Federal Practitioner

HONOLULU – In the clinical experience of Julie C. Harper, MD, an increasing number of women with acne are turning to off-label, long-term treatment with spironolactone.

“Spironolactone is fairly accessible, inexpensive, and effective for our patients,” Dr. Harper, a dermatologist who practices in Birmingham, Ala., said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!

An aldosterone receptor antagonist commonly used to treat high blood pressure and heart failure, spironolactone also has antiandrogenic properties with a proven track record for treating acne and hirsutism. It reduces androgen production, inhibits 5-alpha reductase, and increases sex hormone binding globulin. The dosing range for treating acne is 25 mg to 200 mg per day, but Dr. Harper prefers a maximum dose of 100 mg per day.

According to a systematic review of its use for acne in adult women, the most common side effect is menstrual irregularity, while other common side effects include breast tenderness/swelling, fatigue, and headaches.

“The higher the dose, the higher the rate of side effects,” she said. Concomitant use of an oral contraceptive lessens menstrual irregularities and prevents pregnancies, to avoid exposure during pregnancy and the hypothetical risk of feminization of the male fetus with exposure late in the first trimester. “Early in my career, I used to say if you’re going to be on spironolactone you’re also going to be on an oral contraceptive. But the longer I’ve practiced, I’ve learned that women who have a contraindication to birth control pills or who don’t want to take it can still benefit from an oral antiandrogen by being on spironolactone.”

A large retrospective analysis of 14-year data concluded that routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne. “If you’re between the ages of 18 and 45, healthy, and not taking other medications where I’m worried about potassium levels, I’m not checking those levels at all,” Dr. Harper said.

Spironolactone labeling includes a boxed warning regarding the potential for tumorigenicity based on rat studies, but the dosages used in those studies were 25-250 times higher than the exposure dose in humans, Dr. Harper said.

Results from a systematic review and meta-analysis of seven studies in the medical literature found no evidence of an increased risk of breast cancer in women with exposure to spironolactone. “However, the certainty of the evidence was low and future studies are needed, including among diverse populations such as younger individuals and those with acne or hirsutism,” the study authors wrote.

In a separate study, researchers drew from patients in the Humana Insurance database from 2005 to 2017 to address whether spironolactone is associated with an increased risk of recurrence of breast cancer. Recurrent breast cancer was examined in 29,146 women with continuous health insurance for 2 years after a diagnosis of breast cancer. Of these, 746 were prescribed spironolactone, and the remainder were not. The researchers found that 123 women (16.5%) who were prescribed spironolactone had a breast cancer recurrence, compared with 3,649 women (12.8%) with a breast cancer recurrence who had not been prescribed spironolactone (P = .004). Adjusted Cox regression analysis following propensity matching showed no association between spironolactone and increased breast cancer recurrence (adjusted hazard ratio, 0.966; P = .953).

According to Dr. Harper, spironolactone may take about 3 months to kick in. “Likely this is a long-term treatment, and most of the time we’re going to be using it in combination with other acne treatments such as topical retinoids or topical benzoyl peroxide, oral antibiotics, or even isotretinoin.”

A study of long-term spironolactone use in 403 women found that the most common dose prescribed was 100 mg/day, and 68% of the women were concurrently prescribed a topical retinoid, 2.2% an oral antibiotic, and 40.7% an oral contraceptive.

The study population included 32 patients with a history of polycystic ovarian syndrome, 1 with a history of breast cancer, and 5 were hypercoagulable. Patients took the drug for a mean of 471 days. “As opposed to our antibiotics, where the course for patients is generally 3-4 months, when you start someone on spironolactone, they may end up staying on it,” Dr. Harper said.

Dr. Harper disclosed that she serves as an advisor or consultant for Almirall, Cassiopeia, Cutera, EPI, Galderma, L’Oreal, Ortho Dermatologics, Sol Gel, and Vyne. She also serves as a speaker or member of a speaker’s bureau for Almirall, Cassiopeia, Cutera, EPI, Galderma, Journey Almirall, L’Oreal, Ortho Dermatologics, Sun Pharmaceutical Industries, and Vyne.

Medscape and this news organization are owned by the same parent company.

HONOLULU – In the clinical experience of Julie C. Harper, MD, an increasing number of women with acne are turning to off-label, long-term treatment with spironolactone.

“Spironolactone is fairly accessible, inexpensive, and effective for our patients,” Dr. Harper, a dermatologist who practices in Birmingham, Ala., said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!

An aldosterone receptor antagonist commonly used to treat high blood pressure and heart failure, spironolactone also has antiandrogenic properties with a proven track record for treating acne and hirsutism. It reduces androgen production, inhibits 5-alpha reductase, and increases sex hormone binding globulin. The dosing range for treating acne is 25 mg to 200 mg per day, but Dr. Harper prefers a maximum dose of 100 mg per day.

According to a systematic review of its use for acne in adult women, the most common side effect is menstrual irregularity, while other common side effects include breast tenderness/swelling, fatigue, and headaches.

“The higher the dose, the higher the rate of side effects,” she said. Concomitant use of an oral contraceptive lessens menstrual irregularities and prevents pregnancies, to avoid exposure during pregnancy and the hypothetical risk of feminization of the male fetus with exposure late in the first trimester. “Early in my career, I used to say if you’re going to be on spironolactone you’re also going to be on an oral contraceptive. But the longer I’ve practiced, I’ve learned that women who have a contraindication to birth control pills or who don’t want to take it can still benefit from an oral antiandrogen by being on spironolactone.”

A large retrospective analysis of 14-year data concluded that routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne. “If you’re between the ages of 18 and 45, healthy, and not taking other medications where I’m worried about potassium levels, I’m not checking those levels at all,” Dr. Harper said.

Spironolactone labeling includes a boxed warning regarding the potential for tumorigenicity based on rat studies, but the dosages used in those studies were 25-250 times higher than the exposure dose in humans, Dr. Harper said.

Results from a systematic review and meta-analysis of seven studies in the medical literature found no evidence of an increased risk of breast cancer in women with exposure to spironolactone. “However, the certainty of the evidence was low and future studies are needed, including among diverse populations such as younger individuals and those with acne or hirsutism,” the study authors wrote.

In a separate study, researchers drew from patients in the Humana Insurance database from 2005 to 2017 to address whether spironolactone is associated with an increased risk of recurrence of breast cancer. Recurrent breast cancer was examined in 29,146 women with continuous health insurance for 2 years after a diagnosis of breast cancer. Of these, 746 were prescribed spironolactone, and the remainder were not. The researchers found that 123 women (16.5%) who were prescribed spironolactone had a breast cancer recurrence, compared with 3,649 women (12.8%) with a breast cancer recurrence who had not been prescribed spironolactone (P = .004). Adjusted Cox regression analysis following propensity matching showed no association between spironolactone and increased breast cancer recurrence (adjusted hazard ratio, 0.966; P = .953).

According to Dr. Harper, spironolactone may take about 3 months to kick in. “Likely this is a long-term treatment, and most of the time we’re going to be using it in combination with other acne treatments such as topical retinoids or topical benzoyl peroxide, oral antibiotics, or even isotretinoin.”

A study of long-term spironolactone use in 403 women found that the most common dose prescribed was 100 mg/day, and 68% of the women were concurrently prescribed a topical retinoid, 2.2% an oral antibiotic, and 40.7% an oral contraceptive.

The study population included 32 patients with a history of polycystic ovarian syndrome, 1 with a history of breast cancer, and 5 were hypercoagulable. Patients took the drug for a mean of 471 days. “As opposed to our antibiotics, where the course for patients is generally 3-4 months, when you start someone on spironolactone, they may end up staying on it,” Dr. Harper said.

Dr. Harper disclosed that she serves as an advisor or consultant for Almirall, Cassiopeia, Cutera, EPI, Galderma, L’Oreal, Ortho Dermatologics, Sol Gel, and Vyne. She also serves as a speaker or member of a speaker’s bureau for Almirall, Cassiopeia, Cutera, EPI, Galderma, Journey Almirall, L’Oreal, Ortho Dermatologics, Sun Pharmaceutical Industries, and Vyne.

Medscape and this news organization are owned by the same parent company.

HONOLULU – In the clinical experience of Julie C. Harper, MD, an increasing number of women with acne are turning to off-label, long-term treatment with spironolactone.

“Spironolactone is fairly accessible, inexpensive, and effective for our patients,” Dr. Harper, a dermatologist who practices in Birmingham, Ala., said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!

An aldosterone receptor antagonist commonly used to treat high blood pressure and heart failure, spironolactone also has antiandrogenic properties with a proven track record for treating acne and hirsutism. It reduces androgen production, inhibits 5-alpha reductase, and increases sex hormone binding globulin. The dosing range for treating acne is 25 mg to 200 mg per day, but Dr. Harper prefers a maximum dose of 100 mg per day.

According to a systematic review of its use for acne in adult women, the most common side effect is menstrual irregularity, while other common side effects include breast tenderness/swelling, fatigue, and headaches.

“The higher the dose, the higher the rate of side effects,” she said. Concomitant use of an oral contraceptive lessens menstrual irregularities and prevents pregnancies, to avoid exposure during pregnancy and the hypothetical risk of feminization of the male fetus with exposure late in the first trimester. “Early in my career, I used to say if you’re going to be on spironolactone you’re also going to be on an oral contraceptive. But the longer I’ve practiced, I’ve learned that women who have a contraindication to birth control pills or who don’t want to take it can still benefit from an oral antiandrogen by being on spironolactone.”

A large retrospective analysis of 14-year data concluded that routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne. “If you’re between the ages of 18 and 45, healthy, and not taking other medications where I’m worried about potassium levels, I’m not checking those levels at all,” Dr. Harper said.

Spironolactone labeling includes a boxed warning regarding the potential for tumorigenicity based on rat studies, but the dosages used in those studies were 25-250 times higher than the exposure dose in humans, Dr. Harper said.

Results from a systematic review and meta-analysis of seven studies in the medical literature found no evidence of an increased risk of breast cancer in women with exposure to spironolactone. “However, the certainty of the evidence was low and future studies are needed, including among diverse populations such as younger individuals and those with acne or hirsutism,” the study authors wrote.

In a separate study, researchers drew from patients in the Humana Insurance database from 2005 to 2017 to address whether spironolactone is associated with an increased risk of recurrence of breast cancer. Recurrent breast cancer was examined in 29,146 women with continuous health insurance for 2 years after a diagnosis of breast cancer. Of these, 746 were prescribed spironolactone, and the remainder were not. The researchers found that 123 women (16.5%) who were prescribed spironolactone had a breast cancer recurrence, compared with 3,649 women (12.8%) with a breast cancer recurrence who had not been prescribed spironolactone (P = .004). Adjusted Cox regression analysis following propensity matching showed no association between spironolactone and increased breast cancer recurrence (adjusted hazard ratio, 0.966; P = .953).

According to Dr. Harper, spironolactone may take about 3 months to kick in. “Likely this is a long-term treatment, and most of the time we’re going to be using it in combination with other acne treatments such as topical retinoids or topical benzoyl peroxide, oral antibiotics, or even isotretinoin.”

A study of long-term spironolactone use in 403 women found that the most common dose prescribed was 100 mg/day, and 68% of the women were concurrently prescribed a topical retinoid, 2.2% an oral antibiotic, and 40.7% an oral contraceptive.

The study population included 32 patients with a history of polycystic ovarian syndrome, 1 with a history of breast cancer, and 5 were hypercoagulable. Patients took the drug for a mean of 471 days. “As opposed to our antibiotics, where the course for patients is generally 3-4 months, when you start someone on spironolactone, they may end up staying on it,” Dr. Harper said.

