Conference Coverage

NEW YORK — Systemic autoimmune disease is well-recognized as a major risk factor for cardiovascular disease (CVD), but less recognized as a cardiovascular risk factor is a history of pregnancy complications, including preeclampsia, and cardiologists and rheumatologists need to include an obstetric history when managing patients with autoimmune diseases, a specialist in reproductive health in rheumatology told attendees at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.

“Autoimmune diseases, lupus in particular, increase the risk for both cardiovascular disease and maternal placental syndromes,” Lisa R. Sammaritano, MD, a professor at Hospital for Special Surgery in New York City and a specialist in reproductive health issues in rheumatology patients, told attendees. “For those patients who have complications during pregnancy, it further increases their already increased risk for later cardiovascular disease.”
 

CVD Risk Double Whammy

A history of systemic lupus erythematosus (SLE) and problematic pregnancy can be a double whammy for CVD risk. Dr. Sammaritano cited a 2022 meta-analysis that showed patients with SLE had a 2.5 times greater risk for stroke and almost three times greater risk for myocardial infarction than people without SLE.

Maternal placental syndromes include pregnancy loss, restricted fetal growth, preeclampsia, premature membrane rupture, placental abruption, and intrauterine fetal demise, Dr. Sammaritano said. Hypertensive disorders of pregnancy, formerly called adverse pregnancy outcomes, she noted, include gestational hypertension, preeclampsia, and eclampsia.

Pregnancy complications can have an adverse effect on the mother’s postpartum cardiovascular health, Dr. Sammaritano noted, a fact borne out by the cardiovascular health after maternal placental syndromes population-based retrospective cohort study and a 2007 meta-analysis that found a history of preeclampsia doubles the risk for venous thromboembolism, stroke, and ischemic heart disease up to 15 years after pregnancy.

“It is always important to obtain a reproductive health history from patients with autoimmune diseases,” Dr. Sammaritano told this news organization in an interview. “This is an integral part of any medical history. In the usual setting, this includes not only pregnancy history but also use of contraception in reproductive-aged women. Unplanned pregnancy can lead to adverse outcomes in the setting of active or severe autoimmune disease or when teratogenic medications are used.”

Pregnancy history can be a factor in a woman’s cardiovascular health more than 15 years postpartum, even if a woman is no longer planning a pregnancy or is menopausal. “As such, this history is important in assessing every woman’s risk profile for CVD in addition to usual traditional risk factors,” Dr. Sammaritano said.

“It is even more important for women with autoimmune disorders, who have been shown to have an already increased risk for CVD independent of their pregnancy history, likely related to a chronic inflammatory state and other autoimmune-related factors such as presence of antiphospholipid antibodies [aPL] or use of corticosteroids.”

Timing of disease onset is also an issue, she said. “In patients with SLE, for example, onset of CVD is much earlier than in the general population,” Dr. Sammaritano said. “As a result, these patients should likely be assessed for risk — both traditional and other risk factors — earlier than the general population, especially if an adverse obstetric history is present.”

At the younger end of the age continuum, women with autoimmune disease, including SLE and antiphospholipid syndrome, who are pregnant should be put on guideline-directed low-dose aspirin preeclampsia prophylaxis, Dr. Sammaritano said. “Whether every patient with SLE needs this is still uncertain, but certainly, those with a history of renal disease, hypertension, or aPL antibody clearly do,” she added.

The evidence supporting hydroxychloroquine (HCQ) in these patients is controversial, but Dr. Sammaritano noted two meta-analyses, one in 2022 and the other in 2023, that showed that HCQ lowered the risk for preeclampsia in women.

“The clear benefit of HCQ in preventing maternal disease complications, including flare, means we recommend it regardless for all patients with SLE at baseline and during pregnancy [if tolerated],” Dr. Sammaritano said. “The benefit or optimal use of these medications in other autoimmune diseases is less studied and less certain.”

Dr. Sammaritano added in her presentation, “We really need better therapies and, hopefully, those will be on the way, but I think the takeaway message, particularly for practicing rheumatologists and cardiologists, is to ask the question about obstetric history. Many of us don’t. It doesn’t seem relevant in the moment, but it really is in terms of the patient’s long-term risk for cardiovascular disease.”
 

The Case for Treatment During Pregnancy

Prophylaxis against pregnancy complications in patients with autoimmune disease may be achievable, Taryn Youngstein, MBBS, consultant rheumatologist and codirector of the Centre of Excellence in Vasculitis Research, Imperial College London, London, England, told this news organization after Dr. Sammaritano’s presentation. At the 2023 American College of Rheumatology Annual Meeting, her group reported the safety and effectiveness of continuing tocilizumab in pregnant women with Takayasu arteritis, a large-vessel vasculitis predominantly affecting women of reproductive age.

“What traditionally happens is you would stop the biologic particularly before the third trimester because of safety and concerns that the monoclonal antibody is actively transported across the placenta, which means the baby gets much more concentration of the drug than the mum,” Dr. Youngstein said.

It’s a situation physicians must monitor closely, she said. “The mum is donating their immune system to the baby, but they’re also donating drug.”

“In high-risk patients, we would share decision-making with the patient,” Dr. Youngstein continued. “We have decided it’s too high of a risk for us to stop the drug, so we have been continuing the interleukin-6 [IL-6] inhibitor throughout the entire pregnancy.”

The data from Dr. Youngstein’s group showed that pregnant women with Takayasu arteritis who continued IL-6 inhibition therapy all carried to term with healthy births.

“We’ve shown that it’s relatively safe to do that, but you have to be very careful in monitoring the baby,” she said. This includes not giving the infant any live vaccines at birth because it will have the high levels of IL-6 inhibition, she said.

Dr. Sammaritano and Dr. Youngstein had no relevant financial relationships to disclose.

A version of this article appeared on Medscape.com.

NEW YORK — Systemic autoimmune disease is well-recognized as a major risk factor for cardiovascular disease (CVD), but less recognized as a cardiovascular risk factor is a history of pregnancy complications, including preeclampsia, and cardiologists and rheumatologists need to include an obstetric history when managing patients with autoimmune diseases, a specialist in reproductive health in rheumatology told attendees at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.

“Autoimmune diseases, lupus in particular, increase the risk for both cardiovascular disease and maternal placental syndromes,” Lisa R. Sammaritano, MD, a professor at Hospital for Special Surgery in New York City and a specialist in reproductive health issues in rheumatology patients, told attendees. “For those patients who have complications during pregnancy, it further increases their already increased risk for later cardiovascular disease.”
 

CVD Risk Double Whammy

A history of systemic lupus erythematosus (SLE) and problematic pregnancy can be a double whammy for CVD risk. Dr. Sammaritano cited a 2022 meta-analysis that showed patients with SLE had a 2.5 times greater risk for stroke and almost three times greater risk for myocardial infarction than people without SLE.

Maternal placental syndromes include pregnancy loss, restricted fetal growth, preeclampsia, premature membrane rupture, placental abruption, and intrauterine fetal demise, Dr. Sammaritano said. Hypertensive disorders of pregnancy, formerly called adverse pregnancy outcomes, she noted, include gestational hypertension, preeclampsia, and eclampsia.

Pregnancy complications can have an adverse effect on the mother’s postpartum cardiovascular health, Dr. Sammaritano noted, a fact borne out by the cardiovascular health after maternal placental syndromes population-based retrospective cohort study and a 2007 meta-analysis that found a history of preeclampsia doubles the risk for venous thromboembolism, stroke, and ischemic heart disease up to 15 years after pregnancy.

“It is always important to obtain a reproductive health history from patients with autoimmune diseases,” Dr. Sammaritano told this news organization in an interview. “This is an integral part of any medical history. In the usual setting, this includes not only pregnancy history but also use of contraception in reproductive-aged women. Unplanned pregnancy can lead to adverse outcomes in the setting of active or severe autoimmune disease or when teratogenic medications are used.”

Pregnancy history can be a factor in a woman’s cardiovascular health more than 15 years postpartum, even if a woman is no longer planning a pregnancy or is menopausal. “As such, this history is important in assessing every woman’s risk profile for CVD in addition to usual traditional risk factors,” Dr. Sammaritano said.

“It is even more important for women with autoimmune disorders, who have been shown to have an already increased risk for CVD independent of their pregnancy history, likely related to a chronic inflammatory state and other autoimmune-related factors such as presence of antiphospholipid antibodies [aPL] or use of corticosteroids.”

Timing of disease onset is also an issue, she said. “In patients with SLE, for example, onset of CVD is much earlier than in the general population,” Dr. Sammaritano said. “As a result, these patients should likely be assessed for risk — both traditional and other risk factors — earlier than the general population, especially if an adverse obstetric history is present.”

At the younger end of the age continuum, women with autoimmune disease, including SLE and antiphospholipid syndrome, who are pregnant should be put on guideline-directed low-dose aspirin preeclampsia prophylaxis, Dr. Sammaritano said. “Whether every patient with SLE needs this is still uncertain, but certainly, those with a history of renal disease, hypertension, or aPL antibody clearly do,” she added.

The evidence supporting hydroxychloroquine (HCQ) in these patients is controversial, but Dr. Sammaritano noted two meta-analyses, one in 2022 and the other in 2023, that showed that HCQ lowered the risk for preeclampsia in women.

“The clear benefit of HCQ in preventing maternal disease complications, including flare, means we recommend it regardless for all patients with SLE at baseline and during pregnancy [if tolerated],” Dr. Sammaritano said. “The benefit or optimal use of these medications in other autoimmune diseases is less studied and less certain.”

Dr. Sammaritano added in her presentation, “We really need better therapies and, hopefully, those will be on the way, but I think the takeaway message, particularly for practicing rheumatologists and cardiologists, is to ask the question about obstetric history. Many of us don’t. It doesn’t seem relevant in the moment, but it really is in terms of the patient’s long-term risk for cardiovascular disease.”
 

The Case for Treatment During Pregnancy

Prophylaxis against pregnancy complications in patients with autoimmune disease may be achievable, Taryn Youngstein, MBBS, consultant rheumatologist and codirector of the Centre of Excellence in Vasculitis Research, Imperial College London, London, England, told this news organization after Dr. Sammaritano’s presentation. At the 2023 American College of Rheumatology Annual Meeting, her group reported the safety and effectiveness of continuing tocilizumab in pregnant women with Takayasu arteritis, a large-vessel vasculitis predominantly affecting women of reproductive age.

“What traditionally happens is you would stop the biologic particularly before the third trimester because of safety and concerns that the monoclonal antibody is actively transported across the placenta, which means the baby gets much more concentration of the drug than the mum,” Dr. Youngstein said.

It’s a situation physicians must monitor closely, she said. “The mum is donating their immune system to the baby, but they’re also donating drug.”

“In high-risk patients, we would share decision-making with the patient,” Dr. Youngstein continued. “We have decided it’s too high of a risk for us to stop the drug, so we have been continuing the interleukin-6 [IL-6] inhibitor throughout the entire pregnancy.”

The data from Dr. Youngstein’s group showed that pregnant women with Takayasu arteritis who continued IL-6 inhibition therapy all carried to term with healthy births.

“We’ve shown that it’s relatively safe to do that, but you have to be very careful in monitoring the baby,” she said. This includes not giving the infant any live vaccines at birth because it will have the high levels of IL-6 inhibition, she said.

Dr. Sammaritano and Dr. Youngstein had no relevant financial relationships to disclose.

A version of this article appeared on Medscape.com.

NEW YORK — Systemic autoimmune disease is well-recognized as a major risk factor for cardiovascular disease (CVD), but less recognized as a cardiovascular risk factor is a history of pregnancy complications, including preeclampsia, and cardiologists and rheumatologists need to include an obstetric history when managing patients with autoimmune diseases, a specialist in reproductive health in rheumatology told attendees at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.

“Autoimmune diseases, lupus in particular, increase the risk for both cardiovascular disease and maternal placental syndromes,” Lisa R. Sammaritano, MD, a professor at Hospital for Special Surgery in New York City and a specialist in reproductive health issues in rheumatology patients, told attendees. “For those patients who have complications during pregnancy, it further increases their already increased risk for later cardiovascular disease.”
 

CVD Risk Double Whammy

A history of systemic lupus erythematosus (SLE) and problematic pregnancy can be a double whammy for CVD risk. Dr. Sammaritano cited a 2022 meta-analysis that showed patients with SLE had a 2.5 times greater risk for stroke and almost three times greater risk for myocardial infarction than people without SLE.

Maternal placental syndromes include pregnancy loss, restricted fetal growth, preeclampsia, premature membrane rupture, placental abruption, and intrauterine fetal demise, Dr. Sammaritano said. Hypertensive disorders of pregnancy, formerly called adverse pregnancy outcomes, she noted, include gestational hypertension, preeclampsia, and eclampsia.

Pregnancy complications can have an adverse effect on the mother’s postpartum cardiovascular health, Dr. Sammaritano noted, a fact borne out by the cardiovascular health after maternal placental syndromes population-based retrospective cohort study and a 2007 meta-analysis that found a history of preeclampsia doubles the risk for venous thromboembolism, stroke, and ischemic heart disease up to 15 years after pregnancy.

“It is always important to obtain a reproductive health history from patients with autoimmune diseases,” Dr. Sammaritano told this news organization in an interview. “This is an integral part of any medical history. In the usual setting, this includes not only pregnancy history but also use of contraception in reproductive-aged women. Unplanned pregnancy can lead to adverse outcomes in the setting of active or severe autoimmune disease or when teratogenic medications are used.”

Pregnancy history can be a factor in a woman’s cardiovascular health more than 15 years postpartum, even if a woman is no longer planning a pregnancy or is menopausal. “As such, this history is important in assessing every woman’s risk profile for CVD in addition to usual traditional risk factors,” Dr. Sammaritano said.

“It is even more important for women with autoimmune disorders, who have been shown to have an already increased risk for CVD independent of their pregnancy history, likely related to a chronic inflammatory state and other autoimmune-related factors such as presence of antiphospholipid antibodies [aPL] or use of corticosteroids.”

Timing of disease onset is also an issue, she said. “In patients with SLE, for example, onset of CVD is much earlier than in the general population,” Dr. Sammaritano said. “As a result, these patients should likely be assessed for risk — both traditional and other risk factors — earlier than the general population, especially if an adverse obstetric history is present.”

At the younger end of the age continuum, women with autoimmune disease, including SLE and antiphospholipid syndrome, who are pregnant should be put on guideline-directed low-dose aspirin preeclampsia prophylaxis, Dr. Sammaritano said. “Whether every patient with SLE needs this is still uncertain, but certainly, those with a history of renal disease, hypertension, or aPL antibody clearly do,” she added.

The evidence supporting hydroxychloroquine (HCQ) in these patients is controversial, but Dr. Sammaritano noted two meta-analyses, one in 2022 and the other in 2023, that showed that HCQ lowered the risk for preeclampsia in women.

“The clear benefit of HCQ in preventing maternal disease complications, including flare, means we recommend it regardless for all patients with SLE at baseline and during pregnancy [if tolerated],” Dr. Sammaritano said. “The benefit or optimal use of these medications in other autoimmune diseases is less studied and less certain.”

Dr. Sammaritano added in her presentation, “We really need better therapies and, hopefully, those will be on the way, but I think the takeaway message, particularly for practicing rheumatologists and cardiologists, is to ask the question about obstetric history. Many of us don’t. It doesn’t seem relevant in the moment, but it really is in terms of the patient’s long-term risk for cardiovascular disease.”
 

The Case for Treatment During Pregnancy

Prophylaxis against pregnancy complications in patients with autoimmune disease may be achievable, Taryn Youngstein, MBBS, consultant rheumatologist and codirector of the Centre of Excellence in Vasculitis Research, Imperial College London, London, England, told this news organization after Dr. Sammaritano’s presentation. At the 2023 American College of Rheumatology Annual Meeting, her group reported the safety and effectiveness of continuing tocilizumab in pregnant women with Takayasu arteritis, a large-vessel vasculitis predominantly affecting women of reproductive age.

“What traditionally happens is you would stop the biologic particularly before the third trimester because of safety and concerns that the monoclonal antibody is actively transported across the placenta, which means the baby gets much more concentration of the drug than the mum,” Dr. Youngstein said.

It’s a situation physicians must monitor closely, she said. “The mum is donating their immune system to the baby, but they’re also donating drug.”

“In high-risk patients, we would share decision-making with the patient,” Dr. Youngstein continued. “We have decided it’s too high of a risk for us to stop the drug, so we have been continuing the interleukin-6 [IL-6] inhibitor throughout the entire pregnancy.”

The data from Dr. Youngstein’s group showed that pregnant women with Takayasu arteritis who continued IL-6 inhibition therapy all carried to term with healthy births.

“We’ve shown that it’s relatively safe to do that, but you have to be very careful in monitoring the baby,” she said. This includes not giving the infant any live vaccines at birth because it will have the high levels of IL-6 inhibition, she said.

Dr. Sammaritano and Dr. Youngstein had no relevant financial relationships to disclose.

A version of this article appeared on Medscape.com.

Lower urinary tract symptoms were significantly associated with lower scores on measures of cognitive impairment in older adults, based on data from approximately 10,000 individuals.

