s safe to prescribe glucagon-like peptide 1 receptor agonists (GLP-1 RAs) to patients with thyroid disorders, such as hypothyroidism, goiter, hyperthyroidism, and nodules.

The concerns often stem from prior animal studies that revealed a link between the medications and abnormal alterations in thyroid C cells.

“What physicians need to understand is that the increased risk of thyroid cancers is specifically in those with a personal or family history of multiple endocrine neoplasia 2 (MEN2) syndrome or medullary thyroid carcinoma [MTC],” said Varney, an assistant professor of family medicine at the University of Virginia (UVA) and obesity medicine director for UVA Health, both in Charlottesville.

MTC is a common manifestation of the MEN2 syndrome, a genetic disorder that affects the endocrine glands and can cause tumors in the thyroid gland. However, MTC is very rare, making up only 3%-5% of all thyroid cancers, Varney said.

More common types of thyroid cancers, such as papillary thyroid cancer, are not contraindications to GLP-1 RAs, said Laura Davisson, MD, MPH, a professor of medicine and director of Medical Weight Management at West Virginia University, Morgantown. Papillary thyroid cancer makes up about 80% of all thyroid cancers.

If physicians are thinking about prescribing GLP-1 RAs, it’s important to learn the specific types of thyroid disorders in a patient or in their family history, Davisson said. A history of thyroid conditions, such as Graves disease, Hashimoto thyroiditis, or disorders requiring a patient to take thyroid medicine, such as levothyroxine, does not preclude a person from taking GLP-1 RAs.

If a patient does not know their family history, then a discussion about whether GLP-1 RAs are right for them should take place, Davisson said.

“They should take into consideration the risks and benefits of the medicine, and the fact that medullary thyroid cancer and MEN2 syndrome are rare, making the chances of them running in their family low,” she said. “If the patient understands the risks, they may decide the potential benefits may outweigh the risks.”

Keep in mind that the elevated risk for medullary thyroid carcinoma has not been clearly demonstrated in humans during clinical trials, only in rodents, Varney added. Rodents are more likely to develop thyroid cancer after exposure to a GLP-1 RA because rodents have higher numbers of GLP-1 receptors in their thyroid cells.

The risk for thyroid cancer is also dose dependent, and the amount of GLP-1 RA that induced thyroid tumors in the rodents was 8-60 times higher than that given to humans, Varney said.

“Nonetheless, there have been case reports of MTC in humans after taking GLP-1 RA,” she said.

 

What About GLP-1 RAs and Pancreatitis?

Pancreatitis is another condition that requires consideration when it comes to prescribing GLP-1 RAs.

While some studies show that GLP-1 RA analogs can increase the risk for pancreatitis, it’s important to know the reason behind pancreatitis before making a prescription decision, said Anila Chadha, MD, a family physician and obesity medicine physician at Dignity Health in Bakersfield, California.

If the pancreatitis is caused by alcohol or is medication induced, GLP-1 RAs are not recommended, Chadha said. If gallbladder stones are behind the pancreatitis, that’s different.

“If a patient has a well-documented history of gallstone-induced pancreatitis and the patient has had a cholecystectomy, it would be OK to prescribe GLP-1 [medications] after shared decision-making with the patient,” she said.

Some patients worry about taking GLP-1 RAs if they have other types of pancreatic disease beyond pancreatitis, said Davisson, but guidelines do not identify conditions such as pancreatic cysts or a family history of pancreatic cancer as contraindications to GLP-1 RAs.

However, be mindful that GLP-1 RA medications can increase gallbladder disease, Chadha said. A 2022 analysis in JAMA Internal Medicine, for example, found that the use of GLP-1 RAs was associated with an increased risk for gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss.

If a history of gallstones is present, physicians should tell patients that GLP-1 RA analogs can increase biliary colic, chances of cholecystitis, or even cholecystitis, Chadha said.

Gallbladder disease itself is not a contraindication, she said, but these patients can experience more disease complications when taking GLP-1 RAs.

Varney recently treated a middle-aged female patient who experienced biliary colic after taking a GLP-1 RA medication. The patient had a starting body mass index (BMI) of about 45 and lost 24% of her starting weight over 12 months using a combination of strengthening and cardiovascular training; a reduced-calorie, high-protein diet; and semaglutide for weight loss, Varney said.

The patient began developing upper gastrointestinal symptoms, including mild biliary colic, without concerning lab findings. An ultrasound revealed that she had new gallstones, compared with an ultrasound a few years prior. Varney started the patient on ursodeoxycholic acid, and over the course of 6 weeks, the patient’s symptoms gradually improved and eventually resolved.

“In a situation like this, many physicians might have discontinued the obesity medication, potentially deciding not to restart it due to the symptoms she was experiencing,” Varney said. “However, I believe it’s important to recognize that these medications offer far more than just weight loss benefits. The positive effects extend to cardiovascular, metabolic, and mental health, which are often overlooked when the focus is solely on the number on the scale or BMI.”

Other medical conditions that GLP-1 RAs may exacerbate include gastroparesis and diabetic retinopathy, Chadha noted. GLP-1 RA drugs can worsen these conditions and are not recommended for patients with such a history.

Nor are GLP-1 RA medications a good idea for patients struggling with severe constipation.

“It is very difficult to tolerate these medications because it can make constipation worse,” Chadha said. “In addition, if a patient struggles with severe heartburn, it can make the tolerability of these medications difficult.”

 

What Patients Should Know Before Using GLP-1 RAs

Not every overweight patient is a good candidate for GLP-1 RAs, and it’s important that doctors explain why the medications may not be right for them, Davisson said.

“If a patient only has a few pounds to lose (15-20 lb) and does not accept that these medications are intended to be a long-term treatment for the chronic diseases of diabetes or obesity, then they might not be a good candidate for the medication,” Davisson said.

Also essential is making sure patients are willing to follow appropriate healthy eating guidelines when on the medications, including getting enough protein and produce to maintain lean body mass and the necessary fiber to keep bowel habits regular.

Varney often hears concerns from physicians about the long-term effects of GLP-1 RAs. She said this class of medications has been used for nearly 20 years to treat type 2 diabetes, and the data over the past two decades have shown that the benefits of GLP-1 RAs far outweigh the risks for most patients.

Recent studies have also highlighted significant long-term benefits, including a marked reduction in cardiovascular events, heart failure, and kidney disease, she said.

“These outcomes underscore the effectiveness and safety of GLP-1 RAs not just for obesity treatment but for improving overall health, particularly in high-risk populations,” she said. “As physicians, it’s crucial to consider this extensive body of evidence when evaluating the use of these medications for patients, especially when the potential health benefits extend well beyond weight loss alone.”

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

Clinicians frequently reach out to Catherine Varney, DO, asking if it’s safe to prescribe glucagon-like peptide 1 receptor agonists (GLP-1 RAs) to patients with thyroid disorders, such as hypothyroidism, goiter, hyperthyroidism, and nodules.

The concerns often stem from prior animal studies that revealed a link between the medications and abnormal alterations in thyroid C cells.

“What physicians need to understand is that the increased risk of thyroid cancers is specifically in those with a personal or family history of multiple endocrine neoplasia 2 (MEN2) syndrome or medullary thyroid carcinoma [MTC],” said Varney, an assistant professor of family medicine at the University of Virginia (UVA) and obesity medicine director for UVA Health, both in Charlottesville.

MTC is a common manifestation of the MEN2 syndrome, a genetic disorder that affects the endocrine glands and can cause tumors in the thyroid gland. However, MTC is very rare, making up only 3%-5% of all thyroid cancers, Varney said.

More common types of thyroid cancers, such as papillary thyroid cancer, are not contraindications to GLP-1 RAs, said Laura Davisson, MD, MPH, a professor of medicine and director of Medical Weight Management at West Virginia University, Morgantown. Papillary thyroid cancer makes up about 80% of all thyroid cancers.

If physicians are thinking about prescribing GLP-1 RAs, it’s important to learn the specific types of thyroid disorders in a patient or in their family history, Davisson said. A history of thyroid conditions, such as Graves disease, Hashimoto thyroiditis, or disorders requiring a patient to take thyroid medicine, such as levothyroxine, does not preclude a person from taking GLP-1 RAs.

If a patient does not know their family history, then a discussion about whether GLP-1 RAs are right for them should take place, Davisson said.

“They should take into consideration the risks and benefits of the medicine, and the fact that medullary thyroid cancer and MEN2 syndrome are rare, making the chances of them running in their family low,” she said. “If the patient understands the risks, they may decide the potential benefits may outweigh the risks.”

Keep in mind that the elevated risk for medullary thyroid carcinoma has not been clearly demonstrated in humans during clinical trials, only in rodents, Varney added. Rodents are more likely to develop thyroid cancer after exposure to a GLP-1 RA because rodents have higher numbers of GLP-1 receptors in their thyroid cells.

The risk for thyroid cancer is also dose dependent, and the amount of GLP-1 RA that induced thyroid tumors in the rodents was 8-60 times higher than that given to humans, Varney said.

“Nonetheless, there have been case reports of MTC in humans after taking GLP-1 RA,” she said.

 

What About GLP-1 RAs and Pancreatitis?

Pancreatitis is another condition that requires consideration when it comes to prescribing GLP-1 RAs.

While some studies show that GLP-1 RA analogs can increase the risk for pancreatitis, it’s important to know the reason behind pancreatitis before making a prescription decision, said Anila Chadha, MD, a family physician and obesity medicine physician at Dignity Health in Bakersfield, California.

If the pancreatitis is caused by alcohol or is medication induced, GLP-1 RAs are not recommended, Chadha said. If gallbladder stones are behind the pancreatitis, that’s different.

“If a patient has a well-documented history of gallstone-induced pancreatitis and the patient has had a cholecystectomy, it would be OK to prescribe GLP-1 [medications] after shared decision-making with the patient,” she said.

Some patients worry about taking GLP-1 RAs if they have other types of pancreatic disease beyond pancreatitis, said Davisson, but guidelines do not identify conditions such as pancreatic cysts or a family history of pancreatic cancer as contraindications to GLP-1 RAs.

However, be mindful that GLP-1 RA medications can increase gallbladder disease, Chadha said. A 2022 analysis in JAMA Internal Medicine, for example, found that the use of GLP-1 RAs was associated with an increased risk for gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss.

If a history of gallstones is present, physicians should tell patients that GLP-1 RA analogs can increase biliary colic, chances of cholecystitis, or even cholecystitis, Chadha said.

Gallbladder disease itself is not a contraindication, she said, but these patients can experience more disease complications when taking GLP-1 RAs.

Varney recently treated a middle-aged female patient who experienced biliary colic after taking a GLP-1 RA medication. The patient had a starting body mass index (BMI) of about 45 and lost 24% of her starting weight over 12 months using a combination of strengthening and cardiovascular training; a reduced-calorie, high-protein diet; and semaglutide for weight loss, Varney said.

The patient began developing upper gastrointestinal symptoms, including mild biliary colic, without concerning lab findings. An ultrasound revealed that she had new gallstones, compared with an ultrasound a few years prior. Varney started the patient on ursodeoxycholic acid, and over the course of 6 weeks, the patient’s symptoms gradually improved and eventually resolved.

“In a situation like this, many physicians might have discontinued the obesity medication, potentially deciding not to restart it due to the symptoms she was experiencing,” Varney said. “However, I believe it’s important to recognize that these medications offer far more than just weight loss benefits. The positive effects extend to cardiovascular, metabolic, and mental health, which are often overlooked when the focus is solely on the number on the scale or BMI.”

Other medical conditions that GLP-1 RAs may exacerbate include gastroparesis and diabetic retinopathy, Chadha noted. GLP-1 RA drugs can worsen these conditions and are not recommended for patients with such a history.

Nor are GLP-1 RA medications a good idea for patients struggling with severe constipation.

“It is very difficult to tolerate these medications because it can make constipation worse,” Chadha said. “In addition, if a patient struggles with severe heartburn, it can make the tolerability of these medications difficult.”

 

What Patients Should Know Before Using GLP-1 RAs

Not every overweight patient is a good candidate for GLP-1 RAs, and it’s important that doctors explain why the medications may not be right for them, Davisson said.

“If a patient only has a few pounds to lose (15-20 lb) and does not accept that these medications are intended to be a long-term treatment for the chronic diseases of diabetes or obesity, then they might not be a good candidate for the medication,” Davisson said.

Also essential is making sure patients are willing to follow appropriate healthy eating guidelines when on the medications, including getting enough protein and produce to maintain lean body mass and the necessary fiber to keep bowel habits regular.

Varney often hears concerns from physicians about the long-term effects of GLP-1 RAs. She said this class of medications has been used for nearly 20 years to treat type 2 diabetes, and the data over the past two decades have shown that the benefits of GLP-1 RAs far outweigh the risks for most patients.

Recent studies have also highlighted significant long-term benefits, including a marked reduction in cardiovascular events, heart failure, and kidney disease, she said.

“These outcomes underscore the effectiveness and safety of GLP-1 RAs not just for obesity treatment but for improving overall health, particularly in high-risk populations,” she said. “As physicians, it’s crucial to consider this extensive body of evidence when evaluating the use of these medications for patients, especially when the potential health benefits extend well beyond weight loss alone.”

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

TOPLINE:

Among older veterans with type 2 diabetes (T2D), the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors as an add-on therapy is associated with a higher risk for peripheral artery disease (PAD)-related surgical events than the use of dipeptidyl peptidase 4 (DPP-4) inhibitors.

METHODOLOGY:

• Some placebo-controlled randomized trials have reported an increased risk for amputation with the use of SGLT2 inhibitors in patients with underlying cardiovascular diseases; however, the evidence remains unconfirmed by other subsequent trials.
• Researchers conducted a retrospective study of US veterans with T2D initiating SGLT2 inhibitors or DPP-4 inhibitors (a reference drug) as an add-on to metformin, sulfonylurea, or insulin treatment alone or in combination.
• The primary outcome was the time to the first surgical event for PAD (amputation, peripheral revascularization and bypass, or peripheral vascular stent).
• A Cox proportional hazards model was used to compare PAD event risk between the SGLT2 inhibitor and DPP-4 inhibitor groups, allowing events up to 90 days or 360 days after stopping SGLT2 inhibitors.

