Federal Practitioner

A new guideline aims to help primary care doctors differentiate pollen food syndrome (PFS) – a cross-reactive allergic reaction to certain raw, but not cooked, plant foods – from other food allergies.

The guideline from the British Society of Allergy and Clinical Immunology (BSACI) focuses on birch tree pollen, the major sensitizing PFS allergen in Northern Europe. Providers may be able to diagnose PFS related to birch pollen from clinical history alone, including the foods involved and the rapidity of symptom onset, write lead author Isabel J. Skypala, PhD, RD, of Imperial College London, and her colleagues.

The new BSACI guideline for diagnosis and management of PFS was published in Clinical & Experimental Allergy.
 

PFS is common and increasingly prevalent

PFS – also called oral allergy syndrome and pollen food allergy syndrome – is common and increasingly prevalent. PFS can begin at any age but usually starts in pollen-sensitized school-age children and adults with seasonal allergic rhinitis.

Symptoms from similar proteins in food

Mild to moderate allergic symptoms develop quickly when people sensitized to birch pollen eat raw plant foods that contain proteins similar to those in the pollen, such as pathogenesis-related protein PR-10. The allergens are broken down by cooking or processing.

Symptoms usually occur immediately or within 15 minutes of eating. Patients may have tingling; itching or soreness in the mouth, throat, or ears; mild lip and oral mucosa angioedema; itchy hands, sneezing, or eye symptoms; tongue or pharynx angioedema; perioral rash; cough; abdominal pain; nausea; and/or worsening of eczema. In children, itch and rash may predominate.
 

Triggers depend on pollen type

PFS triggers vary depending on a person’s pollen sensitization, which is affected by their geographic area and local dietary habits. In the United Kingdom, almost 70% of birch-allergic adults and more than 40% of birch-allergic children have PFS, the authors write.

Typical triggers include eating apples, stone fruits, kiwis, carrots, celery, hazelnuts, almonds, walnuts, soymilk, and peanuts, as well as peeling potatoes or other root vegetables. Freshly prepared vegetable or fruit smoothies or juices, celery, soymilk, raw nuts, large quantities of roasted nuts, and concentrated nut products can cause more severe reactions.
 

Diagnostic clinical history

If a patient answers yes to these questions, they almost certainly have PFS, the authors write:

• Are symptoms caused by raw fruits, nuts, carrots, or celery?
• Are the same trigger foods tolerated when they’re cooked well or roasted?
• Do symptoms come immediately or within a few minutes of eating?
• Do symptoms occur in the oropharynx and include tingling, itching, or swelling?
• Does the patient have seasonal allergic rhinitis or sensitization to pollen?

Testing needed for some cases

Allergy tests may be needed for people who report atypical or severe reactions or who also react to cooked or processed plant foods, such as roasted nuts, nuts in foods, fruits or vegetables in juices and smoothies, and soy products other than milk. Tests may also be needed for people who react to foods that are not linked with PFS, such as cashews, pistachios, macadamias, sesame seeds, beans, lentils, and chickpeas.

Whether PFS reactions also occur to roasted hazelnuts, almonds, walnuts, Brazil nuts, or peanuts, either alone or in composite foods such as chocolates, spreads, desserts, and snacks, is unclear.

An oral food challenge to confirm PFS is needed only if the history and diagnostic tests are inconclusive or if the patient is avoiding multiple foods.
 

Dietary management

PFS is managed by excluding known trigger foods. This becomes challenging for patients with preexisting food allergies and for vegetarians and vegans.

Personalized dietary advice is needed to avoid nutritional imbalance, minimize anxiety and unnecessary food restrictions, and improve quality of life. Reactions after accidental exposure often resolve without medication, and if antihistamines are needed, they rarely require self-injectable devices.
 

Guideline helpful beyond the United Kingdom and birch pollen

Allyson S. Larkin, MD, associate professor of pediatrics at the University of Pittsburgh School of Medicine, told this news organization in an email that the guideline summarizes in great detail the pathophysiology behind PFS and highlights how component testing may help diagnose patients and manage the condition.

“Patients worry very much about the progression and severity of allergic reactions,” said Dr. Larkin, who was not involved in the guideline development.

“As the authors note, recognizing the nutritional consequences of dietary restrictions is important, and nutrition consults and suitable alternative suggestions are very helpful for these patients, especially for those with food allergy or who are vegetarian or vegan.”

Jill A. Poole, MD, professor of medicine and chief of the Division of Allergy and Immunology at the University of Nebraska College of Medicine, Omaha, noted that PFS, although common, is underrecognized by the public and by health care providers.

“People are not allergic to the specific food, but they are allergic to a seasonal allergen, such as birch tree, that cross-reacts with the food protein, which is typically changed with cooking,” she explained in an email.

“This differs from reactions by those who have moderate to severe allergic food-specific reactions that may include systemic reactions like anaphylaxis from eating certain foods,” she said.

“Importantly, the number of cross-reacting foods with seasonal pollens continues to grow, and the extent of testing has expanded in recent years,” advised Dr. Poole, who also was not involved in the guideline development. 

The authors recommend further related research into food immunotherapy and other novel PFS treatments. They also want to raise awareness of factors affecting PFS prevalence, such as increased spread and allergenicity of pollen due to climate change, pollution, the global consumption of previously local traditional foods, and the increase in vegetarian and vegan diets.

The authors, Dr. Larkin, and Dr. Poole report no relevant financial relationships involving this guideline. The guideline was not funded.

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

A new guideline aims to help primary care doctors differentiate pollen food syndrome (PFS) – a cross-reactive allergic reaction to certain raw, but not cooked, plant foods – from other food allergies.

The guideline from the British Society of Allergy and Clinical Immunology (BSACI) focuses on birch tree pollen, the major sensitizing PFS allergen in Northern Europe. Providers may be able to diagnose PFS related to birch pollen from clinical history alone, including the foods involved and the rapidity of symptom onset, write lead author Isabel J. Skypala, PhD, RD, of Imperial College London, and her colleagues.

The new BSACI guideline for diagnosis and management of PFS was published in Clinical & Experimental Allergy.
 

PFS is common and increasingly prevalent

PFS – also called oral allergy syndrome and pollen food allergy syndrome – is common and increasingly prevalent. PFS can begin at any age but usually starts in pollen-sensitized school-age children and adults with seasonal allergic rhinitis.

Symptoms from similar proteins in food

Mild to moderate allergic symptoms develop quickly when people sensitized to birch pollen eat raw plant foods that contain proteins similar to those in the pollen, such as pathogenesis-related protein PR-10. The allergens are broken down by cooking or processing.

Symptoms usually occur immediately or within 15 minutes of eating. Patients may have tingling; itching or soreness in the mouth, throat, or ears; mild lip and oral mucosa angioedema; itchy hands, sneezing, or eye symptoms; tongue or pharynx angioedema; perioral rash; cough; abdominal pain; nausea; and/or worsening of eczema. In children, itch and rash may predominate.
 

Triggers depend on pollen type

PFS triggers vary depending on a person’s pollen sensitization, which is affected by their geographic area and local dietary habits. In the United Kingdom, almost 70% of birch-allergic adults and more than 40% of birch-allergic children have PFS, the authors write.

Typical triggers include eating apples, stone fruits, kiwis, carrots, celery, hazelnuts, almonds, walnuts, soymilk, and peanuts, as well as peeling potatoes or other root vegetables. Freshly prepared vegetable or fruit smoothies or juices, celery, soymilk, raw nuts, large quantities of roasted nuts, and concentrated nut products can cause more severe reactions.
 

Diagnostic clinical history

If a patient answers yes to these questions, they almost certainly have PFS, the authors write:

• Are symptoms caused by raw fruits, nuts, carrots, or celery?
• Are the same trigger foods tolerated when they’re cooked well or roasted?
• Do symptoms come immediately or within a few minutes of eating?
• Do symptoms occur in the oropharynx and include tingling, itching, or swelling?
• Does the patient have seasonal allergic rhinitis or sensitization to pollen?

Testing needed for some cases

Allergy tests may be needed for people who report atypical or severe reactions or who also react to cooked or processed plant foods, such as roasted nuts, nuts in foods, fruits or vegetables in juices and smoothies, and soy products other than milk. Tests may also be needed for people who react to foods that are not linked with PFS, such as cashews, pistachios, macadamias, sesame seeds, beans, lentils, and chickpeas.

Whether PFS reactions also occur to roasted hazelnuts, almonds, walnuts, Brazil nuts, or peanuts, either alone or in composite foods such as chocolates, spreads, desserts, and snacks, is unclear.

An oral food challenge to confirm PFS is needed only if the history and diagnostic tests are inconclusive or if the patient is avoiding multiple foods.
 

Dietary management

PFS is managed by excluding known trigger foods. This becomes challenging for patients with preexisting food allergies and for vegetarians and vegans.

Personalized dietary advice is needed to avoid nutritional imbalance, minimize anxiety and unnecessary food restrictions, and improve quality of life. Reactions after accidental exposure often resolve without medication, and if antihistamines are needed, they rarely require self-injectable devices.
 

Guideline helpful beyond the United Kingdom and birch pollen

Allyson S. Larkin, MD, associate professor of pediatrics at the University of Pittsburgh School of Medicine, told this news organization in an email that the guideline summarizes in great detail the pathophysiology behind PFS and highlights how component testing may help diagnose patients and manage the condition.

“Patients worry very much about the progression and severity of allergic reactions,” said Dr. Larkin, who was not involved in the guideline development.

“As the authors note, recognizing the nutritional consequences of dietary restrictions is important, and nutrition consults and suitable alternative suggestions are very helpful for these patients, especially for those with food allergy or who are vegetarian or vegan.”

Jill A. Poole, MD, professor of medicine and chief of the Division of Allergy and Immunology at the University of Nebraska College of Medicine, Omaha, noted that PFS, although common, is underrecognized by the public and by health care providers.

“People are not allergic to the specific food, but they are allergic to a seasonal allergen, such as birch tree, that cross-reacts with the food protein, which is typically changed with cooking,” she explained in an email.

“This differs from reactions by those who have moderate to severe allergic food-specific reactions that may include systemic reactions like anaphylaxis from eating certain foods,” she said.

“Importantly, the number of cross-reacting foods with seasonal pollens continues to grow, and the extent of testing has expanded in recent years,” advised Dr. Poole, who also was not involved in the guideline development. 

The authors recommend further related research into food immunotherapy and other novel PFS treatments. They also want to raise awareness of factors affecting PFS prevalence, such as increased spread and allergenicity of pollen due to climate change, pollution, the global consumption of previously local traditional foods, and the increase in vegetarian and vegan diets.

The authors, Dr. Larkin, and Dr. Poole report no relevant financial relationships involving this guideline. The guideline was not funded.

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

A new guideline aims to help primary care doctors differentiate pollen food syndrome (PFS) – a cross-reactive allergic reaction to certain raw, but not cooked, plant foods – from other food allergies.

The guideline from the British Society of Allergy and Clinical Immunology (BSACI) focuses on birch tree pollen, the major sensitizing PFS allergen in Northern Europe. Providers may be able to diagnose PFS related to birch pollen from clinical history alone, including the foods involved and the rapidity of symptom onset, write lead author Isabel J. Skypala, PhD, RD, of Imperial College London, and her colleagues.

The new BSACI guideline for diagnosis and management of PFS was published in Clinical & Experimental Allergy.
 

PFS is common and increasingly prevalent

PFS – also called oral allergy syndrome and pollen food allergy syndrome – is common and increasingly prevalent. PFS can begin at any age but usually starts in pollen-sensitized school-age children and adults with seasonal allergic rhinitis.

Symptoms from similar proteins in food

Mild to moderate allergic symptoms develop quickly when people sensitized to birch pollen eat raw plant foods that contain proteins similar to those in the pollen, such as pathogenesis-related protein PR-10. The allergens are broken down by cooking or processing.

Symptoms usually occur immediately or within 15 minutes of eating. Patients may have tingling; itching or soreness in the mouth, throat, or ears; mild lip and oral mucosa angioedema; itchy hands, sneezing, or eye symptoms; tongue or pharynx angioedema; perioral rash; cough; abdominal pain; nausea; and/or worsening of eczema. In children, itch and rash may predominate.
 

Triggers depend on pollen type

PFS triggers vary depending on a person’s pollen sensitization, which is affected by their geographic area and local dietary habits. In the United Kingdom, almost 70% of birch-allergic adults and more than 40% of birch-allergic children have PFS, the authors write.

Typical triggers include eating apples, stone fruits, kiwis, carrots, celery, hazelnuts, almonds, walnuts, soymilk, and peanuts, as well as peeling potatoes or other root vegetables. Freshly prepared vegetable or fruit smoothies or juices, celery, soymilk, raw nuts, large quantities of roasted nuts, and concentrated nut products can cause more severe reactions.
 

Diagnostic clinical history

If a patient answers yes to these questions, they almost certainly have PFS, the authors write:

• Are symptoms caused by raw fruits, nuts, carrots, or celery?
• Are the same trigger foods tolerated when they’re cooked well or roasted?
• Do symptoms come immediately or within a few minutes of eating?
• Do symptoms occur in the oropharynx and include tingling, itching, or swelling?
• Does the patient have seasonal allergic rhinitis or sensitization to pollen?

Testing needed for some cases

Allergy tests may be needed for people who report atypical or severe reactions or who also react to cooked or processed plant foods, such as roasted nuts, nuts in foods, fruits or vegetables in juices and smoothies, and soy products other than milk. Tests may also be needed for people who react to foods that are not linked with PFS, such as cashews, pistachios, macadamias, sesame seeds, beans, lentils, and chickpeas.

Whether PFS reactions also occur to roasted hazelnuts, almonds, walnuts, Brazil nuts, or peanuts, either alone or in composite foods such as chocolates, spreads, desserts, and snacks, is unclear.

An oral food challenge to confirm PFS is needed only if the history and diagnostic tests are inconclusive or if the patient is avoiding multiple foods.
 

Dietary management

PFS is managed by excluding known trigger foods. This becomes challenging for patients with preexisting food allergies and for vegetarians and vegans.

Personalized dietary advice is needed to avoid nutritional imbalance, minimize anxiety and unnecessary food restrictions, and improve quality of life. Reactions after accidental exposure often resolve without medication, and if antihistamines are needed, they rarely require self-injectable devices.
 

Guideline helpful beyond the United Kingdom and birch pollen

Allyson S. Larkin, MD, associate professor of pediatrics at the University of Pittsburgh School of Medicine, told this news organization in an email that the guideline summarizes in great detail the pathophysiology behind PFS and highlights how component testing may help diagnose patients and manage the condition.

“Patients worry very much about the progression and severity of allergic reactions,” said Dr. Larkin, who was not involved in the guideline development.

“As the authors note, recognizing the nutritional consequences of dietary restrictions is important, and nutrition consults and suitable alternative suggestions are very helpful for these patients, especially for those with food allergy or who are vegetarian or vegan.”

