Safety concerns persist for out-of-hospital births in the United States with multiple potential risk factors and few safety requirements, according to a paper published in the American Journal of Obstetrics and Gynecology.

In 2022, the Centers for Disease Control and Prevention (CDC) reported the highest number of planned home births in 30 years. The numbers rose 12% from 2020 to 2021, the latest period for which complete data are available. Home births rose from 45,646 (1.26% of births) in 2020 to 51,642 (1.41% of births).

Amos Grünebaum, MD, and Frank A. Chervenak, MD, with Northwell Health, and the Department of Obstetrics and Gynecology, Lenox Hill Hospital, Zucker School of Medicine in New Hyde Park, New York, reviewed the latest safety data surrounding community births in the United States along with well-known perinatal risks and safety requirements for safe out-of-hospital births.

“Most planned home births continue to have one or more risk factors that are associated with an increase in adverse pregnancy outcomes,” they wrote.
 

Birth Certificate Data Analyzed

The researchers used the CDC birth certificate database and analyzed deliveries between 2016 and 2022 regarding the incidence of perinatal risks in community births. The risks included were prior cesarean, first baby, mother older than 35 years, twins, breech presentation, gestational age of less than 37 weeks or more than 41 weeks, newborn weight over 4,000 grams, adequacy of prenatal care, grand multiparity (5 or more prior pregnancies), and a prepregnancy body mass index of at least 35.

The incidence of perinatal risks for out-of-hospital births ranged individually from 0.2% to 28.54% among birthing center births and 0.32% to 24.4% for planned home births.

“The ACOG committee opinion on home births states that for every 1000 home births, 3.9 babies will die,” the authors noted, or about twice the risk of hospital births. The deaths are “potentially avoidable with easy access to an operating room,” they wrote.

Among the safety concerns for perinatal morbidity and mortality in community births, the authors cited the lack of:

• Appropriate patient selection for out-of-hospital births through standardized guidelines.
• Availability of a Certified Nurse Midwife, a Certified Midwife, or midwife whose education and licensure meet International Confederation of Midwives’ (ICM) Global Standards for Midwifery Education.
• Providers practicing obstetrics within an integrated and regulated health system with ready access and availability of board-certified obstetricians to provide consultation for qualified midwives.
• Standardized guidelines on when transport to a hospital is necessary.

“While prerequisites for a safe out-of-hospital delivery may be in place in other high-income countries, these prerequisites have not been actualized in the United States,” the authors wrote.

Incorporating Patient Preferences Into Delivery Models

Yalda Afshar, MD, PhD, maternal-fetal medicine subspecialist and a physician-scientist at UCLA Health in California, said obstetricians are responsible for offering the most evidence-based care to pregnant people.

“What this birth certificate data demonstrates,” she said, “is a tendency among birthing people to opt for out-of-hospital births, despite documented risks to both the pregnant person and the neonate. This underscores the need to persist in educating on risk stratification, risk reduction, and safe birthing practices, while also fostering innovation. Innovation should stem from our commitment to incorporate the preferences of pregnant people into our healthcare delivery model.”

Dr. Afshar, who was not part of the study, said clinicians should develop innovative ways to effectively meet the needs of pregnant patients while ensuring their safety and well-being.

“Ideally, we would establish safe environments within hospital systems and centers that emulate home-like birthing experiences, thereby mitigating risks for these families,” she said.

Though not explicitly stated in the data, she added, it is crucial to emphasize the need for continuous risk assessment throughout pregnancy and childbirth, “with a paramount focus on the safety of the pregnant individual.”

The authors and Dr. Afshar have no relevant financial disclosures.

Safety concerns persist for out-of-hospital births in the United States with multiple potential risk factors and few safety requirements, according to a paper published in the American Journal of Obstetrics and Gynecology.

In 2022, the Centers for Disease Control and Prevention (CDC) reported the highest number of planned home births in 30 years. The numbers rose 12% from 2020 to 2021, the latest period for which complete data are available. Home births rose from 45,646 (1.26% of births) in 2020 to 51,642 (1.41% of births).