TAKEAWAY:

• After propensity score weighting, 76,072 episodes of SGLT2 inhibitor use (94% empagliflozin, 4% canagliflozin, and 2% dapagliflozin) and 75,833 episodes of DPP-4 inhibitor use (45% saxagliptin, 34% alogliptin, 15% sitagliptin, and 6% linagliptin) were included.
• Participants had a median age of 69 years and a median duration of diabetes of 10.1 years.
• SGLT2 inhibitor users had higher PAD-related surgical events than DPP-4 inhibitor users (874 vs 780), with event rates of 11.2 vs 10.0 per 1000 person-years (adjusted hazard ratio [aHR], 1.18).
• The cumulative probability of PAD-related surgical events at 4 years was higher for SGLT2 inhibitor users than for DPP-4 inhibitor users (4.0% vs 2.8%, respectively).
• The results remained consistent after 90 and 360 days of stopping SGLT2 inhibitors.
• SGLT2 inhibitor use was also associated with a higher risk for amputation (aHR, 1.15) and revascularization (aHR, 1.25) events than DPP-4 inhibitor use.

IN PRACTICE:

“These results underscore the need to determine the safety of [SGLT2 inhibitor] use among patients with diabetes who remain at very high risk for PAD,” the authors wrote.

SOURCE:

This study was led by Katherine E. Griffin, Geriatric Research Education and Clinical Center, Tennessee Valley Healthcare System, Nashville, and published online in Diabetes Care.

LIMITATIONS:

The study excluded patients whose initial diabetes treatment was not metformin, insulin, or sulfonylurea, which might have influenced the interpretation of the results. The median follow-up period of approximately 0.7 years for both groups may have affected the number of amputations and revascularization events observed. The study population primarily comprised White men, limiting generalizability to women and other demographic groups.

DISCLOSURES:

The study received funding through an investigator-initiated grant from the Veterans Affairs Clinical Science Research and Development. Two authors received partial research support through a grant from the Center for Diabetes Translation Research. All authors received partial support from the VETWISE-LHS Center of Innovation. No potential conflicts of interest relevant to the article were reported.

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

TOPLINE:

Among older veterans with type 2 diabetes (T2D), the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors as an add-on therapy is associated with a higher risk for peripheral artery disease (PAD)-related surgical events than the use of dipeptidyl peptidase 4 (DPP-4) inhibitors.

METHODOLOGY:

• Some placebo-controlled randomized trials have reported an increased risk for amputation with the use of SGLT2 inhibitors in patients with underlying cardiovascular diseases; however, the evidence remains unconfirmed by other subsequent trials.
• Researchers conducted a retrospective study of US veterans with T2D initiating SGLT2 inhibitors or DPP-4 inhibitors (a reference drug) as an add-on to metformin, sulfonylurea, or insulin treatment alone or in combination.
• The primary outcome was the time to the first surgical event for PAD (amputation, peripheral revascularization and bypass, or peripheral vascular stent).
• A Cox proportional hazards model was used to compare PAD event risk between the SGLT2 inhibitor and DPP-4 inhibitor groups, allowing events up to 90 days or 360 days after stopping SGLT2 inhibitors.

TAKEAWAY:

• After propensity score weighting, 76,072 episodes of SGLT2 inhibitor use (94% empagliflozin, 4% canagliflozin, and 2% dapagliflozin) and 75,833 episodes of DPP-4 inhibitor use (45% saxagliptin, 34% alogliptin, 15% sitagliptin, and 6% linagliptin) were included.
• Participants had a median age of 69 years and a median duration of diabetes of 10.1 years.
• SGLT2 inhibitor users had higher PAD-related surgical events than DPP-4 inhibitor users (874 vs 780), with event rates of 11.2 vs 10.0 per 1000 person-years (adjusted hazard ratio [aHR], 1.18).
• The cumulative probability of PAD-related surgical events at 4 years was higher for SGLT2 inhibitor users than for DPP-4 inhibitor users (4.0% vs 2.8%, respectively).
• The results remained consistent after 90 and 360 days of stopping SGLT2 inhibitors.
• SGLT2 inhibitor use was also associated with a higher risk for amputation (aHR, 1.15) and revascularization (aHR, 1.25) events than DPP-4 inhibitor use.

IN PRACTICE:

“These results underscore the need to determine the safety of [SGLT2 inhibitor] use among patients with diabetes who remain at very high risk for PAD,” the authors wrote.

SOURCE:

This study was led by Katherine E. Griffin, Geriatric Research Education and Clinical Center, Tennessee Valley Healthcare System, Nashville, and published online in Diabetes Care.

LIMITATIONS:

The study excluded patients whose initial diabetes treatment was not metformin, insulin, or sulfonylurea, which might have influenced the interpretation of the results. The median follow-up period of approximately 0.7 years for both groups may have affected the number of amputations and revascularization events observed. The study population primarily comprised White men, limiting generalizability to women and other demographic groups.

DISCLOSURES:

The study received funding through an investigator-initiated grant from the Veterans Affairs Clinical Science Research and Development. Two authors received partial research support through a grant from the Center for Diabetes Translation Research. All authors received partial support from the VETWISE-LHS Center of Innovation. No potential conflicts of interest relevant to the article were reported.

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

TOPLINE:

Among older veterans with type 2 diabetes (T2D), the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors as an add-on therapy is associated with a higher risk for peripheral artery disease (PAD)-related surgical events than the use of dipeptidyl peptidase 4 (DPP-4) inhibitors.

METHODOLOGY:

• Some placebo-controlled randomized trials have reported an increased risk for amputation with the use of SGLT2 inhibitors in patients with underlying cardiovascular diseases; however, the evidence remains unconfirmed by other subsequent trials.
• Researchers conducted a retrospective study of US veterans with T2D initiating SGLT2 inhibitors or DPP-4 inhibitors (a reference drug) as an add-on to metformin, sulfonylurea, or insulin treatment alone or in combination.
• The primary outcome was the time to the first surgical event for PAD (amputation, peripheral revascularization and bypass, or peripheral vascular stent).
• A Cox proportional hazards model was used to compare PAD event risk between the SGLT2 inhibitor and DPP-4 inhibitor groups, allowing events up to 90 days or 360 days after stopping SGLT2 inhibitors.

TAKEAWAY:

• After propensity score weighting, 76,072 episodes of SGLT2 inhibitor use (94% empagliflozin, 4% canagliflozin, and 2% dapagliflozin) and 75,833 episodes of DPP-4 inhibitor use (45% saxagliptin, 34% alogliptin, 15% sitagliptin, and 6% linagliptin) were included.
• Participants had a median age of 69 years and a median duration of diabetes of 10.1 years.
• SGLT2 inhibitor users had higher PAD-related surgical events than DPP-4 inhibitor users (874 vs 780), with event rates of 11.2 vs 10.0 per 1000 person-years (adjusted hazard ratio [aHR], 1.18).
• The cumulative probability of PAD-related surgical events at 4 years was higher for SGLT2 inhibitor users than for DPP-4 inhibitor users (4.0% vs 2.8%, respectively).
• The results remained consistent after 90 and 360 days of stopping SGLT2 inhibitors.
• SGLT2 inhibitor use was also associated with a higher risk for amputation (aHR, 1.15) and revascularization (aHR, 1.25) events than DPP-4 inhibitor use.

IN PRACTICE:

“These results underscore the need to determine the safety of [SGLT2 inhibitor] use among patients with diabetes who remain at very high risk for PAD,” the authors wrote.

SOURCE:

This study was led by Katherine E. Griffin, Geriatric Research Education and Clinical Center, Tennessee Valley Healthcare System, Nashville, and published online in Diabetes Care.

LIMITATIONS:

The study excluded patients whose initial diabetes treatment was not metformin, insulin, or sulfonylurea, which might have influenced the interpretation of the results. The median follow-up period of approximately 0.7 years for both groups may have affected the number of amputations and revascularization events observed. The study population primarily comprised White men, limiting generalizability to women and other demographic groups.

DISCLOSURES:

The study received funding through an investigator-initiated grant from the Veterans Affairs Clinical Science Research and Development. Two authors received partial research support through a grant from the Center for Diabetes Translation Research. All authors received partial support from the VETWISE-LHS Center of Innovation. No potential conflicts of interest relevant to the article were reported.

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

Cultural competency is one of the most important values in the practice of medicine. Defined as the “ability to collaborate effectively with individuals from different cultures,” this type of competence “improves healthcare experiences and outcomes.” But within the context of cultural familiarity, it’s equally important to “understand that each person is an individual and may or may not adhere to certain cultural beliefs or practices common in his or her culture,” according to the Agency for Healthcare Research and Quality’s (AHRQ’s) Health Literacy Universal Precautions Toolkit.

Sarah Candler, MD, MPH, an internal medicine physician specializing in primary care for older adults in Washington, DC, said that the medical code of ethics consists of several pillars, with patient autonomy as the “first and most primary of those pillars.” She calls the balance of patient autonomy and cultural respect a “complicated tightrope to walk,” but says that these ethical principles can inform medical decisions and the patient-physician relationship.

 

Cultural Familiarity

It’s important to be as familiar as possible with the patient’s culture, Santina Wheat, MD, program director, Northwestern McGaw Family Medicine Residency at Delnor Hospital, Geneva, told this news organization. “For example, we serve many Orthodox Jewish patients. We had a meeting with rabbis from the community to present to us what religious laws might affect our patients. Until recently, I was delivering babies, and there was always a 24-hour emergency rabbi on call if an Orthodox patient wanted the input of a rabbi into her decisions.”

Jay W. Lee, MD, MPH, a member of the board of directors of the American Academy of Family Physicians, also sets out to educate himself about the cultural norms of his patients if they come from populations he’s not familiar with. “For example, this comes up when a new refugee population comes to the United States — most recently, there was a population of Afghan refugees,” Lee told this news organization.

Lee spent “a lot of time trying to learn about their cultural norms,” which prepared him to “ask more targeted questions about the patient’s understanding of the tests we were ordering or treatment options we were bringing forward.”

Lee, also the medical director at Integrated Health Partners of Southern California and associate clinical professor of family medicine at the University of California, Irvine, said it might be best if the physician is “language congruent or culturally similar.” Lee is of Asian descent and also speaks Spanish fluently. “I enjoy cultural exchanges with my patients, and I encourage patients to find a physician who’s the best fit.” But being from the same culture isn’t absolutely necessary for building relationships with the patient. “The key is offering the patient autonomy” while understanding the cultural context.

 

Don’t Assume ... Always Ask

Cultural familiarity doesn’t equate with stereotyping, Wheat emphasized. “Proceeding without assumptions opens the opportunity to ask questions for clarification and understanding and to improve patient care,” said Lee.

Sara Glass, PhD, LCSW, agrees. She’s the clinical director of Soul Wellness NYC, New York City, a psychotherapy practice that specializes in treating trauma. Based on her own experiences, she knows that some physicians and other healthcare professionals confuse cultural sensitivity with cultural stereotyping.

Glass, formerly Hasidic and ultra-Orthodox, shared an example from her own life. During the delivery of her second child, she sustained a vaginal tear. At her 6-week postpartum visit, her ob/gyn said, “Just remind me when you’re in your ninth month next time, and I can sew it up right after you deliver.”

Much of this physician’s practice “consisted of Hasidic women who looked just like me, wearing the same garb — head coverings such as wigs and scarves and long skirts. Most women in that community have multiple pregnancies,” Glass told this news organization. “My sister has 10 children, and that’s not unusual. The doctor simply assumed I’d be going on to have more babies without asking if that’s what I wanted.”

Glass says she was also never given information by her physician about the range of available contraceptive options. The rabbis of the Hasidic sect to which Glass belonged allowed women to practice contraception for 6 months following childbirth, or for longer, in the setting of certain medical conditions, but only certain types of birth control were religiously permissible. Other options were not mentioned to her by her physician, and she didn’t know that they existed.

Making no assumptions applies not only to patients from other cultures but also to all patients — including members of “mainstream American culture.”

Candler recalls a young patient with a new baby, who shared “how exhausted she was and how much time, energy, and work it took to care for children,” Candler recounted. “To me, it sounded as though she didn’t want another child, and I was about to offer contraception when it occurred to me to first ask if she wanted to have more children.” Candler was surprised when the patient said that, although she wasn’t actively looking to become pregnant again, she didn’t want to take preventive measures. “I’m so glad I asked, rather than simply assuming.”

 

Culture Is Mutable

Important questions to ask patients include whether there are aspects of their culture or religion that might affect their care — which can include medications they may feel uncomfortable using — and what family members they want to have involved in clinical discussions and decisions, said Wheat.

Lee described treating a refugee from Afghanistan who was in her sixth month of pregnancy. “I quickly needed to learn about what her expectations were for her care and my presence as a male on her care team,” he recounted. Lee arranged for the patient to receive prenatal care from a different clinician and arranged for follow-up for her husband and children. “Everyone had good results.”

Candler noted that some patients choose their physician specifically because that practitioner is conversant with their culture and respectful of its mores — especially when physicians share the same culture as the patient. But that level of familiarity can make it easy to forget to ask questions about the experience of the individual patient within that culture.

Moreover, Glass suggested, some physicians who treat patients from a particular culture or religious group may be concerned about offending them or antagonizing religious leaders if they discuss medical options that aren’t accepted or practiced in that community or culture, such as vasectomy for male contraception. “But that deprives patients of knowing what choices are available and making truly informed decisions.”