Dr. Harper disclosed that she serves as an advisor or consultant for Almirall, Cassiopeia, Cutera, EPI, Galderma, L’Oreal, Ortho Dermatologics, Sol Gel, and Vyne. She also serves as a speaker or member of a speaker’s bureau for Almirall, Cassiopeia, Cutera, EPI, Galderma, Journey Almirall, L’Oreal, Ortho Dermatologics, Sun Pharmaceutical Industries, and Vyne.

Medscape and this news organization are owned by the same parent company.

Hydroxyurea (HU) is a safe, effective drug for treating sickle cell disease (SCD), first approved for this condition by the U.S. Food and Drug Administration in 1998. Despite the fact that most insurance plans cover HU, a new study showed that it is prescribed to fewer than 25% of patients with SCD. More recently approved SCD treatments are prescribed to fewer than 5% of adult patients.

Ohio State University

“There are several factors that are contributing to the slow uptake in these medications. Firstly, some newer medications are expensive and can require complicated insurance approvals as well as trips to doctors’ offices or infusion sites that are difficult to access for rural populations. Secondly, there are major challenges in transitioning pediatric SCD patients to receiving adequate care as adults,” lead study author Robert M. Cronin, MD, of the department of internal medicine at the Ohio State University, Columbus, said in an interview.

The retrospective study, published in Blood Advances, looked at private insurance claims of patients with SCD in the United States from 2016 to 2020. A total of 7,957 participants were included in the analysis (all were ≥ 18 years, median age 37, 61.2% female). Primary outcomes analyzed were the utilization of hydroxyurea, l-glutamine, and crizanlizumab (all shown in clinical trials to decrease acute vaso-occlusive pain), and voxelotor (approved for patients with SCD with lower hemoglobin levels).

Among study participants who had two or more pain episodes in a year, 31.5% were prescribed hydroxyurea, 3.2% l-glutamine, 2.3% crizanlizumab, and 2.9% voxelotor. Any combination therapy of drugs to decrease vaso-occlusive pain was used in about 3% of the study participants, and combinations of newer therapies were used in only 0.3%.

In contrast to these statistics, Dr. Cronin said, “All adults with sickle cell anemia should be at least offered treatment with hydroxyurea, and up to 63% of individuals with SCD have at least one vaso-occlusive pain episode in a year, making them eligible for crizanlizumab, l-glutamine, or both.”

As patients with SCD grew older, their odds of being prescribed hydroxyurea, l-glutamine, and crizanlizumab all decreased. Dr. Cronin speculated about the reasons for this decline. “It’s a huge problem to find adult providers who are knowledgeable about SCD. When pediatric patients become adults, they often can’t find anybody who knows about their disease,” he said.

Study results supported the hypothesis that rural location was a barrier to care. Not residing in a “super rural” geographic location was associated with nearly three times the likelihood of crizanlizumab prescription (odds ratio, 2.93; 95% confidence interval, 1.16-7.42).

Duke Health

“There is geographic variability as expected, with limitations in rural areas,” said Nirmish R. Shah, MD, director of the sickle cell transition program at Duke Health in Durham, N.C. Dr. Shah was not associated with the study.

Dr. Shah commented that he found the study’s findings unsurprising. He also noted that its results were based solely on data from private insurance databases and that some of the drugs included in the study were approved just before the COVID-19 pandemic began – another possible factor in their being underprescribed for patients with SCD.

Dr. Cronin warned that despite the study’s limitations, the actual situation for patients with SCD in the United States may be even worse than the data indicate, saying “A lot of people with SCD are actually on governmental insurance, and they may be even less likely to be getting access to these newer drugs, due to less robust coverage and more hurdles to jump through before getting treatment approved.”

Dr. Cronin disclosed no conflicts of interest. Dr. Shah reported ties with Emmaus, Novartis, GBT, Forma, Agios, Vertex, and Bluebird Bio.
 

Hydroxyurea (HU) is a safe, effective drug for treating sickle cell disease (SCD), first approved for this condition by the U.S. Food and Drug Administration in 1998. Despite the fact that most insurance plans cover HU, a new study showed that it is prescribed to fewer than 25% of patients with SCD. More recently approved SCD treatments are prescribed to fewer than 5% of adult patients.

Ohio State University

“There are several factors that are contributing to the slow uptake in these medications. Firstly, some newer medications are expensive and can require complicated insurance approvals as well as trips to doctors’ offices or infusion sites that are difficult to access for rural populations. Secondly, there are major challenges in transitioning pediatric SCD patients to receiving adequate care as adults,” lead study author Robert M. Cronin, MD, of the department of internal medicine at the Ohio State University, Columbus, said in an interview.

The retrospective study, published in Blood Advances, looked at private insurance claims of patients with SCD in the United States from 2016 to 2020. A total of 7,957 participants were included in the analysis (all were ≥ 18 years, median age 37, 61.2% female). Primary outcomes analyzed were the utilization of hydroxyurea, l-glutamine, and crizanlizumab (all shown in clinical trials to decrease acute vaso-occlusive pain), and voxelotor (approved for patients with SCD with lower hemoglobin levels).

Among study participants who had two or more pain episodes in a year, 31.5% were prescribed hydroxyurea, 3.2% l-glutamine, 2.3% crizanlizumab, and 2.9% voxelotor. Any combination therapy of drugs to decrease vaso-occlusive pain was used in about 3% of the study participants, and combinations of newer therapies were used in only 0.3%.

In contrast to these statistics, Dr. Cronin said, “All adults with sickle cell anemia should be at least offered treatment with hydroxyurea, and up to 63% of individuals with SCD have at least one vaso-occlusive pain episode in a year, making them eligible for crizanlizumab, l-glutamine, or both.”

As patients with SCD grew older, their odds of being prescribed hydroxyurea, l-glutamine, and crizanlizumab all decreased. Dr. Cronin speculated about the reasons for this decline. “It’s a huge problem to find adult providers who are knowledgeable about SCD. When pediatric patients become adults, they often can’t find anybody who knows about their disease,” he said.

Study results supported the hypothesis that rural location was a barrier to care. Not residing in a “super rural” geographic location was associated with nearly three times the likelihood of crizanlizumab prescription (odds ratio, 2.93; 95% confidence interval, 1.16-7.42).

Duke Health

“There is geographic variability as expected, with limitations in rural areas,” said Nirmish R. Shah, MD, director of the sickle cell transition program at Duke Health in Durham, N.C. Dr. Shah was not associated with the study.

Dr. Shah commented that he found the study’s findings unsurprising. He also noted that its results were based solely on data from private insurance databases and that some of the drugs included in the study were approved just before the COVID-19 pandemic began – another possible factor in their being underprescribed for patients with SCD.

Dr. Cronin warned that despite the study’s limitations, the actual situation for patients with SCD in the United States may be even worse than the data indicate, saying “A lot of people with SCD are actually on governmental insurance, and they may be even less likely to be getting access to these newer drugs, due to less robust coverage and more hurdles to jump through before getting treatment approved.”

Dr. Cronin disclosed no conflicts of interest. Dr. Shah reported ties with Emmaus, Novartis, GBT, Forma, Agios, Vertex, and Bluebird Bio.
 

Hydroxyurea (HU) is a safe, effective drug for treating sickle cell disease (SCD), first approved for this condition by the U.S. Food and Drug Administration in 1998. Despite the fact that most insurance plans cover HU, a new study showed that it is prescribed to fewer than 25% of patients with SCD. More recently approved SCD treatments are prescribed to fewer than 5% of adult patients.

Ohio State University

“There are several factors that are contributing to the slow uptake in these medications. Firstly, some newer medications are expensive and can require complicated insurance approvals as well as trips to doctors’ offices or infusion sites that are difficult to access for rural populations. Secondly, there are major challenges in transitioning pediatric SCD patients to receiving adequate care as adults,” lead study author Robert M. Cronin, MD, of the department of internal medicine at the Ohio State University, Columbus, said in an interview.

The retrospective study, published in Blood Advances, looked at private insurance claims of patients with SCD in the United States from 2016 to 2020. A total of 7,957 participants were included in the analysis (all were ≥ 18 years, median age 37, 61.2% female). Primary outcomes analyzed were the utilization of hydroxyurea, l-glutamine, and crizanlizumab (all shown in clinical trials to decrease acute vaso-occlusive pain), and voxelotor (approved for patients with SCD with lower hemoglobin levels).

Among study participants who had two or more pain episodes in a year, 31.5% were prescribed hydroxyurea, 3.2% l-glutamine, 2.3% crizanlizumab, and 2.9% voxelotor. Any combination therapy of drugs to decrease vaso-occlusive pain was used in about 3% of the study participants, and combinations of newer therapies were used in only 0.3%.

In contrast to these statistics, Dr. Cronin said, “All adults with sickle cell anemia should be at least offered treatment with hydroxyurea, and up to 63% of individuals with SCD have at least one vaso-occlusive pain episode in a year, making them eligible for crizanlizumab, l-glutamine, or both.”

As patients with SCD grew older, their odds of being prescribed hydroxyurea, l-glutamine, and crizanlizumab all decreased. Dr. Cronin speculated about the reasons for this decline. “It’s a huge problem to find adult providers who are knowledgeable about SCD. When pediatric patients become adults, they often can’t find anybody who knows about their disease,” he said.

Study results supported the hypothesis that rural location was a barrier to care. Not residing in a “super rural” geographic location was associated with nearly three times the likelihood of crizanlizumab prescription (odds ratio, 2.93; 95% confidence interval, 1.16-7.42).

Duke Health

“There is geographic variability as expected, with limitations in rural areas,” said Nirmish R. Shah, MD, director of the sickle cell transition program at Duke Health in Durham, N.C. Dr. Shah was not associated with the study.

Dr. Shah commented that he found the study’s findings unsurprising. He also noted that its results were based solely on data from private insurance databases and that some of the drugs included in the study were approved just before the COVID-19 pandemic began – another possible factor in their being underprescribed for patients with SCD.

Dr. Cronin warned that despite the study’s limitations, the actual situation for patients with SCD in the United States may be even worse than the data indicate, saying “A lot of people with SCD are actually on governmental insurance, and they may be even less likely to be getting access to these newer drugs, due to less robust coverage and more hurdles to jump through before getting treatment approved.”

Dr. Cronin disclosed no conflicts of interest. Dr. Shah reported ties with Emmaus, Novartis, GBT, Forma, Agios, Vertex, and Bluebird Bio.
 

A new study confirms that a plant-based diet with exercise can lower the risk of prostate cancer progressing or recurring.

The findings, which were reported at the 2023 ASCO Genitourinary Cancers Symposium in February, are based on a study of 2,038 men (median age, 64 years) with prostate cancer at stage T1, T2, or T3a.

“Consuming a whole foods plant-based diet may be an option to decrease risk for recurrence and improve overall survivorship,” said Vivian N. Liu, a clinical research coordinator at the University of California, San Francisco, who presented the findings.

The patients were interviewed about their diets at about 31.5 months after diagnosis. The study group was broken down into four groups based on how much of their diet consisted of a plant-based diet. Men in the highest quintile group who consumed at least 2.4 servings daily of fruit, 4.2 servings of vegetables, 2.6 servings of dairy, and 1.2 servings of meat (not seafood), had a 52% lower risk of progression (hazard ratio, 0.48; 95% confidence interval, 0.36-0.65; P-trend < 0.001) and a 53% lower risk of recurrence (HR, 0.47; 95% CI, 0.32-0.68; P-trend < 0.001), which was statistically significant. This compares with men in the lowest quintile who consumed 0.8 servings a day of fruit, 2.1 servings of vegetables, 3.1 servings of dairy, and 1.4 servings of meat. The findings were adjusted for total caloric intake, race, and smoking status.