Amos Grünebaum, MD, and Frank A. Chervenak, MD, with Northwell Health, and the Department of Obstetrics and Gynecology, Lenox Hill Hospital, Zucker School of Medicine in New Hyde Park, New York, reviewed the latest safety data surrounding community births in the United States along with well-known perinatal risks and safety requirements for safe out-of-hospital births.

“Most planned home births continue to have one or more risk factors that are associated with an increase in adverse pregnancy outcomes,” they wrote.
 

Birth Certificate Data Analyzed

The researchers used the CDC birth certificate database and analyzed deliveries between 2016 and 2022 regarding the incidence of perinatal risks in community births. The risks included were prior cesarean, first baby, mother older than 35 years, twins, breech presentation, gestational age of less than 37 weeks or more than 41 weeks, newborn weight over 4,000 grams, adequacy of prenatal care, grand multiparity (5 or more prior pregnancies), and a prepregnancy body mass index of at least 35.

The incidence of perinatal risks for out-of-hospital births ranged individually from 0.2% to 28.54% among birthing center births and 0.32% to 24.4% for planned home births.

“The ACOG committee opinion on home births states that for every 1000 home births, 3.9 babies will die,” the authors noted, or about twice the risk of hospital births. The deaths are “potentially avoidable with easy access to an operating room,” they wrote.

Among the safety concerns for perinatal morbidity and mortality in community births, the authors cited the lack of:

• Appropriate patient selection for out-of-hospital births through standardized guidelines.
• Availability of a Certified Nurse Midwife, a Certified Midwife, or midwife whose education and licensure meet International Confederation of Midwives’ (ICM) Global Standards for Midwifery Education.
• Providers practicing obstetrics within an integrated and regulated health system with ready access and availability of board-certified obstetricians to provide consultation for qualified midwives.
• Standardized guidelines on when transport to a hospital is necessary.

“While prerequisites for a safe out-of-hospital delivery may be in place in other high-income countries, these prerequisites have not been actualized in the United States,” the authors wrote.

Incorporating Patient Preferences Into Delivery Models

Yalda Afshar, MD, PhD, maternal-fetal medicine subspecialist and a physician-scientist at UCLA Health in California, said obstetricians are responsible for offering the most evidence-based care to pregnant people.

“What this birth certificate data demonstrates,” she said, “is a tendency among birthing people to opt for out-of-hospital births, despite documented risks to both the pregnant person and the neonate. This underscores the need to persist in educating on risk stratification, risk reduction, and safe birthing practices, while also fostering innovation. Innovation should stem from our commitment to incorporate the preferences of pregnant people into our healthcare delivery model.”

Dr. Afshar, who was not part of the study, said clinicians should develop innovative ways to effectively meet the needs of pregnant patients while ensuring their safety and well-being.

“Ideally, we would establish safe environments within hospital systems and centers that emulate home-like birthing experiences, thereby mitigating risks for these families,” she said.

Though not explicitly stated in the data, she added, it is crucial to emphasize the need for continuous risk assessment throughout pregnancy and childbirth, “with a paramount focus on the safety of the pregnant individual.”

The authors and Dr. Afshar have no relevant financial disclosures.

Safety concerns persist for out-of-hospital births in the United States with multiple potential risk factors and few safety requirements, according to a paper published in the American Journal of Obstetrics and Gynecology.

In 2022, the Centers for Disease Control and Prevention (CDC) reported the highest number of planned home births in 30 years. The numbers rose 12% from 2020 to 2021, the latest period for which complete data are available. Home births rose from 45,646 (1.26% of births) in 2020 to 51,642 (1.41% of births).

Amos Grünebaum, MD, and Frank A. Chervenak, MD, with Northwell Health, and the Department of Obstetrics and Gynecology, Lenox Hill Hospital, Zucker School of Medicine in New Hyde Park, New York, reviewed the latest safety data surrounding community births in the United States along with well-known perinatal risks and safety requirements for safe out-of-hospital births.

“Most planned home births continue to have one or more risk factors that are associated with an increase in adverse pregnancy outcomes,” they wrote.
 