Jill A. Poole, MD, professor of medicine and chief of the Division of Allergy and Immunology at the University of Nebraska College of Medicine, Omaha, noted that PFS, although common, is underrecognized by the public and by health care providers.

“People are not allergic to the specific food, but they are allergic to a seasonal allergen, such as birch tree, that cross-reacts with the food protein, which is typically changed with cooking,” she explained in an email.

“This differs from reactions by those who have moderate to severe allergic food-specific reactions that may include systemic reactions like anaphylaxis from eating certain foods,” she said.

“Importantly, the number of cross-reacting foods with seasonal pollens continues to grow, and the extent of testing has expanded in recent years,” advised Dr. Poole, who also was not involved in the guideline development. 

The authors recommend further related research into food immunotherapy and other novel PFS treatments. They also want to raise awareness of factors affecting PFS prevalence, such as increased spread and allergenicity of pollen due to climate change, pollution, the global consumption of previously local traditional foods, and the increase in vegetarian and vegan diets.

The authors, Dr. Larkin, and Dr. Poole report no relevant financial relationships involving this guideline. The guideline was not funded.

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

Mexican researchers found no direct association between SARS-CoV-2 vaccination and worsening symptoms among 60 patients with Parkinson’s disease. Nonmotor symptoms seemed to improve after SARS-CoV-2 vaccination, although the investigators could not verify a causal relationship.

Vaccination programs should continue for patients with Parkinson’s disease, they said, reporting their clinical results at the International Congress of Parkinson’s Disease and Movement Disorders.

The International Parkinson and Movement Disorder Society has recommended vaccining patients with Parkinson’s disease. “All approved mRNA-based and viral vector vaccines are not expected to interact with Parkinson’s disease, but patients [still] report concern with regard to the benefits, risks, and safeness in Parkinson’s disease,” Mayela Rodríguez-Violante, MD, MSc, and colleagues wrote in an abstract of their findings.

Social isolation may be contributing to these beliefs and concerns, though this is inconclusive.

Investigators from Mexico City conducted a retrospective study of patients with Parkinson’s disease to see how COVID-19 vaccination affected motor and nonmotor symptoms. They enlisted 60 patients (66.7% were male; aged 65.7 ± 11.35 years) who received either a vector-viral vaccine (Vaxzevria Coronavirus) or an mRNA vaccine (BNT162b2).

A Wilcoxon signed-rank test assessed scale differences before and after vaccination, measuring motor involvement (Unified Parkinson’s Disease Rating Scale), nonmotor involvement (Non-Motor Rating Scale [NMSS]), cognitive impairment (Montreal Cognitive Assessment), and quality of life (8-item Parkinson’s Disease Questionnaire index).

Investigators found no significant difference between scales, although they did notice a marked improvement in non-motor symptoms.

“The main takeaway is that vaccination against COVID-19 does not appear to worsen motor or nonmotor symptoms in persons with Parkinson’s disease. The benefits outweigh the risks,” said Dr. Rodríguez-Violante, the study’s lead author and a movement disorder specialist at the National Institute of Neurology and Neurosurgery, Mexico City.

Next steps are to increase the sample size to see if it’s possible to have a similar number in terms of type of vaccine, said Dr. Rodríguez-Violante. “Also, the data presented refers to primary series doses so booster effects will also be studied.”

Few studies have looked at vaccines and their possible effects on this patient population. However, a 2021 study of 181 patients with Parkinson’s disease reported that 2 (1.1%) had adverse effects after receiving the BNT162b2 mRNA vaccine. One of the patients, a 61-year-old woman with a decade-long history of Parkinson’s disease, developed severe, continuous, generalized dyskinesia 6 hours after a first dose of vaccine. The second patient was 79 years old and had Parkinson’s disease for 5 years. She developed fever, confusion, delusions, and continuous severe dyskinesia for 3 days following her vaccination.

“This highlights that there is a variability in the response triggered by the vaccine that might likely depend on individual immunological profiles … clinicians should be aware of this possibility and monitor their patients after they receive their vaccination,” Roberto Erro, MD, PhD and colleagues wrote in the Movement Disorders journal.

Mexican researchers found no direct association between SARS-CoV-2 vaccination and worsening symptoms among 60 patients with Parkinson’s disease. Nonmotor symptoms seemed to improve after SARS-CoV-2 vaccination, although the investigators could not verify a causal relationship.

Vaccination programs should continue for patients with Parkinson’s disease, they said, reporting their clinical results at the International Congress of Parkinson’s Disease and Movement Disorders.

The International Parkinson and Movement Disorder Society has recommended vaccining patients with Parkinson’s disease. “All approved mRNA-based and viral vector vaccines are not expected to interact with Parkinson’s disease, but patients [still] report concern with regard to the benefits, risks, and safeness in Parkinson’s disease,” Mayela Rodríguez-Violante, MD, MSc, and colleagues wrote in an abstract of their findings.

Social isolation may be contributing to these beliefs and concerns, though this is inconclusive.

Investigators from Mexico City conducted a retrospective study of patients with Parkinson’s disease to see how COVID-19 vaccination affected motor and nonmotor symptoms. They enlisted 60 patients (66.7% were male; aged 65.7 ± 11.35 years) who received either a vector-viral vaccine (Vaxzevria Coronavirus) or an mRNA vaccine (BNT162b2).

A Wilcoxon signed-rank test assessed scale differences before and after vaccination, measuring motor involvement (Unified Parkinson’s Disease Rating Scale), nonmotor involvement (Non-Motor Rating Scale [NMSS]), cognitive impairment (Montreal Cognitive Assessment), and quality of life (8-item Parkinson’s Disease Questionnaire index).

Investigators found no significant difference between scales, although they did notice a marked improvement in non-motor symptoms.

“The main takeaway is that vaccination against COVID-19 does not appear to worsen motor or nonmotor symptoms in persons with Parkinson’s disease. The benefits outweigh the risks,” said Dr. Rodríguez-Violante, the study’s lead author and a movement disorder specialist at the National Institute of Neurology and Neurosurgery, Mexico City.

Next steps are to increase the sample size to see if it’s possible to have a similar number in terms of type of vaccine, said Dr. Rodríguez-Violante. “Also, the data presented refers to primary series doses so booster effects will also be studied.”

Few studies have looked at vaccines and their possible effects on this patient population. However, a 2021 study of 181 patients with Parkinson’s disease reported that 2 (1.1%) had adverse effects after receiving the BNT162b2 mRNA vaccine. One of the patients, a 61-year-old woman with a decade-long history of Parkinson’s disease, developed severe, continuous, generalized dyskinesia 6 hours after a first dose of vaccine. The second patient was 79 years old and had Parkinson’s disease for 5 years. She developed fever, confusion, delusions, and continuous severe dyskinesia for 3 days following her vaccination.

“This highlights that there is a variability in the response triggered by the vaccine that might likely depend on individual immunological profiles … clinicians should be aware of this possibility and monitor their patients after they receive their vaccination,” Roberto Erro, MD, PhD and colleagues wrote in the Movement Disorders journal.

Mexican researchers found no direct association between SARS-CoV-2 vaccination and worsening symptoms among 60 patients with Parkinson’s disease. Nonmotor symptoms seemed to improve after SARS-CoV-2 vaccination, although the investigators could not verify a causal relationship.

Vaccination programs should continue for patients with Parkinson’s disease, they said, reporting their clinical results at the International Congress of Parkinson’s Disease and Movement Disorders.

The International Parkinson and Movement Disorder Society has recommended vaccining patients with Parkinson’s disease. “All approved mRNA-based and viral vector vaccines are not expected to interact with Parkinson’s disease, but patients [still] report concern with regard to the benefits, risks, and safeness in Parkinson’s disease,” Mayela Rodríguez-Violante, MD, MSc, and colleagues wrote in an abstract of their findings.

Social isolation may be contributing to these beliefs and concerns, though this is inconclusive.

Investigators from Mexico City conducted a retrospective study of patients with Parkinson’s disease to see how COVID-19 vaccination affected motor and nonmotor symptoms. They enlisted 60 patients (66.7% were male; aged 65.7 ± 11.35 years) who received either a vector-viral vaccine (Vaxzevria Coronavirus) or an mRNA vaccine (BNT162b2).

A Wilcoxon signed-rank test assessed scale differences before and after vaccination, measuring motor involvement (Unified Parkinson’s Disease Rating Scale), nonmotor involvement (Non-Motor Rating Scale [NMSS]), cognitive impairment (Montreal Cognitive Assessment), and quality of life (8-item Parkinson’s Disease Questionnaire index).

Investigators found no significant difference between scales, although they did notice a marked improvement in non-motor symptoms.

“The main takeaway is that vaccination against COVID-19 does not appear to worsen motor or nonmotor symptoms in persons with Parkinson’s disease. The benefits outweigh the risks,” said Dr. Rodríguez-Violante, the study’s lead author and a movement disorder specialist at the National Institute of Neurology and Neurosurgery, Mexico City.

Next steps are to increase the sample size to see if it’s possible to have a similar number in terms of type of vaccine, said Dr. Rodríguez-Violante. “Also, the data presented refers to primary series doses so booster effects will also be studied.”

Few studies have looked at vaccines and their possible effects on this patient population. However, a 2021 study of 181 patients with Parkinson’s disease reported that 2 (1.1%) had adverse effects after receiving the BNT162b2 mRNA vaccine. One of the patients, a 61-year-old woman with a decade-long history of Parkinson’s disease, developed severe, continuous, generalized dyskinesia 6 hours after a first dose of vaccine. The second patient was 79 years old and had Parkinson’s disease for 5 years. She developed fever, confusion, delusions, and continuous severe dyskinesia for 3 days following her vaccination.

“This highlights that there is a variability in the response triggered by the vaccine that might likely depend on individual immunological profiles … clinicians should be aware of this possibility and monitor their patients after they receive their vaccination,” Roberto Erro, MD, PhD and colleagues wrote in the Movement Disorders journal.

The Food and Drug Administration has approved terlipressin (Terlivaz), the first and only drug approved for patients with hepatorenal syndrome (HRS).

HRS is characterized by progressive deterioration in kidney function in people with advanced liver disease.

Terlipressin is an injectable synthetic vasopressin analogue indicated for patients with HRS who are experiencing rapid deterioration of kidney function (type 1 HRS). The condition affects an estimated 35,000 Americans annually.

The safety and efficacy of terlipressin for type 1 HRS was assessed in the phase 3 CONFIRM trial, which involved 300 patients in the United States and Canada.

Patients received an injection of terlipressin (0.85 mg) or placebo every 6 hours for a maximum of 14 days. The dose was adjusted on the basis of changes in kidney function.

Twenty-nine percent of patients in the terlipressin group experienced improvement in kidney function, vs. 16% in the placebo group.

The CONFIRM trial met its primary endpoint of verified HRS reversal, defined as renal function improvement, avoidance of dialysis, and short-term survival (P = .012).

To achieve this endpoint, patients had to have two consecutive serum creatinine (SCr) values of ≤ 1.5 mg/dL at least 2 hours apart by day 14 or be discharged from the hospital.

The most commonly observed adverse reactions that occurred in at least 4% of patients treated with terlipressin were abdominal pain (19.5%), nausea (16%), respiratory failure (15.5%), diarrhea (13%), and dyspnea (12.5%).

Results of the CONFIRM trial were published in The New England Journal of Medicine.

“Diagnosing and treating HRS can be challenging, and every minute counts when managing patients who have it,” said Steven Romano, MD, executive vice president and chief scientific officer at Mallinckrodt, which makes the drug.

“Terlivaz gives physicians the first FDA-approved option for treating HRS patients with rapid reduction in kidney function that may help them improve kidney function and lessen the associated need for renal replacement therapy, such as dialysis,” Dr. Romano said.

The company plans to launch the product in the coming weeks.

The application for terlipressin for HRS was granted priority review and fast-track status, as well as orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

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

The Food and Drug Administration has approved terlipressin (Terlivaz), the first and only drug approved for patients with hepatorenal syndrome (HRS).

HRS is characterized by progressive deterioration in kidney function in people with advanced liver disease.

Terlipressin is an injectable synthetic vasopressin analogue indicated for patients with HRS who are experiencing rapid deterioration of kidney function (type 1 HRS). The condition affects an estimated 35,000 Americans annually.

The safety and efficacy of terlipressin for type 1 HRS was assessed in the phase 3 CONFIRM trial, which involved 300 patients in the United States and Canada.

Patients received an injection of terlipressin (0.85 mg) or placebo every 6 hours for a maximum of 14 days. The dose was adjusted on the basis of changes in kidney function.

Twenty-nine percent of patients in the terlipressin group experienced improvement in kidney function, vs. 16% in the placebo group.

The CONFIRM trial met its primary endpoint of verified HRS reversal, defined as renal function improvement, avoidance of dialysis, and short-term survival (P = .012).

To achieve this endpoint, patients had to have two consecutive serum creatinine (SCr) values of ≤ 1.5 mg/dL at least 2 hours apart by day 14 or be discharged from the hospital.

The most commonly observed adverse reactions that occurred in at least 4% of patients treated with terlipressin were abdominal pain (19.5%), nausea (16%), respiratory failure (15.5%), diarrhea (13%), and dyspnea (12.5%).

Results of the CONFIRM trial were published in The New England Journal of Medicine.

“Diagnosing and treating HRS can be challenging, and every minute counts when managing patients who have it,” said Steven Romano, MD, executive vice president and chief scientific officer at Mallinckrodt, which makes the drug.

“Terlivaz gives physicians the first FDA-approved option for treating HRS patients with rapid reduction in kidney function that may help them improve kidney function and lessen the associated need for renal replacement therapy, such as dialysis,” Dr. Romano said.

The company plans to launch the product in the coming weeks.

The application for terlipressin for HRS was granted priority review and fast-track status, as well as orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

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

The Food and Drug Administration has approved terlipressin (Terlivaz), the first and only drug approved for patients with hepatorenal syndrome (HRS).

HRS is characterized by progressive deterioration in kidney function in people with advanced liver disease.

Terlipressin is an injectable synthetic vasopressin analogue indicated for patients with HRS who are experiencing rapid deterioration of kidney function (type 1 HRS). The condition affects an estimated 35,000 Americans annually.

The safety and efficacy of terlipressin for type 1 HRS was assessed in the phase 3 CONFIRM trial, which involved 300 patients in the United States and Canada.

Patients received an injection of terlipressin (0.85 mg) or placebo every 6 hours for a maximum of 14 days. The dose was adjusted on the basis of changes in kidney function.

Twenty-nine percent of patients in the terlipressin group experienced improvement in kidney function, vs. 16% in the placebo group.

The CONFIRM trial met its primary endpoint of verified HRS reversal, defined as renal function improvement, avoidance of dialysis, and short-term survival (P = .012).

To achieve this endpoint, patients had to have two consecutive serum creatinine (SCr) values of ≤ 1.5 mg/dL at least 2 hours apart by day 14 or be discharged from the hospital.