“We know that lower urinary tract symptoms are very common in aging men and women;” however, older adults often underreport symptoms and avoid seeking treatment, Belinda Williams, MD, of the University of Alabama, Birmingham, said in a presentation at the annual meeting of the American Geriatrics Society.

“Evidence also shows us that the incidence of lower urinary tract symptoms (LUTS) is higher in patients with dementia,” she said. However, the association between cognitive impairment and LUTS has not been well studied, she said.

To address this knowledge gap, Dr. Williams and colleagues reviewed data from older adults with and without LUTS who were enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort study including 30,239 Black or White adults aged 45 years and older who completed telephone or in-home assessments in 2003-2007 and in 2013-2017.

The study population included 6062 women and 4438 men who responded to questionnaires about LUTS and completed several cognitive tests via telephone in 2019-2010. The tests evaluated verbal fluency, executive function, and memory, and included the Six-Item Screener, Animal Naming, Letter F naming, and word list learning; lower scores indicated poorer cognitive performance.

Participants who met the criteria for LUTS were categorized as having mild, moderate, or severe symptoms.

The researchers controlled for age, race, education, income, and urban/rural setting in a multivariate analysis. The mean ages of the women and men were 69 years and 63 years, respectively; 41% and 32% were Black, 59% and 68% were White.

Overall, 70% of women and 62% of men reported LUTS; 6.2% and 8.2%, respectively, met criteria for cognitive impairment. The association between cognitive impairment and LUTS was statistically significant for all specific tests (P < .01), but not for the global cognitive domain tests.

Black men were more likely to report LUTS than White men, but LUTS reports were similar between Black and White women.

Moderate LUTS was the most common degree of severity for men and women (54% and 64%, respectively).

The most common symptom overall was pre-toilet leakage (urge urinary incontinence), reported by 94% of women and 91% of men. The next most common symptoms for men and women were nocturia and urgency.

“We found that, across the board, in all the cognitive tests, LUTS were associated with lower cognitive test scores,” Dr. Williams said in her presentation. Little differences were seen on the Six-Item Screener, she noted, but when they further analyzed the data using scores lower than 4 to indicate cognitive impairment, they found significant association with LUTS, she said.

The results showing that the presence of LUTS was consistently associated with lower cognitive test scores of verbal fluency, executive function, and memory, are applicable in clinical practice, Dr. Williams said in her presentation.

“Recognizing the subtle changes in cognition among older adults with LUTS may impact treatment decisions,” she said. “For example, we can encourage and advise our patients to be physically and cognitively active and to avoid anticholinergic medications.”

Next steps for research include analyzing longitudinal changes in cognition among participants with and without LUTS, said Dr. Williams.

During a question-and-answer session, Dr. Williams agreed with a comment that incorporating cognitive screening strategies in to LUTS clinical pathways might be helpful, such as conducting a baseline Montreal Cognitive Assessment Test (MoCA) in patients with LUTS. “Periodic repeat MoCAs thereafter can help assess decline in cognition,” she said.

The study was supported by the National Institutes of Neurological Disorders and Stroke and the National Institute on Aging. The researchers had no financial conflicts to disclose.

Lower urinary tract symptoms were significantly associated with lower scores on measures of cognitive impairment in older adults, based on data from approximately 10,000 individuals.

“We know that lower urinary tract symptoms are very common in aging men and women;” however, older adults often underreport symptoms and avoid seeking treatment, Belinda Williams, MD, of the University of Alabama, Birmingham, said in a presentation at the annual meeting of the American Geriatrics Society.

“Evidence also shows us that the incidence of lower urinary tract symptoms (LUTS) is higher in patients with dementia,” she said. However, the association between cognitive impairment and LUTS has not been well studied, she said.

To address this knowledge gap, Dr. Williams and colleagues reviewed data from older adults with and without LUTS who were enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort study including 30,239 Black or White adults aged 45 years and older who completed telephone or in-home assessments in 2003-2007 and in 2013-2017.

The study population included 6062 women and 4438 men who responded to questionnaires about LUTS and completed several cognitive tests via telephone in 2019-2010. The tests evaluated verbal fluency, executive function, and memory, and included the Six-Item Screener, Animal Naming, Letter F naming, and word list learning; lower scores indicated poorer cognitive performance.

Participants who met the criteria for LUTS were categorized as having mild, moderate, or severe symptoms.

The researchers controlled for age, race, education, income, and urban/rural setting in a multivariate analysis. The mean ages of the women and men were 69 years and 63 years, respectively; 41% and 32% were Black, 59% and 68% were White.

Overall, 70% of women and 62% of men reported LUTS; 6.2% and 8.2%, respectively, met criteria for cognitive impairment. The association between cognitive impairment and LUTS was statistically significant for all specific tests (P < .01), but not for the global cognitive domain tests.

Black men were more likely to report LUTS than White men, but LUTS reports were similar between Black and White women.

Moderate LUTS was the most common degree of severity for men and women (54% and 64%, respectively).

The most common symptom overall was pre-toilet leakage (urge urinary incontinence), reported by 94% of women and 91% of men. The next most common symptoms for men and women were nocturia and urgency.

“We found that, across the board, in all the cognitive tests, LUTS were associated with lower cognitive test scores,” Dr. Williams said in her presentation. Little differences were seen on the Six-Item Screener, she noted, but when they further analyzed the data using scores lower than 4 to indicate cognitive impairment, they found significant association with LUTS, she said.

The results showing that the presence of LUTS was consistently associated with lower cognitive test scores of verbal fluency, executive function, and memory, are applicable in clinical practice, Dr. Williams said in her presentation.

“Recognizing the subtle changes in cognition among older adults with LUTS may impact treatment decisions,” she said. “For example, we can encourage and advise our patients to be physically and cognitively active and to avoid anticholinergic medications.”

Next steps for research include analyzing longitudinal changes in cognition among participants with and without LUTS, said Dr. Williams.

During a question-and-answer session, Dr. Williams agreed with a comment that incorporating cognitive screening strategies in to LUTS clinical pathways might be helpful, such as conducting a baseline Montreal Cognitive Assessment Test (MoCA) in patients with LUTS. “Periodic repeat MoCAs thereafter can help assess decline in cognition,” she said.

The study was supported by the National Institutes of Neurological Disorders and Stroke and the National Institute on Aging. The researchers had no financial conflicts to disclose.

Lower urinary tract symptoms were significantly associated with lower scores on measures of cognitive impairment in older adults, based on data from approximately 10,000 individuals.

“We know that lower urinary tract symptoms are very common in aging men and women;” however, older adults often underreport symptoms and avoid seeking treatment, Belinda Williams, MD, of the University of Alabama, Birmingham, said in a presentation at the annual meeting of the American Geriatrics Society.

“Evidence also shows us that the incidence of lower urinary tract symptoms (LUTS) is higher in patients with dementia,” she said. However, the association between cognitive impairment and LUTS has not been well studied, she said.

To address this knowledge gap, Dr. Williams and colleagues reviewed data from older adults with and without LUTS who were enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort study including 30,239 Black or White adults aged 45 years and older who completed telephone or in-home assessments in 2003-2007 and in 2013-2017.

The study population included 6062 women and 4438 men who responded to questionnaires about LUTS and completed several cognitive tests via telephone in 2019-2010. The tests evaluated verbal fluency, executive function, and memory, and included the Six-Item Screener, Animal Naming, Letter F naming, and word list learning; lower scores indicated poorer cognitive performance.

Participants who met the criteria for LUTS were categorized as having mild, moderate, or severe symptoms.

The researchers controlled for age, race, education, income, and urban/rural setting in a multivariate analysis. The mean ages of the women and men were 69 years and 63 years, respectively; 41% and 32% were Black, 59% and 68% were White.

Overall, 70% of women and 62% of men reported LUTS; 6.2% and 8.2%, respectively, met criteria for cognitive impairment. The association between cognitive impairment and LUTS was statistically significant for all specific tests (P < .01), but not for the global cognitive domain tests.

Black men were more likely to report LUTS than White men, but LUTS reports were similar between Black and White women.

Moderate LUTS was the most common degree of severity for men and women (54% and 64%, respectively).

The most common symptom overall was pre-toilet leakage (urge urinary incontinence), reported by 94% of women and 91% of men. The next most common symptoms for men and women were nocturia and urgency.

“We found that, across the board, in all the cognitive tests, LUTS were associated with lower cognitive test scores,” Dr. Williams said in her presentation. Little differences were seen on the Six-Item Screener, she noted, but when they further analyzed the data using scores lower than 4 to indicate cognitive impairment, they found significant association with LUTS, she said.

The results showing that the presence of LUTS was consistently associated with lower cognitive test scores of verbal fluency, executive function, and memory, are applicable in clinical practice, Dr. Williams said in her presentation.

“Recognizing the subtle changes in cognition among older adults with LUTS may impact treatment decisions,” she said. “For example, we can encourage and advise our patients to be physically and cognitively active and to avoid anticholinergic medications.”

Next steps for research include analyzing longitudinal changes in cognition among participants with and without LUTS, said Dr. Williams.

During a question-and-answer session, Dr. Williams agreed with a comment that incorporating cognitive screening strategies in to LUTS clinical pathways might be helpful, such as conducting a baseline Montreal Cognitive Assessment Test (MoCA) in patients with LUTS. “Periodic repeat MoCAs thereafter can help assess decline in cognition,” she said.

The study was supported by the National Institutes of Neurological Disorders and Stroke and the National Institute on Aging. The researchers had no financial conflicts to disclose.

The topic of head and neck cancer is especially timely since the disease is evolving. A hematologist/oncologist with the Association of VA Hematology/Oncology (AVAHO) told colleagues that specialists are grappling with how to de-escalate treatment.

Molly Tokaz, MD, of Veterans Affairs Puget Sound Health Care and the University of Washington said tobacco is fading as a cause as fewer people smoke, and that human papillomavirus (HPV) is triggering more cases. HPV-positive patients have better prognoses, raising the prospect that their treatment could be adjusted.

“Instead of increasing the amount of therapy we're giving, we’re trying to peel it back,” she said. “If they’re going to respond no matter what we do, why are we going in with these huge weapons of mass destruction if we can get the same results with something more like a light infantry?”

Tokaz spoke about deescalating therapy at a May 2024 regional AVAHO meeting in Seattle that was focused on head and neck cancer. She elaborated on her presentation in an interview with Federal Practitioner. according to Tokaz, 90% of head and neck cancers are mucosal squamous cell carcinomas (SCC). HPV is associated specifically with nasopharyngeal cancer, which is distinct from SCC, and oropharyngeal cancer, which has been linked to better prognoses.

HPV-positive head and neck cancer is a unique entity with its own epidemiology, clinical prognosis, and treatment. “Patients tend to be younger without the same number of comorbid conditions,” Tokaz said. “Some of them are never smokers or light smokers. So, it's a different demographic than we’ve seen traditionally.”

The bad news is that HPV-associated head and neck cancer numbers are on the rise. Fortunately, outcomes tend to be better for the HPV-positive forms.

As for therapy for head and neck cancer, immunotherapy and targeted therapy play smaller roles than in some other cancers because the form tends to be diagnosed in early stages before metastases appear. Surgery, chemotherapy, and radiation remain the major treatments. According to Tokaz’s presentation, surgery, or radiation—often with minimal adjuvant chemotherapy—can be appropriate for the earliest stage I and II cases of head and neck SCC. (She noted that HPV-positive oropharyngeal squamous cell carcinoma has its own staging system.)

Stage I and II cases make up 15% of new diagnoses and have a 5-year survival rate of > 70%. “In the earliest days, our main role was to make radiation work better and reduce it while adding a minimum amount of toxicity mutations,” she said. “Chemotherapy can help, but it’s only demonstrated improvement in overall survival in patients with positive surgical margins and extracapsular extension.”

In Stage III, IVA, and IVB cases, which make up 70% of new diagnoses, chemotherapy plus radiation is recommended. Five-year survival drops to 30% to 50%. Finally, 10% of new diagnoses are Stage IVC, which is incurable and median survival is < 1 year.

Since HPV-positive patients generally have better prognoses, oncologists are considering how to adjust their treatment. However, Tokaz notes that clinical trials have not shown a benefit from less intensive treatment in these patients. “At this point, we still treat them the same way as HPV-negative patients. But it's an ongoing area of research.”

Researchers are also exploring how to optimize regimens in patients ineligible for treatment with the chemotherapy agent cisplatin. “These folks have been traditionally excluded from clinical trials because they’re sicker,” Tokaz explained. “Researchers normally want the fittest and the best patients [in trials]. If you give a drug to someone with a lot of other comorbid conditions, they might not do as well with it, and it makes your drug look bad.”

Figuring out how to treat these patients is an especially urgent task in head and neck cancer because so many patients are frail and have comorbidities. More globally, Tokaz said the rise of HPV-related head and neck cancer highlights the importance of HPV vaccination, which is crucial for preventing cervical and anal cancer in addition to head and neck cancer. “HPV vaccination for children and young adults is crucial.”

Molly Tokaz, MD, reported no relevant financial relationships.

The topic of head and neck cancer is especially timely since the disease is evolving. A hematologist/oncologist with the Association of VA Hematology/Oncology (AVAHO) told colleagues that specialists are grappling with how to de-escalate treatment.

Molly Tokaz, MD, of Veterans Affairs Puget Sound Health Care and the University of Washington said tobacco is fading as a cause as fewer people smoke, and that human papillomavirus (HPV) is triggering more cases. HPV-positive patients have better prognoses, raising the prospect that their treatment could be adjusted.

“Instead of increasing the amount of therapy we're giving, we’re trying to peel it back,” she said. “If they’re going to respond no matter what we do, why are we going in with these huge weapons of mass destruction if we can get the same results with something more like a light infantry?”

Tokaz spoke about deescalating therapy at a May 2024 regional AVAHO meeting in Seattle that was focused on head and neck cancer. She elaborated on her presentation in an interview with Federal Practitioner. according to Tokaz, 90% of head and neck cancers are mucosal squamous cell carcinomas (SCC). HPV is associated specifically with nasopharyngeal cancer, which is distinct from SCC, and oropharyngeal cancer, which has been linked to better prognoses.

HPV-positive head and neck cancer is a unique entity with its own epidemiology, clinical prognosis, and treatment. “Patients tend to be younger without the same number of comorbid conditions,” Tokaz said. “Some of them are never smokers or light smokers. So, it's a different demographic than we’ve seen traditionally.”

The bad news is that HPV-associated head and neck cancer numbers are on the rise. Fortunately, outcomes tend to be better for the HPV-positive forms.

As for therapy for head and neck cancer, immunotherapy and targeted therapy play smaller roles than in some other cancers because the form tends to be diagnosed in early stages before metastases appear. Surgery, chemotherapy, and radiation remain the major treatments. According to Tokaz’s presentation, surgery, or radiation—often with minimal adjuvant chemotherapy—can be appropriate for the earliest stage I and II cases of head and neck SCC. (She noted that HPV-positive oropharyngeal squamous cell carcinoma has its own staging system.)

Stage I and II cases make up 15% of new diagnoses and have a 5-year survival rate of > 70%. “In the earliest days, our main role was to make radiation work better and reduce it while adding a minimum amount of toxicity mutations,” she said. “Chemotherapy can help, but it’s only demonstrated improvement in overall survival in patients with positive surgical margins and extracapsular extension.”

In Stage III, IVA, and IVB cases, which make up 70% of new diagnoses, chemotherapy plus radiation is recommended. Five-year survival drops to 30% to 50%. Finally, 10% of new diagnoses are Stage IVC, which is incurable and median survival is < 1 year.

Since HPV-positive patients generally have better prognoses, oncologists are considering how to adjust their treatment. However, Tokaz notes that clinical trials have not shown a benefit from less intensive treatment in these patients. “At this point, we still treat them the same way as HPV-negative patients. But it's an ongoing area of research.”

Researchers are also exploring how to optimize regimens in patients ineligible for treatment with the chemotherapy agent cisplatin. “These folks have been traditionally excluded from clinical trials because they’re sicker,” Tokaz explained. “Researchers normally want the fittest and the best patients [in trials]. If you give a drug to someone with a lot of other comorbid conditions, they might not do as well with it, and it makes your drug look bad.”

Figuring out how to treat these patients is an especially urgent task in head and neck cancer because so many patients are frail and have comorbidities. More globally, Tokaz said the rise of HPV-related head and neck cancer highlights the importance of HPV vaccination, which is crucial for preventing cervical and anal cancer in addition to head and neck cancer. “HPV vaccination for children and young adults is crucial.”

Molly Tokaz, MD, reported no relevant financial relationships.

The topic of head and neck cancer is especially timely since the disease is evolving. A hematologist/oncologist with the Association of VA Hematology/Oncology (AVAHO) told colleagues that specialists are grappling with how to de-escalate treatment.

Molly Tokaz, MD, of Veterans Affairs Puget Sound Health Care and the University of Washington said tobacco is fading as a cause as fewer people smoke, and that human papillomavirus (HPV) is triggering more cases. HPV-positive patients have better prognoses, raising the prospect that their treatment could be adjusted.

“Instead of increasing the amount of therapy we're giving, we’re trying to peel it back,” she said. “If they’re going to respond no matter what we do, why are we going in with these huge weapons of mass destruction if we can get the same results with something more like a light infantry?”