Birth Certificate Data Analyzed

The researchers used the CDC birth certificate database and analyzed deliveries between 2016 and 2022 regarding the incidence of perinatal risks in community births. The risks included were prior cesarean, first baby, mother older than 35 years, twins, breech presentation, gestational age of less than 37 weeks or more than 41 weeks, newborn weight over 4,000 grams, adequacy of prenatal care, grand multiparity (5 or more prior pregnancies), and a prepregnancy body mass index of at least 35.

The incidence of perinatal risks for out-of-hospital births ranged individually from 0.2% to 28.54% among birthing center births and 0.32% to 24.4% for planned home births.

“The ACOG committee opinion on home births states that for every 1000 home births, 3.9 babies will die,” the authors noted, or about twice the risk of hospital births. The deaths are “potentially avoidable with easy access to an operating room,” they wrote.

Among the safety concerns for perinatal morbidity and mortality in community births, the authors cited the lack of:

• Appropriate patient selection for out-of-hospital births through standardized guidelines.
• Availability of a Certified Nurse Midwife, a Certified Midwife, or midwife whose education and licensure meet International Confederation of Midwives’ (ICM) Global Standards for Midwifery Education.
• Providers practicing obstetrics within an integrated and regulated health system with ready access and availability of board-certified obstetricians to provide consultation for qualified midwives.
• Standardized guidelines on when transport to a hospital is necessary.

“While prerequisites for a safe out-of-hospital delivery may be in place in other high-income countries, these prerequisites have not been actualized in the United States,” the authors wrote.

Incorporating Patient Preferences Into Delivery Models

Yalda Afshar, MD, PhD, maternal-fetal medicine subspecialist and a physician-scientist at UCLA Health in California, said obstetricians are responsible for offering the most evidence-based care to pregnant people.

“What this birth certificate data demonstrates,” she said, “is a tendency among birthing people to opt for out-of-hospital births, despite documented risks to both the pregnant person and the neonate. This underscores the need to persist in educating on risk stratification, risk reduction, and safe birthing practices, while also fostering innovation. Innovation should stem from our commitment to incorporate the preferences of pregnant people into our healthcare delivery model.”

Dr. Afshar, who was not part of the study, said clinicians should develop innovative ways to effectively meet the needs of pregnant patients while ensuring their safety and well-being.

“Ideally, we would establish safe environments within hospital systems and centers that emulate home-like birthing experiences, thereby mitigating risks for these families,” she said.

Though not explicitly stated in the data, she added, it is crucial to emphasize the need for continuous risk assessment throughout pregnancy and childbirth, “with a paramount focus on the safety of the pregnant individual.”

The authors and Dr. Afshar have no relevant financial disclosures.

TOPLINE:

A recent survey highlighted ethical concerns US oncologists have about using artificial intelligence (AI) to help make cancer treatment decisions and revealed some contradictory views about how best to integrate these tools into practice. Most respondents, for instance, said patients should not be expected to understand how AI tools work, but many also felt patients could make treatment decisions based on AI-generated recommendations. Most oncologists also felt responsible for protecting patients from biased AI, but few were confident that they could do so.

METHODOLOGY:

• The US Food and Drug Administration (FDA) has  for use in various medical specialties over the past few decades, and increasingly, AI tools are being integrated into cancer care.
• However, the uptake of these tools in oncology has raised ethical questions and concerns, including challenges with AI bias, error, or misuse, as well as issues explaining how an AI model reached a result.
• In the current study, researchers asked 204 oncologists from 37 states for their views on the ethical implications of using AI for cancer care.
• Among the survey respondents, 64% were men and 63% were non-Hispanic White; 29% were from academic practices, 47% had received some education on AI use in healthcare, and 45% were familiar with clinical decision models.
• The researchers assessed respondents’ answers to various questions, including whether to provide informed consent for AI use and how oncologists would approach a scenario where the AI model and the oncologist recommended a different treatment regimen.