For men over 65 years old, researchers found that a plant-based diet was associated with lower risk of recurrence (HR, 0.41; 95% CI, 0.24-0.7; P-trend = 0.03). And for those who exercised daily – in this case walking at a fast pace more than 3 times a week – a plant-based diet had a 56% (HR, 0.33; 95% CI, 0.26-0.73) lower risk of progression in the highest quintile group and a 59% decrease in recurrence (HR, 0.41; 95% CI, 0.25-0.68).

A new analysis like this, Ms. Liu said, “could guide people to make better, more healthful choices across their whole diet rather than adding or removing select foods.”

The primary endpoint was progression including recurrence, secondary treatment, bone metastases, and death due to prostate cancer, and the secondary endpoint was recurrence (PSA > 0.2ng/mL at 2 consecutive follow-up visits or during secondary treatment). At 7.4 years follow-up, there were 204 cases of progression.

“Fruits and vegetables contain antioxidants and anti-inflammatory components as well as dietary fiber that improve glucose control and reduce inflammation,” Ms. Liu said. In contrast, she said, animal-based foods may increase insulin resistance and insulin levels and boost levels of insulin-like growth factor 1, which is associated with prostate cancer risk. More studies, especially randomized controlled trials, are needed to provide evidence whether healthful plant-based foods and prostate cancer progression are connected.

NYU Langone Health urologist Natasha Gupta, MD, published a systematic review in 2022 on the impact of a plant-based diet on prostate cancer.* The review, which included 5 interventional studies and 11 observational studies, found that consuming a plant-based diet was associated with improvements in general health for men with prostate cancer. The observational studies found either a lower risk of prostate cancer or no significant difference.

“Patients often ask if there is anything that they can do to reduce the risk of recurrence, and it is great to be able to tell patients that a healthy lifestyle including plant-based foods and physical activity is helpful,” Dr. Gupta said.

The review’s coauthor, Stacy Loeb, MD, also of NYU Langone Health, said the new study was “a well-done observational study by experts in nutritional epidemiology from UCSF. It adds to a large body of evidence showing that plant-based diets improve health outcomes.”

“In the short-term, purchasing plant-based protein sources, such as beans and lentils, is less expensive than buying meat. Plant-based diets also reduce the risk of obesity, diabetes, and cardiovascular disease, which are associated with hundreds of thousands of dollars over a lifetime,” she said.

Limitations of the new study included the small number of non-White participants and self-reporting of diet. The study doesn’t examine the cost of various diets or the availability of plant-based foods like fresh produce, which can be limited in some neighborhoods.

Ms. Liu and colleagues plan to conduct a study that examines postdiagnostic plant-based diets in relation to prostate cancer–specific mortality. She and her team will also examine the plant-based dietary indices in relation to prostate cancer–specific quality of life at 2, 5, and 10 years from baseline.

The study authors, Dr. Loeb, and Dr. Gupta report no disclosures.

Correction, 3/17/23: An earlier version of this article misstated the name of NYU Langone Health.

A new study confirms that a plant-based diet with exercise can lower the risk of prostate cancer progressing or recurring.

The findings, which were reported at the 2023 ASCO Genitourinary Cancers Symposium in February, are based on a study of 2,038 men (median age, 64 years) with prostate cancer at stage T1, T2, or T3a.

“Consuming a whole foods plant-based diet may be an option to decrease risk for recurrence and improve overall survivorship,” said Vivian N. Liu, a clinical research coordinator at the University of California, San Francisco, who presented the findings.

The patients were interviewed about their diets at about 31.5 months after diagnosis. The study group was broken down into four groups based on how much of their diet consisted of a plant-based diet. Men in the highest quintile group who consumed at least 2.4 servings daily of fruit, 4.2 servings of vegetables, 2.6 servings of dairy, and 1.2 servings of meat (not seafood), had a 52% lower risk of progression (hazard ratio, 0.48; 95% confidence interval, 0.36-0.65; P-trend < 0.001) and a 53% lower risk of recurrence (HR, 0.47; 95% CI, 0.32-0.68; P-trend < 0.001), which was statistically significant. This compares with men in the lowest quintile who consumed 0.8 servings a day of fruit, 2.1 servings of vegetables, 3.1 servings of dairy, and 1.4 servings of meat. The findings were adjusted for total caloric intake, race, and smoking status.

For men over 65 years old, researchers found that a plant-based diet was associated with lower risk of recurrence (HR, 0.41; 95% CI, 0.24-0.7; P-trend = 0.03). And for those who exercised daily – in this case walking at a fast pace more than 3 times a week – a plant-based diet had a 56% (HR, 0.33; 95% CI, 0.26-0.73) lower risk of progression in the highest quintile group and a 59% decrease in recurrence (HR, 0.41; 95% CI, 0.25-0.68).

A new analysis like this, Ms. Liu said, “could guide people to make better, more healthful choices across their whole diet rather than adding or removing select foods.”

The primary endpoint was progression including recurrence, secondary treatment, bone metastases, and death due to prostate cancer, and the secondary endpoint was recurrence (PSA > 0.2ng/mL at 2 consecutive follow-up visits or during secondary treatment). At 7.4 years follow-up, there were 204 cases of progression.

“Fruits and vegetables contain antioxidants and anti-inflammatory components as well as dietary fiber that improve glucose control and reduce inflammation,” Ms. Liu said. In contrast, she said, animal-based foods may increase insulin resistance and insulin levels and boost levels of insulin-like growth factor 1, which is associated with prostate cancer risk. More studies, especially randomized controlled trials, are needed to provide evidence whether healthful plant-based foods and prostate cancer progression are connected.

NYU Langone Health urologist Natasha Gupta, MD, published a systematic review in 2022 on the impact of a plant-based diet on prostate cancer.* The review, which included 5 interventional studies and 11 observational studies, found that consuming a plant-based diet was associated with improvements in general health for men with prostate cancer. The observational studies found either a lower risk of prostate cancer or no significant difference.

“Patients often ask if there is anything that they can do to reduce the risk of recurrence, and it is great to be able to tell patients that a healthy lifestyle including plant-based foods and physical activity is helpful,” Dr. Gupta said.

The review’s coauthor, Stacy Loeb, MD, also of NYU Langone Health, said the new study was “a well-done observational study by experts in nutritional epidemiology from UCSF. It adds to a large body of evidence showing that plant-based diets improve health outcomes.”

“In the short-term, purchasing plant-based protein sources, such as beans and lentils, is less expensive than buying meat. Plant-based diets also reduce the risk of obesity, diabetes, and cardiovascular disease, which are associated with hundreds of thousands of dollars over a lifetime,” she said.

Limitations of the new study included the small number of non-White participants and self-reporting of diet. The study doesn’t examine the cost of various diets or the availability of plant-based foods like fresh produce, which can be limited in some neighborhoods.

Ms. Liu and colleagues plan to conduct a study that examines postdiagnostic plant-based diets in relation to prostate cancer–specific mortality. She and her team will also examine the plant-based dietary indices in relation to prostate cancer–specific quality of life at 2, 5, and 10 years from baseline.

The study authors, Dr. Loeb, and Dr. Gupta report no disclosures.

Correction, 3/17/23: An earlier version of this article misstated the name of NYU Langone Health.

A new study confirms that a plant-based diet with exercise can lower the risk of prostate cancer progressing or recurring.

The findings, which were reported at the 2023 ASCO Genitourinary Cancers Symposium in February, are based on a study of 2,038 men (median age, 64 years) with prostate cancer at stage T1, T2, or T3a.

“Consuming a whole foods plant-based diet may be an option to decrease risk for recurrence and improve overall survivorship,” said Vivian N. Liu, a clinical research coordinator at the University of California, San Francisco, who presented the findings.

The patients were interviewed about their diets at about 31.5 months after diagnosis. The study group was broken down into four groups based on how much of their diet consisted of a plant-based diet. Men in the highest quintile group who consumed at least 2.4 servings daily of fruit, 4.2 servings of vegetables, 2.6 servings of dairy, and 1.2 servings of meat (not seafood), had a 52% lower risk of progression (hazard ratio, 0.48; 95% confidence interval, 0.36-0.65; P-trend < 0.001) and a 53% lower risk of recurrence (HR, 0.47; 95% CI, 0.32-0.68; P-trend < 0.001), which was statistically significant. This compares with men in the lowest quintile who consumed 0.8 servings a day of fruit, 2.1 servings of vegetables, 3.1 servings of dairy, and 1.4 servings of meat. The findings were adjusted for total caloric intake, race, and smoking status.

For men over 65 years old, researchers found that a plant-based diet was associated with lower risk of recurrence (HR, 0.41; 95% CI, 0.24-0.7; P-trend = 0.03). And for those who exercised daily – in this case walking at a fast pace more than 3 times a week – a plant-based diet had a 56% (HR, 0.33; 95% CI, 0.26-0.73) lower risk of progression in the highest quintile group and a 59% decrease in recurrence (HR, 0.41; 95% CI, 0.25-0.68).

A new analysis like this, Ms. Liu said, “could guide people to make better, more healthful choices across their whole diet rather than adding or removing select foods.”

The primary endpoint was progression including recurrence, secondary treatment, bone metastases, and death due to prostate cancer, and the secondary endpoint was recurrence (PSA > 0.2ng/mL at 2 consecutive follow-up visits or during secondary treatment). At 7.4 years follow-up, there were 204 cases of progression.

“Fruits and vegetables contain antioxidants and anti-inflammatory components as well as dietary fiber that improve glucose control and reduce inflammation,” Ms. Liu said. In contrast, she said, animal-based foods may increase insulin resistance and insulin levels and boost levels of insulin-like growth factor 1, which is associated with prostate cancer risk. More studies, especially randomized controlled trials, are needed to provide evidence whether healthful plant-based foods and prostate cancer progression are connected.

NYU Langone Health urologist Natasha Gupta, MD, published a systematic review in 2022 on the impact of a plant-based diet on prostate cancer.* The review, which included 5 interventional studies and 11 observational studies, found that consuming a plant-based diet was associated with improvements in general health for men with prostate cancer. The observational studies found either a lower risk of prostate cancer or no significant difference.

“Patients often ask if there is anything that they can do to reduce the risk of recurrence, and it is great to be able to tell patients that a healthy lifestyle including plant-based foods and physical activity is helpful,” Dr. Gupta said.

The review’s coauthor, Stacy Loeb, MD, also of NYU Langone Health, said the new study was “a well-done observational study by experts in nutritional epidemiology from UCSF. It adds to a large body of evidence showing that plant-based diets improve health outcomes.”

“In the short-term, purchasing plant-based protein sources, such as beans and lentils, is less expensive than buying meat. Plant-based diets also reduce the risk of obesity, diabetes, and cardiovascular disease, which are associated with hundreds of thousands of dollars over a lifetime,” she said.

Limitations of the new study included the small number of non-White participants and self-reporting of diet. The study doesn’t examine the cost of various diets or the availability of plant-based foods like fresh produce, which can be limited in some neighborhoods.

Ms. Liu and colleagues plan to conduct a study that examines postdiagnostic plant-based diets in relation to prostate cancer–specific mortality. She and her team will also examine the plant-based dietary indices in relation to prostate cancer–specific quality of life at 2, 5, and 10 years from baseline.