Tokaz spoke about deescalating therapy at a May 2024 regional AVAHO meeting in Seattle that was focused on head and neck cancer. She elaborated on her presentation in an interview with Federal Practitioner. according to Tokaz, 90% of head and neck cancers are mucosal squamous cell carcinomas (SCC). HPV is associated specifically with nasopharyngeal cancer, which is distinct from SCC, and oropharyngeal cancer, which has been linked to better prognoses.

HPV-positive head and neck cancer is a unique entity with its own epidemiology, clinical prognosis, and treatment. “Patients tend to be younger without the same number of comorbid conditions,” Tokaz said. “Some of them are never smokers or light smokers. So, it's a different demographic than we’ve seen traditionally.”

The bad news is that HPV-associated head and neck cancer numbers are on the rise. Fortunately, outcomes tend to be better for the HPV-positive forms.

As for therapy for head and neck cancer, immunotherapy and targeted therapy play smaller roles than in some other cancers because the form tends to be diagnosed in early stages before metastases appear. Surgery, chemotherapy, and radiation remain the major treatments. According to Tokaz’s presentation, surgery, or radiation—often with minimal adjuvant chemotherapy—can be appropriate for the earliest stage I and II cases of head and neck SCC. (She noted that HPV-positive oropharyngeal squamous cell carcinoma has its own staging system.)

Stage I and II cases make up 15% of new diagnoses and have a 5-year survival rate of > 70%. “In the earliest days, our main role was to make radiation work better and reduce it while adding a minimum amount of toxicity mutations,” she said. “Chemotherapy can help, but it’s only demonstrated improvement in overall survival in patients with positive surgical margins and extracapsular extension.”

In Stage III, IVA, and IVB cases, which make up 70% of new diagnoses, chemotherapy plus radiation is recommended. Five-year survival drops to 30% to 50%. Finally, 10% of new diagnoses are Stage IVC, which is incurable and median survival is < 1 year.

Since HPV-positive patients generally have better prognoses, oncologists are considering how to adjust their treatment. However, Tokaz notes that clinical trials have not shown a benefit from less intensive treatment in these patients. “At this point, we still treat them the same way as HPV-negative patients. But it's an ongoing area of research.”

Researchers are also exploring how to optimize regimens in patients ineligible for treatment with the chemotherapy agent cisplatin. “These folks have been traditionally excluded from clinical trials because they’re sicker,” Tokaz explained. “Researchers normally want the fittest and the best patients [in trials]. If you give a drug to someone with a lot of other comorbid conditions, they might not do as well with it, and it makes your drug look bad.”

Figuring out how to treat these patients is an especially urgent task in head and neck cancer because so many patients are frail and have comorbidities. More globally, Tokaz said the rise of HPV-related head and neck cancer highlights the importance of HPV vaccination, which is crucial for preventing cervical and anal cancer in addition to head and neck cancer. “HPV vaccination for children and young adults is crucial.”

Molly Tokaz, MD, reported no relevant financial relationships.

TORONTO — Driven by evidence that early access to autism services improves long-term outcomes, an evolution is rapidly unfolding to accelerate the diagnosis, often with the direct participation of pediatricians, according to a series of studies presented at the Pediatric Academic Societies annual meeting.

Accelerated Diagnosis

In one study, 80% of the evaluations were conducted within 6 weeks of patient enrollment, according to Corinna Rea, MD, a clinician in the primary care center at Boston Children’s Hospital as well as an assistant professor at Harvard Medical School, Boston, Massachusetts.

This outcome was drawn from a pilot study with 179 children suspected of autism spectrum disorder (ASD) by clinicians in a pediatric clinic. All were under the age of 3 years. In the first step, families completed the Bayley-4 Social-Emotional and Adaptive Behavior Scale.

The next step was a virtual assessment by a trained clinician using the TELE-ADS-PEDs (TAP) tool developed by Vanderbilt University, Nashville, Tennessee. Patients and families participated from their homes. The diagnosis of ASD was made by a psychologist using the patient’s history and data provided by the two assessment tools.

Through this approach, the median time to diagnosis was 30 days, according to Dr. Rea. Relative to a median time of 168 days to diagnosis among patients considered likely to have ASD at Dr. Rea’s center in the year prior to this pilot study, the time was reduced significantly (P < .001).

All patients in the study were subsequently evaluated by traditional methods. One hundred percent of the ASD diagnoses were confirmed with traditional assessment.

On the basis of these data, the accelerated approach “seems efficient and quite accurate,” Dr. Rea reported. When family members were surveyed at the end of the pilot study, 60% were satisfied and 28% were moderately satisfied. Although 59% reported that they would have preferred an in-person assessment, approximately 90% agreed the child’s development was mostly or completely captured in the accelerated assessment.

Dr. Rea pointed out that the psychologists participating in this study offered the opinion that home-based assessments are in their experience better than in-person evaluations due to the more natural behavior of the child in their own environment. However, she said that the diagnostic approach in the pilot study is still being modified, and one of the goals is to make virtual assessment more acceptable to the families.
 

A Commercialized Diagnostic Approach

A similar approach has been commercialized by a firm called As You Are, according to Steven D. Hicks, MD, PhD, who is an associate professor of pediatrics at Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Dr. Hicks is a principal in the enterprise, which is also assessing ASD virtually.

Trained pediatricians are evaluating patients with multiple tools in addition to TAP, including the Childhood Autism Rating Scale (CARS) and the Diagnostic and Statistical Manual (DSM-V) checklist for ASD. The company, which began offering this diagnostic service in 2022, now employs more than 30 pediatricians who participated in a 1-month training program.

At the 2024 PAS meeting, quality assurance data were presented on 215 (2.2%) of the 9632 children evaluated between February 2023 and March 2024. The diagnostic assessments of these randomly selected children were reviewed by one of three randomly assigned experts (a developmental pediatrician, a child psychologist, or a pediatrician with 7 years’ diagnostic experience) blinded to the initial scoring.

The diagnostic agreement was 94%, according to the data presented, providing a specificity of 90% and a sensitivity of 90% for ASD. The commercialized diagnostic approach is providing a diagnosis in a mean time of 29 days from initial contact, compared with delays that typically exceed 1 year for many children with suspected ASD, according to Dr. Hicks.

Additional Studies Aim at Streamlining Diagnosis

Two additional studies also evaluated strategies to streamline the diagnosis of ASD. Both were positive. In one, the accuracy and time to diagnosis among pediatricians trained in TAP and CARS were compared with those of ASD specialists in a dedicated autism clinic. Both were located at Nemours Children’s Health Center, Wilmington, Delaware.

In this study, presented by Meghan Harrison, DO, an attending pediatrician at Nemours Children’s Health, time to diagnosis among the 39 patients evaluated by pediatricians relative to the 349 patients evaluated at the dedicated ASD center (2.0 vs 5.1 months; P = .001) was significantly shorter. The age at diagnosis in the pediatrician-assessed population (27.5 vs 36.5 months; P < .001) was also significantly younger.

In another study, led by Ashely L. Early, MSW, a clinical social worker at the Medical University of South Carolina, Charleston, South Carolina, switching to a screening tool called the Rapid Interactive Screening Test for Autism in Toddlers (RITA-1) reduced the wait time to evaluation by approximately 5 months relative to previous practice with a more cumbersome screening method.
 

An ‘Urgent Need’ to Accelerate Diagnosis

In most places in the United States, children suspected of ASD are referred to specialists for confirmation of the diagnosis, which is needed to quality for ASD services, according to Katherine Zuckerman, MD, a professor of pediatrics the Oregon Health and Science University, Portland, Oregon. Dr. Zuckerman, who was moderator of the session in which all four of these abstracts were presented, explained that there is an urgent need to accelerate the time to diagnosis, which involves long delays for many if not most children with ASD. This is important because treatment and supportive services for ASD are almost always dependent on a diagnosis.

“There are tons of data to show that earlier access to ASD services has important patient benefits, including higher IQs,” she said. Other benefits she listed include a better quality of life for the child and the family.

“It can provide a huge reduction in family stress,” she added, suggesting that early interventions favorably modify the trajectory of the disability over time with accruing benefits.

“The lifetime costs of ASD exceed cancer and most other disease, so there are major implications for the cumulative cost of ASD management,” Dr. Zuckerman said. She suggested that the studies presented at the meeting reflect a likely evolution in who evaluates children for ASD and how quickly the evaluation is performed.

Dr. Rea, Dr. Harrison, Dr. Zuckerman, and Ms. Early reported no potential conflicts of interest. In addition to his executive role in As You Are, Dr. Hicks has financial relationships with Quadrant Biosciences and Spectrum Solutions.

TORONTO — Driven by evidence that early access to autism services improves long-term outcomes, an evolution is rapidly unfolding to accelerate the diagnosis, often with the direct participation of pediatricians, according to a series of studies presented at the Pediatric Academic Societies annual meeting.

Accelerated Diagnosis

In one study, 80% of the evaluations were conducted within 6 weeks of patient enrollment, according to Corinna Rea, MD, a clinician in the primary care center at Boston Children’s Hospital as well as an assistant professor at Harvard Medical School, Boston, Massachusetts.

This outcome was drawn from a pilot study with 179 children suspected of autism spectrum disorder (ASD) by clinicians in a pediatric clinic. All were under the age of 3 years. In the first step, families completed the Bayley-4 Social-Emotional and Adaptive Behavior Scale.

The next step was a virtual assessment by a trained clinician using the TELE-ADS-PEDs (TAP) tool developed by Vanderbilt University, Nashville, Tennessee. Patients and families participated from their homes. The diagnosis of ASD was made by a psychologist using the patient’s history and data provided by the two assessment tools.

Through this approach, the median time to diagnosis was 30 days, according to Dr. Rea. Relative to a median time of 168 days to diagnosis among patients considered likely to have ASD at Dr. Rea’s center in the year prior to this pilot study, the time was reduced significantly (P < .001).

All patients in the study were subsequently evaluated by traditional methods. One hundred percent of the ASD diagnoses were confirmed with traditional assessment.

On the basis of these data, the accelerated approach “seems efficient and quite accurate,” Dr. Rea reported. When family members were surveyed at the end of the pilot study, 60% were satisfied and 28% were moderately satisfied. Although 59% reported that they would have preferred an in-person assessment, approximately 90% agreed the child’s development was mostly or completely captured in the accelerated assessment.

Dr. Rea pointed out that the psychologists participating in this study offered the opinion that home-based assessments are in their experience better than in-person evaluations due to the more natural behavior of the child in their own environment. However, she said that the diagnostic approach in the pilot study is still being modified, and one of the goals is to make virtual assessment more acceptable to the families.
 

A Commercialized Diagnostic Approach

A similar approach has been commercialized by a firm called As You Are, according to Steven D. Hicks, MD, PhD, who is an associate professor of pediatrics at Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Dr. Hicks is a principal in the enterprise, which is also assessing ASD virtually.

Trained pediatricians are evaluating patients with multiple tools in addition to TAP, including the Childhood Autism Rating Scale (CARS) and the Diagnostic and Statistical Manual (DSM-V) checklist for ASD. The company, which began offering this diagnostic service in 2022, now employs more than 30 pediatricians who participated in a 1-month training program.

At the 2024 PAS meeting, quality assurance data were presented on 215 (2.2%) of the 9632 children evaluated between February 2023 and March 2024. The diagnostic assessments of these randomly selected children were reviewed by one of three randomly assigned experts (a developmental pediatrician, a child psychologist, or a pediatrician with 7 years’ diagnostic experience) blinded to the initial scoring.

The diagnostic agreement was 94%, according to the data presented, providing a specificity of 90% and a sensitivity of 90% for ASD. The commercialized diagnostic approach is providing a diagnosis in a mean time of 29 days from initial contact, compared with delays that typically exceed 1 year for many children with suspected ASD, according to Dr. Hicks.

Additional Studies Aim at Streamlining Diagnosis

Two additional studies also evaluated strategies to streamline the diagnosis of ASD. Both were positive. In one, the accuracy and time to diagnosis among pediatricians trained in TAP and CARS were compared with those of ASD specialists in a dedicated autism clinic. Both were located at Nemours Children’s Health Center, Wilmington, Delaware.

In this study, presented by Meghan Harrison, DO, an attending pediatrician at Nemours Children’s Health, time to diagnosis among the 39 patients evaluated by pediatricians relative to the 349 patients evaluated at the dedicated ASD center (2.0 vs 5.1 months; P = .001) was significantly shorter. The age at diagnosis in the pediatrician-assessed population (27.5 vs 36.5 months; P < .001) was also significantly younger.

In another study, led by Ashely L. Early, MSW, a clinical social worker at the Medical University of South Carolina, Charleston, South Carolina, switching to a screening tool called the Rapid Interactive Screening Test for Autism in Toddlers (RITA-1) reduced the wait time to evaluation by approximately 5 months relative to previous practice with a more cumbersome screening method.
 

An ‘Urgent Need’ to Accelerate Diagnosis

In most places in the United States, children suspected of ASD are referred to specialists for confirmation of the diagnosis, which is needed to quality for ASD services, according to Katherine Zuckerman, MD, a professor of pediatrics the Oregon Health and Science University, Portland, Oregon. Dr. Zuckerman, who was moderator of the session in which all four of these abstracts were presented, explained that there is an urgent need to accelerate the time to diagnosis, which involves long delays for many if not most children with ASD. This is important because treatment and supportive services for ASD are almost always dependent on a diagnosis.

“There are tons of data to show that earlier access to ASD services has important patient benefits, including higher IQs,” she said. Other benefits she listed include a better quality of life for the child and the family.

“It can provide a huge reduction in family stress,” she added, suggesting that early interventions favorably modify the trajectory of the disability over time with accruing benefits.

“The lifetime costs of ASD exceed cancer and most other disease, so there are major implications for the cumulative cost of ASD management,” Dr. Zuckerman said. She suggested that the studies presented at the meeting reflect a likely evolution in who evaluates children for ASD and how quickly the evaluation is performed.

Dr. Rea, Dr. Harrison, Dr. Zuckerman, and Ms. Early reported no potential conflicts of interest. In addition to his executive role in As You Are, Dr. Hicks has financial relationships with Quadrant Biosciences and Spectrum Solutions.

TORONTO — Driven by evidence that early access to autism services improves long-term outcomes, an evolution is rapidly unfolding to accelerate the diagnosis, often with the direct participation of pediatricians, according to a series of studies presented at the Pediatric Academic Societies annual meeting.

Accelerated Diagnosis

In one study, 80% of the evaluations were conducted within 6 weeks of patient enrollment, according to Corinna Rea, MD, a clinician in the primary care center at Boston Children’s Hospital as well as an assistant professor at Harvard Medical School, Boston, Massachusetts.

This outcome was drawn from a pilot study with 179 children suspected of autism spectrum disorder (ASD) by clinicians in a pediatric clinic. All were under the age of 3 years. In the first step, families completed the Bayley-4 Social-Emotional and Adaptive Behavior Scale.

The next step was a virtual assessment by a trained clinician using the TELE-ADS-PEDs (TAP) tool developed by Vanderbilt University, Nashville, Tennessee. Patients and families participated from their homes. The diagnosis of ASD was made by a psychologist using the patient’s history and data provided by the two assessment tools.

Through this approach, the median time to diagnosis was 30 days, according to Dr. Rea. Relative to a median time of 168 days to diagnosis among patients considered likely to have ASD at Dr. Rea’s center in the year prior to this pilot study, the time was reduced significantly (P < .001).

All patients in the study were subsequently evaluated by traditional methods. One hundred percent of the ASD diagnoses were confirmed with traditional assessment.

On the basis of these data, the accelerated approach “seems efficient and quite accurate,” Dr. Rea reported. When family members were surveyed at the end of the pilot study, 60% were satisfied and 28% were moderately satisfied. Although 59% reported that they would have preferred an in-person assessment, approximately 90% agreed the child’s development was mostly or completely captured in the accelerated assessment.

Dr. Rea pointed out that the psychologists participating in this study offered the opinion that home-based assessments are in their experience better than in-person evaluations due to the more natural behavior of the child in their own environment. However, she said that the diagnostic approach in the pilot study is still being modified, and one of the goals is to make virtual assessment more acceptable to the families.
 

A Commercialized Diagnostic Approach

A similar approach has been commercialized by a firm called As You Are, according to Steven D. Hicks, MD, PhD, who is an associate professor of pediatrics at Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Dr. Hicks is a principal in the enterprise, which is also assessing ASD virtually.

Trained pediatricians are evaluating patients with multiple tools in addition to TAP, including the Childhood Autism Rating Scale (CARS) and the Diagnostic and Statistical Manual (DSM-V) checklist for ASD. The company, which began offering this diagnostic service in 2022, now employs more than 30 pediatricians who participated in a 1-month training program.

At the 2024 PAS meeting, quality assurance data were presented on 215 (2.2%) of the 9632 children evaluated between February 2023 and March 2024. The diagnostic assessments of these randomly selected children were reviewed by one of three randomly assigned experts (a developmental pediatrician, a child psychologist, or a pediatrician with 7 years’ diagnostic experience) blinded to the initial scoring.