TAKEAWAY:

• Overall, 81% of oncologists supported having patient consent to use an AI model during treatment decisions, and 85% felt that oncologists needed to be able to explain an AI-based clinical decision model to use it in the clinic; however, only 23% felt that patients also needed to be able to explain an AI model.
• When an AI decision model recommended a different treatment regimen than the treating oncologist, the most common response (36.8%) was to present both options to the patient and let the patient decide. Oncologists from academic settings were about 2.5 times more likely than those from other settings to let the patient decide. About 34% of respondents said they would present both options but recommend the oncologist’s regimen, whereas about 22% said they would present both but recommend the AI’s regimen. A small percentage would only present the oncologist’s regimen (5%) or the AI’s regimen (about 2.5%).
• About three of four respondents (76.5%) agreed that oncologists should protect patients from biased AI tools; however, only about one of four (27.9%) felt confident they could identify biased AI models.
• Most oncologists (91%) felt that AI developers were responsible for the medico-legal problems associated with AI use; less than half (47%) said oncologists or hospitals (43%) shared this responsibility.

IN PRACTICE:

“Together, these data characterize barriers that may impede the ethical adoption of AI into cancer care. The findings suggest that the implementation of AI in oncology must include rigorous assessments of its effect on care decisions, as well as decisional responsibility when problems related to AI use arise,” the authors concluded.

SOURCE:

The study, with first author Andrew Hantel, MD, from Dana-Farber Cancer Institute, Boston, was published last month in JAMA Network Open.

LIMITATIONS:

The study had a moderate sample size and response rate, although demographics of participating oncologists appear to be nationally representative. The cross-sectional study design limited the generalizability of the findings over time as AI is integrated into cancer care.

DISCLOSURES:

The study was funded by the National Cancer Institute, the Dana-Farber McGraw/Patterson Research Fund, and the Mark Foundation Emerging Leader Award. Dr. Hantel reported receiving personal fees from AbbVie, AstraZeneca, the American Journal of Managed Care, Genentech, and GSK.

A version of this article appeared on Medscape.com.

TOPLINE:

A recent survey highlighted ethical concerns US oncologists have about using artificial intelligence (AI) to help make cancer treatment decisions and revealed some contradictory views about how best to integrate these tools into practice. Most respondents, for instance, said patients should not be expected to understand how AI tools work, but many also felt patients could make treatment decisions based on AI-generated recommendations. Most oncologists also felt responsible for protecting patients from biased AI, but few were confident that they could do so.

METHODOLOGY:

• The US Food and Drug Administration (FDA) has  for use in various medical specialties over the past few decades, and increasingly, AI tools are being integrated into cancer care.
• However, the uptake of these tools in oncology has raised ethical questions and concerns, including challenges with AI bias, error, or misuse, as well as issues explaining how an AI model reached a result.
• In the current study, researchers asked 204 oncologists from 37 states for their views on the ethical implications of using AI for cancer care.
• Among the survey respondents, 64% were men and 63% were non-Hispanic White; 29% were from academic practices, 47% had received some education on AI use in healthcare, and 45% were familiar with clinical decision models.
• The researchers assessed respondents’ answers to various questions, including whether to provide informed consent for AI use and how oncologists would approach a scenario where the AI model and the oncologist recommended a different treatment regimen.

TAKEAWAY:

• Overall, 81% of oncologists supported having patient consent to use an AI model during treatment decisions, and 85% felt that oncologists needed to be able to explain an AI-based clinical decision model to use it in the clinic; however, only 23% felt that patients also needed to be able to explain an AI model.
• When an AI decision model recommended a different treatment regimen than the treating oncologist, the most common response (36.8%) was to present both options to the patient and let the patient decide. Oncologists from academic settings were about 2.5 times more likely than those from other settings to let the patient decide. About 34% of respondents said they would present both options but recommend the oncologist’s regimen, whereas about 22% said they would present both but recommend the AI’s regimen. A small percentage would only present the oncologist’s regimen (5%) or the AI’s regimen (about 2.5%).
• About three of four respondents (76.5%) agreed that oncologists should protect patients from biased AI tools; however, only about one of four (27.9%) felt confident they could identify biased AI models.
• Most oncologists (91%) felt that AI developers were responsible for the medico-legal problems associated with AI use; less than half (47%) said oncologists or hospitals (43%) shared this responsibility.