The study authors, Dr. Loeb, and Dr. Gupta report no disclosures.

Correction, 3/17/23: An earlier version of this article misstated the name of NYU Langone Health.

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

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

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

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

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

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

Atopic dermatitis (AD) monotherapy with the lebrikizumab, an interleukin-13 inhibitor, was shown to be both effective and safe in the induction periods of the phase 3 ADvocate1 and ADvocate2 trials, researchers reported in the New England Journal of Medicine.

The identically designed, 52-week, randomized, double-blind, placebo-controlled trials enrolled 851 adolescents and adults with moderate to severe AD and included a 16-week induction period followed by a 36-week maintenance period. At week 16, the results “show a rapid onset of action in multiple domains of the disease, such as skin clearance and itch,” wrote lead author Jonathan Silverberg, MD, PhD, director of clinical research and contact dermatitis, at George Washington University, Washington, and colleagues. “Although 16 weeks of treatment with lebrikizumab is not sufficient to assess its long-term safety, the results from the induction period of these two trials suggest a safety profile that is consistent with findings in previous trials,” they added.

Results presented at the European Academy of Dermatology and Venereology 2022 annual meeting, but not yet published, showed similar efficacy maintained through the end of the trial.

Eligible patients were randomly assigned to receive either lebrikizumab 250 mg (with a 500-mg loading dose given at baseline and at week 2) or placebo, administered subcutaneously every 2 weeks, with concomitant topical or systemic treatments prohibited through week 16 except when deemed appropriate as rescue therapy. In such cases, moderate-potency topical glucocorticoids were preferred as first-line rescue therapy, while the study drug was discontinued if systemic therapy was needed.

In both trials, the primary efficacy outcome – a score of 0 or 1 on the Investigator’s Global Assessment (IGA) – and a reduction of at least 2 points from baseline at week 16, was met by more patients treated with lebrikizumab than with placebo: 43.1% vs. 12.7% respectively in trial 1 (P < .001); and 33.2% vs. 10.8% in trial 2 (P < .001).

Similarly, in both trials, a higher percentage of the lebrikizumab than placebo patients had an EASI-75 response (75% improvement in the Eczema Area and Severity Index score): 58.8% vs. 16.2% (P < .001) in trial 1 and 52.1% vs. 18.1% (P < .001) in trial 2.

Improvement in itch was also significantly better in patients treated with lebrikizumab, compared with placebo. This was measured by a reduction of at least 4 points in the Pruritus NRS from baseline to week 16 and a reduction in the Sleep-Loss Scale score of at least 2 points from baseline to week 16 (P < .001 for both measures in both trials).

A higher percentage of placebo vs. lebrikizumab patients discontinued the trials during the induction phases (14.9% vs. 7.1% in trial 1 and 11.0% vs. 7.8% in trial 2), and the use of rescue medication was approximately three times and two times higher in both placebo groups respectively.

Conjunctivitis was the most common adverse event, occurring consistently more frequently in patients treated with lebrikizumab, compared with placebo (7.4% vs. 2.8% in trial 1 and 7.5% vs. 2.1% in trial 2).

“Although several theories have been proposed for the pathogenesis of conjunctivitis in patients with atopic dermatitis treated with this class of biologic agents, the mechanism remains unclear and warrants further study,” the investigators wrote.

Asked to comment on the new results, Zelma Chiesa Fuxench, MD, who was not involved in the research, said they “continue to demonstrate the superior efficacy and favorable safety profile” of lebrikizumab in adolescents and adults and support the results of earlier phase 2 studies. “The results of these studies thus far continue to offer more hope and the possibility of a better future for our patients with atopic dermatitis who are still struggling to achieve control of their disease.”

Dr. Chiesa Fuxench from the department of dermatology at the University of Pennsylvania, Philadelphia, said she looks forward to reviewing the full study results in which patients who achieved the primary outcomes of interest were then rerandomized to either placebo, or lebrikizumab every 2 weeks or every 4 weeks for the 36-week maintenance period “because we know that there is data for other biologics in atopic dermatitis (such as tralokinumab) that demonstrate that a decrease in the frequency of injections may be possible for patients who achieve disease control after an initial 16 weeks of therapy every 2 weeks.”

The research was supported by Dermira, a wholly owned subsidiary of Eli Lilly. Dr. Silverberg disclosed he is a consultant for Dermira and Eli Lilly, as are other coauthors on the paper who additionally disclosed grants from Dermira and other relationships with Eli Lilly such as advisory board membership and having received lecture fees. Three authors are Eli Lilly employees. Dr. Chiesa Fuxench disclosed that she is a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, Abbvie, and Incyte for which she has received honoraria for work related to AD. Dr. Chiesa Fuxench has also been a recipient of research grants from Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.

Atopic dermatitis (AD) monotherapy with the lebrikizumab, an interleukin-13 inhibitor, was shown to be both effective and safe in the induction periods of the phase 3 ADvocate1 and ADvocate2 trials, researchers reported in the New England Journal of Medicine.

The identically designed, 52-week, randomized, double-blind, placebo-controlled trials enrolled 851 adolescents and adults with moderate to severe AD and included a 16-week induction period followed by a 36-week maintenance period. At week 16, the results “show a rapid onset of action in multiple domains of the disease, such as skin clearance and itch,” wrote lead author Jonathan Silverberg, MD, PhD, director of clinical research and contact dermatitis, at George Washington University, Washington, and colleagues. “Although 16 weeks of treatment with lebrikizumab is not sufficient to assess its long-term safety, the results from the induction period of these two trials suggest a safety profile that is consistent with findings in previous trials,” they added.

Results presented at the European Academy of Dermatology and Venereology 2022 annual meeting, but not yet published, showed similar efficacy maintained through the end of the trial.

Eligible patients were randomly assigned to receive either lebrikizumab 250 mg (with a 500-mg loading dose given at baseline and at week 2) or placebo, administered subcutaneously every 2 weeks, with concomitant topical or systemic treatments prohibited through week 16 except when deemed appropriate as rescue therapy. In such cases, moderate-potency topical glucocorticoids were preferred as first-line rescue therapy, while the study drug was discontinued if systemic therapy was needed.

In both trials, the primary efficacy outcome – a score of 0 or 1 on the Investigator’s Global Assessment (IGA) – and a reduction of at least 2 points from baseline at week 16, was met by more patients treated with lebrikizumab than with placebo: 43.1% vs. 12.7% respectively in trial 1 (P < .001); and 33.2% vs. 10.8% in trial 2 (P < .001).

Similarly, in both trials, a higher percentage of the lebrikizumab than placebo patients had an EASI-75 response (75% improvement in the Eczema Area and Severity Index score): 58.8% vs. 16.2% (P < .001) in trial 1 and 52.1% vs. 18.1% (P < .001) in trial 2.

Improvement in itch was also significantly better in patients treated with lebrikizumab, compared with placebo. This was measured by a reduction of at least 4 points in the Pruritus NRS from baseline to week 16 and a reduction in the Sleep-Loss Scale score of at least 2 points from baseline to week 16 (P < .001 for both measures in both trials).

A higher percentage of placebo vs. lebrikizumab patients discontinued the trials during the induction phases (14.9% vs. 7.1% in trial 1 and 11.0% vs. 7.8% in trial 2), and the use of rescue medication was approximately three times and two times higher in both placebo groups respectively.

Conjunctivitis was the most common adverse event, occurring consistently more frequently in patients treated with lebrikizumab, compared with placebo (7.4% vs. 2.8% in trial 1 and 7.5% vs. 2.1% in trial 2).

“Although several theories have been proposed for the pathogenesis of conjunctivitis in patients with atopic dermatitis treated with this class of biologic agents, the mechanism remains unclear and warrants further study,” the investigators wrote.

Asked to comment on the new results, Zelma Chiesa Fuxench, MD, who was not involved in the research, said they “continue to demonstrate the superior efficacy and favorable safety profile” of lebrikizumab in adolescents and adults and support the results of earlier phase 2 studies. “The results of these studies thus far continue to offer more hope and the possibility of a better future for our patients with atopic dermatitis who are still struggling to achieve control of their disease.”

Dr. Chiesa Fuxench from the department of dermatology at the University of Pennsylvania, Philadelphia, said she looks forward to reviewing the full study results in which patients who achieved the primary outcomes of interest were then rerandomized to either placebo, or lebrikizumab every 2 weeks or every 4 weeks for the 36-week maintenance period “because we know that there is data for other biologics in atopic dermatitis (such as tralokinumab) that demonstrate that a decrease in the frequency of injections may be possible for patients who achieve disease control after an initial 16 weeks of therapy every 2 weeks.”

The research was supported by Dermira, a wholly owned subsidiary of Eli Lilly. Dr. Silverberg disclosed he is a consultant for Dermira and Eli Lilly, as are other coauthors on the paper who additionally disclosed grants from Dermira and other relationships with Eli Lilly such as advisory board membership and having received lecture fees. Three authors are Eli Lilly employees. Dr. Chiesa Fuxench disclosed that she is a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, Abbvie, and Incyte for which she has received honoraria for work related to AD. Dr. Chiesa Fuxench has also been a recipient of research grants from Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.

Atopic dermatitis (AD) monotherapy with the lebrikizumab, an interleukin-13 inhibitor, was shown to be both effective and safe in the induction periods of the phase 3 ADvocate1 and ADvocate2 trials, researchers reported in the New England Journal of Medicine.

The identically designed, 52-week, randomized, double-blind, placebo-controlled trials enrolled 851 adolescents and adults with moderate to severe AD and included a 16-week induction period followed by a 36-week maintenance period. At week 16, the results “show a rapid onset of action in multiple domains of the disease, such as skin clearance and itch,” wrote lead author Jonathan Silverberg, MD, PhD, director of clinical research and contact dermatitis, at George Washington University, Washington, and colleagues. “Although 16 weeks of treatment with lebrikizumab is not sufficient to assess its long-term safety, the results from the induction period of these two trials suggest a safety profile that is consistent with findings in previous trials,” they added.

Results presented at the European Academy of Dermatology and Venereology 2022 annual meeting, but not yet published, showed similar efficacy maintained through the end of the trial.

Eligible patients were randomly assigned to receive either lebrikizumab 250 mg (with a 500-mg loading dose given at baseline and at week 2) or placebo, administered subcutaneously every 2 weeks, with concomitant topical or systemic treatments prohibited through week 16 except when deemed appropriate as rescue therapy. In such cases, moderate-potency topical glucocorticoids were preferred as first-line rescue therapy, while the study drug was discontinued if systemic therapy was needed.

In both trials, the primary efficacy outcome – a score of 0 or 1 on the Investigator’s Global Assessment (IGA) – and a reduction of at least 2 points from baseline at week 16, was met by more patients treated with lebrikizumab than with placebo: 43.1% vs. 12.7% respectively in trial 1 (P < .001); and 33.2% vs. 10.8% in trial 2 (P < .001).

Similarly, in both trials, a higher percentage of the lebrikizumab than placebo patients had an EASI-75 response (75% improvement in the Eczema Area and Severity Index score): 58.8% vs. 16.2% (P < .001) in trial 1 and 52.1% vs. 18.1% (P < .001) in trial 2.

Improvement in itch was also significantly better in patients treated with lebrikizumab, compared with placebo. This was measured by a reduction of at least 4 points in the Pruritus NRS from baseline to week 16 and a reduction in the Sleep-Loss Scale score of at least 2 points from baseline to week 16 (P < .001 for both measures in both trials).