The diagnostic agreement was 94%, according to the data presented, providing a specificity of 90% and a sensitivity of 90% for ASD. The commercialized diagnostic approach is providing a diagnosis in a mean time of 29 days from initial contact, compared with delays that typically exceed 1 year for many children with suspected ASD, according to Dr. Hicks.

Additional Studies Aim at Streamlining Diagnosis

Two additional studies also evaluated strategies to streamline the diagnosis of ASD. Both were positive. In one, the accuracy and time to diagnosis among pediatricians trained in TAP and CARS were compared with those of ASD specialists in a dedicated autism clinic. Both were located at Nemours Children’s Health Center, Wilmington, Delaware.

In this study, presented by Meghan Harrison, DO, an attending pediatrician at Nemours Children’s Health, time to diagnosis among the 39 patients evaluated by pediatricians relative to the 349 patients evaluated at the dedicated ASD center (2.0 vs 5.1 months; P = .001) was significantly shorter. The age at diagnosis in the pediatrician-assessed population (27.5 vs 36.5 months; P < .001) was also significantly younger.

In another study, led by Ashely L. Early, MSW, a clinical social worker at the Medical University of South Carolina, Charleston, South Carolina, switching to a screening tool called the Rapid Interactive Screening Test for Autism in Toddlers (RITA-1) reduced the wait time to evaluation by approximately 5 months relative to previous practice with a more cumbersome screening method.
 

An ‘Urgent Need’ to Accelerate Diagnosis

In most places in the United States, children suspected of ASD are referred to specialists for confirmation of the diagnosis, which is needed to quality for ASD services, according to Katherine Zuckerman, MD, a professor of pediatrics the Oregon Health and Science University, Portland, Oregon. Dr. Zuckerman, who was moderator of the session in which all four of these abstracts were presented, explained that there is an urgent need to accelerate the time to diagnosis, which involves long delays for many if not most children with ASD. This is important because treatment and supportive services for ASD are almost always dependent on a diagnosis.

“There are tons of data to show that earlier access to ASD services has important patient benefits, including higher IQs,” she said. Other benefits she listed include a better quality of life for the child and the family.

“It can provide a huge reduction in family stress,” she added, suggesting that early interventions favorably modify the trajectory of the disability over time with accruing benefits.

“The lifetime costs of ASD exceed cancer and most other disease, so there are major implications for the cumulative cost of ASD management,” Dr. Zuckerman said. She suggested that the studies presented at the meeting reflect a likely evolution in who evaluates children for ASD and how quickly the evaluation is performed.

Dr. Rea, Dr. Harrison, Dr. Zuckerman, and Ms. Early reported no potential conflicts of interest. In addition to his executive role in As You Are, Dr. Hicks has financial relationships with Quadrant Biosciences and Spectrum Solutions.

Lower intake of dietary protein in midlife was a significant independent predictor of all-cause mortality in later life, based on data from a cohort study of more than 8000 men.

The Recommended Dietary Allowance of dietary protein intake is 0.8 g/kg body weight, but previous studies of the effect of dietary protein on all-cause mortality have yielded inconsistent results, Pedro Joaquin Ayau Aguilar, MD, of the University of Hawaii, Honolulu, said in a presentation at the annual meeting of the American Geriatrics Society.

To better examine these effects, Dr. Aguilar and colleagues reviewed data from 7486 participants in the Kuakini Honolulu Heart Program (HHP), a prospective cohort study of Japanese-American men in Hawaii.

Participants underwent a baseline exam in 1965-1968 at ages 45-68 years and were followed for mortality until December 31, 2022. The researchers created quintiles of dietary protein/kg categorized as plant or animal source, trained dietitians worked with participants to complete a 24-hour diet recall, and the primary outcome was all-cause mortality.

Overall, the mean protein intake in the study population was 1.5 g/kg body weight; the mean animal protein and plant protein intakes were 1.1 g/kg and 0.4 g/kg, respectively.

In an age-adjusted analysis, mortality rates per 1,000 person-years were significantly higher with lower total protein intake, with rates of 39.7 per 1,000 person-years and 36.8 per 1,000 person-years in the first and fifth quintiles, respectively (P < .0001).
 

Data Show Consistency Across Protein Types

Trends were similar for animal protein and plant protein intake, with mortality rates of 39.6 and 36.5 per 1000 person-years for the first and fifth quintiles, respectively.

“All of these categories had a significant trend, with the lowest quintile showing the highest mortality rate,” Dr. Aguilar said in his presentation.

The study was limited by several factors including the homogeneous population of Japanese men, and the inability to make conclusions about cause and effect, Dr. Aguilar said. However, the results were strengthened by the large cohort, long follow-up, and complete mortality surveillance, he added.

As for the study’s clinical implications, “I believe it adds to the body of evidence on how nutrition impacts health and [the data] can help us better advise our patients on their macronutrient intake to better optimize their health,” Dr. Aguilar said in a question-and-answer session following the presentation.

Looking ahead, “More research is needed to more accurately define which type of protein and in which amounts are optimal for health,” as well as how other macronutrients in different stages of life affect health span and life span, he said.

Although a minimum Recommended Daily Allowance of dietary protein is 0.8 g/kg body weight, the relationship between dietary protein intake and all-cause mortality remains unclear, said Shelly Gray, PharmD, professor of pharmacy at the University of Washington School of Pharmacy, said in an interview.

Dr. Gray, who served as a moderator for the session in which the study was presented, agreed that more research is needed before clinical implications can be discussed.

The study was supported by the Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii; Kuakini Medical Center, Honolulu, Hawaii; and the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Gray had no financial conflicts to disclose.

Lower intake of dietary protein in midlife was a significant independent predictor of all-cause mortality in later life, based on data from a cohort study of more than 8000 men.

The Recommended Dietary Allowance of dietary protein intake is 0.8 g/kg body weight, but previous studies of the effect of dietary protein on all-cause mortality have yielded inconsistent results, Pedro Joaquin Ayau Aguilar, MD, of the University of Hawaii, Honolulu, said in a presentation at the annual meeting of the American Geriatrics Society.

To better examine these effects, Dr. Aguilar and colleagues reviewed data from 7486 participants in the Kuakini Honolulu Heart Program (HHP), a prospective cohort study of Japanese-American men in Hawaii.

Participants underwent a baseline exam in 1965-1968 at ages 45-68 years and were followed for mortality until December 31, 2022. The researchers created quintiles of dietary protein/kg categorized as plant or animal source, trained dietitians worked with participants to complete a 24-hour diet recall, and the primary outcome was all-cause mortality.

Overall, the mean protein intake in the study population was 1.5 g/kg body weight; the mean animal protein and plant protein intakes were 1.1 g/kg and 0.4 g/kg, respectively.

In an age-adjusted analysis, mortality rates per 1,000 person-years were significantly higher with lower total protein intake, with rates of 39.7 per 1,000 person-years and 36.8 per 1,000 person-years in the first and fifth quintiles, respectively (P < .0001).
 

Data Show Consistency Across Protein Types

Trends were similar for animal protein and plant protein intake, with mortality rates of 39.6 and 36.5 per 1000 person-years for the first and fifth quintiles, respectively.

“All of these categories had a significant trend, with the lowest quintile showing the highest mortality rate,” Dr. Aguilar said in his presentation.

The study was limited by several factors including the homogeneous population of Japanese men, and the inability to make conclusions about cause and effect, Dr. Aguilar said. However, the results were strengthened by the large cohort, long follow-up, and complete mortality surveillance, he added.

As for the study’s clinical implications, “I believe it adds to the body of evidence on how nutrition impacts health and [the data] can help us better advise our patients on their macronutrient intake to better optimize their health,” Dr. Aguilar said in a question-and-answer session following the presentation.

Looking ahead, “More research is needed to more accurately define which type of protein and in which amounts are optimal for health,” as well as how other macronutrients in different stages of life affect health span and life span, he said.

Although a minimum Recommended Daily Allowance of dietary protein is 0.8 g/kg body weight, the relationship between dietary protein intake and all-cause mortality remains unclear, said Shelly Gray, PharmD, professor of pharmacy at the University of Washington School of Pharmacy, said in an interview.

Dr. Gray, who served as a moderator for the session in which the study was presented, agreed that more research is needed before clinical implications can be discussed.

The study was supported by the Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii; Kuakini Medical Center, Honolulu, Hawaii; and the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Gray had no financial conflicts to disclose.

Lower intake of dietary protein in midlife was a significant independent predictor of all-cause mortality in later life, based on data from a cohort study of more than 8000 men.

The Recommended Dietary Allowance of dietary protein intake is 0.8 g/kg body weight, but previous studies of the effect of dietary protein on all-cause mortality have yielded inconsistent results, Pedro Joaquin Ayau Aguilar, MD, of the University of Hawaii, Honolulu, said in a presentation at the annual meeting of the American Geriatrics Society.

To better examine these effects, Dr. Aguilar and colleagues reviewed data from 7486 participants in the Kuakini Honolulu Heart Program (HHP), a prospective cohort study of Japanese-American men in Hawaii.

Participants underwent a baseline exam in 1965-1968 at ages 45-68 years and were followed for mortality until December 31, 2022. The researchers created quintiles of dietary protein/kg categorized as plant or animal source, trained dietitians worked with participants to complete a 24-hour diet recall, and the primary outcome was all-cause mortality.

Overall, the mean protein intake in the study population was 1.5 g/kg body weight; the mean animal protein and plant protein intakes were 1.1 g/kg and 0.4 g/kg, respectively.

In an age-adjusted analysis, mortality rates per 1,000 person-years were significantly higher with lower total protein intake, with rates of 39.7 per 1,000 person-years and 36.8 per 1,000 person-years in the first and fifth quintiles, respectively (P < .0001).
 

Data Show Consistency Across Protein Types

Trends were similar for animal protein and plant protein intake, with mortality rates of 39.6 and 36.5 per 1000 person-years for the first and fifth quintiles, respectively.

“All of these categories had a significant trend, with the lowest quintile showing the highest mortality rate,” Dr. Aguilar said in his presentation.

The study was limited by several factors including the homogeneous population of Japanese men, and the inability to make conclusions about cause and effect, Dr. Aguilar said. However, the results were strengthened by the large cohort, long follow-up, and complete mortality surveillance, he added.

As for the study’s clinical implications, “I believe it adds to the body of evidence on how nutrition impacts health and [the data] can help us better advise our patients on their macronutrient intake to better optimize their health,” Dr. Aguilar said in a question-and-answer session following the presentation.

Looking ahead, “More research is needed to more accurately define which type of protein and in which amounts are optimal for health,” as well as how other macronutrients in different stages of life affect health span and life span, he said.

Although a minimum Recommended Daily Allowance of dietary protein is 0.8 g/kg body weight, the relationship between dietary protein intake and all-cause mortality remains unclear, said Shelly Gray, PharmD, professor of pharmacy at the University of Washington School of Pharmacy, said in an interview.

Dr. Gray, who served as a moderator for the session in which the study was presented, agreed that more research is needed before clinical implications can be discussed.

The study was supported by the Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii; Kuakini Medical Center, Honolulu, Hawaii; and the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Gray had no financial conflicts to disclose.

It’s becoming clear that the adolescent brain is particularly vulnerable to cannabis, especially today’s higher-potency products, which put teens at risk for impaired brain development; mental health issues, including psychosis; and cannabis-use disorder (CUD). 

That was the message delivered by Yasmin Hurd, PhD, director of the Addiction Institute at Mount Sinai in New York, during a press briefing at the American Psychiatric Association (APA) 2024 annual meeting. 

“We’re actually in historic times in that we now have highly concentrated, highly potent cannabis products that are administered in various routes,” Dr. Hurd told reporters. 

Tetrahydrocannabinol (THC) concentrations in cannabis products have increased over the years, from around 2%-4% to 15%-24% now, Dr. Hurd noted.

The impact of high-potency cannabis products and increased risk for CUD and mental health problems, particularly in adolescents, “must be taken seriously, especially in light of the current mental health crisis,” Dr. Hurd and colleagues wrote in a commentary on the developmental trajectory of CUD published simultaneously in the American Journal of Psychiatry. 
 

Dramatic Increase in Teen Cannabis Use

A recent study from Oregon Health & Science University showed that adolescent cannabis abuse in the United States has increased dramatically, by about 245%, since 2000. 

“Drug abuse is often driven by what is in front of you,” Nora Volkow, MD, director of the National Institute on Drug Abuse, noted in an interview. 

“Right now, cannabis is widely available. So, guess what? Cannabis becomes the drug that people take. Nicotine is much harder to get. It is regulated to a much greater extent than cannabis, so fewer teenagers are consuming nicotine than are consuming cannabis,” Dr. Volkow said. 

Cannabis exposure during neurodevelopment has the potential to alter the endocannabinoid system, which in turn, can affect the development of neural pathways that mediate reward; emotional regulation; and multiple cognitive domains including executive functioning and decision-making, learning, abstraction, and attention — all processes central to substance use disorder and other psychiatric disorders, Dr. Hurd said at the briefing.

Dr. Volkow said that cannabis use in adolescence and young adulthood is “very concerning because that’s also the age of risk for psychosis, particularly schizophrenia, with one study showing that use of cannabis in high doses can trigger psychotic episodes, particularly among young males.”

Dr. Hurd noted that not all young people who use cannabis develop CUD, “but a significant number do,” and large-scale studies have consistently reported two main factors associated with CUD risk.

The first is age, both for the onset and frequency of use at younger age. Those who start using cannabis before age 16 years are at the highest risk for CUD. The risk for CUD also increases significantly among youth who use cannabis at least weekly, with the highest prevalence among youth who use cannabis daily. One large study linked increased frequency of use with up to a 17-fold increased risk for CUD.

The second factor consistently associated with the risk for CUD is biologic sex, with CUD rates typically higher in male individuals.
 

Treatment Challenges

For young people who develop CUD, access to and uptake of treatment can be challenging.

“Given that the increased potency of cannabis and cannabinoid products is expected to increase CUD risk, it is disturbing that less than 10% of youth who meet the criteria for a substance use disorder, including CUD, receive treatment,” Dr. Hurd and colleagues point out in their commentary. 

Another challenge is that treatment strategies for CUD are currently limited and consist mainly of motivational enhancement and cognitive-behavioral therapies. 

“Clearly new treatment strategies are needed to address the mounting challenge of CUD risk in teens and young adults,” Dr. Hurd and colleagues wrote. 

Summing up, Dr. Hurd told reporters, “We now know that most psychiatric disorders have a developmental origin, and the adolescent time period is a critical window for cannabis use disorder risk.”

Yet, on a positive note, the “plasticity of the developing brain that makes it vulnerable to cannabis use disorder and psychiatric comorbidities also provides an opportunity for prevention and early intervention to change that trajectory,” Dr. Hurd said. 

The changing legal landscape of cannabis — the US Drug Enforcement Agency is moving forward with plans to move marijuana from a Schedule I to a Schedule III controlled substance under the Controlled Substance Act — makes addressing these risks all the timelier. 

“As states vie to leverage tax dollars from the growing cannabis industry, a significant portion of such funds must be used for early intervention/prevention strategies to reduce the impact of cannabis on the developing brain,” Dr. Hurd and colleagues wrote. 

This research was supported in part by the National Institute on Drug Abuse and the National Institutes of Health. Dr. Hurd and Dr. Volkow have no relevant disclosures. 

A version of this article appeared on Medscape.com.

It’s becoming clear that the adolescent brain is particularly vulnerable to cannabis, especially today’s higher-potency products, which put teens at risk for impaired brain development; mental health issues, including psychosis; and cannabis-use disorder (CUD). 

That was the message delivered by Yasmin Hurd, PhD, director of the Addiction Institute at Mount Sinai in New York, during a press briefing at the American Psychiatric Association (APA) 2024 annual meeting. 

“We’re actually in historic times in that we now have highly concentrated, highly potent cannabis products that are administered in various routes,” Dr. Hurd told reporters. 

Tetrahydrocannabinol (THC) concentrations in cannabis products have increased over the years, from around 2%-4% to 15%-24% now, Dr. Hurd noted.

The impact of high-potency cannabis products and increased risk for CUD and mental health problems, particularly in adolescents, “must be taken seriously, especially in light of the current mental health crisis,” Dr. Hurd and colleagues wrote in a commentary on the developmental trajectory of CUD published simultaneously in the American Journal of Psychiatry. 
 

Dramatic Increase in Teen Cannabis Use

A recent study from Oregon Health & Science University showed that adolescent cannabis abuse in the United States has increased dramatically, by about 245%, since 2000. 

“Drug abuse is often driven by what is in front of you,” Nora Volkow, MD, director of the National Institute on Drug Abuse, noted in an interview. 

“Right now, cannabis is widely available. So, guess what? Cannabis becomes the drug that people take. Nicotine is much harder to get. It is regulated to a much greater extent than cannabis, so fewer teenagers are consuming nicotine than are consuming cannabis,” Dr. Volkow said. 

Cannabis exposure during neurodevelopment has the potential to alter the endocannabinoid system, which in turn, can affect the development of neural pathways that mediate reward; emotional regulation; and multiple cognitive domains including executive functioning and decision-making, learning, abstraction, and attention — all processes central to substance use disorder and other psychiatric disorders, Dr. Hurd said at the briefing.