IN PRACTICE:

“Together, these data characterize barriers that may impede the ethical adoption of AI into cancer care. The findings suggest that the implementation of AI in oncology must include rigorous assessments of its effect on care decisions, as well as decisional responsibility when problems related to AI use arise,” the authors concluded.

SOURCE:

The study, with first author Andrew Hantel, MD, from Dana-Farber Cancer Institute, Boston, was published last month in JAMA Network Open.

LIMITATIONS:

The study had a moderate sample size and response rate, although demographics of participating oncologists appear to be nationally representative. The cross-sectional study design limited the generalizability of the findings over time as AI is integrated into cancer care.

DISCLOSURES:

The study was funded by the National Cancer Institute, the Dana-Farber McGraw/Patterson Research Fund, and the Mark Foundation Emerging Leader Award. Dr. Hantel reported receiving personal fees from AbbVie, AstraZeneca, the American Journal of Managed Care, Genentech, and GSK.

A version of this article appeared on Medscape.com.

TOPLINE:

A recent survey highlighted ethical concerns US oncologists have about using artificial intelligence (AI) to help make cancer treatment decisions and revealed some contradictory views about how best to integrate these tools into practice. Most respondents, for instance, said patients should not be expected to understand how AI tools work, but many also felt patients could make treatment decisions based on AI-generated recommendations. Most oncologists also felt responsible for protecting patients from biased AI, but few were confident that they could do so.

METHODOLOGY:

• The US Food and Drug Administration (FDA) has  for use in various medical specialties over the past few decades, and increasingly, AI tools are being integrated into cancer care.
• However, the uptake of these tools in oncology has raised ethical questions and concerns, including challenges with AI bias, error, or misuse, as well as issues explaining how an AI model reached a result.
• In the current study, researchers asked 204 oncologists from 37 states for their views on the ethical implications of using AI for cancer care.
• Among the survey respondents, 64% were men and 63% were non-Hispanic White; 29% were from academic practices, 47% had received some education on AI use in healthcare, and 45% were familiar with clinical decision models.
• The researchers assessed respondents’ answers to various questions, including whether to provide informed consent for AI use and how oncologists would approach a scenario where the AI model and the oncologist recommended a different treatment regimen.

TAKEAWAY:

• Overall, 81% of oncologists supported having patient consent to use an AI model during treatment decisions, and 85% felt that oncologists needed to be able to explain an AI-based clinical decision model to use it in the clinic; however, only 23% felt that patients also needed to be able to explain an AI model.
• When an AI decision model recommended a different treatment regimen than the treating oncologist, the most common response (36.8%) was to present both options to the patient and let the patient decide. Oncologists from academic settings were about 2.5 times more likely than those from other settings to let the patient decide. About 34% of respondents said they would present both options but recommend the oncologist’s regimen, whereas about 22% said they would present both but recommend the AI’s regimen. A small percentage would only present the oncologist’s regimen (5%) or the AI’s regimen (about 2.5%).
• About three of four respondents (76.5%) agreed that oncologists should protect patients from biased AI tools; however, only about one of four (27.9%) felt confident they could identify biased AI models.
• Most oncologists (91%) felt that AI developers were responsible for the medico-legal problems associated with AI use; less than half (47%) said oncologists or hospitals (43%) shared this responsibility.

IN PRACTICE:

“Together, these data characterize barriers that may impede the ethical adoption of AI into cancer care. The findings suggest that the implementation of AI in oncology must include rigorous assessments of its effect on care decisions, as well as decisional responsibility when problems related to AI use arise,” the authors concluded.

SOURCE:

The study, with first author Andrew Hantel, MD, from Dana-Farber Cancer Institute, Boston, was published last month in JAMA Network Open.

LIMITATIONS:

The study had a moderate sample size and response rate, although demographics of participating oncologists appear to be nationally representative. The cross-sectional study design limited the generalizability of the findings over time as AI is integrated into cancer care.