A higher percentage of placebo vs. lebrikizumab patients discontinued the trials during the induction phases (14.9% vs. 7.1% in trial 1 and 11.0% vs. 7.8% in trial 2), and the use of rescue medication was approximately three times and two times higher in both placebo groups respectively.

Conjunctivitis was the most common adverse event, occurring consistently more frequently in patients treated with lebrikizumab, compared with placebo (7.4% vs. 2.8% in trial 1 and 7.5% vs. 2.1% in trial 2).

“Although several theories have been proposed for the pathogenesis of conjunctivitis in patients with atopic dermatitis treated with this class of biologic agents, the mechanism remains unclear and warrants further study,” the investigators wrote.

Asked to comment on the new results, Zelma Chiesa Fuxench, MD, who was not involved in the research, said they “continue to demonstrate the superior efficacy and favorable safety profile” of lebrikizumab in adolescents and adults and support the results of earlier phase 2 studies. “The results of these studies thus far continue to offer more hope and the possibility of a better future for our patients with atopic dermatitis who are still struggling to achieve control of their disease.”

Dr. Chiesa Fuxench from the department of dermatology at the University of Pennsylvania, Philadelphia, said she looks forward to reviewing the full study results in which patients who achieved the primary outcomes of interest were then rerandomized to either placebo, or lebrikizumab every 2 weeks or every 4 weeks for the 36-week maintenance period “because we know that there is data for other biologics in atopic dermatitis (such as tralokinumab) that demonstrate that a decrease in the frequency of injections may be possible for patients who achieve disease control after an initial 16 weeks of therapy every 2 weeks.”

The research was supported by Dermira, a wholly owned subsidiary of Eli Lilly. Dr. Silverberg disclosed he is a consultant for Dermira and Eli Lilly, as are other coauthors on the paper who additionally disclosed grants from Dermira and other relationships with Eli Lilly such as advisory board membership and having received lecture fees. Three authors are Eli Lilly employees. Dr. Chiesa Fuxench disclosed that she is a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, Abbvie, and Incyte for which she has received honoraria for work related to AD. Dr. Chiesa Fuxench has also been a recipient of research grants from Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.

Higher blood caffeine levels appear to reduce the risks for both adiposity and type 2 diabetes, the results of a new study suggest.

Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.

In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.

The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”

Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.

The work was published online March 14 in BMJ Medicine.

“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.

“It does not, however, prove cause and effect.”

The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”

Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”

“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.

Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.

Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m² in BMI (P < .001).

For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).

Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).

Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).

Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.

They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).

The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.

“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”

The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.

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

Higher blood caffeine levels appear to reduce the risks for both adiposity and type 2 diabetes, the results of a new study suggest.

Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.

In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.

The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”

Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.

The work was published online March 14 in BMJ Medicine.

“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.

“It does not, however, prove cause and effect.”

The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”

Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”

“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.

Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.

Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m² in BMI (P < .001).

For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).

Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).

Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).

Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.

They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).

The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.

“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”

The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.

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

Higher blood caffeine levels appear to reduce the risks for both adiposity and type 2 diabetes, the results of a new study suggest.

Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.

In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.

The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”

Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.

The work was published online March 14 in BMJ Medicine.

“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.

“It does not, however, prove cause and effect.”

The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”

Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”

“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.

Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.

Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m² in BMI (P < .001).

For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).

Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).

Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).

Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.

They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).

The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.

“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”

The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.

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

A qualitative study of breast cancer screening–age women finds that few women identified breast density as a risk factor for breast cancer.

Most women did not feel confident they knew what actions could mitigate breast cancer risk, leading researchers to the conclusion that comprehensive education about breast cancer risks and prevention strategies is needed.

The study was published earlier this year in JAMA Network Open.

“Forty [percent] to 50% of women who undergo mammography fall into the two highest breast density categories,” said the study’s lead author Christine Gunn, PhD, of the Dartmouth Institute for Health Policy and Clinical Practice, N.H. “Breast cancer risk increases from 1.2-4.0 times depending on the level of breast density. By comparison, a first-degree family history of breast cancer, particularly in premenopausal women, confers a two-fold higher breast cancer risk.”

Dr. Gunn’s study is based on a survey of 2,306 women (between 40 and 76 years old) that was conducted between 2019 and 2020. The goal was to determine how well women understood cancer risks associated with dense breast tissue. The final analysis included 1,858 women (9% Asian, 27% Black, 14% Hispanic, 43% White, and 7% other race or ethnicity).

Breast density was thought to be a greater risk than not having children, drinking daily, and having had a prior breast biopsy, according to 52%, 53%, and 48% of respondents, respectively. Breast density was believed to be a lesser breast cancer risk than having a first-degree relative with breast cancer by 93% of women, and 65% of women felt it was a lesser risk than being overweight or obese.

Of the 61 women who completed follow-up interviews, 6 described breast density as a contributing factor to breast cancer risk. And, 17 women did not know whether it was possible to reduce their breast cancer risk.
 

Doctors must notify patients in writing

Breast tissue falls under one of four categories: fatty tissue, scattered areas of dense fibroglandular tissue, many areas of glandular and connective tissue, or extremely dense tissue. The tissue is considered dense if it falls under heterogeneously dense or extremely dense, and in those cases, follow-up testing with ultrasound or MRI may be necessary. This is important, Dr. Gunn said, because dense tissue can make “it harder to find cancers because connective tissue appears white on the mammogram, potentially masking tumors.”

Prior studies have found that many clinicians are uncomfortable counseling patients on the implications of breast density and cancer risk, the authors wrote.

However, under the Mammography Quality Standards Act, which was updated on March 10, the Food and Drug Administration requires that patients be provided with a mammography report summary that “identifies whether the patient has dense or nondense breast tissue.” The report, which should be written in lay language, should also specify the “significance” of the dense tissue.

While some states mandate notification regardless of the density level, most only notify women if heterogeneously dense or extremely dense tissue has been identified, Dr. Gunn said. But the rules are inconsistent, she said. In some facilities in Massachusetts, for example, women may receive a mammography report letter and a separate breast density letter. “For some, it has been really confusing. They received a letter saying that their mammography was normal and then another one saying that they have dense breasts – resulting in a lot of uncertainty and anxiety. We don’t want to overly alarm people. We want them to understand their risk,” she said.

Breast density can be considered among other risk factors, including alcohol use, obesity, diet, parity, prior breast biopsy, and inherited unfavorable genetic mutations. “If the total lifetime risk is above 20%, that opens up further screening options, such as a breast MRI, which will catch more cancers than a breast mammogram by itself,” Dr. Gunn said.

“The challenges for physicians and patients around collecting and understanding breast density information in the context of other risk factors can potentially lead to disparities in who gets to know their risk and who doesn’t,” Dr. Gunn said. It would be possible, she speculated, to create or use existing risk calculators integrated into medical records and populated with information gathered in premammography visit questionnaires. Ideally, a radiologist could hand the patient results in real time at the end of the mammography visit, integrating risk estimates with mammography findings to make recommendations.

This study was supported by grant RSG-133017-CPHPS from the American Cancer Society.
 

A qualitative study of breast cancer screening–age women finds that few women identified breast density as a risk factor for breast cancer.

Most women did not feel confident they knew what actions could mitigate breast cancer risk, leading researchers to the conclusion that comprehensive education about breast cancer risks and prevention strategies is needed.

The study was published earlier this year in JAMA Network Open.

“Forty [percent] to 50% of women who undergo mammography fall into the two highest breast density categories,” said the study’s lead author Christine Gunn, PhD, of the Dartmouth Institute for Health Policy and Clinical Practice, N.H. “Breast cancer risk increases from 1.2-4.0 times depending on the level of breast density. By comparison, a first-degree family history of breast cancer, particularly in premenopausal women, confers a two-fold higher breast cancer risk.”

Dr. Gunn’s study is based on a survey of 2,306 women (between 40 and 76 years old) that was conducted between 2019 and 2020. The goal was to determine how well women understood cancer risks associated with dense breast tissue. The final analysis included 1,858 women (9% Asian, 27% Black, 14% Hispanic, 43% White, and 7% other race or ethnicity).

Breast density was thought to be a greater risk than not having children, drinking daily, and having had a prior breast biopsy, according to 52%, 53%, and 48% of respondents, respectively. Breast density was believed to be a lesser breast cancer risk than having a first-degree relative with breast cancer by 93% of women, and 65% of women felt it was a lesser risk than being overweight or obese.

Of the 61 women who completed follow-up interviews, 6 described breast density as a contributing factor to breast cancer risk. And, 17 women did not know whether it was possible to reduce their breast cancer risk.
 

Doctors must notify patients in writing

Breast tissue falls under one of four categories: fatty tissue, scattered areas of dense fibroglandular tissue, many areas of glandular and connective tissue, or extremely dense tissue. The tissue is considered dense if it falls under heterogeneously dense or extremely dense, and in those cases, follow-up testing with ultrasound or MRI may be necessary. This is important, Dr. Gunn said, because dense tissue can make “it harder to find cancers because connective tissue appears white on the mammogram, potentially masking tumors.”

Prior studies have found that many clinicians are uncomfortable counseling patients on the implications of breast density and cancer risk, the authors wrote.

However, under the Mammography Quality Standards Act, which was updated on March 10, the Food and Drug Administration requires that patients be provided with a mammography report summary that “identifies whether the patient has dense or nondense breast tissue.” The report, which should be written in lay language, should also specify the “significance” of the dense tissue.

While some states mandate notification regardless of the density level, most only notify women if heterogeneously dense or extremely dense tissue has been identified, Dr. Gunn said. But the rules are inconsistent, she said. In some facilities in Massachusetts, for example, women may receive a mammography report letter and a separate breast density letter. “For some, it has been really confusing. They received a letter saying that their mammography was normal and then another one saying that they have dense breasts – resulting in a lot of uncertainty and anxiety. We don’t want to overly alarm people. We want them to understand their risk,” she said.

Breast density can be considered among other risk factors, including alcohol use, obesity, diet, parity, prior breast biopsy, and inherited unfavorable genetic mutations. “If the total lifetime risk is above 20%, that opens up further screening options, such as a breast MRI, which will catch more cancers than a breast mammogram by itself,” Dr. Gunn said.

“The challenges for physicians and patients around collecting and understanding breast density information in the context of other risk factors can potentially lead to disparities in who gets to know their risk and who doesn’t,” Dr. Gunn said. It would be possible, she speculated, to create or use existing risk calculators integrated into medical records and populated with information gathered in premammography visit questionnaires. Ideally, a radiologist could hand the patient results in real time at the end of the mammography visit, integrating risk estimates with mammography findings to make recommendations.

This study was supported by grant RSG-133017-CPHPS from the American Cancer Society.
 

A qualitative study of breast cancer screening–age women finds that few women identified breast density as a risk factor for breast cancer.

Most women did not feel confident they knew what actions could mitigate breast cancer risk, leading researchers to the conclusion that comprehensive education about breast cancer risks and prevention strategies is needed.

The study was published earlier this year in JAMA Network Open.

“Forty [percent] to 50% of women who undergo mammography fall into the two highest breast density categories,” said the study’s lead author Christine Gunn, PhD, of the Dartmouth Institute for Health Policy and Clinical Practice, N.H. “Breast cancer risk increases from 1.2-4.0 times depending on the level of breast density. By comparison, a first-degree family history of breast cancer, particularly in premenopausal women, confers a two-fold higher breast cancer risk.”

Dr. Gunn’s study is based on a survey of 2,306 women (between 40 and 76 years old) that was conducted between 2019 and 2020. The goal was to determine how well women understood cancer risks associated with dense breast tissue. The final analysis included 1,858 women (9% Asian, 27% Black, 14% Hispanic, 43% White, and 7% other race or ethnicity).