The most commonly observed adverse reactions that occurred in at least 4% of patients treated with terlipressin were abdominal pain (19.5%), nausea (16%), respiratory failure (15.5%), diarrhea (13%), and dyspnea (12.5%).

Results of the CONFIRM trial were published in The New England Journal of Medicine.

“Diagnosing and treating HRS can be challenging, and every minute counts when managing patients who have it,” said Steven Romano, MD, executive vice president and chief scientific officer at Mallinckrodt, which makes the drug.

“Terlivaz gives physicians the first FDA-approved option for treating HRS patients with rapid reduction in kidney function that may help them improve kidney function and lessen the associated need for renal replacement therapy, such as dialysis,” Dr. Romano said.

The company plans to launch the product in the coming weeks.

The application for terlipressin for HRS was granted priority review and fast-track status, as well as orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

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

The past decade has witnessed a rapid expansion of genetic tests, including new instruments to inform patients who have been diagnosed with breast cancer about the risk of recurrence and to guide their treatment.

But the clinical significance of many of the inherited mutations that can now be identified remains unclear, and experts are torn on when and how to deploy all the new tests available. Patients are sometimes left paying out-of-pocket for exams that are not yet the standard of care, and even the most up-to-date oncologists may be uncertain how to incorporate the flood of new information into what used to be standard treatment protocols.

A quarter-century ago, Myriad Genetics introduced the first breast cancer genetic test for BRCA mutations, two genes associated with a substantially elevated risk of getting breast cancer, opening the door to a new era in genetic testing. BRCA1 and BRCA2 mutations account for as many as half of all hereditary breast cancers, and people with a problematic mutation on one of those genes have a 45%-72% chance of developing breast cancer during their lifetimes. They may also be at higher risk for ovarian and other cancers than people without harmful BRCA mutations.

But the clinical significance is murkier for many other genetic tests.

Testing for BRCA1 and BRCA2 genes used to cost thousands of dollars. Now, for a fraction of that, doctors can order multigene test panels from commercial labs that look for mutations in dozens of genes. Some direct-to-consumer companies offer screening panels for a few hundred dollars, though their reliability varies.

When Jen Carbary was diagnosed with breast cancer in 2017 at age 44, genetic testing identified a mutation in a gene called PALB2 that significantly increases the risk of developing breast cancer. Guidelines suggest that breast cancer patients with a PALB2 mutation, much like those with BRCA1 and BRCA2 mutations, consider having a mastectomy to reduce the chance of a breast cancer recurrence.

“I wish genetic testing was the standard of care,” said Ms. Carbary, who owed nothing for the test because her insurer covered the cost.

Ms. Carbary, who lives in Sterling Heights, Mich., said the test results affirmed the decision she had already made to have a double mastectomy and provided important information for family members, including her 21-year-old daughter and 18-year-old son, who will likely be tested in their mid-20s or early 30s.

But some breast cancer experts are concerned that widespread testing may also identify genetic mutations whose impact is unclear, creating anxiety and leading to further testing and to treatment of questionable value that could raise costs for the health care system.

It can also confuse patients.

“It happens a lot, that patients find their way to us after getting confusing results elsewhere,” said Mark Robson, MD, chief of the breast medicine service at Memorial Sloan Kettering Cancer Center, New York. Robson said the cancer center has a clinical genetics service, staffed by doctors and genetic counselors, that helps people make decisions about how to manage genetic testing results.

For people diagnosed with breast cancer, many professional groups, including the influential National Comprehensive Cancer Network, recommend limiting testing to certain people, including those with high-risk factors, such as a family history of breast cancer; those who are 45 or younger when they’re diagnosed; and those with Ashkenazi Jewish ancestry.

But in 2019, the American Society of Breast Surgeons recommended a different approach: Offer genetic testing to all patients who are diagnosed with or have a personal history of breast cancer. The recommendation was controversial.

“The NCCN guidelines [cover] most of the women who needed testing, but we wanted to get them all,” said Eric Manahan, MD, a general surgeon in Dalton, Georgia, and a member of the surgeons group’s board of directors.

Mutations on other genes that are associated with breast cancer are much less common than BRCA1 and BRCA2 mutations and generally don’t increase the risk of developing breast cancer as much. The cancer-causing impact of these genes may be less clear than that of the BRCA genes, which have been tested for since the mid-1990s.

And the appropriate response to the less common mutations – whether to consider a risk-reducing mastectomy or stepped-up screening – is often unclear.

“Things get sloppier and sloppier when you look at other genes,” said Steven Katz, MD, MPH, a professor of medicine and health management and policy at the University of Michigan. “The risks tend to be lower for different cancers, and less certain and more variable. You might walk away wondering: ‘Why’d I have to know that?’ ”

After people are diagnosed with breast cancer, genetic testing can help inform their decisions about the types of surgery to pursue – for example, a high risk of recurrence or a new breast cancer might persuade some to opt for more extensive surgery, such as a double mastectomy. Testing can also provide important information to family members about their potential cancer risk.

(This type of “germline” genetic testing, as it’s called, looks at mutations in the genes that people inherit from their parents. It is different from genomic tumor tests that look at specific genes or proteins in the cancer cells and can help doctors understand the rate at which the cancer cells are dividing, for example, and the likelihood of a cancer recurrence.)

Increasingly, germline genetic testing can also help guide other treatment decisions. Some patients with metastatic breast cancer who have BRCA1 or BRCA2 mutations may be good candidates for poly (ADP-ribose) polymerase inhibitors, cancer drugs that target tumors with mutations in those genes.

But genetic testing that uncovers inherited mutations in many other genes yields less clearly actionable information, even though positive results may alarm people.

At Memorial Sloan Kettering, cancer specialists focus on “therapeutic actionability,” said Dr. Robson. Will testing help someone decide whether she should get a double mastectomy or provide other important guidance? “A policy of testing everyone will identify very few additional BRCA breast mutations but will cost a lot.”

As a result, doctors are debating how best to deploy and incorporate new genetic knowledge. Insurers are trying to figure out which to pay for.

There is both underuse of tests that science says are relevant and overuse of tests that experts say provide information that can’t be interpreted with any scientific certainty.

The result may be confusion for patients newly diagnosed with breast cancer as they confront the expense of genetic tests and sometimes little guidance on the proper treatment.

Some doctors say the first step is to make sure that the small group of people who would clearly benefit are getting the genetic tests whose meaning is clearly understood. Only 15% of breast cancer patients who met select NCCN testing guidelines for inherited cancer received genetic testing, according to a 2017 study that examined data from a national household health survey between 2005 and 2015.

“I would argue that our focus needs to be on the people who are at high risk for breast cancer that aren’t even identified yet,” said Tuya Pal, MD, associate director for cancer health disparities at Vanderbilt-Ingram Cancer Center and vice chair of the NCCN guidelines panel for genetic/familial high-risk assessment of breast, ovarian, and pancreatic cancers.

Patients may fall through the cracks because no one tells them they should be tested. In one analysis, 56% of high-risk breast cancer patients who didn’t get genetic testing said their doctors didn’t recommend it.

Even if doctors recommend genetic testing, they may lack the expertise to determine which tests people need and how to interpret the results. That’s the role of genetic counselors, but their ranks are stretched thin.

The consequences can be serious. In a study of 666 breast cancer patients who received genetic testing, half of those at average risk for inherited cancer got double mastectomies based on test results that found “variants of uncertain significance,” which aren’t clinically actionable. As many as half of surgeons reported managing such patients the same way as those with cancer-causing mutations.

“The bulk of our research would say that there is still room for improvement in terms of clinicians getting the understanding they need,” said Allison Kurian, MD, director of the women’s clinical cancer genetics program at Stanford (Calif.) University and a coauthor of the study.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The past decade has witnessed a rapid expansion of genetic tests, including new instruments to inform patients who have been diagnosed with breast cancer about the risk of recurrence and to guide their treatment.

But the clinical significance of many of the inherited mutations that can now be identified remains unclear, and experts are torn on when and how to deploy all the new tests available. Patients are sometimes left paying out-of-pocket for exams that are not yet the standard of care, and even the most up-to-date oncologists may be uncertain how to incorporate the flood of new information into what used to be standard treatment protocols.

A quarter-century ago, Myriad Genetics introduced the first breast cancer genetic test for BRCA mutations, two genes associated with a substantially elevated risk of getting breast cancer, opening the door to a new era in genetic testing. BRCA1 and BRCA2 mutations account for as many as half of all hereditary breast cancers, and people with a problematic mutation on one of those genes have a 45%-72% chance of developing breast cancer during their lifetimes. They may also be at higher risk for ovarian and other cancers than people without harmful BRCA mutations.

But the clinical significance is murkier for many other genetic tests.

Testing for BRCA1 and BRCA2 genes used to cost thousands of dollars. Now, for a fraction of that, doctors can order multigene test panels from commercial labs that look for mutations in dozens of genes. Some direct-to-consumer companies offer screening panels for a few hundred dollars, though their reliability varies.

When Jen Carbary was diagnosed with breast cancer in 2017 at age 44, genetic testing identified a mutation in a gene called PALB2 that significantly increases the risk of developing breast cancer. Guidelines suggest that breast cancer patients with a PALB2 mutation, much like those with BRCA1 and BRCA2 mutations, consider having a mastectomy to reduce the chance of a breast cancer recurrence.

“I wish genetic testing was the standard of care,” said Ms. Carbary, who owed nothing for the test because her insurer covered the cost.

Ms. Carbary, who lives in Sterling Heights, Mich., said the test results affirmed the decision she had already made to have a double mastectomy and provided important information for family members, including her 21-year-old daughter and 18-year-old son, who will likely be tested in their mid-20s or early 30s.

But some breast cancer experts are concerned that widespread testing may also identify genetic mutations whose impact is unclear, creating anxiety and leading to further testing and to treatment of questionable value that could raise costs for the health care system.

It can also confuse patients.

“It happens a lot, that patients find their way to us after getting confusing results elsewhere,” said Mark Robson, MD, chief of the breast medicine service at Memorial Sloan Kettering Cancer Center, New York. Robson said the cancer center has a clinical genetics service, staffed by doctors and genetic counselors, that helps people make decisions about how to manage genetic testing results.

For people diagnosed with breast cancer, many professional groups, including the influential National Comprehensive Cancer Network, recommend limiting testing to certain people, including those with high-risk factors, such as a family history of breast cancer; those who are 45 or younger when they’re diagnosed; and those with Ashkenazi Jewish ancestry.

But in 2019, the American Society of Breast Surgeons recommended a different approach: Offer genetic testing to all patients who are diagnosed with or have a personal history of breast cancer. The recommendation was controversial.

“The NCCN guidelines [cover] most of the women who needed testing, but we wanted to get them all,” said Eric Manahan, MD, a general surgeon in Dalton, Georgia, and a member of the surgeons group’s board of directors.

Mutations on other genes that are associated with breast cancer are much less common than BRCA1 and BRCA2 mutations and generally don’t increase the risk of developing breast cancer as much. The cancer-causing impact of these genes may be less clear than that of the BRCA genes, which have been tested for since the mid-1990s.

And the appropriate response to the less common mutations – whether to consider a risk-reducing mastectomy or stepped-up screening – is often unclear.

“Things get sloppier and sloppier when you look at other genes,” said Steven Katz, MD, MPH, a professor of medicine and health management and policy at the University of Michigan. “The risks tend to be lower for different cancers, and less certain and more variable. You might walk away wondering: ‘Why’d I have to know that?’ ”

After people are diagnosed with breast cancer, genetic testing can help inform their decisions about the types of surgery to pursue – for example, a high risk of recurrence or a new breast cancer might persuade some to opt for more extensive surgery, such as a double mastectomy. Testing can also provide important information to family members about their potential cancer risk.

(This type of “germline” genetic testing, as it’s called, looks at mutations in the genes that people inherit from their parents. It is different from genomic tumor tests that look at specific genes or proteins in the cancer cells and can help doctors understand the rate at which the cancer cells are dividing, for example, and the likelihood of a cancer recurrence.)

Increasingly, germline genetic testing can also help guide other treatment decisions. Some patients with metastatic breast cancer who have BRCA1 or BRCA2 mutations may be good candidates for poly (ADP-ribose) polymerase inhibitors, cancer drugs that target tumors with mutations in those genes.

But genetic testing that uncovers inherited mutations in many other genes yields less clearly actionable information, even though positive results may alarm people.

At Memorial Sloan Kettering, cancer specialists focus on “therapeutic actionability,” said Dr. Robson. Will testing help someone decide whether she should get a double mastectomy or provide other important guidance? “A policy of testing everyone will identify very few additional BRCA breast mutations but will cost a lot.”

As a result, doctors are debating how best to deploy and incorporate new genetic knowledge. Insurers are trying to figure out which to pay for.

There is both underuse of tests that science says are relevant and overuse of tests that experts say provide information that can’t be interpreted with any scientific certainty.

The result may be confusion for patients newly diagnosed with breast cancer as they confront the expense of genetic tests and sometimes little guidance on the proper treatment.

Some doctors say the first step is to make sure that the small group of people who would clearly benefit are getting the genetic tests whose meaning is clearly understood. Only 15% of breast cancer patients who met select NCCN testing guidelines for inherited cancer received genetic testing, according to a 2017 study that examined data from a national household health survey between 2005 and 2015.

“I would argue that our focus needs to be on the people who are at high risk for breast cancer that aren’t even identified yet,” said Tuya Pal, MD, associate director for cancer health disparities at Vanderbilt-Ingram Cancer Center and vice chair of the NCCN guidelines panel for genetic/familial high-risk assessment of breast, ovarian, and pancreatic cancers.

Patients may fall through the cracks because no one tells them they should be tested. In one analysis, 56% of high-risk breast cancer patients who didn’t get genetic testing said their doctors didn’t recommend it.

Even if doctors recommend genetic testing, they may lack the expertise to determine which tests people need and how to interpret the results. That’s the role of genetic counselors, but their ranks are stretched thin.

The consequences can be serious. In a study of 666 breast cancer patients who received genetic testing, half of those at average risk for inherited cancer got double mastectomies based on test results that found “variants of uncertain significance,” which aren’t clinically actionable. As many as half of surgeons reported managing such patients the same way as those with cancer-causing mutations.

“The bulk of our research would say that there is still room for improvement in terms of clinicians getting the understanding they need,” said Allison Kurian, MD, director of the women’s clinical cancer genetics program at Stanford (Calif.) University and a coauthor of the study.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The past decade has witnessed a rapid expansion of genetic tests, including new instruments to inform patients who have been diagnosed with breast cancer about the risk of recurrence and to guide their treatment.

But the clinical significance of many of the inherited mutations that can now be identified remains unclear, and experts are torn on when and how to deploy all the new tests available. Patients are sometimes left paying out-of-pocket for exams that are not yet the standard of care, and even the most up-to-date oncologists may be uncertain how to incorporate the flood of new information into what used to be standard treatment protocols.