This is especially important because “culture is mutable,” said Candler, and religious or cultural practices can “look one way on paper but be implemented, adopted, or executed in a completely different way by every human being who lives in that culture.” The best cultural competency “comes from continuing to build relationships with our patients. But even in a single visit, a single hospitalization, we should get to know patients as human beings, not just members of a given culture.”

There are cultures in which families want to be the liaison between the patient and the physician and to make decisions on the patient’s behalf. “I always ask patients what role they want their family members to play even if the cultural expectation is that the family will be heavily involved,” Candler said.

Sometimes, this can be awkward, and families might become upset. Candler described an elderly, frail patient who was diagnosed with end-stage cancer. She had always relied heavily on family to care for her. Concerned about overburdening them, she didn’t want them to know her diagnosis. The patient was mentally competent to make that decision.

“Usually, I would have had the family at the bedside so I could be sure everyone was appropriately informed and prepared for what lay ahead, but in this case, I couldn’t do so,” Candler said. “I had to inform her entire care team not to discuss the cancer diagnosis with any family members because this was the patient’s express wish. And when the family asked me if the diagnosis was cancer, I had to respond, ‘I’m so sorry, but your loved one doesn’t want us to discuss details of her diagnosis.’”

Other patients don’t want to know their own diagnosis and specifically ask Candler to inform a family member. “I’ve had patients request that I tell their children. They want their children to make decisions on their behalf.”

The main thing, Candler emphasized, is to “ask the patient, make sure the patient is competent to make that decision, thoroughly document the patient’s decision in the chart, and respect whatever that decision is.”

 

You Can Revisit the Questions

Having a longitudinal relationship means that the physician can revisit the same questions at different junctures because people’s perspectives sometimes change over time. “Discussing what a patient wants isn’t necessarily a one-time occurrence,” Wheat said. For example, “I’ve had situations where a patient has been a member of Jehovah’s Witnesses and won’t accept blood products — like transfusions — in treatment. I tell these patients that if an emergent situation arises, I would like to have the conversation again.”

Of course, sometimes patients are seen in the emergency department or in other situations where the physician has no prior relationship with them. “I always go into a room, especially with new patients, aiming to build rapport, communicate with a high level of respect, introduce myself, explain my approach, and understand the patient’s wishes,” Lee said. “As scenarios play out, I ask in multiple ways for the patient to confirm those wishes.”

He acknowledges that this can be time-consuming, “but it helps ensure the care that patient receives is complete, thorough, comprehensive, and respectful of the patient’s values and wishes.”

Candler disclosed paid part-time clinical work at CuraCapitol Primary Care Services, volunteer advocacy (reimbursed for travel) for the American College of Physicians, volunteer advocacy (reimbursed for travel) for the American Medical Association while serving on their Task Force to Preserve the Patient-Physician Relationship, and serving as a partner representative (reimbursed for time) for the AHRQ’s Person-Centered Care Planning Partnership, representing the American College of Physicians. Lee, Wheat, and Glass disclosed no relevant financial relationships.

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

Cultural competency is one of the most important values in the practice of medicine. Defined as the “ability to collaborate effectively with individuals from different cultures,” this type of competence “improves healthcare experiences and outcomes.” But within the context of cultural familiarity, it’s equally important to “understand that each person is an individual and may or may not adhere to certain cultural beliefs or practices common in his or her culture,” according to the Agency for Healthcare Research and Quality’s (AHRQ’s) Health Literacy Universal Precautions Toolkit.

Sarah Candler, MD, MPH, an internal medicine physician specializing in primary care for older adults in Washington, DC, said that the medical code of ethics consists of several pillars, with patient autonomy as the “first and most primary of those pillars.” She calls the balance of patient autonomy and cultural respect a “complicated tightrope to walk,” but says that these ethical principles can inform medical decisions and the patient-physician relationship.

 

Cultural Familiarity

It’s important to be as familiar as possible with the patient’s culture, Santina Wheat, MD, program director, Northwestern McGaw Family Medicine Residency at Delnor Hospital, Geneva, told this news organization. “For example, we serve many Orthodox Jewish patients. We had a meeting with rabbis from the community to present to us what religious laws might affect our patients. Until recently, I was delivering babies, and there was always a 24-hour emergency rabbi on call if an Orthodox patient wanted the input of a rabbi into her decisions.”

Jay W. Lee, MD, MPH, a member of the board of directors of the American Academy of Family Physicians, also sets out to educate himself about the cultural norms of his patients if they come from populations he’s not familiar with. “For example, this comes up when a new refugee population comes to the United States — most recently, there was a population of Afghan refugees,” Lee told this news organization.

Lee spent “a lot of time trying to learn about their cultural norms,” which prepared him to “ask more targeted questions about the patient’s understanding of the tests we were ordering or treatment options we were bringing forward.”

Lee, also the medical director at Integrated Health Partners of Southern California and associate clinical professor of family medicine at the University of California, Irvine, said it might be best if the physician is “language congruent or culturally similar.” Lee is of Asian descent and also speaks Spanish fluently. “I enjoy cultural exchanges with my patients, and I encourage patients to find a physician who’s the best fit.” But being from the same culture isn’t absolutely necessary for building relationships with the patient. “The key is offering the patient autonomy” while understanding the cultural context.

 

Don’t Assume ... Always Ask

Cultural familiarity doesn’t equate with stereotyping, Wheat emphasized. “Proceeding without assumptions opens the opportunity to ask questions for clarification and understanding and to improve patient care,” said Lee.

Sara Glass, PhD, LCSW, agrees. She’s the clinical director of Soul Wellness NYC, New York City, a psychotherapy practice that specializes in treating trauma. Based on her own experiences, she knows that some physicians and other healthcare professionals confuse cultural sensitivity with cultural stereotyping.

Glass, formerly Hasidic and ultra-Orthodox, shared an example from her own life. During the delivery of her second child, she sustained a vaginal tear. At her 6-week postpartum visit, her ob/gyn said, “Just remind me when you’re in your ninth month next time, and I can sew it up right after you deliver.”

Much of this physician’s practice “consisted of Hasidic women who looked just like me, wearing the same garb — head coverings such as wigs and scarves and long skirts. Most women in that community have multiple pregnancies,” Glass told this news organization. “My sister has 10 children, and that’s not unusual. The doctor simply assumed I’d be going on to have more babies without asking if that’s what I wanted.”

Glass says she was also never given information by her physician about the range of available contraceptive options. The rabbis of the Hasidic sect to which Glass belonged allowed women to practice contraception for 6 months following childbirth, or for longer, in the setting of certain medical conditions, but only certain types of birth control were religiously permissible. Other options were not mentioned to her by her physician, and she didn’t know that they existed.

Making no assumptions applies not only to patients from other cultures but also to all patients — including members of “mainstream American culture.”

Candler recalls a young patient with a new baby, who shared “how exhausted she was and how much time, energy, and work it took to care for children,” Candler recounted. “To me, it sounded as though she didn’t want another child, and I was about to offer contraception when it occurred to me to first ask if she wanted to have more children.” Candler was surprised when the patient said that, although she wasn’t actively looking to become pregnant again, she didn’t want to take preventive measures. “I’m so glad I asked, rather than simply assuming.”

 

Culture Is Mutable

Important questions to ask patients include whether there are aspects of their culture or religion that might affect their care — which can include medications they may feel uncomfortable using — and what family members they want to have involved in clinical discussions and decisions, said Wheat.

Lee described treating a refugee from Afghanistan who was in her sixth month of pregnancy. “I quickly needed to learn about what her expectations were for her care and my presence as a male on her care team,” he recounted. Lee arranged for the patient to receive prenatal care from a different clinician and arranged for follow-up for her husband and children. “Everyone had good results.”

Candler noted that some patients choose their physician specifically because that practitioner is conversant with their culture and respectful of its mores — especially when physicians share the same culture as the patient. But that level of familiarity can make it easy to forget to ask questions about the experience of the individual patient within that culture.

Moreover, Glass suggested, some physicians who treat patients from a particular culture or religious group may be concerned about offending them or antagonizing religious leaders if they discuss medical options that aren’t accepted or practiced in that community or culture, such as vasectomy for male contraception. “But that deprives patients of knowing what choices are available and making truly informed decisions.”

This is especially important because “culture is mutable,” said Candler, and religious or cultural practices can “look one way on paper but be implemented, adopted, or executed in a completely different way by every human being who lives in that culture.” The best cultural competency “comes from continuing to build relationships with our patients. But even in a single visit, a single hospitalization, we should get to know patients as human beings, not just members of a given culture.”

There are cultures in which families want to be the liaison between the patient and the physician and to make decisions on the patient’s behalf. “I always ask patients what role they want their family members to play even if the cultural expectation is that the family will be heavily involved,” Candler said.

Sometimes, this can be awkward, and families might become upset. Candler described an elderly, frail patient who was diagnosed with end-stage cancer. She had always relied heavily on family to care for her. Concerned about overburdening them, she didn’t want them to know her diagnosis. The patient was mentally competent to make that decision.

“Usually, I would have had the family at the bedside so I could be sure everyone was appropriately informed and prepared for what lay ahead, but in this case, I couldn’t do so,” Candler said. “I had to inform her entire care team not to discuss the cancer diagnosis with any family members because this was the patient’s express wish. And when the family asked me if the diagnosis was cancer, I had to respond, ‘I’m so sorry, but your loved one doesn’t want us to discuss details of her diagnosis.’”

Other patients don’t want to know their own diagnosis and specifically ask Candler to inform a family member. “I’ve had patients request that I tell their children. They want their children to make decisions on their behalf.”

The main thing, Candler emphasized, is to “ask the patient, make sure the patient is competent to make that decision, thoroughly document the patient’s decision in the chart, and respect whatever that decision is.”

 

You Can Revisit the Questions

Having a longitudinal relationship means that the physician can revisit the same questions at different junctures because people’s perspectives sometimes change over time. “Discussing what a patient wants isn’t necessarily a one-time occurrence,” Wheat said. For example, “I’ve had situations where a patient has been a member of Jehovah’s Witnesses and won’t accept blood products — like transfusions — in treatment. I tell these patients that if an emergent situation arises, I would like to have the conversation again.”

Of course, sometimes patients are seen in the emergency department or in other situations where the physician has no prior relationship with them. “I always go into a room, especially with new patients, aiming to build rapport, communicate with a high level of respect, introduce myself, explain my approach, and understand the patient’s wishes,” Lee said. “As scenarios play out, I ask in multiple ways for the patient to confirm those wishes.”

He acknowledges that this can be time-consuming, “but it helps ensure the care that patient receives is complete, thorough, comprehensive, and respectful of the patient’s values and wishes.”

Candler disclosed paid part-time clinical work at CuraCapitol Primary Care Services, volunteer advocacy (reimbursed for travel) for the American College of Physicians, volunteer advocacy (reimbursed for travel) for the American Medical Association while serving on their Task Force to Preserve the Patient-Physician Relationship, and serving as a partner representative (reimbursed for time) for the AHRQ’s Person-Centered Care Planning Partnership, representing the American College of Physicians. Lee, Wheat, and Glass disclosed no relevant financial relationships.

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

Cultural competency is one of the most important values in the practice of medicine. Defined as the “ability to collaborate effectively with individuals from different cultures,” this type of competence “improves healthcare experiences and outcomes.” But within the context of cultural familiarity, it’s equally important to “understand that each person is an individual and may or may not adhere to certain cultural beliefs or practices common in his or her culture,” according to the Agency for Healthcare Research and Quality’s (AHRQ’s) Health Literacy Universal Precautions Toolkit.

Sarah Candler, MD, MPH, an internal medicine physician specializing in primary care for older adults in Washington, DC, said that the medical code of ethics consists of several pillars, with patient autonomy as the “first and most primary of those pillars.” She calls the balance of patient autonomy and cultural respect a “complicated tightrope to walk,” but says that these ethical principles can inform medical decisions and the patient-physician relationship.

 

Cultural Familiarity

It’s important to be as familiar as possible with the patient’s culture, Santina Wheat, MD, program director, Northwestern McGaw Family Medicine Residency at Delnor Hospital, Geneva, told this news organization. “For example, we serve many Orthodox Jewish patients. We had a meeting with rabbis from the community to present to us what religious laws might affect our patients. Until recently, I was delivering babies, and there was always a 24-hour emergency rabbi on call if an Orthodox patient wanted the input of a rabbi into her decisions.”

Jay W. Lee, MD, MPH, a member of the board of directors of the American Academy of Family Physicians, also sets out to educate himself about the cultural norms of his patients if they come from populations he’s not familiar with. “For example, this comes up when a new refugee population comes to the United States — most recently, there was a population of Afghan refugees,” Lee told this news organization.

Lee spent “a lot of time trying to learn about their cultural norms,” which prepared him to “ask more targeted questions about the patient’s understanding of the tests we were ordering or treatment options we were bringing forward.”

Lee, also the medical director at Integrated Health Partners of Southern California and associate clinical professor of family medicine at the University of California, Irvine, said it might be best if the physician is “language congruent or culturally similar.” Lee is of Asian descent and also speaks Spanish fluently. “I enjoy cultural exchanges with my patients, and I encourage patients to find a physician who’s the best fit.” But being from the same culture isn’t absolutely necessary for building relationships with the patient. “The key is offering the patient autonomy” while understanding the cultural context.

 

Don’t Assume ... Always Ask

Cultural familiarity doesn’t equate with stereotyping, Wheat emphasized. “Proceeding without assumptions opens the opportunity to ask questions for clarification and understanding and to improve patient care,” said Lee.

Sara Glass, PhD, LCSW, agrees. She’s the clinical director of Soul Wellness NYC, New York City, a psychotherapy practice that specializes in treating trauma. Based on her own experiences, she knows that some physicians and other healthcare professionals confuse cultural sensitivity with cultural stereotyping.