Breast density was thought to be a greater risk than not having children, drinking daily, and having had a prior breast biopsy, according to 52%, 53%, and 48% of respondents, respectively. Breast density was believed to be a lesser breast cancer risk than having a first-degree relative with breast cancer by 93% of women, and 65% of women felt it was a lesser risk than being overweight or obese.

Of the 61 women who completed follow-up interviews, 6 described breast density as a contributing factor to breast cancer risk. And, 17 women did not know whether it was possible to reduce their breast cancer risk.
 

Doctors must notify patients in writing

Breast tissue falls under one of four categories: fatty tissue, scattered areas of dense fibroglandular tissue, many areas of glandular and connective tissue, or extremely dense tissue. The tissue is considered dense if it falls under heterogeneously dense or extremely dense, and in those cases, follow-up testing with ultrasound or MRI may be necessary. This is important, Dr. Gunn said, because dense tissue can make “it harder to find cancers because connective tissue appears white on the mammogram, potentially masking tumors.”

Prior studies have found that many clinicians are uncomfortable counseling patients on the implications of breast density and cancer risk, the authors wrote.

However, under the Mammography Quality Standards Act, which was updated on March 10, the Food and Drug Administration requires that patients be provided with a mammography report summary that “identifies whether the patient has dense or nondense breast tissue.” The report, which should be written in lay language, should also specify the “significance” of the dense tissue.

While some states mandate notification regardless of the density level, most only notify women if heterogeneously dense or extremely dense tissue has been identified, Dr. Gunn said. But the rules are inconsistent, she said. In some facilities in Massachusetts, for example, women may receive a mammography report letter and a separate breast density letter. “For some, it has been really confusing. They received a letter saying that their mammography was normal and then another one saying that they have dense breasts – resulting in a lot of uncertainty and anxiety. We don’t want to overly alarm people. We want them to understand their risk,” she said.

Breast density can be considered among other risk factors, including alcohol use, obesity, diet, parity, prior breast biopsy, and inherited unfavorable genetic mutations. “If the total lifetime risk is above 20%, that opens up further screening options, such as a breast MRI, which will catch more cancers than a breast mammogram by itself,” Dr. Gunn said.

“The challenges for physicians and patients around collecting and understanding breast density information in the context of other risk factors can potentially lead to disparities in who gets to know their risk and who doesn’t,” Dr. Gunn said. It would be possible, she speculated, to create or use existing risk calculators integrated into medical records and populated with information gathered in premammography visit questionnaires. Ideally, a radiologist could hand the patient results in real time at the end of the mammography visit, integrating risk estimates with mammography findings to make recommendations.

This study was supported by grant RSG-133017-CPHPS from the American Cancer Society.
 

Researchers have developed and validated an artificial intelligence (AI) tool that can accurately distinguish ulcerative colitis (UC) remission from activity (inflammation) in biopsies and help predict flare-ups.

The AI tool predicted UC disease activity with 89% accuracy and inflammation at the biopsy site with 80% accuracy. Its ability to stratify risk of UC flare was on par with human pathologists.

“This tool in the near future will speed up, simplify, and standardize histological assessment of ulcerative colitis and provide the clinician with accurate prognostic information in real time,” co–lead author Marietta Iacucci, MD, PhD, from the University of Birmingham (England), and University College Cork (Ireland), said in an interview.

“The tool needs to be refined and further validated before it is ready for daily clinical practice. That work is ongoing now,” Dr. Iacucci said.

The researchers describe their advanced AI-based computer-aided detection tool in a study published online in Gastroenterology.
 

‘Strong’ performance

They used 535 digitized biopsies from 273 patients with UC (mean age, 48 years; 41% women) to develop and test the tool. They used a subset of 118 to train it to distinguish remission from activity, 42 to calibrate it, and 375 to test it. An additional 154 biopsies from 58 patients with UC were used to externally validate the tool.

The model also was tested to predict the corresponding endoscopic assessment and occurrence of flares at 12 months.

UC disease activity was defined by three different histologic indices: the Robarts Histopathology Index (RHI), the Nancy Histological Index (NHI), and the newly developed PICaSSO Histologic Remission Index (PHRI).

The AI tool had “strong diagnostic performance to detect disease activity” (PHRI > 0) with an overall area under the receiver operating characteristic curve of 0.87 and sensitivity and specificity of 89% and 85%, respectively.

The researchers note that, while the AI tool was trained for the PHRI, its sensitivity for RHI and NHI histologic remission/activity was also high (94% and 89%, respectively).

Despite the different mix of severity grades, the AI model “maintained a good diagnostic performance, proving its applicability outside the original development setting,” they reported.

The AI tool could also predict the presence of endoscopic inflammation in the biopsy area with about 80% accuracy.

“Though imperfect, this result is consistent with human-assessed correlation between endoscopy and histology,” the researchers noted.

The model predicted the corresponding endoscopic remission/activity with 79% and 82% accuracy for UCEIS and PICaSSO, respectively.

The hazard ratios for disease flare-up between the AI system and pathologists assessed by PHRI was similar (4.64 and 3.56, respectively), “demonstrating the ability of the computer to stratify the risk of flare comparably well to pathologists,” they added. 

Both histology and outcome prediction were confirmed in the external validation cohort.

The AI system delivered results in an average of 9.8 seconds per slide.
 

Potential ‘game changer’

UC is a “complex condition to predict, and developing machine learning–derived systems to make this diagnostic job quicker and more accurate could be a game changer,” Dr. Iacucci said in a news release.

With refinement, the AI tool will have an impact on both clinical trials and daily practice, the researchers wrote. In clinical practice, histological reporting remains “largely descriptive and nonstandard, thus would greatly benefit from a quick and objective assessment. Similarly, clinical trials in UC could efficiently overcome costly central readings.”

Assessing and measuring improvement in endoscopy and histology are difficult parts of treating UC, said David Hudesman, MD, codirector of the Inflammatory Bowel Disease Center at New York University Langone Health.

“We do not know how much improvement is associated with improved long-term outcomes,” Dr. Hudesman said in an interview. “For example, does a patient need complete healing or is 50% better enough?” Dr. Hudesman was not involved with the current research.

“This study showed that AI can predict – with good accuracy – endoscopy and histology scores, as well as 1-year patient outcomes. If this is validated in larger studies, AI can help determine if we should adjust/change therapies or continue, which is very important,” he said.

This research was supported by the National Institute for Health Research Birmingham Biomedical Research Centre. Dr. Iacucci and Dr. Hudesman reported no relevant financial relationships.

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

Researchers have developed and validated an artificial intelligence (AI) tool that can accurately distinguish ulcerative colitis (UC) remission from activity (inflammation) in biopsies and help predict flare-ups.

The AI tool predicted UC disease activity with 89% accuracy and inflammation at the biopsy site with 80% accuracy. Its ability to stratify risk of UC flare was on par with human pathologists.

“This tool in the near future will speed up, simplify, and standardize histological assessment of ulcerative colitis and provide the clinician with accurate prognostic information in real time,” co–lead author Marietta Iacucci, MD, PhD, from the University of Birmingham (England), and University College Cork (Ireland), said in an interview.

“The tool needs to be refined and further validated before it is ready for daily clinical practice. That work is ongoing now,” Dr. Iacucci said.

The researchers describe their advanced AI-based computer-aided detection tool in a study published online in Gastroenterology.
 

‘Strong’ performance

They used 535 digitized biopsies from 273 patients with UC (mean age, 48 years; 41% women) to develop and test the tool. They used a subset of 118 to train it to distinguish remission from activity, 42 to calibrate it, and 375 to test it. An additional 154 biopsies from 58 patients with UC were used to externally validate the tool.

The model also was tested to predict the corresponding endoscopic assessment and occurrence of flares at 12 months.

UC disease activity was defined by three different histologic indices: the Robarts Histopathology Index (RHI), the Nancy Histological Index (NHI), and the newly developed PICaSSO Histologic Remission Index (PHRI).

The AI tool had “strong diagnostic performance to detect disease activity” (PHRI > 0) with an overall area under the receiver operating characteristic curve of 0.87 and sensitivity and specificity of 89% and 85%, respectively.

The researchers note that, while the AI tool was trained for the PHRI, its sensitivity for RHI and NHI histologic remission/activity was also high (94% and 89%, respectively).

Despite the different mix of severity grades, the AI model “maintained a good diagnostic performance, proving its applicability outside the original development setting,” they reported.

The AI tool could also predict the presence of endoscopic inflammation in the biopsy area with about 80% accuracy.

“Though imperfect, this result is consistent with human-assessed correlation between endoscopy and histology,” the researchers noted.

The model predicted the corresponding endoscopic remission/activity with 79% and 82% accuracy for UCEIS and PICaSSO, respectively.

The hazard ratios for disease flare-up between the AI system and pathologists assessed by PHRI was similar (4.64 and 3.56, respectively), “demonstrating the ability of the computer to stratify the risk of flare comparably well to pathologists,” they added. 

Both histology and outcome prediction were confirmed in the external validation cohort.

The AI system delivered results in an average of 9.8 seconds per slide.
 

Potential ‘game changer’

UC is a “complex condition to predict, and developing machine learning–derived systems to make this diagnostic job quicker and more accurate could be a game changer,” Dr. Iacucci said in a news release.

With refinement, the AI tool will have an impact on both clinical trials and daily practice, the researchers wrote. In clinical practice, histological reporting remains “largely descriptive and nonstandard, thus would greatly benefit from a quick and objective assessment. Similarly, clinical trials in UC could efficiently overcome costly central readings.”

Assessing and measuring improvement in endoscopy and histology are difficult parts of treating UC, said David Hudesman, MD, codirector of the Inflammatory Bowel Disease Center at New York University Langone Health.

“We do not know how much improvement is associated with improved long-term outcomes,” Dr. Hudesman said in an interview. “For example, does a patient need complete healing or is 50% better enough?” Dr. Hudesman was not involved with the current research.

“This study showed that AI can predict – with good accuracy – endoscopy and histology scores, as well as 1-year patient outcomes. If this is validated in larger studies, AI can help determine if we should adjust/change therapies or continue, which is very important,” he said.

This research was supported by the National Institute for Health Research Birmingham Biomedical Research Centre. Dr. Iacucci and Dr. Hudesman reported no relevant financial relationships.

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

Researchers have developed and validated an artificial intelligence (AI) tool that can accurately distinguish ulcerative colitis (UC) remission from activity (inflammation) in biopsies and help predict flare-ups.

The AI tool predicted UC disease activity with 89% accuracy and inflammation at the biopsy site with 80% accuracy. Its ability to stratify risk of UC flare was on par with human pathologists.

“This tool in the near future will speed up, simplify, and standardize histological assessment of ulcerative colitis and provide the clinician with accurate prognostic information in real time,” co–lead author Marietta Iacucci, MD, PhD, from the University of Birmingham (England), and University College Cork (Ireland), said in an interview.

“The tool needs to be refined and further validated before it is ready for daily clinical practice. That work is ongoing now,” Dr. Iacucci said.

The researchers describe their advanced AI-based computer-aided detection tool in a study published online in Gastroenterology.
 

‘Strong’ performance

They used 535 digitized biopsies from 273 patients with UC (mean age, 48 years; 41% women) to develop and test the tool. They used a subset of 118 to train it to distinguish remission from activity, 42 to calibrate it, and 375 to test it. An additional 154 biopsies from 58 patients with UC were used to externally validate the tool.

The model also was tested to predict the corresponding endoscopic assessment and occurrence of flares at 12 months.