Dr. Volkow said that cannabis use in adolescence and young adulthood is “very concerning because that’s also the age of risk for psychosis, particularly schizophrenia, with one study showing that use of cannabis in high doses can trigger psychotic episodes, particularly among young males.”

Dr. Hurd noted that not all young people who use cannabis develop CUD, “but a significant number do,” and large-scale studies have consistently reported two main factors associated with CUD risk.

The first is age, both for the onset and frequency of use at younger age. Those who start using cannabis before age 16 years are at the highest risk for CUD. The risk for CUD also increases significantly among youth who use cannabis at least weekly, with the highest prevalence among youth who use cannabis daily. One large study linked increased frequency of use with up to a 17-fold increased risk for CUD.

The second factor consistently associated with the risk for CUD is biologic sex, with CUD rates typically higher in male individuals.
 

Treatment Challenges

For young people who develop CUD, access to and uptake of treatment can be challenging.

“Given that the increased potency of cannabis and cannabinoid products is expected to increase CUD risk, it is disturbing that less than 10% of youth who meet the criteria for a substance use disorder, including CUD, receive treatment,” Dr. Hurd and colleagues point out in their commentary. 

Another challenge is that treatment strategies for CUD are currently limited and consist mainly of motivational enhancement and cognitive-behavioral therapies. 

“Clearly new treatment strategies are needed to address the mounting challenge of CUD risk in teens and young adults,” Dr. Hurd and colleagues wrote. 

Summing up, Dr. Hurd told reporters, “We now know that most psychiatric disorders have a developmental origin, and the adolescent time period is a critical window for cannabis use disorder risk.”

Yet, on a positive note, the “plasticity of the developing brain that makes it vulnerable to cannabis use disorder and psychiatric comorbidities also provides an opportunity for prevention and early intervention to change that trajectory,” Dr. Hurd said. 

The changing legal landscape of cannabis — the US Drug Enforcement Agency is moving forward with plans to move marijuana from a Schedule I to a Schedule III controlled substance under the Controlled Substance Act — makes addressing these risks all the timelier. 

“As states vie to leverage tax dollars from the growing cannabis industry, a significant portion of such funds must be used for early intervention/prevention strategies to reduce the impact of cannabis on the developing brain,” Dr. Hurd and colleagues wrote. 

This research was supported in part by the National Institute on Drug Abuse and the National Institutes of Health. Dr. Hurd and Dr. Volkow have no relevant disclosures. 

A version of this article appeared on Medscape.com.

It’s becoming clear that the adolescent brain is particularly vulnerable to cannabis, especially today’s higher-potency products, which put teens at risk for impaired brain development; mental health issues, including psychosis; and cannabis-use disorder (CUD). 

That was the message delivered by Yasmin Hurd, PhD, director of the Addiction Institute at Mount Sinai in New York, during a press briefing at the American Psychiatric Association (APA) 2024 annual meeting. 

“We’re actually in historic times in that we now have highly concentrated, highly potent cannabis products that are administered in various routes,” Dr. Hurd told reporters. 

Tetrahydrocannabinol (THC) concentrations in cannabis products have increased over the years, from around 2%-4% to 15%-24% now, Dr. Hurd noted.

The impact of high-potency cannabis products and increased risk for CUD and mental health problems, particularly in adolescents, “must be taken seriously, especially in light of the current mental health crisis,” Dr. Hurd and colleagues wrote in a commentary on the developmental trajectory of CUD published simultaneously in the American Journal of Psychiatry. 
 

Dramatic Increase in Teen Cannabis Use

A recent study from Oregon Health & Science University showed that adolescent cannabis abuse in the United States has increased dramatically, by about 245%, since 2000. 

“Drug abuse is often driven by what is in front of you,” Nora Volkow, MD, director of the National Institute on Drug Abuse, noted in an interview. 

“Right now, cannabis is widely available. So, guess what? Cannabis becomes the drug that people take. Nicotine is much harder to get. It is regulated to a much greater extent than cannabis, so fewer teenagers are consuming nicotine than are consuming cannabis,” Dr. Volkow said. 

Cannabis exposure during neurodevelopment has the potential to alter the endocannabinoid system, which in turn, can affect the development of neural pathways that mediate reward; emotional regulation; and multiple cognitive domains including executive functioning and decision-making, learning, abstraction, and attention — all processes central to substance use disorder and other psychiatric disorders, Dr. Hurd said at the briefing.

Dr. Volkow said that cannabis use in adolescence and young adulthood is “very concerning because that’s also the age of risk for psychosis, particularly schizophrenia, with one study showing that use of cannabis in high doses can trigger psychotic episodes, particularly among young males.”

Dr. Hurd noted that not all young people who use cannabis develop CUD, “but a significant number do,” and large-scale studies have consistently reported two main factors associated with CUD risk.

The first is age, both for the onset and frequency of use at younger age. Those who start using cannabis before age 16 years are at the highest risk for CUD. The risk for CUD also increases significantly among youth who use cannabis at least weekly, with the highest prevalence among youth who use cannabis daily. One large study linked increased frequency of use with up to a 17-fold increased risk for CUD.

The second factor consistently associated with the risk for CUD is biologic sex, with CUD rates typically higher in male individuals.
 

Treatment Challenges

For young people who develop CUD, access to and uptake of treatment can be challenging.

“Given that the increased potency of cannabis and cannabinoid products is expected to increase CUD risk, it is disturbing that less than 10% of youth who meet the criteria for a substance use disorder, including CUD, receive treatment,” Dr. Hurd and colleagues point out in their commentary. 

Another challenge is that treatment strategies for CUD are currently limited and consist mainly of motivational enhancement and cognitive-behavioral therapies. 

“Clearly new treatment strategies are needed to address the mounting challenge of CUD risk in teens and young adults,” Dr. Hurd and colleagues wrote. 

Summing up, Dr. Hurd told reporters, “We now know that most psychiatric disorders have a developmental origin, and the adolescent time period is a critical window for cannabis use disorder risk.”

Yet, on a positive note, the “plasticity of the developing brain that makes it vulnerable to cannabis use disorder and psychiatric comorbidities also provides an opportunity for prevention and early intervention to change that trajectory,” Dr. Hurd said. 

The changing legal landscape of cannabis — the US Drug Enforcement Agency is moving forward with plans to move marijuana from a Schedule I to a Schedule III controlled substance under the Controlled Substance Act — makes addressing these risks all the timelier. 

“As states vie to leverage tax dollars from the growing cannabis industry, a significant portion of such funds must be used for early intervention/prevention strategies to reduce the impact of cannabis on the developing brain,” Dr. Hurd and colleagues wrote. 

This research was supported in part by the National Institute on Drug Abuse and the National Institutes of Health. Dr. Hurd and Dr. Volkow have no relevant disclosures. 

A version of this article appeared on Medscape.com.

TORONTO — An ambitious effort at a busy pediatrics clinic to improve follow-up in children and adolescents with a positive depression screen improved this quality metric, and it produced a fundamental change in approach.

“It was a big culture shift,” reported Landon B. Krantz, MD, a clinical fellow in the Division of General and Community Pediatrics at Cincinnati Children’s Hospital in Ohio. From a baseline position of screening, risk identification, and then referral, “we are now taking ownership of the process.”

Based on the substantial risk posed by significant levels of depression, guidelines recommend follow-up for any patient 12 years or older who has a positive screen, according to Dr. Krantz. At his center, they found only 19% had a documented follow-up within 30 days, even though timely intervention is important.

“Nearly half of suicide events in adolescents occur within 30 days after a positive PHQ-9 [9-question Patient Health Questionnaire] is completed,” said Dr. Krantz when presenting his data at the Pediatric Academic Societies annual meeting.

The issue has gained more urgency because of the substantial increase over the past several years in children presenting with depression and suicidal thoughts, according to Dr. Krantz. He said many are characterizing the upsurge as a mental health crisis in the pediatric age group.
 

Improving Follow-Up

The goal of the initiative launched at six primary care practices in Cincinnati was to increase the proportion of children with a positive screen for depression who have a follow-up within 30 days. The goal at the outset was to increase the proportion to 35%.

“We know that a lot of children would receive follow-up at centers outside of our system,” said Dr. Krantz, explaining why the goal was relatively modest. Based on the likelihood that many follow-up visits would not be captured, he expected the final data would represent an underestimate.

Depression at baseline was defined as a score of 10 or higher on the PHQ-9 or any positive answer to item 9 on this screening tool, which asks specifically about thoughts of self-harm.

To be counted, follow-up had to be a documented encounter, whether by phone call, in-person visit, or telehealth visit.

“We needed patients to be checked. We did not count a prescription refill as a true follow-up,” Dr. Krantz specified.

There were numerous strategies implemented to improve follow-up, not least of which was an educational program to reinforce the importance and value of follow-up that was disseminated to clinicians in all of the participating clinics. Medical assistants were instructed to schedule a follow-up appointment for all patients who tested positive before they left the office. A target of 3 weeks was a strategy of overcorrection when so many patients were missing the initial 30-day window by just a few days.

The approach also involved an enhanced collaboration with psychologists to which patients were referred. Asking for expedited appointments when appropriate ensured that those at highest risk were prioritized, although Dr. Krantz said that this step was planned carefully to avoid overwhelming the mental health team.

“We monitored this and made sure it was not increasing the burden for psychologists from a capacity standpoint,” he said.

Other steps, like a depression action plan, which Dr. Krantz compared to an asthma action plan, were also implemented to reduce the risk of losing symptomatic patients before the chance for an effective treatment.

When compared with the 19% 30-day follow-up rate in the preintervention sample of 589 children, the 43.8% 30-day follow-up rate achieved in the 764 patients identified after implementation beat the original goal.

The improvement in follow-up was relatively consistent across all six clinics, which Dr. Krantz believes reflected a broad and shared change in a sense of responsibility for confirming that symptoms of depression were being addressed. Patients were still referred for psychological help, but referral was no longer considered enough.

“Children with mental health issues are still our patients in primary care,” said Dr. Krantz, who considers this an important change in orientation.

While the goal was to schedule patients for a follow-up at the time of a positive depression screen, Dr. Krantz described one important accommodation.

“The screen for depression was being performed in most cases during well visits, so patients and their families were not expecting to be discussing this issue,” he said. The diagnosis might be a particular surprise to parents who were not aware of any symptoms. In this case, Dr. Krantz said patients and families were given time to process the information and were contacted after a week to discuss further workup.

It is also notable that about one third of patients met the criteria for depression by answering positively to the PHQ-9 item on self-harm when they did not meet the 10 or more threshold depression score overall. In other words, these patients would have been missed without this criterion.

In the participating Cincinnati pediatric clinics, about 12%-13% of adolescents met the criteria for depression, which Dr. Krantz said is consistent with reports in the literature. He said the range is about 6%-24%.

Although outcomes were not tracked, there is evidence that early intervention for depression yields better outcomes than delayed intervention, according to Dr. Krantz. Based on approximately 600 positive screens for depression per year at his pediatric clinics, he estimated that his data predict at least 25% more patients will receive timely follow-up.
 

Seeking Solutions to a Growing Problem

There are several studies documenting the growing problem of adolescent depression and suicide and, for this reason, the topic is attracting a lot of attention, according to Corinna Rea, MD, MPH, a pediatrician working in the primary care center at Boston Children’s Hospital in Massachusetts.

Dr. Rea was not involved with the study, but when asked to comment, she said: “The results of this study were encouraging because we know that getting patients to care quickly is probably important.” She also agreed that referring patients with depression for care might not be enough, noting that a lot of patients do not follow up on recommendations to pursue a consultation or treatment.

“I am now involved in a project with the American Academy of Pediatrics to address this issue,” Dr. Rae said. She thinks that more work in this area is needed and agreed with Dr. Krantz that pediatricians should verify that children with depression are getting help even when other specialists are providing the treatment.

Dr. Krantz and Dr. Rae report no potential conflicts of interest.

TORONTO — An ambitious effort at a busy pediatrics clinic to improve follow-up in children and adolescents with a positive depression screen improved this quality metric, and it produced a fundamental change in approach.

“It was a big culture shift,” reported Landon B. Krantz, MD, a clinical fellow in the Division of General and Community Pediatrics at Cincinnati Children’s Hospital in Ohio. From a baseline position of screening, risk identification, and then referral, “we are now taking ownership of the process.”

Based on the substantial risk posed by significant levels of depression, guidelines recommend follow-up for any patient 12 years or older who has a positive screen, according to Dr. Krantz. At his center, they found only 19% had a documented follow-up within 30 days, even though timely intervention is important.

“Nearly half of suicide events in adolescents occur within 30 days after a positive PHQ-9 [9-question Patient Health Questionnaire] is completed,” said Dr. Krantz when presenting his data at the Pediatric Academic Societies annual meeting.

The issue has gained more urgency because of the substantial increase over the past several years in children presenting with depression and suicidal thoughts, according to Dr. Krantz. He said many are characterizing the upsurge as a mental health crisis in the pediatric age group.
 

Improving Follow-Up

The goal of the initiative launched at six primary care practices in Cincinnati was to increase the proportion of children with a positive screen for depression who have a follow-up within 30 days. The goal at the outset was to increase the proportion to 35%.

“We know that a lot of children would receive follow-up at centers outside of our system,” said Dr. Krantz, explaining why the goal was relatively modest. Based on the likelihood that many follow-up visits would not be captured, he expected the final data would represent an underestimate.

Depression at baseline was defined as a score of 10 or higher on the PHQ-9 or any positive answer to item 9 on this screening tool, which asks specifically about thoughts of self-harm.

To be counted, follow-up had to be a documented encounter, whether by phone call, in-person visit, or telehealth visit.

“We needed patients to be checked. We did not count a prescription refill as a true follow-up,” Dr. Krantz specified.

There were numerous strategies implemented to improve follow-up, not least of which was an educational program to reinforce the importance and value of follow-up that was disseminated to clinicians in all of the participating clinics. Medical assistants were instructed to schedule a follow-up appointment for all patients who tested positive before they left the office. A target of 3 weeks was a strategy of overcorrection when so many patients were missing the initial 30-day window by just a few days.

The approach also involved an enhanced collaboration with psychologists to which patients were referred. Asking for expedited appointments when appropriate ensured that those at highest risk were prioritized, although Dr. Krantz said that this step was planned carefully to avoid overwhelming the mental health team.

“We monitored this and made sure it was not increasing the burden for psychologists from a capacity standpoint,” he said.

Other steps, like a depression action plan, which Dr. Krantz compared to an asthma action plan, were also implemented to reduce the risk of losing symptomatic patients before the chance for an effective treatment.

When compared with the 19% 30-day follow-up rate in the preintervention sample of 589 children, the 43.8% 30-day follow-up rate achieved in the 764 patients identified after implementation beat the original goal.

The improvement in follow-up was relatively consistent across all six clinics, which Dr. Krantz believes reflected a broad and shared change in a sense of responsibility for confirming that symptoms of depression were being addressed. Patients were still referred for psychological help, but referral was no longer considered enough.

“Children with mental health issues are still our patients in primary care,” said Dr. Krantz, who considers this an important change in orientation.

While the goal was to schedule patients for a follow-up at the time of a positive depression screen, Dr. Krantz described one important accommodation.

“The screen for depression was being performed in most cases during well visits, so patients and their families were not expecting to be discussing this issue,” he said. The diagnosis might be a particular surprise to parents who were not aware of any symptoms. In this case, Dr. Krantz said patients and families were given time to process the information and were contacted after a week to discuss further workup.

It is also notable that about one third of patients met the criteria for depression by answering positively to the PHQ-9 item on self-harm when they did not meet the 10 or more threshold depression score overall. In other words, these patients would have been missed without this criterion.

In the participating Cincinnati pediatric clinics, about 12%-13% of adolescents met the criteria for depression, which Dr. Krantz said is consistent with reports in the literature. He said the range is about 6%-24%.

Although outcomes were not tracked, there is evidence that early intervention for depression yields better outcomes than delayed intervention, according to Dr. Krantz. Based on approximately 600 positive screens for depression per year at his pediatric clinics, he estimated that his data predict at least 25% more patients will receive timely follow-up.
 

Seeking Solutions to a Growing Problem

There are several studies documenting the growing problem of adolescent depression and suicide and, for this reason, the topic is attracting a lot of attention, according to Corinna Rea, MD, MPH, a pediatrician working in the primary care center at Boston Children’s Hospital in Massachusetts.

Dr. Rea was not involved with the study, but when asked to comment, she said: “The results of this study were encouraging because we know that getting patients to care quickly is probably important.” She also agreed that referring patients with depression for care might not be enough, noting that a lot of patients do not follow up on recommendations to pursue a consultation or treatment.

“I am now involved in a project with the American Academy of Pediatrics to address this issue,” Dr. Rae said. She thinks that more work in this area is needed and agreed with Dr. Krantz that pediatricians should verify that children with depression are getting help even when other specialists are providing the treatment.

Dr. Krantz and Dr. Rae report no potential conflicts of interest.

TORONTO — An ambitious effort at a busy pediatrics clinic to improve follow-up in children and adolescents with a positive depression screen improved this quality metric, and it produced a fundamental change in approach.

“It was a big culture shift,” reported Landon B. Krantz, MD, a clinical fellow in the Division of General and Community Pediatrics at Cincinnati Children’s Hospital in Ohio. From a baseline position of screening, risk identification, and then referral, “we are now taking ownership of the process.”