Glass, formerly Hasidic and ultra-Orthodox, shared an example from her own life. During the delivery of her second child, she sustained a vaginal tear. At her 6-week postpartum visit, her ob/gyn said, “Just remind me when you’re in your ninth month next time, and I can sew it up right after you deliver.”

Much of this physician’s practice “consisted of Hasidic women who looked just like me, wearing the same garb — head coverings such as wigs and scarves and long skirts. Most women in that community have multiple pregnancies,” Glass told this news organization. “My sister has 10 children, and that’s not unusual. The doctor simply assumed I’d be going on to have more babies without asking if that’s what I wanted.”

Glass says she was also never given information by her physician about the range of available contraceptive options. The rabbis of the Hasidic sect to which Glass belonged allowed women to practice contraception for 6 months following childbirth, or for longer, in the setting of certain medical conditions, but only certain types of birth control were religiously permissible. Other options were not mentioned to her by her physician, and she didn’t know that they existed.

Making no assumptions applies not only to patients from other cultures but also to all patients — including members of “mainstream American culture.”

Candler recalls a young patient with a new baby, who shared “how exhausted she was and how much time, energy, and work it took to care for children,” Candler recounted. “To me, it sounded as though she didn’t want another child, and I was about to offer contraception when it occurred to me to first ask if she wanted to have more children.” Candler was surprised when the patient said that, although she wasn’t actively looking to become pregnant again, she didn’t want to take preventive measures. “I’m so glad I asked, rather than simply assuming.”

 

Culture Is Mutable

Important questions to ask patients include whether there are aspects of their culture or religion that might affect their care — which can include medications they may feel uncomfortable using — and what family members they want to have involved in clinical discussions and decisions, said Wheat.

Lee described treating a refugee from Afghanistan who was in her sixth month of pregnancy. “I quickly needed to learn about what her expectations were for her care and my presence as a male on her care team,” he recounted. Lee arranged for the patient to receive prenatal care from a different clinician and arranged for follow-up for her husband and children. “Everyone had good results.”

Candler noted that some patients choose their physician specifically because that practitioner is conversant with their culture and respectful of its mores — especially when physicians share the same culture as the patient. But that level of familiarity can make it easy to forget to ask questions about the experience of the individual patient within that culture.

Moreover, Glass suggested, some physicians who treat patients from a particular culture or religious group may be concerned about offending them or antagonizing religious leaders if they discuss medical options that aren’t accepted or practiced in that community or culture, such as vasectomy for male contraception. “But that deprives patients of knowing what choices are available and making truly informed decisions.”

This is especially important because “culture is mutable,” said Candler, and religious or cultural practices can “look one way on paper but be implemented, adopted, or executed in a completely different way by every human being who lives in that culture.” The best cultural competency “comes from continuing to build relationships with our patients. But even in a single visit, a single hospitalization, we should get to know patients as human beings, not just members of a given culture.”

There are cultures in which families want to be the liaison between the patient and the physician and to make decisions on the patient’s behalf. “I always ask patients what role they want their family members to play even if the cultural expectation is that the family will be heavily involved,” Candler said.

Sometimes, this can be awkward, and families might become upset. Candler described an elderly, frail patient who was diagnosed with end-stage cancer. She had always relied heavily on family to care for her. Concerned about overburdening them, she didn’t want them to know her diagnosis. The patient was mentally competent to make that decision.

“Usually, I would have had the family at the bedside so I could be sure everyone was appropriately informed and prepared for what lay ahead, but in this case, I couldn’t do so,” Candler said. “I had to inform her entire care team not to discuss the cancer diagnosis with any family members because this was the patient’s express wish. And when the family asked me if the diagnosis was cancer, I had to respond, ‘I’m so sorry, but your loved one doesn’t want us to discuss details of her diagnosis.’”

Other patients don’t want to know their own diagnosis and specifically ask Candler to inform a family member. “I’ve had patients request that I tell their children. They want their children to make decisions on their behalf.”

The main thing, Candler emphasized, is to “ask the patient, make sure the patient is competent to make that decision, thoroughly document the patient’s decision in the chart, and respect whatever that decision is.”

 

You Can Revisit the Questions

Having a longitudinal relationship means that the physician can revisit the same questions at different junctures because people’s perspectives sometimes change over time. “Discussing what a patient wants isn’t necessarily a one-time occurrence,” Wheat said. For example, “I’ve had situations where a patient has been a member of Jehovah’s Witnesses and won’t accept blood products — like transfusions — in treatment. I tell these patients that if an emergent situation arises, I would like to have the conversation again.”

Of course, sometimes patients are seen in the emergency department or in other situations where the physician has no prior relationship with them. “I always go into a room, especially with new patients, aiming to build rapport, communicate with a high level of respect, introduce myself, explain my approach, and understand the patient’s wishes,” Lee said. “As scenarios play out, I ask in multiple ways for the patient to confirm those wishes.”

He acknowledges that this can be time-consuming, “but it helps ensure the care that patient receives is complete, thorough, comprehensive, and respectful of the patient’s values and wishes.”

Candler disclosed paid part-time clinical work at CuraCapitol Primary Care Services, volunteer advocacy (reimbursed for travel) for the American College of Physicians, volunteer advocacy (reimbursed for travel) for the American Medical Association while serving on their Task Force to Preserve the Patient-Physician Relationship, and serving as a partner representative (reimbursed for time) for the AHRQ’s Person-Centered Care Planning Partnership, representing the American College of Physicians. Lee, Wheat, and Glass disclosed no relevant financial relationships.

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

Interventions during holidays and school vacations can help prevent children and adults gaining weight, according to a recent systematic review and meta-analysis published in Obesity Reviews.

Evidence suggests that certain times of the year, such as the Christmas holidays and summer vacations, are associated with weight gain. In adults, up to 50% of the total annual weight gain occurs during December.

In 2023, the United Nations Children’s Fund reported that more than four million children younger than 5 years and nearly 50 million children and adolescents aged 5-19 years in Latin America and the Caribbean were affected by overweight. Among adults, more than 50% of individuals in every country in the region live with obesity.

These alarming figures call for urgent action from governments, healthcare professionals, and multidisciplinary teams to implement prevention strategies and promote further research.

 

Study Significance

Michelle Maree Haby de Sosa, PhD, an epidemiologist and researcher at the Department of Chemical-Biological and Nutritional Sciences at the University of Sonora, Hermosillo, Mexico, led the study. She explained that the research team first conducted a narrative review on weight gain during the festive season. “We found that the 6 weeks between December and mid-January represent a critical period when people gain half the weight they put on all year. This highlights the importance of addressing obesity and overweight by promoting lifestyle changes and prevention strategies to tackle this public health issue.”

The researchers then conducted a systematic review of global interventions not only to publish findings but also to educate healthcare professionals and stakeholders. They searched databases such as Medline, EMBASE, PsycINFO, SciELO, LILACS, and Cochrane, focusing on randomized controlled trials. These were supplemented with gray literature and references from relevant articles, as well as additional data requested from study authors.

 

Key Findings

The review included studies from the United States (10), the United Kingdom (one), and Chile (one). Of these, two had a low risk for bias, two moderate, seven high, and one critical.

Most interventions targeted school-aged children or adults. According to Haby de Sosa, achieving consistent results in adolescents was challenging due to the difficulty of changing behaviors in this age group. In contrast, interventions for school-aged children were implemented primarily during day camp visits, where participants were divided into control and intervention groups.

The interventions included nutrition classes, physical activity, and the provision of healthy meals, which resulted in less weight gain compared with control groups.

In children, the meta-analysis of four of seven studies conducted during summer vacations (six interventions) found a small but significant reduction in body mass index z-scores in the intervention group (−0.06; 95% CI, −0.10 to −0.01; P = .01; I² = 0%; very low-certainty evidence).

Among adults, interventions also generally proved effective, despite variations in implementation. A meta-analysis of five studies involving 462 participants (234 intervention, 228 control) showed a slight reduction in body weight (−0.99 kg; 95% CI, −2.15 to 0.18; P = 0.10; I² = 89%).

Three key intervention areas were identified: Nutrition, physical activity, and psychological support including behavioral and cognitive elements. Strict diets were generally not a priority; instead, participants were advised to reduce consumption of high-calorie food and sugary beverages while increasing their intake of vegetables.

 

Promising Interventions

The study highlighted specific interventions for children and adults:

• Children: 6- to 8-week summer camps with daily physical activities such as sports and crafts, complemented by free, nutritious meals.
• Adults: Daily weight monitoring paired with nutrition counseling based on social cognitive theory. Interventions lasted 4 to 8 weeks, spanning mid-November to early January.

Expert Recommendations

Carlos Cristi-Montero, PhD, a researcher at Pontificia Universidad Católica de Valparaíso, Chile, and an author of a Chilean intervention study, shared insights with this news organization.

He emphasized the importance of portion control for children. “During the holidays, families prepare calorie-rich dishes but often fail to consider portion sizes,” he noted. “Children are treated like adults, which contributes to excessive caloric intake. Our interventions focused on teaching people about portion control, the caloric content of their meals, and the risks of overweight and obesity, as well as the benefits of healthy eating.”

He also stressed the importance of evaluating not just weight but body composition, using tools like dual-energy x-ray absorptiometry to measure fat and muscle mass.

Cristi-Montero also highlighted the importance of physical activity: “We emphasize the value of exercise and staying active as key strategies to prevent weight gain.”

 

Steps for Successful Interventions

Educating teachers and parents to reinforce healthy behaviors is also vital, according to Cristi-Montero, as obesity impacts not only metabolic health but also academic performance and mental health.

Both Haby de Sosa and Cristi-Montero agreed that primary care professionals have an important role in driving effective interventions, alongside participation in research to refine prevention strategies. Multidisciplinary teams — including nutritionists, psychologists, exercise specialists, teachers, and parents — can play a part in preventing weight gain during holidays.

 

Future Directions

The University of Sonora research team is currently conducting a controlled trial in Hermosillo, Mexico, involving adult participants divided into intervention and control groups. Preliminary results, already published online, highlight the effectiveness of strategies such as nutrition education, physical activity, regular weight goals, and psychological support in promoting habit changes.

“Interventions to prevent weight gain during the holidays and summer vacations are necessary,” the authors concluded, emphasizing the need for further research to evaluate their effectiveness in the region.

Haby de Sosa or Cristi-Montero declared no relevant financial conflicts of interest.

Natalia Martínez Medina, disclosed the following: Consultant or advisor for: AstraZeneca (former); Sanofi (former). Speaker or a member of a speaker’s bureau for: AstraZeneca (former); Sanofi (former). Research funding from: AstraZeneca (former); Sanofi (former). Contracted researcher for: AstraZeneca (former); Sanofi (former). Employee of: AstraZeneca (former); Sanofi (former).

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

Interventions during holidays and school vacations can help prevent children and adults gaining weight, according to a recent systematic review and meta-analysis published in Obesity Reviews.

Evidence suggests that certain times of the year, such as the Christmas holidays and summer vacations, are associated with weight gain. In adults, up to 50% of the total annual weight gain occurs during December.

In 2023, the United Nations Children’s Fund reported that more than four million children younger than 5 years and nearly 50 million children and adolescents aged 5-19 years in Latin America and the Caribbean were affected by overweight. Among adults, more than 50% of individuals in every country in the region live with obesity.

These alarming figures call for urgent action from governments, healthcare professionals, and multidisciplinary teams to implement prevention strategies and promote further research.

 

Study Significance

Michelle Maree Haby de Sosa, PhD, an epidemiologist and researcher at the Department of Chemical-Biological and Nutritional Sciences at the University of Sonora, Hermosillo, Mexico, led the study. She explained that the research team first conducted a narrative review on weight gain during the festive season. “We found that the 6 weeks between December and mid-January represent a critical period when people gain half the weight they put on all year. This highlights the importance of addressing obesity and overweight by promoting lifestyle changes and prevention strategies to tackle this public health issue.”

The researchers then conducted a systematic review of global interventions not only to publish findings but also to educate healthcare professionals and stakeholders. They searched databases such as Medline, EMBASE, PsycINFO, SciELO, LILACS, and Cochrane, focusing on randomized controlled trials. These were supplemented with gray literature and references from relevant articles, as well as additional data requested from study authors.

 

Key Findings

The review included studies from the United States (10), the United Kingdom (one), and Chile (one). Of these, two had a low risk for bias, two moderate, seven high, and one critical.

Most interventions targeted school-aged children or adults. According to Haby de Sosa, achieving consistent results in adolescents was challenging due to the difficulty of changing behaviors in this age group. In contrast, interventions for school-aged children were implemented primarily during day camp visits, where participants were divided into control and intervention groups.

The interventions included nutrition classes, physical activity, and the provision of healthy meals, which resulted in less weight gain compared with control groups.

In children, the meta-analysis of four of seven studies conducted during summer vacations (six interventions) found a small but significant reduction in body mass index z-scores in the intervention group (−0.06; 95% CI, −0.10 to −0.01; P = .01; I² = 0%; very low-certainty evidence).

Among adults, interventions also generally proved effective, despite variations in implementation. A meta-analysis of five studies involving 462 participants (234 intervention, 228 control) showed a slight reduction in body weight (−0.99 kg; 95% CI, −2.15 to 0.18; P = 0.10; I² = 89%).

Three key intervention areas were identified: Nutrition, physical activity, and psychological support including behavioral and cognitive elements. Strict diets were generally not a priority; instead, participants were advised to reduce consumption of high-calorie food and sugary beverages while increasing their intake of vegetables.

 

Promising Interventions

The study highlighted specific interventions for children and adults:

• Children: 6- to 8-week summer camps with daily physical activities such as sports and crafts, complemented by free, nutritious meals.
• Adults: Daily weight monitoring paired with nutrition counseling based on social cognitive theory. Interventions lasted 4 to 8 weeks, spanning mid-November to early January.

Expert Recommendations

Carlos Cristi-Montero, PhD, a researcher at Pontificia Universidad Católica de Valparaíso, Chile, and an author of a Chilean intervention study, shared insights with this news organization.