A quarter-century ago, Myriad Genetics introduced the first breast cancer genetic test for BRCA mutations, two genes associated with a substantially elevated risk of getting breast cancer, opening the door to a new era in genetic testing. BRCA1 and BRCA2 mutations account for as many as half of all hereditary breast cancers, and people with a problematic mutation on one of those genes have a 45%-72% chance of developing breast cancer during their lifetimes. They may also be at higher risk for ovarian and other cancers than people without harmful BRCA mutations.

But the clinical significance is murkier for many other genetic tests.

Testing for BRCA1 and BRCA2 genes used to cost thousands of dollars. Now, for a fraction of that, doctors can order multigene test panels from commercial labs that look for mutations in dozens of genes. Some direct-to-consumer companies offer screening panels for a few hundred dollars, though their reliability varies.

When Jen Carbary was diagnosed with breast cancer in 2017 at age 44, genetic testing identified a mutation in a gene called PALB2 that significantly increases the risk of developing breast cancer. Guidelines suggest that breast cancer patients with a PALB2 mutation, much like those with BRCA1 and BRCA2 mutations, consider having a mastectomy to reduce the chance of a breast cancer recurrence.

“I wish genetic testing was the standard of care,” said Ms. Carbary, who owed nothing for the test because her insurer covered the cost.

Ms. Carbary, who lives in Sterling Heights, Mich., said the test results affirmed the decision she had already made to have a double mastectomy and provided important information for family members, including her 21-year-old daughter and 18-year-old son, who will likely be tested in their mid-20s or early 30s.

But some breast cancer experts are concerned that widespread testing may also identify genetic mutations whose impact is unclear, creating anxiety and leading to further testing and to treatment of questionable value that could raise costs for the health care system.

It can also confuse patients.

“It happens a lot, that patients find their way to us after getting confusing results elsewhere,” said Mark Robson, MD, chief of the breast medicine service at Memorial Sloan Kettering Cancer Center, New York. Robson said the cancer center has a clinical genetics service, staffed by doctors and genetic counselors, that helps people make decisions about how to manage genetic testing results.

For people diagnosed with breast cancer, many professional groups, including the influential National Comprehensive Cancer Network, recommend limiting testing to certain people, including those with high-risk factors, such as a family history of breast cancer; those who are 45 or younger when they’re diagnosed; and those with Ashkenazi Jewish ancestry.

But in 2019, the American Society of Breast Surgeons recommended a different approach: Offer genetic testing to all patients who are diagnosed with or have a personal history of breast cancer. The recommendation was controversial.

“The NCCN guidelines [cover] most of the women who needed testing, but we wanted to get them all,” said Eric Manahan, MD, a general surgeon in Dalton, Georgia, and a member of the surgeons group’s board of directors.

Mutations on other genes that are associated with breast cancer are much less common than BRCA1 and BRCA2 mutations and generally don’t increase the risk of developing breast cancer as much. The cancer-causing impact of these genes may be less clear than that of the BRCA genes, which have been tested for since the mid-1990s.

And the appropriate response to the less common mutations – whether to consider a risk-reducing mastectomy or stepped-up screening – is often unclear.

“Things get sloppier and sloppier when you look at other genes,” said Steven Katz, MD, MPH, a professor of medicine and health management and policy at the University of Michigan. “The risks tend to be lower for different cancers, and less certain and more variable. You might walk away wondering: ‘Why’d I have to know that?’ ”

After people are diagnosed with breast cancer, genetic testing can help inform their decisions about the types of surgery to pursue – for example, a high risk of recurrence or a new breast cancer might persuade some to opt for more extensive surgery, such as a double mastectomy. Testing can also provide important information to family members about their potential cancer risk.

(This type of “germline” genetic testing, as it’s called, looks at mutations in the genes that people inherit from their parents. It is different from genomic tumor tests that look at specific genes or proteins in the cancer cells and can help doctors understand the rate at which the cancer cells are dividing, for example, and the likelihood of a cancer recurrence.)

Increasingly, germline genetic testing can also help guide other treatment decisions. Some patients with metastatic breast cancer who have BRCA1 or BRCA2 mutations may be good candidates for poly (ADP-ribose) polymerase inhibitors, cancer drugs that target tumors with mutations in those genes.

But genetic testing that uncovers inherited mutations in many other genes yields less clearly actionable information, even though positive results may alarm people.

At Memorial Sloan Kettering, cancer specialists focus on “therapeutic actionability,” said Dr. Robson. Will testing help someone decide whether she should get a double mastectomy or provide other important guidance? “A policy of testing everyone will identify very few additional BRCA breast mutations but will cost a lot.”

As a result, doctors are debating how best to deploy and incorporate new genetic knowledge. Insurers are trying to figure out which to pay for.

There is both underuse of tests that science says are relevant and overuse of tests that experts say provide information that can’t be interpreted with any scientific certainty.

The result may be confusion for patients newly diagnosed with breast cancer as they confront the expense of genetic tests and sometimes little guidance on the proper treatment.

Some doctors say the first step is to make sure that the small group of people who would clearly benefit are getting the genetic tests whose meaning is clearly understood. Only 15% of breast cancer patients who met select NCCN testing guidelines for inherited cancer received genetic testing, according to a 2017 study that examined data from a national household health survey between 2005 and 2015.

“I would argue that our focus needs to be on the people who are at high risk for breast cancer that aren’t even identified yet,” said Tuya Pal, MD, associate director for cancer health disparities at Vanderbilt-Ingram Cancer Center and vice chair of the NCCN guidelines panel for genetic/familial high-risk assessment of breast, ovarian, and pancreatic cancers.

Patients may fall through the cracks because no one tells them they should be tested. In one analysis, 56% of high-risk breast cancer patients who didn’t get genetic testing said their doctors didn’t recommend it.

Even if doctors recommend genetic testing, they may lack the expertise to determine which tests people need and how to interpret the results. That’s the role of genetic counselors, but their ranks are stretched thin.

The consequences can be serious. In a study of 666 breast cancer patients who received genetic testing, half of those at average risk for inherited cancer got double mastectomies based on test results that found “variants of uncertain significance,” which aren’t clinically actionable. As many as half of surgeons reported managing such patients the same way as those with cancer-causing mutations.

“The bulk of our research would say that there is still room for improvement in terms of clinicians getting the understanding they need,” said Allison Kurian, MD, director of the women’s clinical cancer genetics program at Stanford (Calif.) University and a coauthor of the study.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

STOCKHOLM – Shivering upon repeated short exposures to cold improves glucose tolerance, decreases fasting blood glucose and lipid levels, and markedly reduces blood pressure, show new study results in adults with obesity and overweight.

Presenting the preliminary findings at the annual meeting of the European Association for the Study of Diabetes, Adam Sellers, a PhD student from Maastricht (the Netherlands) University, said: “The results are highly promising and may eventually suggest an alternative treatment or preventative measure for type 2 diabetes.”

Dr. Sellers found that 10 daily 1-hour sessions of shivering at 10° C led to 85% of participants showing a drop in fasting glucose, and a 32% drop in lipid levels, as well as a blood pressure drop of around 8% overall.

Although cold exposure is known to increase brown fat, Dr. Sellers doesn’t believe this explains his findings. “This research, in addition to two other prior studies, suggest that shivering and skeletal muscle may play a more important role than brown fat,” he said.

“Muscle can contract mechanically – [the concept of the] shivers – thereby generating heat, and there is considerably more muscle than brown fat in a human, so shivering can burn more calories and produce more heat,” he explained.

He added that, in the future, “in a similar way to saunas and steam rooms, there might be cold rooms where people go and sit in the cold room and shiver, or possibly patients attend hospital and shivering is induced.”

Audience member Anna Krook, PhD, professor of integrative physiology at the Karolinska Institute, Stockholm, commented on the work, saying the results are “potent” and demonstrate the metabolic effect of shivering. “One thing that struck me was, given the time the subject had to spend – 1 hour shivering over 10 days, I wonder if 1 hour of exercise would show similarly potent effects, and perhaps for those people who cannot perform exercise for whatever reason this might be a good alternative.”

She pointed out that, in terms of translation into practice, it “really depends on how tolerable this is. It also shows how important our muscle is in regulating metabolism. The study showed that you had to be shivering, and it wasn’t just enough to be cold, which has implications for the role of brown fat, especially when we consider the small amount of brown fat we have compared to muscle, which can be half of body weight.”

And Denis P. Blondin, PhD, said: “The reality is that we know it can be difficult and even painful for individuals with obesity to perform exercise, and therefore, cold exposure offers a passive way of improving our metabolic profile and cardiovascular health.”

“Some will argue that it is unrealistic to propose cold exposure as a therapy, but people overlook the fact that cold exposure [mostly through cold-water immersion] has increased in popularity over the past 5 years and has also been a cultural staple for many Nordic countries, albeit often performed with heat exposure as well [see the use of saunas and cold-water swimming in Finland and other Nordic countries],” added Dr. Blondin, of the faculty of medicine and health sciences, University of Sherbrooke (Que.)

“While it can certainly be uncomfortable at first (like starting an exercise program), we adapt very quickly,” he added.
 

1 hour in a cold-water suit to induce shivering

In the current study, Dr. Sellers exposed adults (aged 40-75 years; 11 men and 4 postmenopausal women) with overweight/obesity (body mass index, 27-35 kg/m²) to 10 consecutive cold exposures of at least 1 hour of shivering per cold exposure.

“The shivering in this new research was more intense [than in prior studies] and was induced with a different cold exposure method – a 10° C water-perfused suit [compared with a prior study of 14-15° C, 6 hours/day]. This facilitated a shorter cold exposure duration, deemed feasible for the participants,” explained Dr. Sellers.

“At baseline, participants had glucose and A1c levels at the upper end of the normal criteria [5.5 mmol/l and 5.4%, respectively],” he said, referring to measurements that were suggestive of possible progression to type 2 diabetes.

He explained how the cold exposure was applied. “We induced the cold with a water-perfused suit worn by the participant, through which water flows at 10° C, and this cools the participant. Eventually, the participant starts to shiver, and does so for at least 1 hour every morning for 10 days.”

Participants’ shivering-induced heat production was measured via surface electromyography and visual observation to confirm the presence of shivering. Both before and after the 10-day course of shivering, physiological measurements were taken in the morning while participants were at rest in an overnight fasted state, and under thermoneutral conditions. Blood pressure and fasting blood glucose were measured.

A 2-hour oral glucose tolerance test (OGTT) was conducted twice for each participant: on the morning before the 10-day course of shivering and again on the morning after the final 10th day of shivering.

The primary endpoint was change from before to after the 10-day shivering intervention, as represented by the total area under the curve of glucose levels over time during the OGTT. 

“This provides a measure of the glucose concentrations in the blood before and after the 10 shivering sessions over the 10 days.”

courtesy Sten van Beek

Fasting glucose and blood lipids fall, glucose tolerance improves

After 10 shivering sessions, mean fasting plasma glucose decreased significantly in 13 out of the 15 participants, compared with before the first session (from 5.84 mmol/L to 5.67 mmol/L; P = .013).

Glucose tolerance during the OGTT improved by 6% (P = .041). “We can see that this was not due to a change in their insulin concentrations in the blood,” remarked Dr. Sellers, referring to the finding that plasma insulin concentrations at baseline and during the OGTT did not change.

Fasting plasma triglyceride and free-fatty acid concentrations also decreased significantly by 32% (P = .001) and 11% (P = .036), respectively.

“This is important because free-fatty acids are involved in the role of insulin resistance,” said Dr. Sellers. “In addition, the large reduction in serum triglycerides could have implications for atherosclerosis, which may also be beneficial.”

Dr. Sellers also found that systolic blood pressure decreased by 10 mm Hg or 7.4% (P < .001), while diastolic blood pressure decreased by 7 mm Hg or 8.1% (P < .001) on average. This lowering was seen in all participants.

“Again, quite strikingly, all participants showed” a reduction in blood pressure, said Dr. Sellers, which he noted relates to a decrease in resting heart rate (P = .062).
 

Brown fat or skeletal muscle contraction?

Dr. Sellers pointed out that, despite nonshivering thermogenesis being involved in mild cold acclimation, the data so far suggest that some level of mild muscle activity or shivering appears crucial in provoking the beneficial metabolic effects of cold acclimation.

“Brown fat is a metabolic heating system inside our bodies, burning calories”, explained Dr. Sellers. “This generates heat and prevents calories from being deposited as normal white fat. Brown fat is activated during cold and when we eat, but its activity is less in older adults and in individuals with obesity and diabetes.”

“Going forward, we might investigate the effects of shorter duration – so more intense shivering – to try and elucidate more precisely the optimum duration and intensity of shivering needed,” said Dr. Sellers.

“Our findings are promising and may have important health implications. In future studies, we plan to assess the effect of shivering in adults with type 2 diabetes,” he concluded.

Dr. Seller and Dr. Krook have reported no relevant financial relationships.

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

STOCKHOLM – Shivering upon repeated short exposures to cold improves glucose tolerance, decreases fasting blood glucose and lipid levels, and markedly reduces blood pressure, show new study results in adults with obesity and overweight.

Presenting the preliminary findings at the annual meeting of the European Association for the Study of Diabetes, Adam Sellers, a PhD student from Maastricht (the Netherlands) University, said: “The results are highly promising and may eventually suggest an alternative treatment or preventative measure for type 2 diabetes.”

Dr. Sellers found that 10 daily 1-hour sessions of shivering at 10° C led to 85% of participants showing a drop in fasting glucose, and a 32% drop in lipid levels, as well as a blood pressure drop of around 8% overall.

Although cold exposure is known to increase brown fat, Dr. Sellers doesn’t believe this explains his findings. “This research, in addition to two other prior studies, suggest that shivering and skeletal muscle may play a more important role than brown fat,” he said.

“Muscle can contract mechanically – [the concept of the] shivers – thereby generating heat, and there is considerably more muscle than brown fat in a human, so shivering can burn more calories and produce more heat,” he explained.

He added that, in the future, “in a similar way to saunas and steam rooms, there might be cold rooms where people go and sit in the cold room and shiver, or possibly patients attend hospital and shivering is induced.”

Audience member Anna Krook, PhD, professor of integrative physiology at the Karolinska Institute, Stockholm, commented on the work, saying the results are “potent” and demonstrate the metabolic effect of shivering. “One thing that struck me was, given the time the subject had to spend – 1 hour shivering over 10 days, I wonder if 1 hour of exercise would show similarly potent effects, and perhaps for those people who cannot perform exercise for whatever reason this might be a good alternative.”

She pointed out that, in terms of translation into practice, it “really depends on how tolerable this is. It also shows how important our muscle is in regulating metabolism. The study showed that you had to be shivering, and it wasn’t just enough to be cold, which has implications for the role of brown fat, especially when we consider the small amount of brown fat we have compared to muscle, which can be half of body weight.”