UC disease activity was defined by three different histologic indices: the Robarts Histopathology Index (RHI), the Nancy Histological Index (NHI), and the newly developed PICaSSO Histologic Remission Index (PHRI).

The AI tool had “strong diagnostic performance to detect disease activity” (PHRI > 0) with an overall area under the receiver operating characteristic curve of 0.87 and sensitivity and specificity of 89% and 85%, respectively.

The researchers note that, while the AI tool was trained for the PHRI, its sensitivity for RHI and NHI histologic remission/activity was also high (94% and 89%, respectively).

Despite the different mix of severity grades, the AI model “maintained a good diagnostic performance, proving its applicability outside the original development setting,” they reported.

The AI tool could also predict the presence of endoscopic inflammation in the biopsy area with about 80% accuracy.

“Though imperfect, this result is consistent with human-assessed correlation between endoscopy and histology,” the researchers noted.

The model predicted the corresponding endoscopic remission/activity with 79% and 82% accuracy for UCEIS and PICaSSO, respectively.

The hazard ratios for disease flare-up between the AI system and pathologists assessed by PHRI was similar (4.64 and 3.56, respectively), “demonstrating the ability of the computer to stratify the risk of flare comparably well to pathologists,” they added. 

Both histology and outcome prediction were confirmed in the external validation cohort.

The AI system delivered results in an average of 9.8 seconds per slide.
 

Potential ‘game changer’

UC is a “complex condition to predict, and developing machine learning–derived systems to make this diagnostic job quicker and more accurate could be a game changer,” Dr. Iacucci said in a news release.

With refinement, the AI tool will have an impact on both clinical trials and daily practice, the researchers wrote. In clinical practice, histological reporting remains “largely descriptive and nonstandard, thus would greatly benefit from a quick and objective assessment. Similarly, clinical trials in UC could efficiently overcome costly central readings.”

Assessing and measuring improvement in endoscopy and histology are difficult parts of treating UC, said David Hudesman, MD, codirector of the Inflammatory Bowel Disease Center at New York University Langone Health.

“We do not know how much improvement is associated with improved long-term outcomes,” Dr. Hudesman said in an interview. “For example, does a patient need complete healing or is 50% better enough?” Dr. Hudesman was not involved with the current research.

“This study showed that AI can predict – with good accuracy – endoscopy and histology scores, as well as 1-year patient outcomes. If this is validated in larger studies, AI can help determine if we should adjust/change therapies or continue, which is very important,” he said.

This research was supported by the National Institute for Health Research Birmingham Biomedical Research Centre. Dr. Iacucci and Dr. Hudesman reported no relevant financial relationships.

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

High school students are injuring themselves more severely even as overall injury rates have declined, according to a new study presented at the annual meeting of the American Academy of Orthopaedic Surgeons.

The study compared injuries from a 4-year period ending in 2019 to data from 2005 and 2006. The overall rate of injuries dropped 9%, from 2.51 injuries per 1,000 athletic games or practices to 2.29 per 1,000; injuries requiring less than 1 week of recovery time fell by 13%. But, the number of head and neck injuries increased by 10%, injuries requiring surgery increased by 1%, and injuries leading to medical disqualification jumped by 11%. 

“It’s wonderful that the injury rate is declining,” said Jordan Neoma Pizzarro, a medical student at George Washington University, Washington, who led the study. “But the data does suggest that the injuries that are happening are worse.”

The increases may also reflect increased education and awareness of how to detect concussions and other injuries that need medical attention, said Micah Lissy, MD, MS, an orthopedic surgeon specializing in sports medicine at Michigan State University, East Lansing. Dr. Lissy cautioned against physicians and others taking the data at face value. 

“We need to be implementing preventive measures wherever possible, but I think we can also consider that there may be some confounding factors in the data,” Dr. Lissy told this news organization. 

Ms. Pizzarro and her team analyzed data collected from athletic trainers at 100 high schools across the country for the ongoing National Health School Sports-Related Injury Surveillance Study.

Athletes participating in sports such as football, soccer, basketball, volleyball, and softball were included in the analysis. Trainers report the number of injuries for every competition and practice, also known as “athletic exposures.”

Boys’ football carried the highest injury rate, with 3.96 injuries per 1,000 AEs, amounting to 44% of all injuries reported. Girls’ soccer and boys’ wrestling followed, with injury rates of 2.65 and 1.56, respectively. 

Sprains and strains accounted for 37% of injuries, followed by concussions (21.6%). The head and/or face was the most injured body site, followed by the ankles and/or knees. Most injuries took place during competitions rather than in practices (relative risk, 3.39; 95% confidence interval, 3.28-3.49; P < .05).

Ms. Pizzarro said that an overall increase in intensity, physical contact, and collisions may account for the spike in more severe injuries.

“Kids are encouraged to specialize in one sport early on and stick with it year-round,” she said. “They’re probably becoming more agile and better athletes, but they’re probably also getting more competitive.” 

Dr. Lissy, who has worked with high school athletes as a surgeon, physical therapist, athletic trainer, and coach, said that some of the increases in severity of injuries may reflect trends in sports over the past two decades: Student athletes have become stronger and faster and have put on more muscle mass. 

“When you have something that’s much larger, moving much faster and with more force, you’re going to have more force when you bump into things,” he said. “This can lead to more significant injuries.”

The study was independently supported. Study authors report no relevant financial relationships. 

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

High school students are injuring themselves more severely even as overall injury rates have declined, according to a new study presented at the annual meeting of the American Academy of Orthopaedic Surgeons.

The study compared injuries from a 4-year period ending in 2019 to data from 2005 and 2006. The overall rate of injuries dropped 9%, from 2.51 injuries per 1,000 athletic games or practices to 2.29 per 1,000; injuries requiring less than 1 week of recovery time fell by 13%. But, the number of head and neck injuries increased by 10%, injuries requiring surgery increased by 1%, and injuries leading to medical disqualification jumped by 11%. 

“It’s wonderful that the injury rate is declining,” said Jordan Neoma Pizzarro, a medical student at George Washington University, Washington, who led the study. “But the data does suggest that the injuries that are happening are worse.”

The increases may also reflect increased education and awareness of how to detect concussions and other injuries that need medical attention, said Micah Lissy, MD, MS, an orthopedic surgeon specializing in sports medicine at Michigan State University, East Lansing. Dr. Lissy cautioned against physicians and others taking the data at face value. 

“We need to be implementing preventive measures wherever possible, but I think we can also consider that there may be some confounding factors in the data,” Dr. Lissy told this news organization. 

Ms. Pizzarro and her team analyzed data collected from athletic trainers at 100 high schools across the country for the ongoing National Health School Sports-Related Injury Surveillance Study.

Athletes participating in sports such as football, soccer, basketball, volleyball, and softball were included in the analysis. Trainers report the number of injuries for every competition and practice, also known as “athletic exposures.”

Boys’ football carried the highest injury rate, with 3.96 injuries per 1,000 AEs, amounting to 44% of all injuries reported. Girls’ soccer and boys’ wrestling followed, with injury rates of 2.65 and 1.56, respectively. 

Sprains and strains accounted for 37% of injuries, followed by concussions (21.6%). The head and/or face was the most injured body site, followed by the ankles and/or knees. Most injuries took place during competitions rather than in practices (relative risk, 3.39; 95% confidence interval, 3.28-3.49; P < .05).

Ms. Pizzarro said that an overall increase in intensity, physical contact, and collisions may account for the spike in more severe injuries.

“Kids are encouraged to specialize in one sport early on and stick with it year-round,” she said. “They’re probably becoming more agile and better athletes, but they’re probably also getting more competitive.” 

Dr. Lissy, who has worked with high school athletes as a surgeon, physical therapist, athletic trainer, and coach, said that some of the increases in severity of injuries may reflect trends in sports over the past two decades: Student athletes have become stronger and faster and have put on more muscle mass. 

“When you have something that’s much larger, moving much faster and with more force, you’re going to have more force when you bump into things,” he said. “This can lead to more significant injuries.”

The study was independently supported. Study authors report no relevant financial relationships. 

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

High school students are injuring themselves more severely even as overall injury rates have declined, according to a new study presented at the annual meeting of the American Academy of Orthopaedic Surgeons.

The study compared injuries from a 4-year period ending in 2019 to data from 2005 and 2006. The overall rate of injuries dropped 9%, from 2.51 injuries per 1,000 athletic games or practices to 2.29 per 1,000; injuries requiring less than 1 week of recovery time fell by 13%. But, the number of head and neck injuries increased by 10%, injuries requiring surgery increased by 1%, and injuries leading to medical disqualification jumped by 11%. 

“It’s wonderful that the injury rate is declining,” said Jordan Neoma Pizzarro, a medical student at George Washington University, Washington, who led the study. “But the data does suggest that the injuries that are happening are worse.”

The increases may also reflect increased education and awareness of how to detect concussions and other injuries that need medical attention, said Micah Lissy, MD, MS, an orthopedic surgeon specializing in sports medicine at Michigan State University, East Lansing. Dr. Lissy cautioned against physicians and others taking the data at face value. 

“We need to be implementing preventive measures wherever possible, but I think we can also consider that there may be some confounding factors in the data,” Dr. Lissy told this news organization. 

Ms. Pizzarro and her team analyzed data collected from athletic trainers at 100 high schools across the country for the ongoing National Health School Sports-Related Injury Surveillance Study.

Athletes participating in sports such as football, soccer, basketball, volleyball, and softball were included in the analysis. Trainers report the number of injuries for every competition and practice, also known as “athletic exposures.”

Boys’ football carried the highest injury rate, with 3.96 injuries per 1,000 AEs, amounting to 44% of all injuries reported. Girls’ soccer and boys’ wrestling followed, with injury rates of 2.65 and 1.56, respectively. 

Sprains and strains accounted for 37% of injuries, followed by concussions (21.6%). The head and/or face was the most injured body site, followed by the ankles and/or knees. Most injuries took place during competitions rather than in practices (relative risk, 3.39; 95% confidence interval, 3.28-3.49; P < .05).

Ms. Pizzarro said that an overall increase in intensity, physical contact, and collisions may account for the spike in more severe injuries.

“Kids are encouraged to specialize in one sport early on and stick with it year-round,” she said. “They’re probably becoming more agile and better athletes, but they’re probably also getting more competitive.” 

Dr. Lissy, who has worked with high school athletes as a surgeon, physical therapist, athletic trainer, and coach, said that some of the increases in severity of injuries may reflect trends in sports over the past two decades: Student athletes have become stronger and faster and have put on more muscle mass. 

“When you have something that’s much larger, moving much faster and with more force, you’re going to have more force when you bump into things,” he said. “This can lead to more significant injuries.”

The study was independently supported. Study authors report no relevant financial relationships. 

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

Physicians often struggle with telling patients when they are unsure about a diagnosis. In the absence of clarity, doctors may fear losing a patient’s trust by appearing unsure.

Yet diagnostic uncertainty is an inevitable part of medicine.

“It’s often uncertain what is really going on. People have lots of unspecific symptoms,” said Gordon D. Schiff, MD, a patient safety researcher at Harvard Medical School and Brigham and Women’s Hospital in Boston.

By one estimate, more than one-third of patients are discharged from an emergency department without a clear diagnosis. Physicians may order more tests to try to resolve uncertainty, but this method is not foolproof and may lead to increased health care costs. Physicians can use an uncertain diagnosis as an opportunity to improve conversations with patients, Dr. Schiff said.

“How do you talk to patients about that? How do you convey that?” Dr. Schiff asked.