He emphasized the importance of portion control for children. “During the holidays, families prepare calorie-rich dishes but often fail to consider portion sizes,” he noted. “Children are treated like adults, which contributes to excessive caloric intake. Our interventions focused on teaching people about portion control, the caloric content of their meals, and the risks of overweight and obesity, as well as the benefits of healthy eating.”

He also stressed the importance of evaluating not just weight but body composition, using tools like dual-energy x-ray absorptiometry to measure fat and muscle mass.

Cristi-Montero also highlighted the importance of physical activity: “We emphasize the value of exercise and staying active as key strategies to prevent weight gain.”

 

Steps for Successful Interventions

Educating teachers and parents to reinforce healthy behaviors is also vital, according to Cristi-Montero, as obesity impacts not only metabolic health but also academic performance and mental health.

Both Haby de Sosa and Cristi-Montero agreed that primary care professionals have an important role in driving effective interventions, alongside participation in research to refine prevention strategies. Multidisciplinary teams — including nutritionists, psychologists, exercise specialists, teachers, and parents — can play a part in preventing weight gain during holidays.

 

Future Directions

The University of Sonora research team is currently conducting a controlled trial in Hermosillo, Mexico, involving adult participants divided into intervention and control groups. Preliminary results, already published online, highlight the effectiveness of strategies such as nutrition education, physical activity, regular weight goals, and psychological support in promoting habit changes.

“Interventions to prevent weight gain during the holidays and summer vacations are necessary,” the authors concluded, emphasizing the need for further research to evaluate their effectiveness in the region.

Haby de Sosa or Cristi-Montero declared no relevant financial conflicts of interest.

Natalia Martínez Medina, disclosed the following: Consultant or advisor for: AstraZeneca (former); Sanofi (former). Speaker or a member of a speaker’s bureau for: AstraZeneca (former); Sanofi (former). Research funding from: AstraZeneca (former); Sanofi (former). Contracted researcher for: AstraZeneca (former); Sanofi (former). Employee of: AstraZeneca (former); Sanofi (former).

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

Interventions during holidays and school vacations can help prevent children and adults gaining weight, according to a recent systematic review and meta-analysis published in Obesity Reviews.

Evidence suggests that certain times of the year, such as the Christmas holidays and summer vacations, are associated with weight gain. In adults, up to 50% of the total annual weight gain occurs during December.

In 2023, the United Nations Children’s Fund reported that more than four million children younger than 5 years and nearly 50 million children and adolescents aged 5-19 years in Latin America and the Caribbean were affected by overweight. Among adults, more than 50% of individuals in every country in the region live with obesity.

These alarming figures call for urgent action from governments, healthcare professionals, and multidisciplinary teams to implement prevention strategies and promote further research.

 

Study Significance

Michelle Maree Haby de Sosa, PhD, an epidemiologist and researcher at the Department of Chemical-Biological and Nutritional Sciences at the University of Sonora, Hermosillo, Mexico, led the study. She explained that the research team first conducted a narrative review on weight gain during the festive season. “We found that the 6 weeks between December and mid-January represent a critical period when people gain half the weight they put on all year. This highlights the importance of addressing obesity and overweight by promoting lifestyle changes and prevention strategies to tackle this public health issue.”

The researchers then conducted a systematic review of global interventions not only to publish findings but also to educate healthcare professionals and stakeholders. They searched databases such as Medline, EMBASE, PsycINFO, SciELO, LILACS, and Cochrane, focusing on randomized controlled trials. These were supplemented with gray literature and references from relevant articles, as well as additional data requested from study authors.

 

Key Findings

The review included studies from the United States (10), the United Kingdom (one), and Chile (one). Of these, two had a low risk for bias, two moderate, seven high, and one critical.

Most interventions targeted school-aged children or adults. According to Haby de Sosa, achieving consistent results in adolescents was challenging due to the difficulty of changing behaviors in this age group. In contrast, interventions for school-aged children were implemented primarily during day camp visits, where participants were divided into control and intervention groups.

The interventions included nutrition classes, physical activity, and the provision of healthy meals, which resulted in less weight gain compared with control groups.

In children, the meta-analysis of four of seven studies conducted during summer vacations (six interventions) found a small but significant reduction in body mass index z-scores in the intervention group (−0.06; 95% CI, −0.10 to −0.01; P = .01; I² = 0%; very low-certainty evidence).

Among adults, interventions also generally proved effective, despite variations in implementation. A meta-analysis of five studies involving 462 participants (234 intervention, 228 control) showed a slight reduction in body weight (−0.99 kg; 95% CI, −2.15 to 0.18; P = 0.10; I² = 89%).

Three key intervention areas were identified: Nutrition, physical activity, and psychological support including behavioral and cognitive elements. Strict diets were generally not a priority; instead, participants were advised to reduce consumption of high-calorie food and sugary beverages while increasing their intake of vegetables.

 

Promising Interventions

The study highlighted specific interventions for children and adults:

• Children: 6- to 8-week summer camps with daily physical activities such as sports and crafts, complemented by free, nutritious meals.
• Adults: Daily weight monitoring paired with nutrition counseling based on social cognitive theory. Interventions lasted 4 to 8 weeks, spanning mid-November to early January.

Expert Recommendations

Carlos Cristi-Montero, PhD, a researcher at Pontificia Universidad Católica de Valparaíso, Chile, and an author of a Chilean intervention study, shared insights with this news organization.

He emphasized the importance of portion control for children. “During the holidays, families prepare calorie-rich dishes but often fail to consider portion sizes,” he noted. “Children are treated like adults, which contributes to excessive caloric intake. Our interventions focused on teaching people about portion control, the caloric content of their meals, and the risks of overweight and obesity, as well as the benefits of healthy eating.”

He also stressed the importance of evaluating not just weight but body composition, using tools like dual-energy x-ray absorptiometry to measure fat and muscle mass.

Cristi-Montero also highlighted the importance of physical activity: “We emphasize the value of exercise and staying active as key strategies to prevent weight gain.”

 

Steps for Successful Interventions

Educating teachers and parents to reinforce healthy behaviors is also vital, according to Cristi-Montero, as obesity impacts not only metabolic health but also academic performance and mental health.

Both Haby de Sosa and Cristi-Montero agreed that primary care professionals have an important role in driving effective interventions, alongside participation in research to refine prevention strategies. Multidisciplinary teams — including nutritionists, psychologists, exercise specialists, teachers, and parents — can play a part in preventing weight gain during holidays.

 

Future Directions

The University of Sonora research team is currently conducting a controlled trial in Hermosillo, Mexico, involving adult participants divided into intervention and control groups. Preliminary results, already published online, highlight the effectiveness of strategies such as nutrition education, physical activity, regular weight goals, and psychological support in promoting habit changes.

“Interventions to prevent weight gain during the holidays and summer vacations are necessary,” the authors concluded, emphasizing the need for further research to evaluate their effectiveness in the region.

Haby de Sosa or Cristi-Montero declared no relevant financial conflicts of interest.

Natalia Martínez Medina, disclosed the following: Consultant or advisor for: AstraZeneca (former); Sanofi (former). Speaker or a member of a speaker’s bureau for: AstraZeneca (former); Sanofi (former). Research funding from: AstraZeneca (former); Sanofi (former). Contracted researcher for: AstraZeneca (former); Sanofi (former). Employee of: AstraZeneca (former); Sanofi (former).

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

Hatice became pregnant while working as a medical resident, and her career took a noticeable hit. Her training was downgraded, and her job applications went unanswered. This news organization spoke with her about her experiences and the disadvantages faced by young female doctors with children. 

Hatice, can you tell us about your career path?

I initially started my clinical year at a hospital in Cologne, Germany. Then, 8 months in, I got pregnant with my first child during the first COVID-19 wave. After my maternity leave, I returned to the clinic, and that’s when the problems began.

Where did the issues arise?

Suddenly, I wasn’t allowed into the operating rooms (ORs) and was instead sent to the outpatient clinic. I had to fight for every OR slot until, eventually, I said, “This can’t go on. I want to stay in the hospital and gain my surgical experience, but not if I have to keep struggling for it.”

So, initially, it was about wanting to improve the quality of your ongoing training, as they gave you no path forward for further development? And you attribute this to your maternity leave.

It wasn’t just my perception — I was told as much directly. I returned from maternity leave and was told to work in outpatients and cover shifts. I went to my supervisor and explained that I was unhappy with this. We have an OR log, and I wanted to complete my required cases. He replied, “Well, that’s your fault for getting pregnant right away.” 

In the Cologne/Düsseldorf/Bonn area, there is no shortage of doctors in training. This means that as soon as I leave, there will be new recruits. So my boss actually said to me at the time, “If you’re gone, you’re gone, then the next candidate will come along.”

 

Did you return to work part-time after your maternity leave, or full-time?

I returned full-time and took on all my usual duties. Fortunately, my husband takes on a lot at home. He spent a significant time on parental leave and has often been the one to care for our child when they’re sick. So, if you didn’t know, you wouldn’t necessarily realize at work that I have a child.

What happened next?

I discussed the situation with the senior physician responsible for the OR assignments, but she told me not to worry, as I would eventually get the required signature at the end of my training. But that wasn’t my issue — I wanted the professional training. Feeling stuck, I decided to look for other positions.

Did you apply elsewhere to improve your situation?

Yes, but most of my applications went unanswered, which I didn’t understand. When I followed up, I actually received verbal replies from three hospitals, stating, “We don’t hire women with children.”

You’ve shared your experiences publicly on social media. How has the response been? Have other female doctors had similar experiences?

I think the problem of discrimination against women with children is still taboo. You’d think, with the shortage of doctors, that jobs would be available. But I’ve heard from former classmates who now have children that they face similar career obstacles, especially in fields such as internal medicine, where fulfilling rotations is challenging owing to scheduling bias.

This raises the question of adapting working conditions. In your case, it seems that a change in employer attitudes is also needed. What’s your perspective?

It varies depending on the region. I’ve applied across Germany and found that areas outside major cities such as Cologne, Düsseldorf, and Frankfurt tend to be better. In urban centers with a large applicant pool, the atmosphere is different. In smaller areas, finding a job is easier, especially if you’re fluent in German and experienced.

Do you believe that changing the mindset of employers regarding female staff with children could happen with a generational shift?

Honestly, I doubt it. It’s not just an issue at management level — it’s also present among residents. When someone takes leave, colleagues have to cover, which leads to resentment. Yet many female residents will eventually have children themselves. And it’s often overlooked that many men now share childcare responsibilities or take parental leave. Improving staffing levels would help alleviate these pressures.

Returning to structural issues, how is your situation now — can you continue your training?

I’ve since changed positions and am very happy. I didn’t expect such a positive reception with a child in tow.

Lastly, what changes do you think are needed? Is it enough to speak out about such experiences, or are further solutions necessary?

It’s good that topics such as burnout are openly discussed now. With children, there’s a risk for burnout, as you strive to meet all expectations to avoid career setbacks. But there also needs to be an acceptance that women who are hired may become pregnant and may have more than one child. I’m hopeful that over time, this will become normalized, especially as medicine becomes a more female-dominated field.

Is there anything else you’d like to share?

I wish there were more solidarity among women. It’s disheartening to see competition and infighting. More mutual support among women would make a huge difference.

Thank you, Hatice, and best of luck in your career.

Hatice, who prefers not to disclose her last name for privacy, is a fourth-year ENT specialist in training and shares her journey as a young doctor on Instagram under the name dein.hno.arzt.

This article was translated from Coliquio using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

Hatice became pregnant while working as a medical resident, and her career took a noticeable hit. Her training was downgraded, and her job applications went unanswered. This news organization spoke with her about her experiences and the disadvantages faced by young female doctors with children. 

Hatice, can you tell us about your career path?

I initially started my clinical year at a hospital in Cologne, Germany. Then, 8 months in, I got pregnant with my first child during the first COVID-19 wave. After my maternity leave, I returned to the clinic, and that’s when the problems began.

Where did the issues arise?

Suddenly, I wasn’t allowed into the operating rooms (ORs) and was instead sent to the outpatient clinic. I had to fight for every OR slot until, eventually, I said, “This can’t go on. I want to stay in the hospital and gain my surgical experience, but not if I have to keep struggling for it.”

So, initially, it was about wanting to improve the quality of your ongoing training, as they gave you no path forward for further development? And you attribute this to your maternity leave.

It wasn’t just my perception — I was told as much directly. I returned from maternity leave and was told to work in outpatients and cover shifts. I went to my supervisor and explained that I was unhappy with this. We have an OR log, and I wanted to complete my required cases. He replied, “Well, that’s your fault for getting pregnant right away.” 

In the Cologne/Düsseldorf/Bonn area, there is no shortage of doctors in training. This means that as soon as I leave, there will be new recruits. So my boss actually said to me at the time, “If you’re gone, you’re gone, then the next candidate will come along.”

 

Did you return to work part-time after your maternity leave, or full-time?

I returned full-time and took on all my usual duties. Fortunately, my husband takes on a lot at home. He spent a significant time on parental leave and has often been the one to care for our child when they’re sick. So, if you didn’t know, you wouldn’t necessarily realize at work that I have a child.

What happened next?

I discussed the situation with the senior physician responsible for the OR assignments, but she told me not to worry, as I would eventually get the required signature at the end of my training. But that wasn’t my issue — I wanted the professional training. Feeling stuck, I decided to look for other positions.

Did you apply elsewhere to improve your situation?

Yes, but most of my applications went unanswered, which I didn’t understand. When I followed up, I actually received verbal replies from three hospitals, stating, “We don’t hire women with children.”

You’ve shared your experiences publicly on social media. How has the response been? Have other female doctors had similar experiences?

I think the problem of discrimination against women with children is still taboo. You’d think, with the shortage of doctors, that jobs would be available. But I’ve heard from former classmates who now have children that they face similar career obstacles, especially in fields such as internal medicine, where fulfilling rotations is challenging owing to scheduling bias.