Based on the substantial risk posed by significant levels of depression, guidelines recommend follow-up for any patient 12 years or older who has a positive screen, according to Dr. Krantz. At his center, they found only 19% had a documented follow-up within 30 days, even though timely intervention is important.

“Nearly half of suicide events in adolescents occur within 30 days after a positive PHQ-9 [9-question Patient Health Questionnaire] is completed,” said Dr. Krantz when presenting his data at the Pediatric Academic Societies annual meeting.

The issue has gained more urgency because of the substantial increase over the past several years in children presenting with depression and suicidal thoughts, according to Dr. Krantz. He said many are characterizing the upsurge as a mental health crisis in the pediatric age group.
 

Improving Follow-Up

The goal of the initiative launched at six primary care practices in Cincinnati was to increase the proportion of children with a positive screen for depression who have a follow-up within 30 days. The goal at the outset was to increase the proportion to 35%.

“We know that a lot of children would receive follow-up at centers outside of our system,” said Dr. Krantz, explaining why the goal was relatively modest. Based on the likelihood that many follow-up visits would not be captured, he expected the final data would represent an underestimate.

Depression at baseline was defined as a score of 10 or higher on the PHQ-9 or any positive answer to item 9 on this screening tool, which asks specifically about thoughts of self-harm.

To be counted, follow-up had to be a documented encounter, whether by phone call, in-person visit, or telehealth visit.

“We needed patients to be checked. We did not count a prescription refill as a true follow-up,” Dr. Krantz specified.

There were numerous strategies implemented to improve follow-up, not least of which was an educational program to reinforce the importance and value of follow-up that was disseminated to clinicians in all of the participating clinics. Medical assistants were instructed to schedule a follow-up appointment for all patients who tested positive before they left the office. A target of 3 weeks was a strategy of overcorrection when so many patients were missing the initial 30-day window by just a few days.

The approach also involved an enhanced collaboration with psychologists to which patients were referred. Asking for expedited appointments when appropriate ensured that those at highest risk were prioritized, although Dr. Krantz said that this step was planned carefully to avoid overwhelming the mental health team.

“We monitored this and made sure it was not increasing the burden for psychologists from a capacity standpoint,” he said.

Other steps, like a depression action plan, which Dr. Krantz compared to an asthma action plan, were also implemented to reduce the risk of losing symptomatic patients before the chance for an effective treatment.

When compared with the 19% 30-day follow-up rate in the preintervention sample of 589 children, the 43.8% 30-day follow-up rate achieved in the 764 patients identified after implementation beat the original goal.

The improvement in follow-up was relatively consistent across all six clinics, which Dr. Krantz believes reflected a broad and shared change in a sense of responsibility for confirming that symptoms of depression were being addressed. Patients were still referred for psychological help, but referral was no longer considered enough.

“Children with mental health issues are still our patients in primary care,” said Dr. Krantz, who considers this an important change in orientation.

While the goal was to schedule patients for a follow-up at the time of a positive depression screen, Dr. Krantz described one important accommodation.

“The screen for depression was being performed in most cases during well visits, so patients and their families were not expecting to be discussing this issue,” he said. The diagnosis might be a particular surprise to parents who were not aware of any symptoms. In this case, Dr. Krantz said patients and families were given time to process the information and were contacted after a week to discuss further workup.

It is also notable that about one third of patients met the criteria for depression by answering positively to the PHQ-9 item on self-harm when they did not meet the 10 or more threshold depression score overall. In other words, these patients would have been missed without this criterion.

In the participating Cincinnati pediatric clinics, about 12%-13% of adolescents met the criteria for depression, which Dr. Krantz said is consistent with reports in the literature. He said the range is about 6%-24%.

Although outcomes were not tracked, there is evidence that early intervention for depression yields better outcomes than delayed intervention, according to Dr. Krantz. Based on approximately 600 positive screens for depression per year at his pediatric clinics, he estimated that his data predict at least 25% more patients will receive timely follow-up.
 

Seeking Solutions to a Growing Problem

There are several studies documenting the growing problem of adolescent depression and suicide and, for this reason, the topic is attracting a lot of attention, according to Corinna Rea, MD, MPH, a pediatrician working in the primary care center at Boston Children’s Hospital in Massachusetts.

Dr. Rea was not involved with the study, but when asked to comment, she said: “The results of this study were encouraging because we know that getting patients to care quickly is probably important.” She also agreed that referring patients with depression for care might not be enough, noting that a lot of patients do not follow up on recommendations to pursue a consultation or treatment.

“I am now involved in a project with the American Academy of Pediatrics to address this issue,” Dr. Rae said. She thinks that more work in this area is needed and agreed with Dr. Krantz that pediatricians should verify that children with depression are getting help even when other specialists are providing the treatment.

Dr. Krantz and Dr. Rae report no potential conflicts of interest.

WASHINGTON, DC – A mouth rinse used to identify oral microbiome composition could serve as an early-detection tool for gastric cancer, new evidence suggests.

Researchers found distinct bacterial composition differences in patient samples that point to the potential for oral microbial signatures to be used as biomarkers for assessing gastric cancer risk. 

“Too many patients are being diagnosed too late. There are no formal screening guidelines for gastric cancer, and more than half of patients with gastric cancer do not receive a diagnosis until their cancer is already at an advanced stage,” said Shruthi Reddy Perati, MD, a general surgery resident at Rutgers University Robert Wood Johnson School of Medicine in New Brunswick, New Jersey.

Detecting gastric cancer now generally requires an invasive procedure, such as endoscopy. Therefore, a noninvasive “swish and spit” test could be more accessible and allow for more widespread screening, Dr. Perati said at a May 8 press briefing during which her research (Abstract 949) was previewed for Digestive Disease Week^® (DDW).

Gastric cancer, also known as stomach cancer, is the fourth most common cause of cancer-related death in the world. The United States can expect 26,890 new cases and 10,880 deaths from this type of cancer in 2024, the American Cancer Society estimates.
 

Microbial Signatures Found

Dr. Perati and colleagues collected oral rinse samples from 98 patients: 30 known to have gastric cancer , 30 with precancerous gastric conditions (pre–gastric cancer), and 38 control participants without pre-gastric or gastric cancer. Sixty-two percent were women, 32% were Hispanic, 31% had diabetes, and 18% were smokers.

The researchers analyzed the samples for alpha and beta diversity and conducted differential analysis using the framework called analysis of compositions of microbiomes.

They found distinct differences between the oral microbiomes of the healthy group and those of the groups with gastric cancer and pre–gastric cancer. In addition, the microbiomes of participants with cancer and of those with precancerous conditions were similar.

The results suggest that the microbiome changes may occur as soon as the stomach environment starts to undergo changes that can eventually turn into cancer.

“The oral microbiome may serve as a window into the composition of the stomach environment,” Dr. Perati said.

The investigators created a screening model to detect the most relevant 13 bacterial genera that differed between the control group and the gastric cancer and pre–gastric cancer groups. The tenfold cross-validation model demonstrated good ability to discriminate using bacteria alone (area under the curve [AUC], 0.74) and was further improved with the addition of clinical variables, including demographics and comorbidities (AUC, 0.91), the researchers noted.

As the investigators noted, the model’s performance improved with the addition of clinical variables, said Loren Laine, MD, professor of medicine (digestive diseases) at Yale School of Medicine and chair of DDW 2024.

An AUC of 0.74 using bacteria alone, which increased to 0.91 by adding demographics and comorbidities, “[is] starting to be really meaningful,” Dr. Laine said.

Further studies should evaluate the test’s sensitivity and specificity, Dr. Laine added.
 

Additional Considerations

The microbiome can vary between people and within the same individual over time. Probiotics, antibiotics, and diet can lead to changes in the microbiome, Dr. Perati said.

When asked how these changes could affect the accuracy of an oral rinse test, Dr. Perati said “it’s known that, in general, dietary modifications can have an impact on the diversity and the prevalence of certain bacteria throughout the GI tract.”

Though variance is expected, we’re hoping to see that the differences in the microbiome composition between the malignant groups and the control groups are more significant than those lower-level background changes due to dietary modifications, for example, she added.

The research is in its early days, and the results need to be validated in a larger study, Dr. Perati said.

Ninety-eight patients is “still a very small number,” said Dr. Laine, who co-moderated the press briefing. “More research is needed.”

Still, the study “has huge implications that could eventually lead to the development of noninvasive and accessible early screening for gastric cancer,” she said.

Dr. Perati and Dr. Laine reported no relevant financial relationships. The study was independently supported.

A version of this article appeared on Medscape.com.

WASHINGTON, DC – A mouth rinse used to identify oral microbiome composition could serve as an early-detection tool for gastric cancer, new evidence suggests.

Researchers found distinct bacterial composition differences in patient samples that point to the potential for oral microbial signatures to be used as biomarkers for assessing gastric cancer risk. 

“Too many patients are being diagnosed too late. There are no formal screening guidelines for gastric cancer, and more than half of patients with gastric cancer do not receive a diagnosis until their cancer is already at an advanced stage,” said Shruthi Reddy Perati, MD, a general surgery resident at Rutgers University Robert Wood Johnson School of Medicine in New Brunswick, New Jersey.

Detecting gastric cancer now generally requires an invasive procedure, such as endoscopy. Therefore, a noninvasive “swish and spit” test could be more accessible and allow for more widespread screening, Dr. Perati said at a May 8 press briefing during which her research (Abstract 949) was previewed for Digestive Disease Week^® (DDW).

Gastric cancer, also known as stomach cancer, is the fourth most common cause of cancer-related death in the world. The United States can expect 26,890 new cases and 10,880 deaths from this type of cancer in 2024, the American Cancer Society estimates.
 

Microbial Signatures Found

Dr. Perati and colleagues collected oral rinse samples from 98 patients: 30 known to have gastric cancer , 30 with precancerous gastric conditions (pre–gastric cancer), and 38 control participants without pre-gastric or gastric cancer. Sixty-two percent were women, 32% were Hispanic, 31% had diabetes, and 18% were smokers.

The researchers analyzed the samples for alpha and beta diversity and conducted differential analysis using the framework called analysis of compositions of microbiomes.

They found distinct differences between the oral microbiomes of the healthy group and those of the groups with gastric cancer and pre–gastric cancer. In addition, the microbiomes of participants with cancer and of those with precancerous conditions were similar.

The results suggest that the microbiome changes may occur as soon as the stomach environment starts to undergo changes that can eventually turn into cancer.

“The oral microbiome may serve as a window into the composition of the stomach environment,” Dr. Perati said.

The investigators created a screening model to detect the most relevant 13 bacterial genera that differed between the control group and the gastric cancer and pre–gastric cancer groups. The tenfold cross-validation model demonstrated good ability to discriminate using bacteria alone (area under the curve [AUC], 0.74) and was further improved with the addition of clinical variables, including demographics and comorbidities (AUC, 0.91), the researchers noted.

As the investigators noted, the model’s performance improved with the addition of clinical variables, said Loren Laine, MD, professor of medicine (digestive diseases) at Yale School of Medicine and chair of DDW 2024.

An AUC of 0.74 using bacteria alone, which increased to 0.91 by adding demographics and comorbidities, “[is] starting to be really meaningful,” Dr. Laine said.

Further studies should evaluate the test’s sensitivity and specificity, Dr. Laine added.
 

Additional Considerations

The microbiome can vary between people and within the same individual over time. Probiotics, antibiotics, and diet can lead to changes in the microbiome, Dr. Perati said.

When asked how these changes could affect the accuracy of an oral rinse test, Dr. Perati said “it’s known that, in general, dietary modifications can have an impact on the diversity and the prevalence of certain bacteria throughout the GI tract.”

Though variance is expected, we’re hoping to see that the differences in the microbiome composition between the malignant groups and the control groups are more significant than those lower-level background changes due to dietary modifications, for example, she added.

The research is in its early days, and the results need to be validated in a larger study, Dr. Perati said.

Ninety-eight patients is “still a very small number,” said Dr. Laine, who co-moderated the press briefing. “More research is needed.”

Still, the study “has huge implications that could eventually lead to the development of noninvasive and accessible early screening for gastric cancer,” she said.

Dr. Perati and Dr. Laine reported no relevant financial relationships. The study was independently supported.

A version of this article appeared on Medscape.com.

WASHINGTON, DC – A mouth rinse used to identify oral microbiome composition could serve as an early-detection tool for gastric cancer, new evidence suggests.

Researchers found distinct bacterial composition differences in patient samples that point to the potential for oral microbial signatures to be used as biomarkers for assessing gastric cancer risk. 

“Too many patients are being diagnosed too late. There are no formal screening guidelines for gastric cancer, and more than half of patients with gastric cancer do not receive a diagnosis until their cancer is already at an advanced stage,” said Shruthi Reddy Perati, MD, a general surgery resident at Rutgers University Robert Wood Johnson School of Medicine in New Brunswick, New Jersey.

Detecting gastric cancer now generally requires an invasive procedure, such as endoscopy. Therefore, a noninvasive “swish and spit” test could be more accessible and allow for more widespread screening, Dr. Perati said at a May 8 press briefing during which her research (Abstract 949) was previewed for Digestive Disease Week^® (DDW).

Gastric cancer, also known as stomach cancer, is the fourth most common cause of cancer-related death in the world. The United States can expect 26,890 new cases and 10,880 deaths from this type of cancer in 2024, the American Cancer Society estimates.
 

Microbial Signatures Found

Dr. Perati and colleagues collected oral rinse samples from 98 patients: 30 known to have gastric cancer , 30 with precancerous gastric conditions (pre–gastric cancer), and 38 control participants without pre-gastric or gastric cancer. Sixty-two percent were women, 32% were Hispanic, 31% had diabetes, and 18% were smokers.

The researchers analyzed the samples for alpha and beta diversity and conducted differential analysis using the framework called analysis of compositions of microbiomes.

They found distinct differences between the oral microbiomes of the healthy group and those of the groups with gastric cancer and pre–gastric cancer. In addition, the microbiomes of participants with cancer and of those with precancerous conditions were similar.

The results suggest that the microbiome changes may occur as soon as the stomach environment starts to undergo changes that can eventually turn into cancer.

“The oral microbiome may serve as a window into the composition of the stomach environment,” Dr. Perati said.

The investigators created a screening model to detect the most relevant 13 bacterial genera that differed between the control group and the gastric cancer and pre–gastric cancer groups. The tenfold cross-validation model demonstrated good ability to discriminate using bacteria alone (area under the curve [AUC], 0.74) and was further improved with the addition of clinical variables, including demographics and comorbidities (AUC, 0.91), the researchers noted.

As the investigators noted, the model’s performance improved with the addition of clinical variables, said Loren Laine, MD, professor of medicine (digestive diseases) at Yale School of Medicine and chair of DDW 2024.

An AUC of 0.74 using bacteria alone, which increased to 0.91 by adding demographics and comorbidities, “[is] starting to be really meaningful,” Dr. Laine said.

Further studies should evaluate the test’s sensitivity and specificity, Dr. Laine added.
 

Additional Considerations

The microbiome can vary between people and within the same individual over time. Probiotics, antibiotics, and diet can lead to changes in the microbiome, Dr. Perati said.

When asked how these changes could affect the accuracy of an oral rinse test, Dr. Perati said “it’s known that, in general, dietary modifications can have an impact on the diversity and the prevalence of certain bacteria throughout the GI tract.”

Though variance is expected, we’re hoping to see that the differences in the microbiome composition between the malignant groups and the control groups are more significant than those lower-level background changes due to dietary modifications, for example, she added.

The research is in its early days, and the results need to be validated in a larger study, Dr. Perati said.

Ninety-eight patients is “still a very small number,” said Dr. Laine, who co-moderated the press briefing. “More research is needed.”

Still, the study “has huge implications that could eventually lead to the development of noninvasive and accessible early screening for gastric cancer,” she said.

Dr. Perati and Dr. Laine reported no relevant financial relationships. The study was independently supported.

A version of this article appeared on Medscape.com.

Medications that could have a negative effect on cognition are often used by older adults with dementia, according to data from approximately 13 million individuals presented at the annual meeting of the American Geriatrics Society.

Classes of medications including anticholinergics, antipsychotics, benzodiazepines, and non-benzodiazepine sedatives (Z drugs) have been identified as potentially inappropriate medications (PIMs) in patients with dementia, according to The American Geriatrics Society Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.

The medications that could worsen dementia or cognition are known as CogPIMs, said presenting author Caroline M. Mak, a doctor of pharmacy candidate at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences, New York.

Previous research has characterized the prevalence of use of CogPIMs, but data connecting use of CogPIMs and healthcare use are lacking, Ms. Mak said.

Ms. Mak and colleagues conducted a cross-sectional analysis of data from 2011 to 2015 from the Medical Expenditure Panel Survey (MEPS), a national survey with data on medication and healthcare use. The researchers included approximately 13 million survey respondents older than 65 years with dementia.

Exposure to CogPIMs was defined as filling a prescription for one or more of the CogPIMs during the study period. Population estimates of the prevalence of use of the CogPIMs were created using survey-weighted procedures, and prevalence trends were assessed using the Cochran-Armitage test.