And Denis P. Blondin, PhD, said: “The reality is that we know it can be difficult and even painful for individuals with obesity to perform exercise, and therefore, cold exposure offers a passive way of improving our metabolic profile and cardiovascular health.”

“Some will argue that it is unrealistic to propose cold exposure as a therapy, but people overlook the fact that cold exposure [mostly through cold-water immersion] has increased in popularity over the past 5 years and has also been a cultural staple for many Nordic countries, albeit often performed with heat exposure as well [see the use of saunas and cold-water swimming in Finland and other Nordic countries],” added Dr. Blondin, of the faculty of medicine and health sciences, University of Sherbrooke (Que.)

“While it can certainly be uncomfortable at first (like starting an exercise program), we adapt very quickly,” he added.
 

1 hour in a cold-water suit to induce shivering

In the current study, Dr. Sellers exposed adults (aged 40-75 years; 11 men and 4 postmenopausal women) with overweight/obesity (body mass index, 27-35 kg/m²) to 10 consecutive cold exposures of at least 1 hour of shivering per cold exposure.

“The shivering in this new research was more intense [than in prior studies] and was induced with a different cold exposure method – a 10° C water-perfused suit [compared with a prior study of 14-15° C, 6 hours/day]. This facilitated a shorter cold exposure duration, deemed feasible for the participants,” explained Dr. Sellers.

“At baseline, participants had glucose and A1c levels at the upper end of the normal criteria [5.5 mmol/l and 5.4%, respectively],” he said, referring to measurements that were suggestive of possible progression to type 2 diabetes.

He explained how the cold exposure was applied. “We induced the cold with a water-perfused suit worn by the participant, through which water flows at 10° C, and this cools the participant. Eventually, the participant starts to shiver, and does so for at least 1 hour every morning for 10 days.”

Participants’ shivering-induced heat production was measured via surface electromyography and visual observation to confirm the presence of shivering. Both before and after the 10-day course of shivering, physiological measurements were taken in the morning while participants were at rest in an overnight fasted state, and under thermoneutral conditions. Blood pressure and fasting blood glucose were measured.

A 2-hour oral glucose tolerance test (OGTT) was conducted twice for each participant: on the morning before the 10-day course of shivering and again on the morning after the final 10th day of shivering.

The primary endpoint was change from before to after the 10-day shivering intervention, as represented by the total area under the curve of glucose levels over time during the OGTT. 

“This provides a measure of the glucose concentrations in the blood before and after the 10 shivering sessions over the 10 days.”

courtesy Sten van Beek

Fasting glucose and blood lipids fall, glucose tolerance improves

After 10 shivering sessions, mean fasting plasma glucose decreased significantly in 13 out of the 15 participants, compared with before the first session (from 5.84 mmol/L to 5.67 mmol/L; P = .013).

Glucose tolerance during the OGTT improved by 6% (P = .041). “We can see that this was not due to a change in their insulin concentrations in the blood,” remarked Dr. Sellers, referring to the finding that plasma insulin concentrations at baseline and during the OGTT did not change.

Fasting plasma triglyceride and free-fatty acid concentrations also decreased significantly by 32% (P = .001) and 11% (P = .036), respectively.

“This is important because free-fatty acids are involved in the role of insulin resistance,” said Dr. Sellers. “In addition, the large reduction in serum triglycerides could have implications for atherosclerosis, which may also be beneficial.”

Dr. Sellers also found that systolic blood pressure decreased by 10 mm Hg or 7.4% (P < .001), while diastolic blood pressure decreased by 7 mm Hg or 8.1% (P < .001) on average. This lowering was seen in all participants.

“Again, quite strikingly, all participants showed” a reduction in blood pressure, said Dr. Sellers, which he noted relates to a decrease in resting heart rate (P = .062).
 

Brown fat or skeletal muscle contraction?

Dr. Sellers pointed out that, despite nonshivering thermogenesis being involved in mild cold acclimation, the data so far suggest that some level of mild muscle activity or shivering appears crucial in provoking the beneficial metabolic effects of cold acclimation.

“Brown fat is a metabolic heating system inside our bodies, burning calories”, explained Dr. Sellers. “This generates heat and prevents calories from being deposited as normal white fat. Brown fat is activated during cold and when we eat, but its activity is less in older adults and in individuals with obesity and diabetes.”

“Going forward, we might investigate the effects of shorter duration – so more intense shivering – to try and elucidate more precisely the optimum duration and intensity of shivering needed,” said Dr. Sellers.

“Our findings are promising and may have important health implications. In future studies, we plan to assess the effect of shivering in adults with type 2 diabetes,” he concluded.

Dr. Seller and Dr. Krook have reported no relevant financial relationships.

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

STOCKHOLM – Shivering upon repeated short exposures to cold improves glucose tolerance, decreases fasting blood glucose and lipid levels, and markedly reduces blood pressure, show new study results in adults with obesity and overweight.

Presenting the preliminary findings at the annual meeting of the European Association for the Study of Diabetes, Adam Sellers, a PhD student from Maastricht (the Netherlands) University, said: “The results are highly promising and may eventually suggest an alternative treatment or preventative measure for type 2 diabetes.”

Dr. Sellers found that 10 daily 1-hour sessions of shivering at 10° C led to 85% of participants showing a drop in fasting glucose, and a 32% drop in lipid levels, as well as a blood pressure drop of around 8% overall.

Although cold exposure is known to increase brown fat, Dr. Sellers doesn’t believe this explains his findings. “This research, in addition to two other prior studies, suggest that shivering and skeletal muscle may play a more important role than brown fat,” he said.

“Muscle can contract mechanically – [the concept of the] shivers – thereby generating heat, and there is considerably more muscle than brown fat in a human, so shivering can burn more calories and produce more heat,” he explained.

He added that, in the future, “in a similar way to saunas and steam rooms, there might be cold rooms where people go and sit in the cold room and shiver, or possibly patients attend hospital and shivering is induced.”

Audience member Anna Krook, PhD, professor of integrative physiology at the Karolinska Institute, Stockholm, commented on the work, saying the results are “potent” and demonstrate the metabolic effect of shivering. “One thing that struck me was, given the time the subject had to spend – 1 hour shivering over 10 days, I wonder if 1 hour of exercise would show similarly potent effects, and perhaps for those people who cannot perform exercise for whatever reason this might be a good alternative.”

She pointed out that, in terms of translation into practice, it “really depends on how tolerable this is. It also shows how important our muscle is in regulating metabolism. The study showed that you had to be shivering, and it wasn’t just enough to be cold, which has implications for the role of brown fat, especially when we consider the small amount of brown fat we have compared to muscle, which can be half of body weight.”

And Denis P. Blondin, PhD, said: “The reality is that we know it can be difficult and even painful for individuals with obesity to perform exercise, and therefore, cold exposure offers a passive way of improving our metabolic profile and cardiovascular health.”

“Some will argue that it is unrealistic to propose cold exposure as a therapy, but people overlook the fact that cold exposure [mostly through cold-water immersion] has increased in popularity over the past 5 years and has also been a cultural staple for many Nordic countries, albeit often performed with heat exposure as well [see the use of saunas and cold-water swimming in Finland and other Nordic countries],” added Dr. Blondin, of the faculty of medicine and health sciences, University of Sherbrooke (Que.)

“While it can certainly be uncomfortable at first (like starting an exercise program), we adapt very quickly,” he added.
 

1 hour in a cold-water suit to induce shivering

In the current study, Dr. Sellers exposed adults (aged 40-75 years; 11 men and 4 postmenopausal women) with overweight/obesity (body mass index, 27-35 kg/m²) to 10 consecutive cold exposures of at least 1 hour of shivering per cold exposure.

“The shivering in this new research was more intense [than in prior studies] and was induced with a different cold exposure method – a 10° C water-perfused suit [compared with a prior study of 14-15° C, 6 hours/day]. This facilitated a shorter cold exposure duration, deemed feasible for the participants,” explained Dr. Sellers.

“At baseline, participants had glucose and A1c levels at the upper end of the normal criteria [5.5 mmol/l and 5.4%, respectively],” he said, referring to measurements that were suggestive of possible progression to type 2 diabetes.

He explained how the cold exposure was applied. “We induced the cold with a water-perfused suit worn by the participant, through which water flows at 10° C, and this cools the participant. Eventually, the participant starts to shiver, and does so for at least 1 hour every morning for 10 days.”

Participants’ shivering-induced heat production was measured via surface electromyography and visual observation to confirm the presence of shivering. Both before and after the 10-day course of shivering, physiological measurements were taken in the morning while participants were at rest in an overnight fasted state, and under thermoneutral conditions. Blood pressure and fasting blood glucose were measured.

A 2-hour oral glucose tolerance test (OGTT) was conducted twice for each participant: on the morning before the 10-day course of shivering and again on the morning after the final 10th day of shivering.

The primary endpoint was change from before to after the 10-day shivering intervention, as represented by the total area under the curve of glucose levels over time during the OGTT. 

“This provides a measure of the glucose concentrations in the blood before and after the 10 shivering sessions over the 10 days.”

courtesy Sten van Beek

Fasting glucose and blood lipids fall, glucose tolerance improves

After 10 shivering sessions, mean fasting plasma glucose decreased significantly in 13 out of the 15 participants, compared with before the first session (from 5.84 mmol/L to 5.67 mmol/L; P = .013).

Glucose tolerance during the OGTT improved by 6% (P = .041). “We can see that this was not due to a change in their insulin concentrations in the blood,” remarked Dr. Sellers, referring to the finding that plasma insulin concentrations at baseline and during the OGTT did not change.

Fasting plasma triglyceride and free-fatty acid concentrations also decreased significantly by 32% (P = .001) and 11% (P = .036), respectively.

“This is important because free-fatty acids are involved in the role of insulin resistance,” said Dr. Sellers. “In addition, the large reduction in serum triglycerides could have implications for atherosclerosis, which may also be beneficial.”

Dr. Sellers also found that systolic blood pressure decreased by 10 mm Hg or 7.4% (P < .001), while diastolic blood pressure decreased by 7 mm Hg or 8.1% (P < .001) on average. This lowering was seen in all participants.

“Again, quite strikingly, all participants showed” a reduction in blood pressure, said Dr. Sellers, which he noted relates to a decrease in resting heart rate (P = .062).
 

Brown fat or skeletal muscle contraction?

Dr. Sellers pointed out that, despite nonshivering thermogenesis being involved in mild cold acclimation, the data so far suggest that some level of mild muscle activity or shivering appears crucial in provoking the beneficial metabolic effects of cold acclimation.

“Brown fat is a metabolic heating system inside our bodies, burning calories”, explained Dr. Sellers. “This generates heat and prevents calories from being deposited as normal white fat. Brown fat is activated during cold and when we eat, but its activity is less in older adults and in individuals with obesity and diabetes.”

“Going forward, we might investigate the effects of shorter duration – so more intense shivering – to try and elucidate more precisely the optimum duration and intensity of shivering needed,” said Dr. Sellers.

“Our findings are promising and may have important health implications. In future studies, we plan to assess the effect of shivering in adults with type 2 diabetes,” he concluded.

Dr. Seller and Dr. Krook have reported no relevant financial relationships.

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

Children born to women who develop diabetes either before or during their pregnancy could be at risk for developing attention-deficit/hyperactivity disorder, data from a large multinational cohort study appear to show.

Considering more than 4.5 million mother-child pairs, it was found that children whose mothers had diabetes around the time of their pregnancy were 16% more likely to have ADHD diagnosed than were those whose mothers did not.

An increased risk was seen regardless of the type of diabetes, and regardless of whether or not the diabetes was present before or appeared during the pregnancy.

“We found a small increased risk of ADHD in children born to mothers with diabetes, including pregestational diabetes and gestational diabetes,” Carolyn Cesta, PhD, reported at the annual meeting of the European Association for the Study of Diabetes.

Dr. Cesta, a postdoctoral researcher in the Centre for Pharmacoepidemiology at the Karolinska Institutet in Stockholm noted that the effect sizes seen were lower than had been reported previously.

“This may be because we adjusted for a large number of covariates, including maternal ADHD and psychiatric disorders,” Dr. Cesta said.

ADHD and diabetes

“Previous studies have reported an increase in the risk of ADHD in children born to mothers with diabetes,” explained Dr. Cesta.

However, “these studies have been limited by the use of self-reported data, small sample sizes, lack of adjustment for important confounders, and they’re often limited to [White] populations,” she added. “There’s a lot of heterogeneity between these studies,” she said.

To try to iron out the differences seen in the prior studies, Dr. Cesta and associates looked at data from several databases based in Hong Kong (Clinical Data Analysis and Reporting System), four Nordic countries (Population Health Registers for Finland, Iceland, Norway, and Sweden), and Taiwan (National Health Insurance Database).

To create the matched mother-child pairs, the databases were searched to find women who had children born between 2001 and 2018, and who had follow-up data available up to 2020 on not only their diabetes status and child’s ADHD status, but also other parameters, such as other maternal diagnoses, maternal medications, and a host of sociodemographic factors.

More than 24 potentially confounding or covariates were considered in the analysis, which used Cox proportional hazard regression modeling and propensity score analysis to calculate hazard ratios with 95% confidence intervals.

“We looked at whether [mothers] had a diagnosis of ADHD themselves, or other psychiatric disorders, because there is high heritability for these disorders,” Dr. Cesta said, indicating that all bases had endeavored to be covered.

Main findings

Results showed some differences in the prevalence of diabetes and ADHD between the three cohorts used in the analysis. The prevalence of any maternal diabetes ranged from 8.8% in the Hong Kong cohort to 3.3% in the Taiwan cohort, with a prevalence of 6.8% for the Nordic cohort.

Rates of pregestational diabetes were lowest in the Taiwan and Hong Kong cohorts, at 0.2% and 0.5%, respectively, and 2.2% in the Nordic cohort. Gestational diabetes rates were a respective 3.1%, 7.8%, and 4.6%.

The highest rate of ADHD in children was seen in the Taiwan cohort, at 9.6%, followed by 4.2% for the Hong Kong cohort, and 2.6% for the Nordic cohort.

The hazard ratio for having childhood ADHD was 1.16 when comparing any maternal diabetes to no maternal diabetes, 1.40 comparing mothers with and without pregestational diabetes, and a respective 1.36 and 1.37 comparing those with and without type 1 diabetes, and those with and without type 2 diabetes.

The HR for childhood ADHD comparing mothers with and without gestational diabetes was 1.13.

“Within the analysis for gestational diabetes, we had enough numbers to look at siblings that are discordant for maternal gestational diabetes,” Dr. Cesta said. Essentially “we’re comparing two siblings from the same mother, one that was exposed to gestational diabetes, one that wasn’t,” she explained.

Interestingly there was no association between ADHD and maternal gestational diabetes in the sibling analysis (HR, 1.0).

“When it comes to gestational diabetes, the evidence from our sibling analysis indicate that the association may actually be confounded by shared genetics and environmental factors,” said Dr. Cesta.