This raises the question of adapting working conditions. In your case, it seems that a change in employer attitudes is also needed. What’s your perspective?

It varies depending on the region. I’ve applied across Germany and found that areas outside major cities such as Cologne, Düsseldorf, and Frankfurt tend to be better. In urban centers with a large applicant pool, the atmosphere is different. In smaller areas, finding a job is easier, especially if you’re fluent in German and experienced.

Do you believe that changing the mindset of employers regarding female staff with children could happen with a generational shift?

Honestly, I doubt it. It’s not just an issue at management level — it’s also present among residents. When someone takes leave, colleagues have to cover, which leads to resentment. Yet many female residents will eventually have children themselves. And it’s often overlooked that many men now share childcare responsibilities or take parental leave. Improving staffing levels would help alleviate these pressures.

Returning to structural issues, how is your situation now — can you continue your training?

I’ve since changed positions and am very happy. I didn’t expect such a positive reception with a child in tow.

Lastly, what changes do you think are needed? Is it enough to speak out about such experiences, or are further solutions necessary?

It’s good that topics such as burnout are openly discussed now. With children, there’s a risk for burnout, as you strive to meet all expectations to avoid career setbacks. But there also needs to be an acceptance that women who are hired may become pregnant and may have more than one child. I’m hopeful that over time, this will become normalized, especially as medicine becomes a more female-dominated field.

Is there anything else you’d like to share?

I wish there were more solidarity among women. It’s disheartening to see competition and infighting. More mutual support among women would make a huge difference.

Thank you, Hatice, and best of luck in your career.

Hatice, who prefers not to disclose her last name for privacy, is a fourth-year ENT specialist in training and shares her journey as a young doctor on Instagram under the name dein.hno.arzt.

This article was translated from Coliquio using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

Hatice became pregnant while working as a medical resident, and her career took a noticeable hit. Her training was downgraded, and her job applications went unanswered. This news organization spoke with her about her experiences and the disadvantages faced by young female doctors with children. 

Hatice, can you tell us about your career path?

I initially started my clinical year at a hospital in Cologne, Germany. Then, 8 months in, I got pregnant with my first child during the first COVID-19 wave. After my maternity leave, I returned to the clinic, and that’s when the problems began.

Where did the issues arise?

Suddenly, I wasn’t allowed into the operating rooms (ORs) and was instead sent to the outpatient clinic. I had to fight for every OR slot until, eventually, I said, “This can’t go on. I want to stay in the hospital and gain my surgical experience, but not if I have to keep struggling for it.”

So, initially, it was about wanting to improve the quality of your ongoing training, as they gave you no path forward for further development? And you attribute this to your maternity leave.

It wasn’t just my perception — I was told as much directly. I returned from maternity leave and was told to work in outpatients and cover shifts. I went to my supervisor and explained that I was unhappy with this. We have an OR log, and I wanted to complete my required cases. He replied, “Well, that’s your fault for getting pregnant right away.” 

In the Cologne/Düsseldorf/Bonn area, there is no shortage of doctors in training. This means that as soon as I leave, there will be new recruits. So my boss actually said to me at the time, “If you’re gone, you’re gone, then the next candidate will come along.”

 

Did you return to work part-time after your maternity leave, or full-time?

I returned full-time and took on all my usual duties. Fortunately, my husband takes on a lot at home. He spent a significant time on parental leave and has often been the one to care for our child when they’re sick. So, if you didn’t know, you wouldn’t necessarily realize at work that I have a child.

What happened next?

I discussed the situation with the senior physician responsible for the OR assignments, but she told me not to worry, as I would eventually get the required signature at the end of my training. But that wasn’t my issue — I wanted the professional training. Feeling stuck, I decided to look for other positions.

Did you apply elsewhere to improve your situation?

Yes, but most of my applications went unanswered, which I didn’t understand. When I followed up, I actually received verbal replies from three hospitals, stating, “We don’t hire women with children.”

You’ve shared your experiences publicly on social media. How has the response been? Have other female doctors had similar experiences?

I think the problem of discrimination against women with children is still taboo. You’d think, with the shortage of doctors, that jobs would be available. But I’ve heard from former classmates who now have children that they face similar career obstacles, especially in fields such as internal medicine, where fulfilling rotations is challenging owing to scheduling bias.

This raises the question of adapting working conditions. In your case, it seems that a change in employer attitudes is also needed. What’s your perspective?

It varies depending on the region. I’ve applied across Germany and found that areas outside major cities such as Cologne, Düsseldorf, and Frankfurt tend to be better. In urban centers with a large applicant pool, the atmosphere is different. In smaller areas, finding a job is easier, especially if you’re fluent in German and experienced.

Do you believe that changing the mindset of employers regarding female staff with children could happen with a generational shift?

Honestly, I doubt it. It’s not just an issue at management level — it’s also present among residents. When someone takes leave, colleagues have to cover, which leads to resentment. Yet many female residents will eventually have children themselves. And it’s often overlooked that many men now share childcare responsibilities or take parental leave. Improving staffing levels would help alleviate these pressures.

Returning to structural issues, how is your situation now — can you continue your training?

I’ve since changed positions and am very happy. I didn’t expect such a positive reception with a child in tow.

Lastly, what changes do you think are needed? Is it enough to speak out about such experiences, or are further solutions necessary?

It’s good that topics such as burnout are openly discussed now. With children, there’s a risk for burnout, as you strive to meet all expectations to avoid career setbacks. But there also needs to be an acceptance that women who are hired may become pregnant and may have more than one child. I’m hopeful that over time, this will become normalized, especially as medicine becomes a more female-dominated field.

Is there anything else you’d like to share?

I wish there were more solidarity among women. It’s disheartening to see competition and infighting. More mutual support among women would make a huge difference.

Thank you, Hatice, and best of luck in your career.

Hatice, who prefers not to disclose her last name for privacy, is a fourth-year ENT specialist in training and shares her journey as a young doctor on Instagram under the name dein.hno.arzt.

This article was translated from Coliquio using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

New allergens responsible for contact dermatitis emerge regularly. During the Dermatology Days of Paris 2024 conference, Angèle Soria, MD, PhD, a dermatologist at Tenon Hospital in Paris, France, outlined four major categories driving this trend. Among them are (meth)acrylates found in nail cosmetics used in salons or do-it-yourself false nail kits that can be bought online.

Isothiazolinones

While the prevalence of allergic contact dermatitis remains stable at around 20% of the population, new allergens are introduced due to changes in cosmetic formulations and evolving consumer habits. Recent culprits include methylisothiazolinone (MI), a preservative used in many cosmetics; (meth)acrylates; essential oils; and epoxy resins used in industry and leisure activities.

Around 15 years ago, parabens, commonly used as preservatives in cosmetics, were identified as endocrine disruptors. In response, they were largely replaced by newer preservatives, notably MI. However, this led to a proliferation of allergic contact dermatitis in Europe between 2010 and 2013.

“About 10% of the population that we tested showed allergies to these preservatives, primarily found in cosmetics,” explained Soria. Since 2015, the use of MI in leave-on cosmetics has been prohibited in Europe and its concentration restricted in rinse-off products. However, cosmetics sold online from outside Europe may not comply with these regulations.

MI is also present in water-based paints to prevent mold. “A few years ago, we started seeing patients with facial angioedema, sometimes combined with asthma, caused by these isothiazolinone preservatives, including in patients who are not professional painters,” said Soria. More recently, attention has shifted to MI’s presence in household cleaning products. A 2020 Spanish study found MI in 76% of 34 analyzed cleaning products.

MI-based fungicides are also used to treat leather during transport, which can lead to contact allergies among professionals and consumers alike. Additionally, MI has been identified in children’s toys, including slime gels, and in florists’ gel cubes used to preserve flowers.

“We are therefore surrounded by these preservatives, which are no longer only in cosmetics,” warned the dermatologist.

 

(Meth)acrylates

Another major allergen category is (meth)acrylates, responsible for many cases of allergic contact dermatitis. Acrylates and their derivatives are widely used in everyday items. They are low–molecular weight monomers, sensitizing on contact with the skin. Their polymerized forms include materials like Plexiglas.

“We are currently witnessing an epidemic of contact dermatitis in the general population, mainly due to nail cosmetics, such as semipermanent nail polishes and at-home false nail kits,” reported Soria. Nail cosmetics account for 97% of new sensitization cases involving (meth)acrylates. These allergens often cause severe dermatitis, prompting the European Union to mandate labeling in 2020, warning that these products are “for professional use only” and can “cause allergic reactions.”

Beyond nail cosmetics, these allergens are also found in dental products (such as trays), ECG electrodes, prosthetics, glucose sensors, surgical adhesives, and some electronic devices like earbuds and phone screens. Notably, patients sensitized to acrylates via nail kits may experience reactions during dental treatments involving acrylates.

 

Investigating Essential Oil Use

Essential oils, distinct from vegetable oils like almond or argan, are another known allergen. Often considered risk-free due to their “natural” label, these products are widely used topically, orally, or via inhalation for various purposes, such as treating respiratory infections or creating relaxing atmospheres. However, essential oils contain fragrant molecules like terpenes, which can become highly allergenic over time, especially after repeated exposure.

Soria emphasized the importance of asking patients about their use of essential oils, especially tea tree and lavender oils, which are commonly used but rarely mentioned by patients unless prompted.

 

Epoxy Resins in Recreational Use

Epoxy resins are a growing cause of contact allergies, not just in professional settings such as aeronautics and construction work but also increasingly in recreational activities. Soria highlighted the case of a 12-year-old girl hospitalized for severe facial edema after engaging in resin crafts inspired by TikTok. For 6 months, she had been creating resin objects, such as bowls and cutting boards, using vinyl gloves and a Filtering FacePiece 2 mask under adult supervision.

“The growing popularity and online availability of epoxy resins mean that allergic reactions should now be considered even in nonprofessional contexts,” warned Soria.

 

Clinical Approach

When dermatologists suspect allergic contact dermatitis, the first step is to treat the condition with corticosteroid creams. This is followed by a detailed patient interview to identify suspected allergens in products they’ve used.

Patch testing is then conducted to confirm the allergen. Small chambers containing potential allergens are applied to the upper back for 48 hours without removal. Results are read 2-5 days later, with some cases requiring a 7-day follow-up.

The patient’s occupation is an important factor, as certain professions, such as hairdressing, healthcare, or beauty therapy, are known to trigger allergic contact dermatitis. Similarly, certain hobbies may also play a role. 

A thorough approach ensures accurate diagnosis and targeted prevention strategies.

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

New allergens responsible for contact dermatitis emerge regularly. During the Dermatology Days of Paris 2024 conference, Angèle Soria, MD, PhD, a dermatologist at Tenon Hospital in Paris, France, outlined four major categories driving this trend. Among them are (meth)acrylates found in nail cosmetics used in salons or do-it-yourself false nail kits that can be bought online.

Isothiazolinones

While the prevalence of allergic contact dermatitis remains stable at around 20% of the population, new allergens are introduced due to changes in cosmetic formulations and evolving consumer habits. Recent culprits include methylisothiazolinone (MI), a preservative used in many cosmetics; (meth)acrylates; essential oils; and epoxy resins used in industry and leisure activities.

Around 15 years ago, parabens, commonly used as preservatives in cosmetics, were identified as endocrine disruptors. In response, they were largely replaced by newer preservatives, notably MI. However, this led to a proliferation of allergic contact dermatitis in Europe between 2010 and 2013.

“About 10% of the population that we tested showed allergies to these preservatives, primarily found in cosmetics,” explained Soria. Since 2015, the use of MI in leave-on cosmetics has been prohibited in Europe and its concentration restricted in rinse-off products. However, cosmetics sold online from outside Europe may not comply with these regulations.

MI is also present in water-based paints to prevent mold. “A few years ago, we started seeing patients with facial angioedema, sometimes combined with asthma, caused by these isothiazolinone preservatives, including in patients who are not professional painters,” said Soria. More recently, attention has shifted to MI’s presence in household cleaning products. A 2020 Spanish study found MI in 76% of 34 analyzed cleaning products.

MI-based fungicides are also used to treat leather during transport, which can lead to contact allergies among professionals and consumers alike. Additionally, MI has been identified in children’s toys, including slime gels, and in florists’ gel cubes used to preserve flowers.

“We are therefore surrounded by these preservatives, which are no longer only in cosmetics,” warned the dermatologist.

 

(Meth)acrylates

Another major allergen category is (meth)acrylates, responsible for many cases of allergic contact dermatitis. Acrylates and their derivatives are widely used in everyday items. They are low–molecular weight monomers, sensitizing on contact with the skin. Their polymerized forms include materials like Plexiglas.

“We are currently witnessing an epidemic of contact dermatitis in the general population, mainly due to nail cosmetics, such as semipermanent nail polishes and at-home false nail kits,” reported Soria. Nail cosmetics account for 97% of new sensitization cases involving (meth)acrylates. These allergens often cause severe dermatitis, prompting the European Union to mandate labeling in 2020, warning that these products are “for professional use only” and can “cause allergic reactions.”

Beyond nail cosmetics, these allergens are also found in dental products (such as trays), ECG electrodes, prosthetics, glucose sensors, surgical adhesives, and some electronic devices like earbuds and phone screens. Notably, patients sensitized to acrylates via nail kits may experience reactions during dental treatments involving acrylates.

 

Investigating Essential Oil Use

Essential oils, distinct from vegetable oils like almond or argan, are another known allergen. Often considered risk-free due to their “natural” label, these products are widely used topically, orally, or via inhalation for various purposes, such as treating respiratory infections or creating relaxing atmospheres. However, essential oils contain fragrant molecules like terpenes, which can become highly allergenic over time, especially after repeated exposure.

Soria emphasized the importance of asking patients about their use of essential oils, especially tea tree and lavender oils, which are commonly used but rarely mentioned by patients unless prompted.