To begin to answer these questions, Dr. Schiff and colleagues developed four clinical scenarios carrying unclear diagnoses and asked primary care physicians how they would convey the lack of clarity to patients. The scenarios included an enlarged lymph node in a patient in remission for lymphoma, which could suggest recurrence of the disease but not necessarily; a patient with a new-onset headache; and another patient with an unexplained fever and a respiratory tract infection.

For each vignette, the researchers also asked patient advocates – many of whom had experienced receiving an incorrect diagnosis – for their thoughts on how the conversation should go.

Almost 70 people were consulted (24 primary care physicians, 40 patients, and five experts in informatics and quality and safety). Dr. Schiff and his colleagues produced six standardized elements that should be part of a conversation whenever a diagnosis is unclear.

• The most likely diagnosis, along with any alternatives if this isn’t certain, with phrases such as, “Sometimes we don’t have the answers, but we will keep trying to figure out what is going on.”
• Next steps – lab tests, return visits, etc.
• Expected time frame for patient’s improvement and recovery.
• Full disclosure of the limitations of the physical examination or any lab tests.
• Ways to contact the physician going forward.
• Patient insights on their experience and reaction to what they just heard.

The researchers, who published their findings in JAMA Network Open, recommend that the conversation be transcribed in real time using voice recognition software and a microphone, and then printed for the patient to take home. The physician should make eye contact with the patient during the conversation, they suggested.

“Patients felt it was a conversation, that they actually understood what was said. Most patients felt like they were partners during the encounter,” said Maram Khazen, PhD, a coauthor of the paper, who studies communication dynamics. Dr. Khazen was a visiting postdoctoral fellow with Dr. Schiff during the study, and is now a lecturer at the Max Stern Yezreel Valley College in Israel.

Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston, called the new work “a great start,” but said that the complexity of the field warrants more research into the tool. Dr. Singh was not involved in the study.

Dr. Singh pointed out that many of the patient voices came from spokespeople for advocacy groups, and that these participants are not necessarily representative of actual people with unclear diagnoses.

“The choice of words really matters,” said Dr. Singh, who led a 2018 study that showed that people reacted more negatively when physicians bluntly acknowledged uncertainty than when they walked patients through different possible diagnoses. Dr. Schiff and Dr. Khazen’s framework offers good principles for discussing uncertainty, he added, but further research is needed on the optimal language to use during conversations.

“It’s really encouraging that we’re seeing high-quality research like this, that leverages patient engagement principles,” said Dimitrios Papanagnou, MD, MPH, an emergency medicine physician and vice dean of medicine at Thomas Jefferson University in Philadelphia. 

Dr. Papanagnou, who was not part of the study, called for diverse patients to be part of conversations about diagnostic uncertainty. 

“Are we having patients from diverse experiences, from underrepresented groups, participate in this kind of work?” Dr. Papanagnou asked. Dr. Schiff and Dr. Khazen said they agree that the tool needs to be tested in larger samples of diverse patients.

Some common themes about how to communicate diagnostic uncertainty are emerging in multiple areas of medicine. Dr. Papanagnou helped develop an uncertainty communication checklist for discharging patients from an emergency department to home, with principles similar to those that Dr. Schiff and Dr. Khazen recommend for primary care providers.

The study was funded by Harvard Hospitals’ malpractice insurer, the Controlled Risk Insurance Company. The authors disclosed no relevant financial relationships.

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

Physicians often struggle with telling patients when they are unsure about a diagnosis. In the absence of clarity, doctors may fear losing a patient’s trust by appearing unsure.

Yet diagnostic uncertainty is an inevitable part of medicine.

“It’s often uncertain what is really going on. People have lots of unspecific symptoms,” said Gordon D. Schiff, MD, a patient safety researcher at Harvard Medical School and Brigham and Women’s Hospital in Boston.

By one estimate, more than one-third of patients are discharged from an emergency department without a clear diagnosis. Physicians may order more tests to try to resolve uncertainty, but this method is not foolproof and may lead to increased health care costs. Physicians can use an uncertain diagnosis as an opportunity to improve conversations with patients, Dr. Schiff said.

“How do you talk to patients about that? How do you convey that?” Dr. Schiff asked.

To begin to answer these questions, Dr. Schiff and colleagues developed four clinical scenarios carrying unclear diagnoses and asked primary care physicians how they would convey the lack of clarity to patients. The scenarios included an enlarged lymph node in a patient in remission for lymphoma, which could suggest recurrence of the disease but not necessarily; a patient with a new-onset headache; and another patient with an unexplained fever and a respiratory tract infection.

For each vignette, the researchers also asked patient advocates – many of whom had experienced receiving an incorrect diagnosis – for their thoughts on how the conversation should go.

Almost 70 people were consulted (24 primary care physicians, 40 patients, and five experts in informatics and quality and safety). Dr. Schiff and his colleagues produced six standardized elements that should be part of a conversation whenever a diagnosis is unclear.

• The most likely diagnosis, along with any alternatives if this isn’t certain, with phrases such as, “Sometimes we don’t have the answers, but we will keep trying to figure out what is going on.”
• Next steps – lab tests, return visits, etc.
• Expected time frame for patient’s improvement and recovery.
• Full disclosure of the limitations of the physical examination or any lab tests.
• Ways to contact the physician going forward.
• Patient insights on their experience and reaction to what they just heard.

The researchers, who published their findings in JAMA Network Open, recommend that the conversation be transcribed in real time using voice recognition software and a microphone, and then printed for the patient to take home. The physician should make eye contact with the patient during the conversation, they suggested.

“Patients felt it was a conversation, that they actually understood what was said. Most patients felt like they were partners during the encounter,” said Maram Khazen, PhD, a coauthor of the paper, who studies communication dynamics. Dr. Khazen was a visiting postdoctoral fellow with Dr. Schiff during the study, and is now a lecturer at the Max Stern Yezreel Valley College in Israel.

Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston, called the new work “a great start,” but said that the complexity of the field warrants more research into the tool. Dr. Singh was not involved in the study.

Dr. Singh pointed out that many of the patient voices came from spokespeople for advocacy groups, and that these participants are not necessarily representative of actual people with unclear diagnoses.

“The choice of words really matters,” said Dr. Singh, who led a 2018 study that showed that people reacted more negatively when physicians bluntly acknowledged uncertainty than when they walked patients through different possible diagnoses. Dr. Schiff and Dr. Khazen’s framework offers good principles for discussing uncertainty, he added, but further research is needed on the optimal language to use during conversations.

“It’s really encouraging that we’re seeing high-quality research like this, that leverages patient engagement principles,” said Dimitrios Papanagnou, MD, MPH, an emergency medicine physician and vice dean of medicine at Thomas Jefferson University in Philadelphia. 

Dr. Papanagnou, who was not part of the study, called for diverse patients to be part of conversations about diagnostic uncertainty. 

“Are we having patients from diverse experiences, from underrepresented groups, participate in this kind of work?” Dr. Papanagnou asked. Dr. Schiff and Dr. Khazen said they agree that the tool needs to be tested in larger samples of diverse patients.

Some common themes about how to communicate diagnostic uncertainty are emerging in multiple areas of medicine. Dr. Papanagnou helped develop an uncertainty communication checklist for discharging patients from an emergency department to home, with principles similar to those that Dr. Schiff and Dr. Khazen recommend for primary care providers.

The study was funded by Harvard Hospitals’ malpractice insurer, the Controlled Risk Insurance Company. The authors disclosed no relevant financial relationships.

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

Physicians often struggle with telling patients when they are unsure about a diagnosis. In the absence of clarity, doctors may fear losing a patient’s trust by appearing unsure.

Yet diagnostic uncertainty is an inevitable part of medicine.

“It’s often uncertain what is really going on. People have lots of unspecific symptoms,” said Gordon D. Schiff, MD, a patient safety researcher at Harvard Medical School and Brigham and Women’s Hospital in Boston.

By one estimate, more than one-third of patients are discharged from an emergency department without a clear diagnosis. Physicians may order more tests to try to resolve uncertainty, but this method is not foolproof and may lead to increased health care costs. Physicians can use an uncertain diagnosis as an opportunity to improve conversations with patients, Dr. Schiff said.

“How do you talk to patients about that? How do you convey that?” Dr. Schiff asked.

To begin to answer these questions, Dr. Schiff and colleagues developed four clinical scenarios carrying unclear diagnoses and asked primary care physicians how they would convey the lack of clarity to patients. The scenarios included an enlarged lymph node in a patient in remission for lymphoma, which could suggest recurrence of the disease but not necessarily; a patient with a new-onset headache; and another patient with an unexplained fever and a respiratory tract infection.

For each vignette, the researchers also asked patient advocates – many of whom had experienced receiving an incorrect diagnosis – for their thoughts on how the conversation should go.

Almost 70 people were consulted (24 primary care physicians, 40 patients, and five experts in informatics and quality and safety). Dr. Schiff and his colleagues produced six standardized elements that should be part of a conversation whenever a diagnosis is unclear.

• The most likely diagnosis, along with any alternatives if this isn’t certain, with phrases such as, “Sometimes we don’t have the answers, but we will keep trying to figure out what is going on.”
• Next steps – lab tests, return visits, etc.
• Expected time frame for patient’s improvement and recovery.
• Full disclosure of the limitations of the physical examination or any lab tests.
• Ways to contact the physician going forward.
• Patient insights on their experience and reaction to what they just heard.

The researchers, who published their findings in JAMA Network Open, recommend that the conversation be transcribed in real time using voice recognition software and a microphone, and then printed for the patient to take home. The physician should make eye contact with the patient during the conversation, they suggested.

“Patients felt it was a conversation, that they actually understood what was said. Most patients felt like they were partners during the encounter,” said Maram Khazen, PhD, a coauthor of the paper, who studies communication dynamics. Dr. Khazen was a visiting postdoctoral fellow with Dr. Schiff during the study, and is now a lecturer at the Max Stern Yezreel Valley College in Israel.

Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston, called the new work “a great start,” but said that the complexity of the field warrants more research into the tool. Dr. Singh was not involved in the study.

Dr. Singh pointed out that many of the patient voices came from spokespeople for advocacy groups, and that these participants are not necessarily representative of actual people with unclear diagnoses.

“The choice of words really matters,” said Dr. Singh, who led a 2018 study that showed that people reacted more negatively when physicians bluntly acknowledged uncertainty than when they walked patients through different possible diagnoses. Dr. Schiff and Dr. Khazen’s framework offers good principles for discussing uncertainty, he added, but further research is needed on the optimal language to use during conversations.

“It’s really encouraging that we’re seeing high-quality research like this, that leverages patient engagement principles,” said Dimitrios Papanagnou, MD, MPH, an emergency medicine physician and vice dean of medicine at Thomas Jefferson University in Philadelphia. 

Dr. Papanagnou, who was not part of the study, called for diverse patients to be part of conversations about diagnostic uncertainty. 

“Are we having patients from diverse experiences, from underrepresented groups, participate in this kind of work?” Dr. Papanagnou asked. Dr. Schiff and Dr. Khazen said they agree that the tool needs to be tested in larger samples of diverse patients.

Some common themes about how to communicate diagnostic uncertainty are emerging in multiple areas of medicine. Dr. Papanagnou helped develop an uncertainty communication checklist for discharging patients from an emergency department to home, with principles similar to those that Dr. Schiff and Dr. Khazen recommend for primary care providers.

The study was funded by Harvard Hospitals’ malpractice insurer, the Controlled Risk Insurance Company. The authors disclosed no relevant financial relationships.