“So, future studies should explore the role of specific genetic factors in glycemic control during pregnancy and the relationship between maternal diabetes and ADHD.”

Answering long-standing questions

These data will help a lot in answering questions that clinicians have been asking themselves a long time, commented Jardena Puder, MD, who chaired the session.

“It still remains a bit puzzling that genetic and environmental factors could be responsible, if you see the same effect in type 1 [diabetes], and in type 2 [diabetes], and gestational diabetes,” said Dr. Puder, who is an endocrinologist and diabetologist at the woman-mother-child department at the Vaud University Hospital Center, Lausanne, Switzerland.

Type 1 and type 2 are “very distinct” in terms of the genetic and environmental factors involved, “so, the fact that you see [the effect] in both remains a bit puzzling,” said Dr. Puder.

“I wish we had the numbers to be able to do the sibling analysis for type 1 and type 2, just to see if we could tease anything out,” said Dr. Cesta.

“I do think this is part of the bigger question of what the relationship is between, like, metabolic disorders and psychiatric disorders, because even outside of pregnancy, we see that there’s often a comorbidity with them. So, it’s a good point.”

The next step is to look at the role of treatment and what effects glycemic control might have on the small, but still apparent, association between maternal diabetes and ADHD.

The study had multiple funders including the Hong Kong Research Grant Council, NordForsk, the Research Council of Norway, the Norwegian ADHD Research Network, the Hong Kong Innovation and Technology Commission, and European Horizon 2020.

Dr. Cesta had no conflicts of interest to disclose. Dr. Puder chaired the session in which the findings were presented and made no specific disclosures.

Children born to women who develop diabetes either before or during their pregnancy could be at risk for developing attention-deficit/hyperactivity disorder, data from a large multinational cohort study appear to show.

Considering more than 4.5 million mother-child pairs, it was found that children whose mothers had diabetes around the time of their pregnancy were 16% more likely to have ADHD diagnosed than were those whose mothers did not.

An increased risk was seen regardless of the type of diabetes, and regardless of whether or not the diabetes was present before or appeared during the pregnancy.

“We found a small increased risk of ADHD in children born to mothers with diabetes, including pregestational diabetes and gestational diabetes,” Carolyn Cesta, PhD, reported at the annual meeting of the European Association for the Study of Diabetes.

Dr. Cesta, a postdoctoral researcher in the Centre for Pharmacoepidemiology at the Karolinska Institutet in Stockholm noted that the effect sizes seen were lower than had been reported previously.

“This may be because we adjusted for a large number of covariates, including maternal ADHD and psychiatric disorders,” Dr. Cesta said.

ADHD and diabetes

“Previous studies have reported an increase in the risk of ADHD in children born to mothers with diabetes,” explained Dr. Cesta.

However, “these studies have been limited by the use of self-reported data, small sample sizes, lack of adjustment for important confounders, and they’re often limited to [White] populations,” she added. “There’s a lot of heterogeneity between these studies,” she said.

To try to iron out the differences seen in the prior studies, Dr. Cesta and associates looked at data from several databases based in Hong Kong (Clinical Data Analysis and Reporting System), four Nordic countries (Population Health Registers for Finland, Iceland, Norway, and Sweden), and Taiwan (National Health Insurance Database).

To create the matched mother-child pairs, the databases were searched to find women who had children born between 2001 and 2018, and who had follow-up data available up to 2020 on not only their diabetes status and child’s ADHD status, but also other parameters, such as other maternal diagnoses, maternal medications, and a host of sociodemographic factors.

More than 24 potentially confounding or covariates were considered in the analysis, which used Cox proportional hazard regression modeling and propensity score analysis to calculate hazard ratios with 95% confidence intervals.

“We looked at whether [mothers] had a diagnosis of ADHD themselves, or other psychiatric disorders, because there is high heritability for these disorders,” Dr. Cesta said, indicating that all bases had endeavored to be covered.

Main findings

Results showed some differences in the prevalence of diabetes and ADHD between the three cohorts used in the analysis. The prevalence of any maternal diabetes ranged from 8.8% in the Hong Kong cohort to 3.3% in the Taiwan cohort, with a prevalence of 6.8% for the Nordic cohort.

Rates of pregestational diabetes were lowest in the Taiwan and Hong Kong cohorts, at 0.2% and 0.5%, respectively, and 2.2% in the Nordic cohort. Gestational diabetes rates were a respective 3.1%, 7.8%, and 4.6%.

The highest rate of ADHD in children was seen in the Taiwan cohort, at 9.6%, followed by 4.2% for the Hong Kong cohort, and 2.6% for the Nordic cohort.

The hazard ratio for having childhood ADHD was 1.16 when comparing any maternal diabetes to no maternal diabetes, 1.40 comparing mothers with and without pregestational diabetes, and a respective 1.36 and 1.37 comparing those with and without type 1 diabetes, and those with and without type 2 diabetes.

The HR for childhood ADHD comparing mothers with and without gestational diabetes was 1.13.

“Within the analysis for gestational diabetes, we had enough numbers to look at siblings that are discordant for maternal gestational diabetes,” Dr. Cesta said. Essentially “we’re comparing two siblings from the same mother, one that was exposed to gestational diabetes, one that wasn’t,” she explained.

Interestingly there was no association between ADHD and maternal gestational diabetes in the sibling analysis (HR, 1.0).

“When it comes to gestational diabetes, the evidence from our sibling analysis indicate that the association may actually be confounded by shared genetics and environmental factors,” said Dr. Cesta.

“So, future studies should explore the role of specific genetic factors in glycemic control during pregnancy and the relationship between maternal diabetes and ADHD.”

Answering long-standing questions

These data will help a lot in answering questions that clinicians have been asking themselves a long time, commented Jardena Puder, MD, who chaired the session.

“It still remains a bit puzzling that genetic and environmental factors could be responsible, if you see the same effect in type 1 [diabetes], and in type 2 [diabetes], and gestational diabetes,” said Dr. Puder, who is an endocrinologist and diabetologist at the woman-mother-child department at the Vaud University Hospital Center, Lausanne, Switzerland.

Type 1 and type 2 are “very distinct” in terms of the genetic and environmental factors involved, “so, the fact that you see [the effect] in both remains a bit puzzling,” said Dr. Puder.

“I wish we had the numbers to be able to do the sibling analysis for type 1 and type 2, just to see if we could tease anything out,” said Dr. Cesta.

“I do think this is part of the bigger question of what the relationship is between, like, metabolic disorders and psychiatric disorders, because even outside of pregnancy, we see that there’s often a comorbidity with them. So, it’s a good point.”

The next step is to look at the role of treatment and what effects glycemic control might have on the small, but still apparent, association between maternal diabetes and ADHD.

The study had multiple funders including the Hong Kong Research Grant Council, NordForsk, the Research Council of Norway, the Norwegian ADHD Research Network, the Hong Kong Innovation and Technology Commission, and European Horizon 2020.

Dr. Cesta had no conflicts of interest to disclose. Dr. Puder chaired the session in which the findings were presented and made no specific disclosures.

Children born to women who develop diabetes either before or during their pregnancy could be at risk for developing attention-deficit/hyperactivity disorder, data from a large multinational cohort study appear to show.

Considering more than 4.5 million mother-child pairs, it was found that children whose mothers had diabetes around the time of their pregnancy were 16% more likely to have ADHD diagnosed than were those whose mothers did not.

An increased risk was seen regardless of the type of diabetes, and regardless of whether or not the diabetes was present before or appeared during the pregnancy.

“We found a small increased risk of ADHD in children born to mothers with diabetes, including pregestational diabetes and gestational diabetes,” Carolyn Cesta, PhD, reported at the annual meeting of the European Association for the Study of Diabetes.

Dr. Cesta, a postdoctoral researcher in the Centre for Pharmacoepidemiology at the Karolinska Institutet in Stockholm noted that the effect sizes seen were lower than had been reported previously.

“This may be because we adjusted for a large number of covariates, including maternal ADHD and psychiatric disorders,” Dr. Cesta said.

ADHD and diabetes

“Previous studies have reported an increase in the risk of ADHD in children born to mothers with diabetes,” explained Dr. Cesta.

However, “these studies have been limited by the use of self-reported data, small sample sizes, lack of adjustment for important confounders, and they’re often limited to [White] populations,” she added. “There’s a lot of heterogeneity between these studies,” she said.

To try to iron out the differences seen in the prior studies, Dr. Cesta and associates looked at data from several databases based in Hong Kong (Clinical Data Analysis and Reporting System), four Nordic countries (Population Health Registers for Finland, Iceland, Norway, and Sweden), and Taiwan (National Health Insurance Database).

To create the matched mother-child pairs, the databases were searched to find women who had children born between 2001 and 2018, and who had follow-up data available up to 2020 on not only their diabetes status and child’s ADHD status, but also other parameters, such as other maternal diagnoses, maternal medications, and a host of sociodemographic factors.

More than 24 potentially confounding or covariates were considered in the analysis, which used Cox proportional hazard regression modeling and propensity score analysis to calculate hazard ratios with 95% confidence intervals.

“We looked at whether [mothers] had a diagnosis of ADHD themselves, or other psychiatric disorders, because there is high heritability for these disorders,” Dr. Cesta said, indicating that all bases had endeavored to be covered.

Main findings

Results showed some differences in the prevalence of diabetes and ADHD between the three cohorts used in the analysis. The prevalence of any maternal diabetes ranged from 8.8% in the Hong Kong cohort to 3.3% in the Taiwan cohort, with a prevalence of 6.8% for the Nordic cohort.

Rates of pregestational diabetes were lowest in the Taiwan and Hong Kong cohorts, at 0.2% and 0.5%, respectively, and 2.2% in the Nordic cohort. Gestational diabetes rates were a respective 3.1%, 7.8%, and 4.6%.

The highest rate of ADHD in children was seen in the Taiwan cohort, at 9.6%, followed by 4.2% for the Hong Kong cohort, and 2.6% for the Nordic cohort.

The hazard ratio for having childhood ADHD was 1.16 when comparing any maternal diabetes to no maternal diabetes, 1.40 comparing mothers with and without pregestational diabetes, and a respective 1.36 and 1.37 comparing those with and without type 1 diabetes, and those with and without type 2 diabetes.

The HR for childhood ADHD comparing mothers with and without gestational diabetes was 1.13.

“Within the analysis for gestational diabetes, we had enough numbers to look at siblings that are discordant for maternal gestational diabetes,” Dr. Cesta said. Essentially “we’re comparing two siblings from the same mother, one that was exposed to gestational diabetes, one that wasn’t,” she explained.

Interestingly there was no association between ADHD and maternal gestational diabetes in the sibling analysis (HR, 1.0).

“When it comes to gestational diabetes, the evidence from our sibling analysis indicate that the association may actually be confounded by shared genetics and environmental factors,” said Dr. Cesta.

“So, future studies should explore the role of specific genetic factors in glycemic control during pregnancy and the relationship between maternal diabetes and ADHD.”

Answering long-standing questions

These data will help a lot in answering questions that clinicians have been asking themselves a long time, commented Jardena Puder, MD, who chaired the session.

“It still remains a bit puzzling that genetic and environmental factors could be responsible, if you see the same effect in type 1 [diabetes], and in type 2 [diabetes], and gestational diabetes,” said Dr. Puder, who is an endocrinologist and diabetologist at the woman-mother-child department at the Vaud University Hospital Center, Lausanne, Switzerland.

Type 1 and type 2 are “very distinct” in terms of the genetic and environmental factors involved, “so, the fact that you see [the effect] in both remains a bit puzzling,” said Dr. Puder.

“I wish we had the numbers to be able to do the sibling analysis for type 1 and type 2, just to see if we could tease anything out,” said Dr. Cesta.

“I do think this is part of the bigger question of what the relationship is between, like, metabolic disorders and psychiatric disorders, because even outside of pregnancy, we see that there’s often a comorbidity with them. So, it’s a good point.”

The next step is to look at the role of treatment and what effects glycemic control might have on the small, but still apparent, association between maternal diabetes and ADHD.

The study had multiple funders including the Hong Kong Research Grant Council, NordForsk, the Research Council of Norway, the Norwegian ADHD Research Network, the Hong Kong Innovation and Technology Commission, and European Horizon 2020.

Dr. Cesta had no conflicts of interest to disclose. Dr. Puder chaired the session in which the findings were presented and made no specific disclosures.

Among people with HIV (PWH), coinfection with hepatitis C (HCV) is associated with an 85% increase in risk of myocardial infarction (MI) every decade, a new analysis suggests.

By contrast, the risk increases by 30% every 10 years among PWH without HCV infection.

“There is other evidence that suggests people with HIV and HCV have a greater burden of negative health outcomes,” senior author Keri N. Althoff, PhD, MPH, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, said in an interview. “But the magnitude of ‘greater’ was bigger than I expected.”

“Understanding the difference HCV can make in the risk of MI with increasing age among those with – compared to without – HCV is an important step for understanding additional potential benefits of HCV treatment (among PWH),” she said.

The amplified risk with age occurred even though, overall, the association between HCV coinfection and increased risk of type 1 myocardial infarction (T1MI) was not significant, the analysis showed.

The study was published online in the Journal of the American Heart Association.

How age counts

Dr. Althoff and colleagues analyzed data from 23,361 PWH aged 40-79 who had initiated antiretroviral therapy between 2000 and 2017. The primary outcome was T1MI.

A total of 4,677 participants (20%) had HCV. Eighty-nine T1MIs occurred among PWH with HCV (1.9%) vs. 314 among PWH without HCV (1.7%). In adjusted analyses, HCV was not associated with increased T1MI risk (adjusted hazard ratio, 0.98).

However, the risk of T1MI increased with age and was augmented in those with HCV (aHR per 10-year increase in age, 1.85) vs. those without HCV (aHR, 1.30).

Specifically, compared with those without HCV, the estimated T1MI risk was 17% higher among 50- to 59-year-olds with HCV and 77% higher among those 60 and older; neither association was statistically significant, although the authors suggest this probably was because of the smaller number of participants in the older age categories.

Even without HCV, the risk of T1MI increased in participants who had traditional risk factors. The risk was significantly higher among PWH aged 40-49 with diabetes, hypertension, chronic kidney disease, protease inhibitor (PI) use, and smoking, whereas among PWH aged 50-59, the T1MI risk was significantly greater among those with hypertension, PI use, and smoking.

Among those aged 60 or older, hypertension and low CD4 counts were associated with a significantly increased T1MI risk.

“Clinicians providing health care to people with HIV should know their patients’ HCV status,” Dr. Althoff said, “and provide support regarding HCV treatment and ways to reduce their cardiovascular risk, including smoking cessation, reaching and maintaining a healthy BMI, and substance use treatment.”
 

Truly additive?

American Heart Association expert volunteer Nieca Goldberg, MD, a clinical associate professor of medicine at New York University and medical director of Atria NY, said the increased T1MI risk with coinfection “makes sense” because both HIV and HCV are linked to inflammation.