 

Epoxy Resins in Recreational Use

Epoxy resins are a growing cause of contact allergies, not just in professional settings such as aeronautics and construction work but also increasingly in recreational activities. Soria highlighted the case of a 12-year-old girl hospitalized for severe facial edema after engaging in resin crafts inspired by TikTok. For 6 months, she had been creating resin objects, such as bowls and cutting boards, using vinyl gloves and a Filtering FacePiece 2 mask under adult supervision.

“The growing popularity and online availability of epoxy resins mean that allergic reactions should now be considered even in nonprofessional contexts,” warned Soria.

 

Clinical Approach

When dermatologists suspect allergic contact dermatitis, the first step is to treat the condition with corticosteroid creams. This is followed by a detailed patient interview to identify suspected allergens in products they’ve used.

Patch testing is then conducted to confirm the allergen. Small chambers containing potential allergens are applied to the upper back for 48 hours without removal. Results are read 2-5 days later, with some cases requiring a 7-day follow-up.

The patient’s occupation is an important factor, as certain professions, such as hairdressing, healthcare, or beauty therapy, are known to trigger allergic contact dermatitis. Similarly, certain hobbies may also play a role. 

A thorough approach ensures accurate diagnosis and targeted prevention strategies.

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

New allergens responsible for contact dermatitis emerge regularly. During the Dermatology Days of Paris 2024 conference, Angèle Soria, MD, PhD, a dermatologist at Tenon Hospital in Paris, France, outlined four major categories driving this trend. Among them are (meth)acrylates found in nail cosmetics used in salons or do-it-yourself false nail kits that can be bought online.

Isothiazolinones

While the prevalence of allergic contact dermatitis remains stable at around 20% of the population, new allergens are introduced due to changes in cosmetic formulations and evolving consumer habits. Recent culprits include methylisothiazolinone (MI), a preservative used in many cosmetics; (meth)acrylates; essential oils; and epoxy resins used in industry and leisure activities.

Around 15 years ago, parabens, commonly used as preservatives in cosmetics, were identified as endocrine disruptors. In response, they were largely replaced by newer preservatives, notably MI. However, this led to a proliferation of allergic contact dermatitis in Europe between 2010 and 2013.

“About 10% of the population that we tested showed allergies to these preservatives, primarily found in cosmetics,” explained Soria. Since 2015, the use of MI in leave-on cosmetics has been prohibited in Europe and its concentration restricted in rinse-off products. However, cosmetics sold online from outside Europe may not comply with these regulations.

MI is also present in water-based paints to prevent mold. “A few years ago, we started seeing patients with facial angioedema, sometimes combined with asthma, caused by these isothiazolinone preservatives, including in patients who are not professional painters,” said Soria. More recently, attention has shifted to MI’s presence in household cleaning products. A 2020 Spanish study found MI in 76% of 34 analyzed cleaning products.

MI-based fungicides are also used to treat leather during transport, which can lead to contact allergies among professionals and consumers alike. Additionally, MI has been identified in children’s toys, including slime gels, and in florists’ gel cubes used to preserve flowers.

“We are therefore surrounded by these preservatives, which are no longer only in cosmetics,” warned the dermatologist.

 

(Meth)acrylates

Another major allergen category is (meth)acrylates, responsible for many cases of allergic contact dermatitis. Acrylates and their derivatives are widely used in everyday items. They are low–molecular weight monomers, sensitizing on contact with the skin. Their polymerized forms include materials like Plexiglas.

“We are currently witnessing an epidemic of contact dermatitis in the general population, mainly due to nail cosmetics, such as semipermanent nail polishes and at-home false nail kits,” reported Soria. Nail cosmetics account for 97% of new sensitization cases involving (meth)acrylates. These allergens often cause severe dermatitis, prompting the European Union to mandate labeling in 2020, warning that these products are “for professional use only” and can “cause allergic reactions.”

Beyond nail cosmetics, these allergens are also found in dental products (such as trays), ECG electrodes, prosthetics, glucose sensors, surgical adhesives, and some electronic devices like earbuds and phone screens. Notably, patients sensitized to acrylates via nail kits may experience reactions during dental treatments involving acrylates.

 

Investigating Essential Oil Use

Essential oils, distinct from vegetable oils like almond or argan, are another known allergen. Often considered risk-free due to their “natural” label, these products are widely used topically, orally, or via inhalation for various purposes, such as treating respiratory infections or creating relaxing atmospheres. However, essential oils contain fragrant molecules like terpenes, which can become highly allergenic over time, especially after repeated exposure.

Soria emphasized the importance of asking patients about their use of essential oils, especially tea tree and lavender oils, which are commonly used but rarely mentioned by patients unless prompted.

 

Epoxy Resins in Recreational Use

Epoxy resins are a growing cause of contact allergies, not just in professional settings such as aeronautics and construction work but also increasingly in recreational activities. Soria highlighted the case of a 12-year-old girl hospitalized for severe facial edema after engaging in resin crafts inspired by TikTok. For 6 months, she had been creating resin objects, such as bowls and cutting boards, using vinyl gloves and a Filtering FacePiece 2 mask under adult supervision.

“The growing popularity and online availability of epoxy resins mean that allergic reactions should now be considered even in nonprofessional contexts,” warned Soria.

 

Clinical Approach

When dermatologists suspect allergic contact dermatitis, the first step is to treat the condition with corticosteroid creams. This is followed by a detailed patient interview to identify suspected allergens in products they’ve used.

Patch testing is then conducted to confirm the allergen. Small chambers containing potential allergens are applied to the upper back for 48 hours without removal. Results are read 2-5 days later, with some cases requiring a 7-day follow-up.

The patient’s occupation is an important factor, as certain professions, such as hairdressing, healthcare, or beauty therapy, are known to trigger allergic contact dermatitis. Similarly, certain hobbies may also play a role. 

A thorough approach ensures accurate diagnosis and targeted prevention strategies.

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

TOPLINE:

Survivors of blood or marrow transplant (BMT) face a significant risk of developing cutaneous malignant neoplasms, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, with a cumulative incidence of 27.4% over 30 years, according to the results of a cohort study.

METHODOLOGY:

• The retrospective cohort study included 3880 BMT survivors (median age, 44 years; 55.8% men; 4.9% Black, 12.1 Hispanic, and 74.7% non-Hispanic White individuals) who underwent transplant between 1974 to 2014.
• Participants completed the BMT Survivor Study survey and were followed up for a median of 9.5 years.
• The primary outcomes were the development of subsequent cutaneous malignant neoplasms (BCC, SCC, or melanoma).

TAKEAWAY:

• The 30-year cumulative incidence of any cutaneous malignant neoplasm was 27.4% — 18% for BCC, 9.8% for SCC, and 3.7% for melanoma.
• A higher risk for skin cancer was reported for patients aged 50 years or more (subdistribution hazard ratio [SHR], 2.23; 95% CI, 1.83-2.71), and men (SHR, 1.40; 95% CI, 1.18-1.65).
• Allogeneic BMT with chronic graft-vs-host disease (cGVHD) increased the risk for skin cancer (SHR, 1.84; 95% CI, 1.37-2.47), compared with autologous BMT, while post-BMT immunosuppression increased risk for all types (overall SHR, 1.53; 95% CI, 1.26-1.86).
• The risk for any skin cancer was significantly lower in Black individuals (SHR, 0.14; 95% CI, 0.05-0.37), Hispanic individuals (SHR, 0.29; 95%CI, 0.20-0.62), and patients of other races or who were multiracial (SHR, 0.22; 95% CI, 0.13-0.37) than in non-Hispanic White patients.

IN PRACTICE:

In the study, “risk factors for post-BMT cutaneous malignant neoplasms included pretransplant treatment with a monoclonal antibody, cGVHD, and posttransplant immunosuppression,” the authors wrote, adding that the findings “could inform targeted surveillance of BMT survivors.” Most BMT survivors, “do not undergo routine dermatologic surveillance, highlighting the need to understand risk factors and incorporate risk-informed dermatologic surveillance into survivorship care plans.”

SOURCE:

The study was led by Kristy K. Broman, MD, MPH, University of Alabama at Birmingham, and was published online on December 18 in JAMA Dermatology.

LIMITATIONS:

Limitations included self-reported data and possible underreporting of melanoma cases in the SEER database. Additionally, the study did not capture other risk factors for cutaneous malignant neoplasms such as skin phototype, ultraviolet light exposure, or family history. The duration of posttransplant immunosuppression was not collected, and surveys were administered at variable intervals, though all were completed more than 2 years post BMT.

DISCLOSURES:

The study was supported by the National Cancer Institute (NCI) and the Leukemia and Lymphoma Society. Broman received grants from NCI, the National Center for Advancing Translational Sciences, the American Society of Clinical Oncology, and the American College of Surgeons. Another author reported receiving grants outside this work.

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

TOPLINE:

Survivors of blood or marrow transplant (BMT) face a significant risk of developing cutaneous malignant neoplasms, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, with a cumulative incidence of 27.4% over 30 years, according to the results of a cohort study.

METHODOLOGY:

• The retrospective cohort study included 3880 BMT survivors (median age, 44 years; 55.8% men; 4.9% Black, 12.1 Hispanic, and 74.7% non-Hispanic White individuals) who underwent transplant between 1974 to 2014.
• Participants completed the BMT Survivor Study survey and were followed up for a median of 9.5 years.
• The primary outcomes were the development of subsequent cutaneous malignant neoplasms (BCC, SCC, or melanoma).

TAKEAWAY:

• The 30-year cumulative incidence of any cutaneous malignant neoplasm was 27.4% — 18% for BCC, 9.8% for SCC, and 3.7% for melanoma.
• A higher risk for skin cancer was reported for patients aged 50 years or more (subdistribution hazard ratio [SHR], 2.23; 95% CI, 1.83-2.71), and men (SHR, 1.40; 95% CI, 1.18-1.65).
• Allogeneic BMT with chronic graft-vs-host disease (cGVHD) increased the risk for skin cancer (SHR, 1.84; 95% CI, 1.37-2.47), compared with autologous BMT, while post-BMT immunosuppression increased risk for all types (overall SHR, 1.53; 95% CI, 1.26-1.86).
• The risk for any skin cancer was significantly lower in Black individuals (SHR, 0.14; 95% CI, 0.05-0.37), Hispanic individuals (SHR, 0.29; 95%CI, 0.20-0.62), and patients of other races or who were multiracial (SHR, 0.22; 95% CI, 0.13-0.37) than in non-Hispanic White patients.

IN PRACTICE:

In the study, “risk factors for post-BMT cutaneous malignant neoplasms included pretransplant treatment with a monoclonal antibody, cGVHD, and posttransplant immunosuppression,” the authors wrote, adding that the findings “could inform targeted surveillance of BMT survivors.” Most BMT survivors, “do not undergo routine dermatologic surveillance, highlighting the need to understand risk factors and incorporate risk-informed dermatologic surveillance into survivorship care plans.”

SOURCE:

The study was led by Kristy K. Broman, MD, MPH, University of Alabama at Birmingham, and was published online on December 18 in JAMA Dermatology.

LIMITATIONS:

Limitations included self-reported data and possible underreporting of melanoma cases in the SEER database. Additionally, the study did not capture other risk factors for cutaneous malignant neoplasms such as skin phototype, ultraviolet light exposure, or family history. The duration of posttransplant immunosuppression was not collected, and surveys were administered at variable intervals, though all were completed more than 2 years post BMT.

DISCLOSURES:

The study was supported by the National Cancer Institute (NCI) and the Leukemia and Lymphoma Society. Broman received grants from NCI, the National Center for Advancing Translational Sciences, the American Society of Clinical Oncology, and the American College of Surgeons. Another author reported receiving grants outside this work.

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

TOPLINE:

Survivors of blood or marrow transplant (BMT) face a significant risk of developing cutaneous malignant neoplasms, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, with a cumulative incidence of 27.4% over 30 years, according to the results of a cohort study.

METHODOLOGY:

• The retrospective cohort study included 3880 BMT survivors (median age, 44 years; 55.8% men; 4.9% Black, 12.1 Hispanic, and 74.7% non-Hispanic White individuals) who underwent transplant between 1974 to 2014.
• Participants completed the BMT Survivor Study survey and were followed up for a median of 9.5 years.
• The primary outcomes were the development of subsequent cutaneous malignant neoplasms (BCC, SCC, or melanoma).

TAKEAWAY:

• The 30-year cumulative incidence of any cutaneous malignant neoplasm was 27.4% — 18% for BCC, 9.8% for SCC, and 3.7% for melanoma.
• A higher risk for skin cancer was reported for patients aged 50 years or more (subdistribution hazard ratio [SHR], 2.23; 95% CI, 1.83-2.71), and men (SHR, 1.40; 95% CI, 1.18-1.65).
• Allogeneic BMT with chronic graft-vs-host disease (cGVHD) increased the risk for skin cancer (SHR, 1.84; 95% CI, 1.37-2.47), compared with autologous BMT, while post-BMT immunosuppression increased risk for all types (overall SHR, 1.53; 95% CI, 1.26-1.86).
• The risk for any skin cancer was significantly lower in Black individuals (SHR, 0.14; 95% CI, 0.05-0.37), Hispanic individuals (SHR, 0.29; 95%CI, 0.20-0.62), and patients of other races or who were multiracial (SHR, 0.22; 95% CI, 0.13-0.37) than in non-Hispanic White patients.

IN PRACTICE:

In the study, “risk factors for post-BMT cutaneous malignant neoplasms included pretransplant treatment with a monoclonal antibody, cGVHD, and posttransplant immunosuppression,” the authors wrote, adding that the findings “could inform targeted surveillance of BMT survivors.” Most BMT survivors, “do not undergo routine dermatologic surveillance, highlighting the need to understand risk factors and incorporate risk-informed dermatologic surveillance into survivorship care plans.”