Overall, the prevalence was 15.9%, 11.5%, 7.5%, and 3.8% for use of benzodiazepines, anticholinergics, antipsychotics, and Z drugs, respectively, during the study period.

Of these, benzodiazepines showed a significant trend with an increase in prevalence from 8.9% in 2011 to 16.4% in 2015 (P = .02).

The odds of hospitalization were more than twice as likely in individuals who reported using Z drugs (odds ratio, 2.57; P = .02) based on logistic regression. In addition, exposure to antipsychotics was significantly associated with an increased rate of hospitalization based on a binomial model for incidence rate ratio (IRR, 1.51; P = .02).

The findings were limited by several factors including the cross-sectional design, reliance on self-reports, and the lack of more recent data.

However, the results show that CogPIMs are often used by older adults with dementia, and antipsychotics and Z drugs could be targets for interventions to prevent harm from medication interactions and side effects, the researchers concluded.
 

Findings Highlight Need for Drug Awareness

The current study is important because of the expansion in the aging population and an increase in the number of patients with dementia, Ms. Mak said in an interview. “In both our older population and dementia patients, there are certain medication considerations that we need to take into account, and certain drugs that should be avoided if possible,” she said. Clinicians have been trying to use the Beers criteria to reduce potential medication harm, she noted. “One group of investigators (Hilmer et al.), has proposed a narrower focus on anticholinergic and sedative/hypnotic medication in the Drug Burden Index (DBI); the CogPIMs are a subset of both approaches (Beers and DBI) and represent a collection of medications that pose potential risks to our patients,” said Ms. Mak.

Continued reassessment is needed on appropriateness of anticholinergics, Z drugs, benzodiazepines, and antipsychotics in older patients with dementia, she added.

“Even though the only group to have a significant increase in prevalence [of use] was the benzodiazepine group, we didn’t see a decrease in any of the other groups,” said Ms. Mak. The current research provides a benchmark for CogPIMs use that can be monitored in the future for increases or, ideally, decreases, she said.
 

Part of a Bigger Picture

The current study is part of the work of Team Alice, a national deprescribing group affiliated with the University at Buffalo that was inspired by the tragic death of Alice Brennan, triggered by preventable medication harm, Ms. Mak said in an interview. “Team Alice consists of an array of academic, primary care, health plan, and regional health information partners that have designed patient-driven interventions to reduce medication harm, especially within primary care settings,” she said. “Their mission is to save people like Alice by pursuing multiple strategies to deprescribe unsafe medication, reduce harm, and foster successful aging. By characterizing the use of CogPIMs, we can design better intervention strategies,” she said.

Although Ms. Mak was not surprised by the emergence of benzodiazepines as the most commonly used drug groups, she was surprised by the increase during the study period.

“Unfortunately, our dataset was not rich enough to include reasons for this increase,” she said. In practice, “I have seen patients getting short-term, as needed, prescriptions for a benzodiazepine to address the anxiety and/or insomnia after the loss of a loved one; this may account for a small proportion of benzodiazepine use that appears to be inappropriate because of a lack of associated appropriate diagnosis,” she noted.

Also, the findings of increased hospitalization associated with Z drugs raises concerns, Ms. Mak said. Although the findings are consistent with other research, they illustrate the need for further investigation to identify strategies to prevent this harm, she said. “Not finding associations with hospitalization related to benzodiazepine or anticholinergics was a mild surprise,” Ms. Mak said in an interview. “However, while we know that these drugs can have a negative effect on older people, the effects may not have been severe enough to result in hospitalizations,” she said.

Looking ahead, Ms. Mak said she would like to see the study rerun with a more current data set, especially with regard to benzodiazepines and antipsychotics.
 

Seek Strategies to Reduce Medication Use

The current study was notable for its community-based population and attention to hospitalizations, Shelly Gray, PharmD, a professor of pharmacy at the University of Washington School of Pharmacy, said in an interview.

“Most studies examining potentially inappropriate medications that may impair cognition have been conducted in nursing homes, while this study focuses on community dwelling older adults where most people with dementia live,” said Dr. Gray, who served as a moderator for the session in which the study was presented.

In addition, “A unique aspect of this study was to examine how these medications are related to hospitalizations,” she said.

Given recent efforts to reduce use of potentially inappropriate medications in people with dementia, the increase in prevalence of use over the study period was surprising, especially for benzodiazepines, said Dr. Gray.

In clinical practice, “health care providers should continue to look for opportunities to deprescribe medications that may worsen cognition in people with dementia,” she said. However, more research is needed to examine trends in the years beyond 2015 for a more contemporary picture of medication use in this population, she noted.

The study received no outside funding. The researchers and Dr. Gray had no financial conflicts to disclose.

Medications that could have a negative effect on cognition are often used by older adults with dementia, according to data from approximately 13 million individuals presented at the annual meeting of the American Geriatrics Society.

Classes of medications including anticholinergics, antipsychotics, benzodiazepines, and non-benzodiazepine sedatives (Z drugs) have been identified as potentially inappropriate medications (PIMs) in patients with dementia, according to The American Geriatrics Society Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.

The medications that could worsen dementia or cognition are known as CogPIMs, said presenting author Caroline M. Mak, a doctor of pharmacy candidate at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences, New York.

Previous research has characterized the prevalence of use of CogPIMs, but data connecting use of CogPIMs and healthcare use are lacking, Ms. Mak said.

Ms. Mak and colleagues conducted a cross-sectional analysis of data from 2011 to 2015 from the Medical Expenditure Panel Survey (MEPS), a national survey with data on medication and healthcare use. The researchers included approximately 13 million survey respondents older than 65 years with dementia.

Exposure to CogPIMs was defined as filling a prescription for one or more of the CogPIMs during the study period. Population estimates of the prevalence of use of the CogPIMs were created using survey-weighted procedures, and prevalence trends were assessed using the Cochran-Armitage test.

Overall, the prevalence was 15.9%, 11.5%, 7.5%, and 3.8% for use of benzodiazepines, anticholinergics, antipsychotics, and Z drugs, respectively, during the study period.

Of these, benzodiazepines showed a significant trend with an increase in prevalence from 8.9% in 2011 to 16.4% in 2015 (P = .02).

The odds of hospitalization were more than twice as likely in individuals who reported using Z drugs (odds ratio, 2.57; P = .02) based on logistic regression. In addition, exposure to antipsychotics was significantly associated with an increased rate of hospitalization based on a binomial model for incidence rate ratio (IRR, 1.51; P = .02).

The findings were limited by several factors including the cross-sectional design, reliance on self-reports, and the lack of more recent data.

However, the results show that CogPIMs are often used by older adults with dementia, and antipsychotics and Z drugs could be targets for interventions to prevent harm from medication interactions and side effects, the researchers concluded.
 

Findings Highlight Need for Drug Awareness

The current study is important because of the expansion in the aging population and an increase in the number of patients with dementia, Ms. Mak said in an interview. “In both our older population and dementia patients, there are certain medication considerations that we need to take into account, and certain drugs that should be avoided if possible,” she said. Clinicians have been trying to use the Beers criteria to reduce potential medication harm, she noted. “One group of investigators (Hilmer et al.), has proposed a narrower focus on anticholinergic and sedative/hypnotic medication in the Drug Burden Index (DBI); the CogPIMs are a subset of both approaches (Beers and DBI) and represent a collection of medications that pose potential risks to our patients,” said Ms. Mak.

Continued reassessment is needed on appropriateness of anticholinergics, Z drugs, benzodiazepines, and antipsychotics in older patients with dementia, she added.

“Even though the only group to have a significant increase in prevalence [of use] was the benzodiazepine group, we didn’t see a decrease in any of the other groups,” said Ms. Mak. The current research provides a benchmark for CogPIMs use that can be monitored in the future for increases or, ideally, decreases, she said.
 

Part of a Bigger Picture

The current study is part of the work of Team Alice, a national deprescribing group affiliated with the University at Buffalo that was inspired by the tragic death of Alice Brennan, triggered by preventable medication harm, Ms. Mak said in an interview. “Team Alice consists of an array of academic, primary care, health plan, and regional health information partners that have designed patient-driven interventions to reduce medication harm, especially within primary care settings,” she said. “Their mission is to save people like Alice by pursuing multiple strategies to deprescribe unsafe medication, reduce harm, and foster successful aging. By characterizing the use of CogPIMs, we can design better intervention strategies,” she said.

Although Ms. Mak was not surprised by the emergence of benzodiazepines as the most commonly used drug groups, she was surprised by the increase during the study period.

“Unfortunately, our dataset was not rich enough to include reasons for this increase,” she said. In practice, “I have seen patients getting short-term, as needed, prescriptions for a benzodiazepine to address the anxiety and/or insomnia after the loss of a loved one; this may account for a small proportion of benzodiazepine use that appears to be inappropriate because of a lack of associated appropriate diagnosis,” she noted.

Also, the findings of increased hospitalization associated with Z drugs raises concerns, Ms. Mak said. Although the findings are consistent with other research, they illustrate the need for further investigation to identify strategies to prevent this harm, she said. “Not finding associations with hospitalization related to benzodiazepine or anticholinergics was a mild surprise,” Ms. Mak said in an interview. “However, while we know that these drugs can have a negative effect on older people, the effects may not have been severe enough to result in hospitalizations,” she said.

Looking ahead, Ms. Mak said she would like to see the study rerun with a more current data set, especially with regard to benzodiazepines and antipsychotics.
 

Seek Strategies to Reduce Medication Use

The current study was notable for its community-based population and attention to hospitalizations, Shelly Gray, PharmD, a professor of pharmacy at the University of Washington School of Pharmacy, said in an interview.

“Most studies examining potentially inappropriate medications that may impair cognition have been conducted in nursing homes, while this study focuses on community dwelling older adults where most people with dementia live,” said Dr. Gray, who served as a moderator for the session in which the study was presented.

In addition, “A unique aspect of this study was to examine how these medications are related to hospitalizations,” she said.

Given recent efforts to reduce use of potentially inappropriate medications in people with dementia, the increase in prevalence of use over the study period was surprising, especially for benzodiazepines, said Dr. Gray.

In clinical practice, “health care providers should continue to look for opportunities to deprescribe medications that may worsen cognition in people with dementia,” she said. However, more research is needed to examine trends in the years beyond 2015 for a more contemporary picture of medication use in this population, she noted.

The study received no outside funding. The researchers and Dr. Gray had no financial conflicts to disclose.

Medications that could have a negative effect on cognition are often used by older adults with dementia, according to data from approximately 13 million individuals presented at the annual meeting of the American Geriatrics Society.

Classes of medications including anticholinergics, antipsychotics, benzodiazepines, and non-benzodiazepine sedatives (Z drugs) have been identified as potentially inappropriate medications (PIMs) in patients with dementia, according to The American Geriatrics Society Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.

The medications that could worsen dementia or cognition are known as CogPIMs, said presenting author Caroline M. Mak, a doctor of pharmacy candidate at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences, New York.

Previous research has characterized the prevalence of use of CogPIMs, but data connecting use of CogPIMs and healthcare use are lacking, Ms. Mak said.

Ms. Mak and colleagues conducted a cross-sectional analysis of data from 2011 to 2015 from the Medical Expenditure Panel Survey (MEPS), a national survey with data on medication and healthcare use. The researchers included approximately 13 million survey respondents older than 65 years with dementia.

Exposure to CogPIMs was defined as filling a prescription for one or more of the CogPIMs during the study period. Population estimates of the prevalence of use of the CogPIMs were created using survey-weighted procedures, and prevalence trends were assessed using the Cochran-Armitage test.

Overall, the prevalence was 15.9%, 11.5%, 7.5%, and 3.8% for use of benzodiazepines, anticholinergics, antipsychotics, and Z drugs, respectively, during the study period.

Of these, benzodiazepines showed a significant trend with an increase in prevalence from 8.9% in 2011 to 16.4% in 2015 (P = .02).

The odds of hospitalization were more than twice as likely in individuals who reported using Z drugs (odds ratio, 2.57; P = .02) based on logistic regression. In addition, exposure to antipsychotics was significantly associated with an increased rate of hospitalization based on a binomial model for incidence rate ratio (IRR, 1.51; P = .02).

The findings were limited by several factors including the cross-sectional design, reliance on self-reports, and the lack of more recent data.

However, the results show that CogPIMs are often used by older adults with dementia, and antipsychotics and Z drugs could be targets for interventions to prevent harm from medication interactions and side effects, the researchers concluded.
 

Findings Highlight Need for Drug Awareness

The current study is important because of the expansion in the aging population and an increase in the number of patients with dementia, Ms. Mak said in an interview. “In both our older population and dementia patients, there are certain medication considerations that we need to take into account, and certain drugs that should be avoided if possible,” she said. Clinicians have been trying to use the Beers criteria to reduce potential medication harm, she noted. “One group of investigators (Hilmer et al.), has proposed a narrower focus on anticholinergic and sedative/hypnotic medication in the Drug Burden Index (DBI); the CogPIMs are a subset of both approaches (Beers and DBI) and represent a collection of medications that pose potential risks to our patients,” said Ms. Mak.

Continued reassessment is needed on appropriateness of anticholinergics, Z drugs, benzodiazepines, and antipsychotics in older patients with dementia, she added.

“Even though the only group to have a significant increase in prevalence [of use] was the benzodiazepine group, we didn’t see a decrease in any of the other groups,” said Ms. Mak. The current research provides a benchmark for CogPIMs use that can be monitored in the future for increases or, ideally, decreases, she said.
 

Part of a Bigger Picture

The current study is part of the work of Team Alice, a national deprescribing group affiliated with the University at Buffalo that was inspired by the tragic death of Alice Brennan, triggered by preventable medication harm, Ms. Mak said in an interview. “Team Alice consists of an array of academic, primary care, health plan, and regional health information partners that have designed patient-driven interventions to reduce medication harm, especially within primary care settings,” she said. “Their mission is to save people like Alice by pursuing multiple strategies to deprescribe unsafe medication, reduce harm, and foster successful aging. By characterizing the use of CogPIMs, we can design better intervention strategies,” she said.

Although Ms. Mak was not surprised by the emergence of benzodiazepines as the most commonly used drug groups, she was surprised by the increase during the study period.

“Unfortunately, our dataset was not rich enough to include reasons for this increase,” she said. In practice, “I have seen patients getting short-term, as needed, prescriptions for a benzodiazepine to address the anxiety and/or insomnia after the loss of a loved one; this may account for a small proportion of benzodiazepine use that appears to be inappropriate because of a lack of associated appropriate diagnosis,” she noted.

Also, the findings of increased hospitalization associated with Z drugs raises concerns, Ms. Mak said. Although the findings are consistent with other research, they illustrate the need for further investigation to identify strategies to prevent this harm, she said. “Not finding associations with hospitalization related to benzodiazepine or anticholinergics was a mild surprise,” Ms. Mak said in an interview. “However, while we know that these drugs can have a negative effect on older people, the effects may not have been severe enough to result in hospitalizations,” she said.

Looking ahead, Ms. Mak said she would like to see the study rerun with a more current data set, especially with regard to benzodiazepines and antipsychotics.
 

Seek Strategies to Reduce Medication Use

The current study was notable for its community-based population and attention to hospitalizations, Shelly Gray, PharmD, a professor of pharmacy at the University of Washington School of Pharmacy, said in an interview.

“Most studies examining potentially inappropriate medications that may impair cognition have been conducted in nursing homes, while this study focuses on community dwelling older adults where most people with dementia live,” said Dr. Gray, who served as a moderator for the session in which the study was presented.

In addition, “A unique aspect of this study was to examine how these medications are related to hospitalizations,” she said.

Given recent efforts to reduce use of potentially inappropriate medications in people with dementia, the increase in prevalence of use over the study period was surprising, especially for benzodiazepines, said Dr. Gray.

In clinical practice, “health care providers should continue to look for opportunities to deprescribe medications that may worsen cognition in people with dementia,” she said. However, more research is needed to examine trends in the years beyond 2015 for a more contemporary picture of medication use in this population, she noted.

The study received no outside funding. The researchers and Dr. Gray had no financial conflicts to disclose.

LIVERPOOL, ENGLAND — The IRIS-RA study of the investigational monoclonal antibody drug nipocalimab in patients with rheumatoid arthritis (RA) did not meet its primary endpoint, but there could still be people with moderate to severe RA who might benefit from treatment with the drug, according to information reported at the British Society for Rheumatology annual meeting.

The primary endpoint for the phase 2A trial was the least squares mean change in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) from baseline to 12 weeks of treatment. This was reduced by −1.03 with nipocalimab and by −0.58 with placebo, giving a mean difference of just −0.45 (P = .224).

However, one of the key secondary endpoints was the proportion of patients who had 20% improvement in American College of Rheumatology response criteria (ACR20). Results for this endpoint showed a greater difference in response to nipocalimab vs placebo, with a respective 45.5% and 20.0% (P = .055) of individuals achieving ACR20.

Moreover, an analysis stratifying for anti-citrullinated protein autoantibody (ACPA) levels at baseline found that people with higher levels had a better response to nipocalimab.
 

Choice of Endpoint

“The way this study was powered was to look at a change between the treatment groups of a DAS28-CRP reduction of 1.0,” said Peter C. Taylor, BMBCh, PhD, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in Oxford, England.