However, she said in an interview, “the fact that the authors didn’t control for other, more traditional heart attack risk factors is a limitation. I would like to see a study that takes other risk factors into consideration to see if HCV is truly additive.”

Meanwhile, like Dr. Althoff, she said, “Clinicians should be taking a careful history that includes chronic infections as well as traditional heart risk factors.”

Additional studies are needed, Dr. Althoff agreed. “There are two paths we are keenly interested in pursuing. The first is understanding how metabolic risk factors for MI change after HCV treatment. We are working on this.”

“Ultimately,” she said, “we want to compare MI risk in people with HIV who had successful HCV treatment to those who have not had successful HCV treatment.”

In their current study, they had nearly 2 decades of follow-up, she noted. “Although we don’t need to wait that long, we would like to have close to a decade of potential follow-up time (since 2016, when sofosbuvir/velpatasvir became available) so that we have a large enough sample size to observe a sufficient number of MIs within the first 5 years after successful HCV treatment.”

No commercial funding or relevant disclosures were reported.

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

Among people with HIV (PWH), coinfection with hepatitis C (HCV) is associated with an 85% increase in risk of myocardial infarction (MI) every decade, a new analysis suggests.

By contrast, the risk increases by 30% every 10 years among PWH without HCV infection.

“There is other evidence that suggests people with HIV and HCV have a greater burden of negative health outcomes,” senior author Keri N. Althoff, PhD, MPH, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, said in an interview. “But the magnitude of ‘greater’ was bigger than I expected.”

“Understanding the difference HCV can make in the risk of MI with increasing age among those with – compared to without – HCV is an important step for understanding additional potential benefits of HCV treatment (among PWH),” she said.

The amplified risk with age occurred even though, overall, the association between HCV coinfection and increased risk of type 1 myocardial infarction (T1MI) was not significant, the analysis showed.

The study was published online in the Journal of the American Heart Association.

How age counts

Dr. Althoff and colleagues analyzed data from 23,361 PWH aged 40-79 who had initiated antiretroviral therapy between 2000 and 2017. The primary outcome was T1MI.

A total of 4,677 participants (20%) had HCV. Eighty-nine T1MIs occurred among PWH with HCV (1.9%) vs. 314 among PWH without HCV (1.7%). In adjusted analyses, HCV was not associated with increased T1MI risk (adjusted hazard ratio, 0.98).

However, the risk of T1MI increased with age and was augmented in those with HCV (aHR per 10-year increase in age, 1.85) vs. those without HCV (aHR, 1.30).

Specifically, compared with those without HCV, the estimated T1MI risk was 17% higher among 50- to 59-year-olds with HCV and 77% higher among those 60 and older; neither association was statistically significant, although the authors suggest this probably was because of the smaller number of participants in the older age categories.

Even without HCV, the risk of T1MI increased in participants who had traditional risk factors. The risk was significantly higher among PWH aged 40-49 with diabetes, hypertension, chronic kidney disease, protease inhibitor (PI) use, and smoking, whereas among PWH aged 50-59, the T1MI risk was significantly greater among those with hypertension, PI use, and smoking.

Among those aged 60 or older, hypertension and low CD4 counts were associated with a significantly increased T1MI risk.

“Clinicians providing health care to people with HIV should know their patients’ HCV status,” Dr. Althoff said, “and provide support regarding HCV treatment and ways to reduce their cardiovascular risk, including smoking cessation, reaching and maintaining a healthy BMI, and substance use treatment.”
 

Truly additive?

American Heart Association expert volunteer Nieca Goldberg, MD, a clinical associate professor of medicine at New York University and medical director of Atria NY, said the increased T1MI risk with coinfection “makes sense” because both HIV and HCV are linked to inflammation.

However, she said in an interview, “the fact that the authors didn’t control for other, more traditional heart attack risk factors is a limitation. I would like to see a study that takes other risk factors into consideration to see if HCV is truly additive.”

Meanwhile, like Dr. Althoff, she said, “Clinicians should be taking a careful history that includes chronic infections as well as traditional heart risk factors.”

Additional studies are needed, Dr. Althoff agreed. “There are two paths we are keenly interested in pursuing. The first is understanding how metabolic risk factors for MI change after HCV treatment. We are working on this.”

“Ultimately,” she said, “we want to compare MI risk in people with HIV who had successful HCV treatment to those who have not had successful HCV treatment.”

In their current study, they had nearly 2 decades of follow-up, she noted. “Although we don’t need to wait that long, we would like to have close to a decade of potential follow-up time (since 2016, when sofosbuvir/velpatasvir became available) so that we have a large enough sample size to observe a sufficient number of MIs within the first 5 years after successful HCV treatment.”

No commercial funding or relevant disclosures were reported.

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

Among people with HIV (PWH), coinfection with hepatitis C (HCV) is associated with an 85% increase in risk of myocardial infarction (MI) every decade, a new analysis suggests.

By contrast, the risk increases by 30% every 10 years among PWH without HCV infection.

“There is other evidence that suggests people with HIV and HCV have a greater burden of negative health outcomes,” senior author Keri N. Althoff, PhD, MPH, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, said in an interview. “But the magnitude of ‘greater’ was bigger than I expected.”

“Understanding the difference HCV can make in the risk of MI with increasing age among those with – compared to without – HCV is an important step for understanding additional potential benefits of HCV treatment (among PWH),” she said.

The amplified risk with age occurred even though, overall, the association between HCV coinfection and increased risk of type 1 myocardial infarction (T1MI) was not significant, the analysis showed.

The study was published online in the Journal of the American Heart Association.

How age counts

Dr. Althoff and colleagues analyzed data from 23,361 PWH aged 40-79 who had initiated antiretroviral therapy between 2000 and 2017. The primary outcome was T1MI.

A total of 4,677 participants (20%) had HCV. Eighty-nine T1MIs occurred among PWH with HCV (1.9%) vs. 314 among PWH without HCV (1.7%). In adjusted analyses, HCV was not associated with increased T1MI risk (adjusted hazard ratio, 0.98).

However, the risk of T1MI increased with age and was augmented in those with HCV (aHR per 10-year increase in age, 1.85) vs. those without HCV (aHR, 1.30).

Specifically, compared with those without HCV, the estimated T1MI risk was 17% higher among 50- to 59-year-olds with HCV and 77% higher among those 60 and older; neither association was statistically significant, although the authors suggest this probably was because of the smaller number of participants in the older age categories.

Even without HCV, the risk of T1MI increased in participants who had traditional risk factors. The risk was significantly higher among PWH aged 40-49 with diabetes, hypertension, chronic kidney disease, protease inhibitor (PI) use, and smoking, whereas among PWH aged 50-59, the T1MI risk was significantly greater among those with hypertension, PI use, and smoking.

Among those aged 60 or older, hypertension and low CD4 counts were associated with a significantly increased T1MI risk.

“Clinicians providing health care to people with HIV should know their patients’ HCV status,” Dr. Althoff said, “and provide support regarding HCV treatment and ways to reduce their cardiovascular risk, including smoking cessation, reaching and maintaining a healthy BMI, and substance use treatment.”
 

Truly additive?

American Heart Association expert volunteer Nieca Goldberg, MD, a clinical associate professor of medicine at New York University and medical director of Atria NY, said the increased T1MI risk with coinfection “makes sense” because both HIV and HCV are linked to inflammation.

However, she said in an interview, “the fact that the authors didn’t control for other, more traditional heart attack risk factors is a limitation. I would like to see a study that takes other risk factors into consideration to see if HCV is truly additive.”

Meanwhile, like Dr. Althoff, she said, “Clinicians should be taking a careful history that includes chronic infections as well as traditional heart risk factors.”

Additional studies are needed, Dr. Althoff agreed. “There are two paths we are keenly interested in pursuing. The first is understanding how metabolic risk factors for MI change after HCV treatment. We are working on this.”

“Ultimately,” she said, “we want to compare MI risk in people with HIV who had successful HCV treatment to those who have not had successful HCV treatment.”

In their current study, they had nearly 2 decades of follow-up, she noted. “Although we don’t need to wait that long, we would like to have close to a decade of potential follow-up time (since 2016, when sofosbuvir/velpatasvir became available) so that we have a large enough sample size to observe a sufficient number of MIs within the first 5 years after successful HCV treatment.”

No commercial funding or relevant disclosures were reported.

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

High body mass index (BMI) values are associated with higher survival among metastatic cancer patients treated with first- and second-line immune checkpoint inhibitors (ICIs), but the relationship was only present in males.

That is the conclusion of a new retrospective analysis presented during a poster session given at the annual meeting of the European Society for Medical Oncology. The study sought to better understand ICI outcomes. “These are complex new treatments and, because they harness the immune system, no two patients are likely to respond in the same way. BMI has previously been associated with improved survival in patients with advanced lung cancer treated with immunotherapy. However, the reasons behind this observation, and the implications for treatment are unknown, as is whether this observation is specific for patients with only certain types of cancers,” study author Dwight Owen, MD, said in an email.

He pointed out that the retrospective nature of the findings means that they have no immediate clinical implications. “The reason for the discrepancy in males remains unclear. Although our study included a relatively large number of patients, it is a heterogenous cohort and there may be confounding factors that we haven’t recognized, so these findings need to be replicated in larger cohorts,” said Dr. Owen, a medical oncologist with The Ohio State University Comprehensive Cancer Center, Columbus.

Asked if there is a potential biological explanation for a difference between males and females, Dr. Owen said that this is an area of intense research. One recent study examined whether androgen could help explain why men are more likely than women to both develop and have more aggressive nonreproductive cancers. They concluded that androgen receptor signaling may be leading to loss of effector and proliferative potential of CD8+ T cells in the tumor microenvironment. Once exhausted, these cells do not respond well to stimulation that can occur after ICI treatment.

On the opposite end of the spectrum, cancer cachexia is also a key subject of study. It is characterized by weight loss and is associated with worse clinical outcomes. A cachexia mouse model found that weight loss can lead to more clearance of immune checkpoint antibodies.

Still, much more work needs to be done. “For now, how BMI, obesity, and cachexia relate to other factors, for instance the microbiome and tumor immunogenicity, are still not fully understood,” Dr. Owen said.
 

The study data

The researchers analyzed data from 688 patients with metastatic cancer treated at their center between 2011 and 2017. 94% were White and 5% were Black. 41% were female and the mean age was 61.9 years. The mean BMI was 28.8 kg/m²; 40% of patients had melanoma, 23% had non–small cell lung cancer, 10% had renal cancer, and 27% had another form of cancer.

For every unit decrease in BMI, the researchers observed a 1.8% decrease in mortality (hazard ratio, 0.982; P = .007). Patients with a BMI of 40 or above had better survival than all other patients grouped by 5 BMI increments (that is, 35-40, 30-35, etc.). When separated by sex, males had a significant decrease in mortality for every increase in BMI unit (HR, 0.964; P = .004), but there was no significant difference among women (HR, 1.003; P = .706). The relationship in men held up after adjustment for Eastern Cooperative Oncology Group score, line of therapy, and cancer type (HR, 0.979; P = .0308). The researchers also looked at a separate cohort of 185 normal weight and 15 obese (BMI ≥ 40) NSCLC patients. Median survival was 27.5 months in the obese group and 9.1 months in the normal weight group (HR, 0.474; 95% CI, 0.232-0.969).

Dr. Owen has received research funding through his institution from Bristol-Myers Squibb, Genentech, Pfizer, Palobiofarma, and Onc.AI.

High body mass index (BMI) values are associated with higher survival among metastatic cancer patients treated with first- and second-line immune checkpoint inhibitors (ICIs), but the relationship was only present in males.

That is the conclusion of a new retrospective analysis presented during a poster session given at the annual meeting of the European Society for Medical Oncology. The study sought to better understand ICI outcomes. “These are complex new treatments and, because they harness the immune system, no two patients are likely to respond in the same way. BMI has previously been associated with improved survival in patients with advanced lung cancer treated with immunotherapy. However, the reasons behind this observation, and the implications for treatment are unknown, as is whether this observation is specific for patients with only certain types of cancers,” study author Dwight Owen, MD, said in an email.

He pointed out that the retrospective nature of the findings means that they have no immediate clinical implications. “The reason for the discrepancy in males remains unclear. Although our study included a relatively large number of patients, it is a heterogenous cohort and there may be confounding factors that we haven’t recognized, so these findings need to be replicated in larger cohorts,” said Dr. Owen, a medical oncologist with The Ohio State University Comprehensive Cancer Center, Columbus.

Asked if there is a potential biological explanation for a difference between males and females, Dr. Owen said that this is an area of intense research. One recent study examined whether androgen could help explain why men are more likely than women to both develop and have more aggressive nonreproductive cancers. They concluded that androgen receptor signaling may be leading to loss of effector and proliferative potential of CD8+ T cells in the tumor microenvironment. Once exhausted, these cells do not respond well to stimulation that can occur after ICI treatment.

On the opposite end of the spectrum, cancer cachexia is also a key subject of study. It is characterized by weight loss and is associated with worse clinical outcomes. A cachexia mouse model found that weight loss can lead to more clearance of immune checkpoint antibodies.

Still, much more work needs to be done. “For now, how BMI, obesity, and cachexia relate to other factors, for instance the microbiome and tumor immunogenicity, are still not fully understood,” Dr. Owen said.
 

The study data

The researchers analyzed data from 688 patients with metastatic cancer treated at their center between 2011 and 2017. 94% were White and 5% were Black. 41% were female and the mean age was 61.9 years. The mean BMI was 28.8 kg/m²; 40% of patients had melanoma, 23% had non–small cell lung cancer, 10% had renal cancer, and 27% had another form of cancer.

For every unit decrease in BMI, the researchers observed a 1.8% decrease in mortality (hazard ratio, 0.982; P = .007). Patients with a BMI of 40 or above had better survival than all other patients grouped by 5 BMI increments (that is, 35-40, 30-35, etc.). When separated by sex, males had a significant decrease in mortality for every increase in BMI unit (HR, 0.964; P = .004), but there was no significant difference among women (HR, 1.003; P = .706). The relationship in men held up after adjustment for Eastern Cooperative Oncology Group score, line of therapy, and cancer type (HR, 0.979; P = .0308). The researchers also looked at a separate cohort of 185 normal weight and 15 obese (BMI ≥ 40) NSCLC patients. Median survival was 27.5 months in the obese group and 9.1 months in the normal weight group (HR, 0.474; 95% CI, 0.232-0.969).

Dr. Owen has received research funding through his institution from Bristol-Myers Squibb, Genentech, Pfizer, Palobiofarma, and Onc.AI.

High body mass index (BMI) values are associated with higher survival among metastatic cancer patients treated with first- and second-line immune checkpoint inhibitors (ICIs), but the relationship was only present in males.