SOURCE:

The study was led by Kristy K. Broman, MD, MPH, University of Alabama at Birmingham, and was published online on December 18 in JAMA Dermatology.

LIMITATIONS:

Limitations included self-reported data and possible underreporting of melanoma cases in the SEER database. Additionally, the study did not capture other risk factors for cutaneous malignant neoplasms such as skin phototype, ultraviolet light exposure, or family history. The duration of posttransplant immunosuppression was not collected, and surveys were administered at variable intervals, though all were completed more than 2 years post BMT.

DISCLOSURES:

The study was supported by the National Cancer Institute (NCI) and the Leukemia and Lymphoma Society. Broman received grants from NCI, the National Center for Advancing Translational Sciences, the American Society of Clinical Oncology, and the American College of Surgeons. Another author reported receiving grants outside this work.

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

The question has been lingering for years in medical science circles. Since 2020, when the artificial intelligence (AI) model AlphaFold made it possible to predict protein structures, would the technology open the drug discovery floodgates?

Short answer: No. At least not yet.

The longer answer goes something like this:

A drug target (such as a mutation) is like a lock. The right drug (a protein designed to bind to the mutation, stopping its activity) is the key. But proteins are fidgety and flexible.

“They’re basically molecular springs,” said Gabriel Monteiro da Silva, PhD, a computational chemistry research scientist at Genesis Therapeutics. “Your key can bend and alter the shape of the lock, and if you don’t account for that, your key might fail.”

This is the protein problem in drug development. Another issue making this challenge so vexing is that proteins don’t act in isolation. Their interactions with other proteins, ribonucleic acid, and DNA can affect how they bind to molecules and the shapes they adopt.

Newer versions of AlphaFold, such as AlphaFold Multimer and AlphaFold 3 (the code for which was recently revealed for academic use), can predict many interactions among proteins and between proteins and other molecules. But these tools still have weak points scientists are trying to overcome or work around.

“Those kinds of dynamics and multiple conformations are still quite challenging for the AI models to predict,” said James Zou, PhD, associate professor of biomedical data science at Stanford University in California.

“We’re finding more and more that the only way we can make these structures useful for drug discovery is if we incorporate dynamics, if we incorporate more physics into the model,” said Monteiro da Silva.

Monteiro da Silva spent 3 years during his PhD at Brown University, Providence, Rhode Island, running physics-based simulations in the lab, trying to understand why proteins carrying certain mutations are drug resistant. His results showed how “the changing landscape of shapes that a protein can take” prevented the drug from binding.

It took him 3 years to model just four mutations.

AI can do better — and the struggle is fascinating. By developing models that build on the predictive power of AlphaFold, scientists are uncovering new details about protein activity — insights that can lead to new therapeutics and reveal why existing ones stop working — much faster than they could with traditional methods or AlphaFold alone.

 

New Windows into Protein Dynamics

By predicting protein structural details, AlphaFold models also made it possible to predict pockets where drugs could bind.

A notable step, “but that’s just the starting point,” said Pedro Beltrao, PhD, an associate professor at Institute of Molecular Systems Biology, ETH Zurich in Switzerland. “It’s still very difficult, given a pocket, to actually design the drug or figure out what the pocket binds.”

Going back to the lock-and-key analogy: While he was at Brown, with a team of researchers in the Rubenstein Group, Monteiro da Silva helped create a model to better understand how mutations affect “the shape and dynamics of the lock.” They manipulated the amino acid sequences of proteins, guiding their evolution. This enabled them to use AlphaFold to predict “protein ensembles” and how frequently those ensembles appear. Each ensemble represents the many different shapes a protein can take under given conditions.

“Essentially, it tries to find the most common shapes that a protein will take over an arbitrary amount of time,” Monteiro da Silva said. “If we can predict these ensembles at scale and fast, then we can screen many mutations that cause resistance and develop drugs that will not be affected by that resistance.”

To evaluate their method, the researchers focused on ABL1, a well-studied kinase that causes leukemia. ABL1 can be drugged – unless it carries or develops a mutation that causes drug resistance. Currently there are no drugs that work against proteins carrying those mutations, according to Monteiro da Silva. The researchers used their hybrid AI-meets-physics method to investigate how drugs bind to different ABL1 mutations, screening 100 mutations in just 1 month.

“It’s not going to be perfect for every one of them. But if we have 100 and we get 20 with good accuracy, that’s better than doing four over 3 years,” Monteiro da Silva said.

A forthcoming paper will make their model publicly available in “an easy-to-use graphical interface” that they hope clinicians and medicinal chemists will try out. It can also complement other AI-based tools that dig into protein dynamics, according to Monteiro da Silva.

 

Complementary Tools to Speed Up Discovery 

Another aspect of the protein problem is scale. One protein can interact with hundreds of other proteins, which in turn may interact with hundreds more, all of which comprise the human interactome.

Feixiong Cheng, PhD, helped build PIONEER, a deep learning model that predicts the three-dimensional (3D) structure of interactions between proteins across the interactome.

Most disease mutations disrupt specific interactions between proteins, making their affinity stronger or weaker, explained Cheng. To treat a disease without causing major side effects, scientists need a precise understanding of those interactions.

“From the drug discovery perspective, we cannot just focus on single proteins. We have to understand the protein environment, in particular how the protein interacts with other proteins,” said Cheng, director of Cleveland Clinic Genome Center, Cleveland.

PIONEER helps by blending AlphaFold’s protein structure predictions with next-generation sequencing, a type of genomic research that identifies mutations in the human genome. The model predicts the 3D structure of the places where proteins interact — the binding sites, or interfaces — across the interactome.

“We tell you not only that a binds b, but where on a and where on b the two proteins interact,” said Haiyuan Yu, PhD, director of the Center for Innovative Proteomics, Cornell University, and co-creator of PIONEER.

This can help scientists understand “why a mutation, protein, or even network is a good target for therapeutic discovery,” Cheng said.

The researchers validated PIONEER’s predictions in the lab, testing the impacts of roughly 3000 mutations on 7000 pairs of interacting proteins. Based on their findings, they plan to develop and test treatments for lung and endometrial cancer.

PIONEER can also help scientists home in on how a mutation causes a disease, such as by showing recurrent mutations.

“If you find cancer mutations hitting an interface again and again and again, it means that this is likely to be driving cancer progression,” said Beltrao.

Beltrao’s lab and others have looked for recurrent mutations by using AlphaFold Multimer and AlphaFold 3 to directly model protein interactions. It’s a much slower approach (Pioneer is more than 5000 faster than AlphaFold Multimer, according to Cheng). But it could allow scientists to model interfaces that are not shown by PIONEER.

“You will need many different things to try to come up with a structural modeling of the interactome, and all these will have limitations,” said Beltrao. “Their method is a very good step forward, and there’ll be other approaches that are complementary, to continue to add details.”

 

And It Wouldn’t be an AI Mission Without ChatGPT

Large language models, such as ChatGPT, are another way that scientists are adding details to protein structure predictions. Zou used GPT-4 to “fine tune” a protein language model, called evolutionary scale modeling (ESM-2), which predicts protein structures directly from a protein sequence.

First, they trained ChatGPT on thousands of papers and studies containing information about the functions, biophysical properties, and disease relevance of different mutations. Next, they used the trained model to “teach” ESM-2, boosting its ability “to predict which mutations are likely to have larger effects or smaller effects,” Zou said. The same could be done for a model like AlphaFold, according to Zou.

“They are quite complementary in that the large language model contains a lot more information about the functions and the biophysics of different mutations and proteins as captured in text,” he said, whereas “you can’t give AlphaFold a piece of paper.”

Exactly how AlphaFold makes its predictions is another mystery. “It will somehow learn protein dynamics phenomenologically,” said Monteiro da Silva. He and others are trying to understand how that happens, in hopes of creating even more accurate predictive models. But for the time being, AI-based methods still need assistance from physics.

“The dream is that we achieve a state where we rely on just the fast methods, and they’re accurate enough,” he said. “But we’re so far from that.”

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

The question has been lingering for years in medical science circles. Since 2020, when the artificial intelligence (AI) model AlphaFold made it possible to predict protein structures, would the technology open the drug discovery floodgates?

Short answer: No. At least not yet.

The longer answer goes something like this:

A drug target (such as a mutation) is like a lock. The right drug (a protein designed to bind to the mutation, stopping its activity) is the key. But proteins are fidgety and flexible.

“They’re basically molecular springs,” said Gabriel Monteiro da Silva, PhD, a computational chemistry research scientist at Genesis Therapeutics. “Your key can bend and alter the shape of the lock, and if you don’t account for that, your key might fail.”

This is the protein problem in drug development. Another issue making this challenge so vexing is that proteins don’t act in isolation. Their interactions with other proteins, ribonucleic acid, and DNA can affect how they bind to molecules and the shapes they adopt.

Newer versions of AlphaFold, such as AlphaFold Multimer and AlphaFold 3 (the code for which was recently revealed for academic use), can predict many interactions among proteins and between proteins and other molecules. But these tools still have weak points scientists are trying to overcome or work around.

“Those kinds of dynamics and multiple conformations are still quite challenging for the AI models to predict,” said James Zou, PhD, associate professor of biomedical data science at Stanford University in California.

“We’re finding more and more that the only way we can make these structures useful for drug discovery is if we incorporate dynamics, if we incorporate more physics into the model,” said Monteiro da Silva.

Monteiro da Silva spent 3 years during his PhD at Brown University, Providence, Rhode Island, running physics-based simulations in the lab, trying to understand why proteins carrying certain mutations are drug resistant. His results showed how “the changing landscape of shapes that a protein can take” prevented the drug from binding.

It took him 3 years to model just four mutations.

AI can do better — and the struggle is fascinating. By developing models that build on the predictive power of AlphaFold, scientists are uncovering new details about protein activity — insights that can lead to new therapeutics and reveal why existing ones stop working — much faster than they could with traditional methods or AlphaFold alone.

 

New Windows into Protein Dynamics

By predicting protein structural details, AlphaFold models also made it possible to predict pockets where drugs could bind.

A notable step, “but that’s just the starting point,” said Pedro Beltrao, PhD, an associate professor at Institute of Molecular Systems Biology, ETH Zurich in Switzerland. “It’s still very difficult, given a pocket, to actually design the drug or figure out what the pocket binds.”

Going back to the lock-and-key analogy: While he was at Brown, with a team of researchers in the Rubenstein Group, Monteiro da Silva helped create a model to better understand how mutations affect “the shape and dynamics of the lock.” They manipulated the amino acid sequences of proteins, guiding their evolution. This enabled them to use AlphaFold to predict “protein ensembles” and how frequently those ensembles appear. Each ensemble represents the many different shapes a protein can take under given conditions.

“Essentially, it tries to find the most common shapes that a protein will take over an arbitrary amount of time,” Monteiro da Silva said. “If we can predict these ensembles at scale and fast, then we can screen many mutations that cause resistance and develop drugs that will not be affected by that resistance.”

To evaluate their method, the researchers focused on ABL1, a well-studied kinase that causes leukemia. ABL1 can be drugged – unless it carries or develops a mutation that causes drug resistance. Currently there are no drugs that work against proteins carrying those mutations, according to Monteiro da Silva. The researchers used their hybrid AI-meets-physics method to investigate how drugs bind to different ABL1 mutations, screening 100 mutations in just 1 month.

“It’s not going to be perfect for every one of them. But if we have 100 and we get 20 with good accuracy, that’s better than doing four over 3 years,” Monteiro da Silva said.

A forthcoming paper will make their model publicly available in “an easy-to-use graphical interface” that they hope clinicians and medicinal chemists will try out. It can also complement other AI-based tools that dig into protein dynamics, according to Monteiro da Silva.

 

Complementary Tools to Speed Up Discovery 

Another aspect of the protein problem is scale. One protein can interact with hundreds of other proteins, which in turn may interact with hundreds more, all of which comprise the human interactome.

Feixiong Cheng, PhD, helped build PIONEER, a deep learning model that predicts the three-dimensional (3D) structure of interactions between proteins across the interactome.

Most disease mutations disrupt specific interactions between proteins, making their affinity stronger or weaker, explained Cheng. To treat a disease without causing major side effects, scientists need a precise understanding of those interactions.

“From the drug discovery perspective, we cannot just focus on single proteins. We have to understand the protein environment, in particular how the protein interacts with other proteins,” said Cheng, director of Cleveland Clinic Genome Center, Cleveland.

PIONEER helps by blending AlphaFold’s protein structure predictions with next-generation sequencing, a type of genomic research that identifies mutations in the human genome. The model predicts the 3D structure of the places where proteins interact — the binding sites, or interfaces — across the interactome.

“We tell you not only that a binds b, but where on a and where on b the two proteins interact,” said Haiyuan Yu, PhD, director of the Center for Innovative Proteomics, Cornell University, and co-creator of PIONEER.

This can help scientists understand “why a mutation, protein, or even network is a good target for therapeutic discovery,” Cheng said.

The researchers validated PIONEER’s predictions in the lab, testing the impacts of roughly 3000 mutations on 7000 pairs of interacting proteins. Based on their findings, they plan to develop and test treatments for lung and endometrial cancer.

PIONEER can also help scientists home in on how a mutation causes a disease, such as by showing recurrent mutations.

“If you find cancer mutations hitting an interface again and again and again, it means that this is likely to be driving cancer progression,” said Beltrao.

Beltrao’s lab and others have looked for recurrent mutations by using AlphaFold Multimer and AlphaFold 3 to directly model protein interactions. It’s a much slower approach (Pioneer is more than 5000 faster than AlphaFold Multimer, according to Cheng). But it could allow scientists to model interfaces that are not shown by PIONEER.

“You will need many different things to try to come up with a structural modeling of the interactome, and all these will have limitations,” said Beltrao. “Their method is a very good step forward, and there’ll be other approaches that are complementary, to continue to add details.”