DAS28-CRP was often chosen as the primary endpoint in small proof-of-concept studies, such as IRIS-RA, because it was a “measure of continuous change [that] theoretically, would allow greater sensitivity to change,” Dr. Taylor added.

Sara Freeman/Medscape Medical News

Proof of Concept

IRIS-RA was billed as a “proof-of-concept” study because it was the first time that a monoclonal antibody targeting the neonatal fragment crystallizable receptor (FcRn) was being tested in an RA population.

The study was a randomized double-blind trial in which 33 people with moderate to severe RA who had an inadequate response to tumor necrosis factor (TNF) inhibitors were treated with nipocalimab at a dose of 15 mg/kg given intravenously every 2 weeks, and 20 received a matching placebo. Participants were treated for 10 weeks, and then the primary follow-up was at 12 weeks, with additional follow-up for safety undertaken at 18 weeks.

Nipocalimab is a fully human, immunoglobulin G1 (IgG1) monoclonal antibody that is designed to selectively block the FcRn. By doing so, it essentially stops IgG from being recycled within the immune system, and this in turn lowers IgG levels. That includes potentially harmful ACPAs, among other pathogenic antibodies, Dr. Taylor and fellow investigators explained in their abstract.

“We’ve known for a long time that ACPA have prognostic value, but there’s been controversy about whether or not ACPA are actually pathogenic,” Dr. Taylor said. “So, one of the hypotheses that this study gives rise to is that by blocking FcRn, and thereby reducing, potentially, the concentration of ACPA in the blood, will we actually have efficacy in patients?”
 

Are ACPA Really Lowered?

Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in Leeds, England, questioned the reduction in antibody levels during the discussion that followed.

Although these data had not been presented, Dr. Emery observed that the reduction in IgG was actually greater than that in ACPA, “which is fairly critical. Is it feasible to look to selectively lower normal immunoglobulin over pathogenic autoantibodies?”

Dr. Emery also wanted to know if there “was a floor on the reduction of immunoglobulin” with long-term therapy, “which would be a worry.”

Dr. Taylor responded that total IgG had been reduced by about 65% and ACPA by about 40%. Why this difference exists is not yet clear. It could be because ACPA are part of complexed antibodies.

“Most of these patients are rheumatoid factor [RF]–positive,” said Taylor, pointing out that although IgM “wouldn’t normally be affected by FcRn blockade,” there was a 10% reduction in RF IgM, probably because it was complexed to IgG.

“So, the hypothesis here is that if you look at the clearance of complexes, they’re handled differently in the cytoplasm from the clearance of monomeric IgG. But that’s a hypothesis. It needs further investigation. In vitro, there’s very good, confirmatory evidence to support that. But we’ve yet to explore that more fully in vivo,” Dr. Taylor said.

As for long-term effects, Dr. Taylor responded: “All I can tell you is [that] after the 10-week intervention, that up to an 18-week observation period, immunoglobulin levels recovered very rapidly afterwards. And you mustn’t forget that other isotypes are not affected, unlike rituximab.”
 

Safety and Other Results

With regard to safety, 27 (82%) of nipocalimab- and 12 (60%) of placebo-treated participants experienced at least one treatment-emergent adverse event (TEAE). The most common, occurring in 10% or more of cases, were RA flares (36.4% for nipocalimab vs 15.0% with placebo), headache (12.1% vs 5.0%), and COVID-19 (12.1% vs 0.0%).

There were three serious TEAEs, all in the nipocalimab-treatment group: One was an infection of a burn that had been present at inclusion, another was a deep vein thrombosis that resolved with apixaban treatment, and the other was an infusion-related reaction that resolved with supportive treatment.

Another notable efficacy finding was the proportion of patients achieving DAS28-CRP remission at 12 weeks in the nipocalimab vs the placebo group was substantially greater if considering only people with high baseline ACPA levels, at a respective 40.0% vs 16.7%, when compared with the total population (21.2% vs 10.0%).

Similar findings were seen for the proportion of patients achieving an ACR50, and there were numerically greater reductions in the components of the ACR response criteria such as tender and swollen joints with nipocalimab vs placebo. All of these were exploratory observations, Dr. Taylor emphasized.
 

Combination and Further Trials

Further trials of nipocalimab are planned or are already ongoing in systemic lupus erythematosus, active lupus nephritis, Sjögren disease, and five other diseases.

In RA, nipocalimab is now being tested in combination with the TNF inhibitor certolizumab pegol (Cimzia) in the DAISY-RA trial. This is another proof-of-concept, phase 2A trial with a target accrual of 104 patients.

The IRIS-RA study was funded by Janssen Research & Development. Dr. Taylor serves as a consultant to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB and received research funding from Galapagos, among others. Dr. Emery received research grants paid to his institution from AbbVie, Bristol Myers Squibb (BMS), Pfizer, MSD, and Roche; received consultant fees from BMS, AbbVie, Pfizer, MSD, Novartis, Roche, and UCB; and has undertaken clinical trials and provided expert advice to Pfizer, MSD, AbbVie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, and Lilly.
 

A version of this article appeared on Medscape.com.

LIVERPOOL, ENGLAND — The IRIS-RA study of the investigational monoclonal antibody drug nipocalimab in patients with rheumatoid arthritis (RA) did not meet its primary endpoint, but there could still be people with moderate to severe RA who might benefit from treatment with the drug, according to information reported at the British Society for Rheumatology annual meeting.

The primary endpoint for the phase 2A trial was the least squares mean change in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) from baseline to 12 weeks of treatment. This was reduced by −1.03 with nipocalimab and by −0.58 with placebo, giving a mean difference of just −0.45 (P = .224).

However, one of the key secondary endpoints was the proportion of patients who had 20% improvement in American College of Rheumatology response criteria (ACR20). Results for this endpoint showed a greater difference in response to nipocalimab vs placebo, with a respective 45.5% and 20.0% (P = .055) of individuals achieving ACR20.

Moreover, an analysis stratifying for anti-citrullinated protein autoantibody (ACPA) levels at baseline found that people with higher levels had a better response to nipocalimab.
 

Choice of Endpoint

“The way this study was powered was to look at a change between the treatment groups of a DAS28-CRP reduction of 1.0,” said Peter C. Taylor, BMBCh, PhD, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in Oxford, England.

DAS28-CRP was often chosen as the primary endpoint in small proof-of-concept studies, such as IRIS-RA, because it was a “measure of continuous change [that] theoretically, would allow greater sensitivity to change,” Dr. Taylor added.

Sara Freeman/Medscape Medical News

Proof of Concept

IRIS-RA was billed as a “proof-of-concept” study because it was the first time that a monoclonal antibody targeting the neonatal fragment crystallizable receptor (FcRn) was being tested in an RA population.

The study was a randomized double-blind trial in which 33 people with moderate to severe RA who had an inadequate response to tumor necrosis factor (TNF) inhibitors were treated with nipocalimab at a dose of 15 mg/kg given intravenously every 2 weeks, and 20 received a matching placebo. Participants were treated for 10 weeks, and then the primary follow-up was at 12 weeks, with additional follow-up for safety undertaken at 18 weeks.

Nipocalimab is a fully human, immunoglobulin G1 (IgG1) monoclonal antibody that is designed to selectively block the FcRn. By doing so, it essentially stops IgG from being recycled within the immune system, and this in turn lowers IgG levels. That includes potentially harmful ACPAs, among other pathogenic antibodies, Dr. Taylor and fellow investigators explained in their abstract.

“We’ve known for a long time that ACPA have prognostic value, but there’s been controversy about whether or not ACPA are actually pathogenic,” Dr. Taylor said. “So, one of the hypotheses that this study gives rise to is that by blocking FcRn, and thereby reducing, potentially, the concentration of ACPA in the blood, will we actually have efficacy in patients?”
 

Are ACPA Really Lowered?

Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in Leeds, England, questioned the reduction in antibody levels during the discussion that followed.

Although these data had not been presented, Dr. Emery observed that the reduction in IgG was actually greater than that in ACPA, “which is fairly critical. Is it feasible to look to selectively lower normal immunoglobulin over pathogenic autoantibodies?”

Dr. Emery also wanted to know if there “was a floor on the reduction of immunoglobulin” with long-term therapy, “which would be a worry.”

Dr. Taylor responded that total IgG had been reduced by about 65% and ACPA by about 40%. Why this difference exists is not yet clear. It could be because ACPA are part of complexed antibodies.

“Most of these patients are rheumatoid factor [RF]–positive,” said Taylor, pointing out that although IgM “wouldn’t normally be affected by FcRn blockade,” there was a 10% reduction in RF IgM, probably because it was complexed to IgG.

“So, the hypothesis here is that if you look at the clearance of complexes, they’re handled differently in the cytoplasm from the clearance of monomeric IgG. But that’s a hypothesis. It needs further investigation. In vitro, there’s very good, confirmatory evidence to support that. But we’ve yet to explore that more fully in vivo,” Dr. Taylor said.

As for long-term effects, Dr. Taylor responded: “All I can tell you is [that] after the 10-week intervention, that up to an 18-week observation period, immunoglobulin levels recovered very rapidly afterwards. And you mustn’t forget that other isotypes are not affected, unlike rituximab.”
 

Safety and Other Results

With regard to safety, 27 (82%) of nipocalimab- and 12 (60%) of placebo-treated participants experienced at least one treatment-emergent adverse event (TEAE). The most common, occurring in 10% or more of cases, were RA flares (36.4% for nipocalimab vs 15.0% with placebo), headache (12.1% vs 5.0%), and COVID-19 (12.1% vs 0.0%).

There were three serious TEAEs, all in the nipocalimab-treatment group: One was an infection of a burn that had been present at inclusion, another was a deep vein thrombosis that resolved with apixaban treatment, and the other was an infusion-related reaction that resolved with supportive treatment.

Another notable efficacy finding was the proportion of patients achieving DAS28-CRP remission at 12 weeks in the nipocalimab vs the placebo group was substantially greater if considering only people with high baseline ACPA levels, at a respective 40.0% vs 16.7%, when compared with the total population (21.2% vs 10.0%).

Similar findings were seen for the proportion of patients achieving an ACR50, and there were numerically greater reductions in the components of the ACR response criteria such as tender and swollen joints with nipocalimab vs placebo. All of these were exploratory observations, Dr. Taylor emphasized.
 

Combination and Further Trials

Further trials of nipocalimab are planned or are already ongoing in systemic lupus erythematosus, active lupus nephritis, Sjögren disease, and five other diseases.

In RA, nipocalimab is now being tested in combination with the TNF inhibitor certolizumab pegol (Cimzia) in the DAISY-RA trial. This is another proof-of-concept, phase 2A trial with a target accrual of 104 patients.

The IRIS-RA study was funded by Janssen Research & Development. Dr. Taylor serves as a consultant to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB and received research funding from Galapagos, among others. Dr. Emery received research grants paid to his institution from AbbVie, Bristol Myers Squibb (BMS), Pfizer, MSD, and Roche; received consultant fees from BMS, AbbVie, Pfizer, MSD, Novartis, Roche, and UCB; and has undertaken clinical trials and provided expert advice to Pfizer, MSD, AbbVie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, and Lilly.
 

A version of this article appeared on Medscape.com.

LIVERPOOL, ENGLAND — The IRIS-RA study of the investigational monoclonal antibody drug nipocalimab in patients with rheumatoid arthritis (RA) did not meet its primary endpoint, but there could still be people with moderate to severe RA who might benefit from treatment with the drug, according to information reported at the British Society for Rheumatology annual meeting.

The primary endpoint for the phase 2A trial was the least squares mean change in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) from baseline to 12 weeks of treatment. This was reduced by −1.03 with nipocalimab and by −0.58 with placebo, giving a mean difference of just −0.45 (P = .224).

However, one of the key secondary endpoints was the proportion of patients who had 20% improvement in American College of Rheumatology response criteria (ACR20). Results for this endpoint showed a greater difference in response to nipocalimab vs placebo, with a respective 45.5% and 20.0% (P = .055) of individuals achieving ACR20.

Moreover, an analysis stratifying for anti-citrullinated protein autoantibody (ACPA) levels at baseline found that people with higher levels had a better response to nipocalimab.
 

Choice of Endpoint

“The way this study was powered was to look at a change between the treatment groups of a DAS28-CRP reduction of 1.0,” said Peter C. Taylor, BMBCh, PhD, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in Oxford, England.

DAS28-CRP was often chosen as the primary endpoint in small proof-of-concept studies, such as IRIS-RA, because it was a “measure of continuous change [that] theoretically, would allow greater sensitivity to change,” Dr. Taylor added.

Sara Freeman/Medscape Medical News

Proof of Concept

IRIS-RA was billed as a “proof-of-concept” study because it was the first time that a monoclonal antibody targeting the neonatal fragment crystallizable receptor (FcRn) was being tested in an RA population.

The study was a randomized double-blind trial in which 33 people with moderate to severe RA who had an inadequate response to tumor necrosis factor (TNF) inhibitors were treated with nipocalimab at a dose of 15 mg/kg given intravenously every 2 weeks, and 20 received a matching placebo. Participants were treated for 10 weeks, and then the primary follow-up was at 12 weeks, with additional follow-up for safety undertaken at 18 weeks.

Nipocalimab is a fully human, immunoglobulin G1 (IgG1) monoclonal antibody that is designed to selectively block the FcRn. By doing so, it essentially stops IgG from being recycled within the immune system, and this in turn lowers IgG levels. That includes potentially harmful ACPAs, among other pathogenic antibodies, Dr. Taylor and fellow investigators explained in their abstract.

“We’ve known for a long time that ACPA have prognostic value, but there’s been controversy about whether or not ACPA are actually pathogenic,” Dr. Taylor said. “So, one of the hypotheses that this study gives rise to is that by blocking FcRn, and thereby reducing, potentially, the concentration of ACPA in the blood, will we actually have efficacy in patients?”
 

Are ACPA Really Lowered?

Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in Leeds, England, questioned the reduction in antibody levels during the discussion that followed.

Although these data had not been presented, Dr. Emery observed that the reduction in IgG was actually greater than that in ACPA, “which is fairly critical. Is it feasible to look to selectively lower normal immunoglobulin over pathogenic autoantibodies?”

Dr. Emery also wanted to know if there “was a floor on the reduction of immunoglobulin” with long-term therapy, “which would be a worry.”

Dr. Taylor responded that total IgG had been reduced by about 65% and ACPA by about 40%. Why this difference exists is not yet clear. It could be because ACPA are part of complexed antibodies.

“Most of these patients are rheumatoid factor [RF]–positive,” said Taylor, pointing out that although IgM “wouldn’t normally be affected by FcRn blockade,” there was a 10% reduction in RF IgM, probably because it was complexed to IgG.

“So, the hypothesis here is that if you look at the clearance of complexes, they’re handled differently in the cytoplasm from the clearance of monomeric IgG. But that’s a hypothesis. It needs further investigation. In vitro, there’s very good, confirmatory evidence to support that. But we’ve yet to explore that more fully in vivo,” Dr. Taylor said.

As for long-term effects, Dr. Taylor responded: “All I can tell you is [that] after the 10-week intervention, that up to an 18-week observation period, immunoglobulin levels recovered very rapidly afterwards. And you mustn’t forget that other isotypes are not affected, unlike rituximab.”
 

Safety and Other Results

With regard to safety, 27 (82%) of nipocalimab- and 12 (60%) of placebo-treated participants experienced at least one treatment-emergent adverse event (TEAE). The most common, occurring in 10% or more of cases, were RA flares (36.4% for nipocalimab vs 15.0% with placebo), headache (12.1% vs 5.0%), and COVID-19 (12.1% vs 0.0%).

There were three serious TEAEs, all in the nipocalimab-treatment group: One was an infection of a burn that had been present at inclusion, another was a deep vein thrombosis that resolved with apixaban treatment, and the other was an infusion-related reaction that resolved with supportive treatment.

Another notable efficacy finding was the proportion of patients achieving DAS28-CRP remission at 12 weeks in the nipocalimab vs the placebo group was substantially greater if considering only people with high baseline ACPA levels, at a respective 40.0% vs 16.7%, when compared with the total population (21.2% vs 10.0%).

Similar findings were seen for the proportion of patients achieving an ACR50, and there were numerically greater reductions in the components of the ACR response criteria such as tender and swollen joints with nipocalimab vs placebo. All of these were exploratory observations, Dr. Taylor emphasized.
 

Combination and Further Trials

Further trials of nipocalimab are planned or are already ongoing in systemic lupus erythematosus, active lupus nephritis, Sjögren disease, and five other diseases.

In RA, nipocalimab is now being tested in combination with the TNF inhibitor certolizumab pegol (Cimzia) in the DAISY-RA trial. This is another proof-of-concept, phase 2A trial with a target accrual of 104 patients.

The IRIS-RA study was funded by Janssen Research & Development. Dr. Taylor serves as a consultant to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB and received research funding from Galapagos, among others. Dr. Emery received research grants paid to his institution from AbbVie, Bristol Myers Squibb (BMS), Pfizer, MSD, and Roche; received consultant fees from BMS, AbbVie, Pfizer, MSD, Novartis, Roche, and UCB; and has undertaken clinical trials and provided expert advice to Pfizer, MSD, AbbVie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, and Lilly.
 

A version of this article appeared on Medscape.com.