That is the conclusion of a new retrospective analysis presented during a poster session given at the annual meeting of the European Society for Medical Oncology. The study sought to better understand ICI outcomes. “These are complex new treatments and, because they harness the immune system, no two patients are likely to respond in the same way. BMI has previously been associated with improved survival in patients with advanced lung cancer treated with immunotherapy. However, the reasons behind this observation, and the implications for treatment are unknown, as is whether this observation is specific for patients with only certain types of cancers,” study author Dwight Owen, MD, said in an email.

He pointed out that the retrospective nature of the findings means that they have no immediate clinical implications. “The reason for the discrepancy in males remains unclear. Although our study included a relatively large number of patients, it is a heterogenous cohort and there may be confounding factors that we haven’t recognized, so these findings need to be replicated in larger cohorts,” said Dr. Owen, a medical oncologist with The Ohio State University Comprehensive Cancer Center, Columbus.

Asked if there is a potential biological explanation for a difference between males and females, Dr. Owen said that this is an area of intense research. One recent study examined whether androgen could help explain why men are more likely than women to both develop and have more aggressive nonreproductive cancers. They concluded that androgen receptor signaling may be leading to loss of effector and proliferative potential of CD8+ T cells in the tumor microenvironment. Once exhausted, these cells do not respond well to stimulation that can occur after ICI treatment.

On the opposite end of the spectrum, cancer cachexia is also a key subject of study. It is characterized by weight loss and is associated with worse clinical outcomes. A cachexia mouse model found that weight loss can lead to more clearance of immune checkpoint antibodies.

Still, much more work needs to be done. “For now, how BMI, obesity, and cachexia relate to other factors, for instance the microbiome and tumor immunogenicity, are still not fully understood,” Dr. Owen said.
 

The study data

The researchers analyzed data from 688 patients with metastatic cancer treated at their center between 2011 and 2017. 94% were White and 5% were Black. 41% were female and the mean age was 61.9 years. The mean BMI was 28.8 kg/m²; 40% of patients had melanoma, 23% had non–small cell lung cancer, 10% had renal cancer, and 27% had another form of cancer.

For every unit decrease in BMI, the researchers observed a 1.8% decrease in mortality (hazard ratio, 0.982; P = .007). Patients with a BMI of 40 or above had better survival than all other patients grouped by 5 BMI increments (that is, 35-40, 30-35, etc.). When separated by sex, males had a significant decrease in mortality for every increase in BMI unit (HR, 0.964; P = .004), but there was no significant difference among women (HR, 1.003; P = .706). The relationship in men held up after adjustment for Eastern Cooperative Oncology Group score, line of therapy, and cancer type (HR, 0.979; P = .0308). The researchers also looked at a separate cohort of 185 normal weight and 15 obese (BMI ≥ 40) NSCLC patients. Median survival was 27.5 months in the obese group and 9.1 months in the normal weight group (HR, 0.474; 95% CI, 0.232-0.969).

Dr. Owen has received research funding through his institution from Bristol-Myers Squibb, Genentech, Pfizer, Palobiofarma, and Onc.AI.

People who stay up late may be at greater risk for type 2 diabetes and cardiovascular disease than those who turn in early, according to new research.

In the study involving 51 people, night owls metabolized fat less efficiently, showed less insulin sensitivity, and demonstrated lower physical fitness than early birds, lead author Steven K. Malin, PhD, of Rutgers University, New Brunswick, N.J., and colleagues reported.

Prior publications have suggested that night owls, formally known as “late chronotypes,” have an increased risk of obesity, type 2 diabetes, and cardiovascular disease, Dr. Malin said in an interview. But no previous research involved the gold-standard measurement tools used in this study, including euglycemic clamp and indirect calorimetry to quantify fat metabolism.

Dr. Malin also noted that this is the first study of its kind to characterize metabolism during both rest and exercise.

The study, published in Experimental Physiology, involved 24 early birds and 27 night owls classified by the Morning-Eveningness Questionnaire. All participants were sedentary, reporting less than one hour of structured exercise per week, and had metabolic syndrome according to Adult Treatment Panel III report criteria. Groups were otherwise demographically similar, with average ages in each group of approximately 54-55 years.

Compared with night owls, early birds were more physically active during the morning into midday. During exercise, they metabolized more fat and demonstrated greater physical fitness based on VO_2max readings. At rest, early birds also came out ahead – they had higher fat oxidation and non–oxidative glucose disposal, suggesting more sensitivity to insulin.

“Collectively, this work highlights and supports chronotype as a potential risk factor related to type 2 diabetes and cardiovascular disease risk,” the investigators concluded.
 

Night owls have less metabolic control

Jed Friedman, PhD, director of OU Health Harold Hamm Diabetes Center at the University of Oklahoma Health Sciences Center, Oklahoma City, praised the study for the size of the groups the researchers compared with each other and how well matched those groups were, as well as the “state-of-the-art” measurement tools employed.

The findings show that night owls have “less metabolic control,” Dr. Friedman said in an interview.

“That’s a term that’s frequently invoked in [regard to] prediabetes,” he said. “Blood sugar goes up, because when you’re eating a high carbohydrate diet, your cells aren’t metabolizing sugar properly. That tends to raise your risk for a lot of diseases.”

Dr. Friedman added that the findings align with those of previous studies that have linked less sleep with changes in brain biology, and therefore behavior, especially in dietary choices.

“When you’re tired, the mechanisms for appetite control go haywire,” Dr. Friedman explained. “The evidence suggests that sugar is the primary driver for what people eat when they’re tired. That obviously has implications for diabetes and metabolic syndrome. So sleeping more really can help you control cravings.”

Dr. Friedman also noted that people who are tired tend to engage in less physical activity, further increasing their risk of metabolic issues. To control this risk, he advised people to return to their circadian rhythms, which could mean forgetting the midnight snack.

“Having a daily pattern that’s in sync with chronicity, or these daily rhythms, is associated with greater health,” Dr. Friedman said. “We’re not really made to eat at night. I think this [study] kind of reinforces that.”
 

Can a night owl become an early bird?

When asked if a person’s natural circadian rhythm can be later, Dr. Malin responded that chronotypes may be dictated by genetics and age, as well as external drivers like work schedule. For these reasons, it’s “tricky” to answer whether night owls can turn into early birds and reap the potential health benefits of making that shift.

“Given that so many life factors can influence what our routine entails, it’s hard to know if we [can] truly change our chronotype or if rather we [can] learn to manage,” Dr. Malin said. “In either case, there is some work that suggests people can adopt earlier bedtimes and waketimes through practical recommendations.”

Specifically, he suggested increasing physical activity during the day, and adjusting bedtimes gradually by 15-minute increments.

“Go to bed 15 minutes earlier then wake up 15 minutes earlier,” Dr. Malin said. “In time, and depending on how things are going, this can expand to another 15-minute window. Then, during the earlier time waking up, a person can engage in light physical activity to help with promoting general fitness. If they can get outside with sunlight, that would be great too, as the natural sunlight would provide cues to the circadian system to adjust.”

The study was supported by the National Institutes of Health. The investigators and Dr. Friedman disclosed no conflicts of interest.

People who stay up late may be at greater risk for type 2 diabetes and cardiovascular disease than those who turn in early, according to new research.

In the study involving 51 people, night owls metabolized fat less efficiently, showed less insulin sensitivity, and demonstrated lower physical fitness than early birds, lead author Steven K. Malin, PhD, of Rutgers University, New Brunswick, N.J., and colleagues reported.

Prior publications have suggested that night owls, formally known as “late chronotypes,” have an increased risk of obesity, type 2 diabetes, and cardiovascular disease, Dr. Malin said in an interview. But no previous research involved the gold-standard measurement tools used in this study, including euglycemic clamp and indirect calorimetry to quantify fat metabolism.

Dr. Malin also noted that this is the first study of its kind to characterize metabolism during both rest and exercise.

The study, published in Experimental Physiology, involved 24 early birds and 27 night owls classified by the Morning-Eveningness Questionnaire. All participants were sedentary, reporting less than one hour of structured exercise per week, and had metabolic syndrome according to Adult Treatment Panel III report criteria. Groups were otherwise demographically similar, with average ages in each group of approximately 54-55 years.

Compared with night owls, early birds were more physically active during the morning into midday. During exercise, they metabolized more fat and demonstrated greater physical fitness based on VO_2max readings. At rest, early birds also came out ahead – they had higher fat oxidation and non–oxidative glucose disposal, suggesting more sensitivity to insulin.

“Collectively, this work highlights and supports chronotype as a potential risk factor related to type 2 diabetes and cardiovascular disease risk,” the investigators concluded.
 

Night owls have less metabolic control

Jed Friedman, PhD, director of OU Health Harold Hamm Diabetes Center at the University of Oklahoma Health Sciences Center, Oklahoma City, praised the study for the size of the groups the researchers compared with each other and how well matched those groups were, as well as the “state-of-the-art” measurement tools employed.

The findings show that night owls have “less metabolic control,” Dr. Friedman said in an interview.

“That’s a term that’s frequently invoked in [regard to] prediabetes,” he said. “Blood sugar goes up, because when you’re eating a high carbohydrate diet, your cells aren’t metabolizing sugar properly. That tends to raise your risk for a lot of diseases.”

Dr. Friedman added that the findings align with those of previous studies that have linked less sleep with changes in brain biology, and therefore behavior, especially in dietary choices.

“When you’re tired, the mechanisms for appetite control go haywire,” Dr. Friedman explained. “The evidence suggests that sugar is the primary driver for what people eat when they’re tired. That obviously has implications for diabetes and metabolic syndrome. So sleeping more really can help you control cravings.”

Dr. Friedman also noted that people who are tired tend to engage in less physical activity, further increasing their risk of metabolic issues. To control this risk, he advised people to return to their circadian rhythms, which could mean forgetting the midnight snack.

“Having a daily pattern that’s in sync with chronicity, or these daily rhythms, is associated with greater health,” Dr. Friedman said. “We’re not really made to eat at night. I think this [study] kind of reinforces that.”
 

Can a night owl become an early bird?

When asked if a person’s natural circadian rhythm can be later, Dr. Malin responded that chronotypes may be dictated by genetics and age, as well as external drivers like work schedule. For these reasons, it’s “tricky” to answer whether night owls can turn into early birds and reap the potential health benefits of making that shift.

“Given that so many life factors can influence what our routine entails, it’s hard to know if we [can] truly change our chronotype or if rather we [can] learn to manage,” Dr. Malin said. “In either case, there is some work that suggests people can adopt earlier bedtimes and waketimes through practical recommendations.”

Specifically, he suggested increasing physical activity during the day, and adjusting bedtimes gradually by 15-minute increments.

“Go to bed 15 minutes earlier then wake up 15 minutes earlier,” Dr. Malin said. “In time, and depending on how things are going, this can expand to another 15-minute window. Then, during the earlier time waking up, a person can engage in light physical activity to help with promoting general fitness. If they can get outside with sunlight, that would be great too, as the natural sunlight would provide cues to the circadian system to adjust.”

The study was supported by the National Institutes of Health. The investigators and Dr. Friedman disclosed no conflicts of interest.

People who stay up late may be at greater risk for type 2 diabetes and cardiovascular disease than those who turn in early, according to new research.

In the study involving 51 people, night owls metabolized fat less efficiently, showed less insulin sensitivity, and demonstrated lower physical fitness than early birds, lead author Steven K. Malin, PhD, of Rutgers University, New Brunswick, N.J., and colleagues reported.

Prior publications have suggested that night owls, formally known as “late chronotypes,” have an increased risk of obesity, type 2 diabetes, and cardiovascular disease, Dr. Malin said in an interview. But no previous research involved the gold-standard measurement tools used in this study, including euglycemic clamp and indirect calorimetry to quantify fat metabolism.

Dr. Malin also noted that this is the first study of its kind to characterize metabolism during both rest and exercise.

The study, published in Experimental Physiology, involved 24 early birds and 27 night owls classified by the Morning-Eveningness Questionnaire. All participants were sedentary, reporting less than one hour of structured exercise per week, and had metabolic syndrome according to Adult Treatment Panel III report criteria. Groups were otherwise demographically similar, with average ages in each group of approximately 54-55 years.

Compared with night owls, early birds were more physically active during the morning into midday. During exercise, they metabolized more fat and demonstrated greater physical fitness based on VO_2max readings. At rest, early birds also came out ahead – they had higher fat oxidation and non–oxidative glucose disposal, suggesting more sensitivity to insulin.

“Collectively, this work highlights and supports chronotype as a potential risk factor related to type 2 diabetes and cardiovascular disease risk,” the investigators concluded.
 

Night owls have less metabolic control

Jed Friedman, PhD, director of OU Health Harold Hamm Diabetes Center at the University of Oklahoma Health Sciences Center, Oklahoma City, praised the study for the size of the groups the researchers compared with each other and how well matched those groups were, as well as the “state-of-the-art” measurement tools employed.

The findings show that night owls have “less metabolic control,” Dr. Friedman said in an interview.

“That’s a term that’s frequently invoked in [regard to] prediabetes,” he said. “Blood sugar goes up, because when you’re eating a high carbohydrate diet, your cells aren’t metabolizing sugar properly. That tends to raise your risk for a lot of diseases.”

Dr. Friedman added that the findings align with those of previous studies that have linked less sleep with changes in brain biology, and therefore behavior, especially in dietary choices.

“When you’re tired, the mechanisms for appetite control go haywire,” Dr. Friedman explained. “The evidence suggests that sugar is the primary driver for what people eat when they’re tired. That obviously has implications for diabetes and metabolic syndrome. So sleeping more really can help you control cravings.”

Dr. Friedman also noted that people who are tired tend to engage in less physical activity, further increasing their risk of metabolic issues. To control this risk, he advised people to return to their circadian rhythms, which could mean forgetting the midnight snack.

“Having a daily pattern that’s in sync with chronicity, or these daily rhythms, is associated with greater health,” Dr. Friedman said. “We’re not really made to eat at night. I think this [study] kind of reinforces that.”
 

Can a night owl become an early bird?

When asked if a person’s natural circadian rhythm can be later, Dr. Malin responded that chronotypes may be dictated by genetics and age, as well as external drivers like work schedule. For these reasons, it’s “tricky” to answer whether night owls can turn into early birds and reap the potential health benefits of making that shift.

“Given that so many life factors can influence what our routine entails, it’s hard to know if we [can] truly change our chronotype or if rather we [can] learn to manage,” Dr. Malin said. “In either case, there is some work that suggests people can adopt earlier bedtimes and waketimes through practical recommendations.”

Specifically, he suggested increasing physical activity during the day, and adjusting bedtimes gradually by 15-minute increments.

“Go to bed 15 minutes earlier then wake up 15 minutes earlier,” Dr. Malin said. “In time, and depending on how things are going, this can expand to another 15-minute window. Then, during the earlier time waking up, a person can engage in light physical activity to help with promoting general fitness. If they can get outside with sunlight, that would be great too, as the natural sunlight would provide cues to the circadian system to adjust.”

The study was supported by the National Institutes of Health. The investigators and Dr. Friedman disclosed no conflicts of interest.