DISCLOSURES:

The study was funded by the National Cancer Institute, the Dana-Farber McGraw/Patterson Research Fund, and the Mark Foundation Emerging Leader Award. Dr. Hantel reported receiving personal fees from AbbVie, AstraZeneca, the American Journal of Managed Care, Genentech, and GSK.

A version of this article appeared on Medscape.com.

TOPLINE:

For individuals aged 45-49 years at average risk for colorectal cancer (CRC), the adenoma detection rate (ADR) in screening colonoscopies is 28%, which is comparable with rates seen in those aged 50-54 years.

METHODOLOGY:

• The rising incidence of CRC in younger populations prompted most guidelines to recommend screening to start at age 45. The impact of lowering the screening age on adenoma and sessile serrated lesion detection rates remains unclear, however.
• Researchers conducted a systematic review and meta-analysis of 16 studies; all studies were retrospective except one.
• Patients aged 45-49 years undergoing colonoscopy for any indication were included, with a separate analysis of patients in that age group at average CRC risk undergoing screening colonoscopies.
• The primary outcome was the overall detection rates of adenomas and sessile serrated lesions for colonoscopies performed for any indication.

TAKEAWAY:

• Across 15 studies, 41,709 adenomas were detected in 150,436 colonoscopies performed for any indication, resulting in a pooled overall ADR of 23.1%.
• Across six studies, 1162 sessile serrated lesions were reported in 11,457 colonoscopies performed for any indication, with a pooled detection rate of 6.3%.
• Across seven studies, the pooled ADR in screening colonoscopies performed on individuals with average CRC risk was 28.2%, which is comparable with that of 50- to 54-year-old individuals undergoing screening colonoscopy. There was not enough data to calculate the sessile serrated lesion detection rate in average-risk patients.
• The ADR was higher in the United States and Canada (26.1%) compared with studies from Asia (16.9%).

IN PRACTICE:

“The comparable detection rates of precancerous lesions in this age group to those 50 to 54 years old support starting CRC screening at 45 years of age,” the authors wrote.

SOURCE:

This study, led by Mohamed Abdallah, MD, Division of Gastroenterology and Hepatology, University of Minnesota Medical Center, Minneapolis, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The inclusion of retrospective studies has an inherent bias. The heterogeneity between studies may limit the generalizability of the findings. Some studies that reported detection rates included individuals at both average and high risk for CRC, so they could not be used to evaluate ADRs in individuals with an average risk for CRC. Data duplication could not be ruled out.

DISCLOSURES:

The study did not receive any funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

For individuals aged 45-49 years at average risk for colorectal cancer (CRC), the adenoma detection rate (ADR) in screening colonoscopies is 28%, which is comparable with rates seen in those aged 50-54 years.

METHODOLOGY:

• The rising incidence of CRC in younger populations prompted most guidelines to recommend screening to start at age 45. The impact of lowering the screening age on adenoma and sessile serrated lesion detection rates remains unclear, however.
• Researchers conducted a systematic review and meta-analysis of 16 studies; all studies were retrospective except one.
• Patients aged 45-49 years undergoing colonoscopy for any indication were included, with a separate analysis of patients in that age group at average CRC risk undergoing screening colonoscopies.
• The primary outcome was the overall detection rates of adenomas and sessile serrated lesions for colonoscopies performed for any indication.

TAKEAWAY:

• Across 15 studies, 41,709 adenomas were detected in 150,436 colonoscopies performed for any indication, resulting in a pooled overall ADR of 23.1%.
• Across six studies, 1162 sessile serrated lesions were reported in 11,457 colonoscopies performed for any indication, with a pooled detection rate of 6.3%.
• Across seven studies, the pooled ADR in screening colonoscopies performed on individuals with average CRC risk was 28.2%, which is comparable with that of 50- to 54-year-old individuals undergoing screening colonoscopy. There was not enough data to calculate the sessile serrated lesion detection rate in average-risk patients.
• The ADR was higher in the United States and Canada (26.1%) compared with studies from Asia (16.9%).

IN PRACTICE:

“The comparable detection rates of precancerous lesions in this age group to those 50 to 54 years old support starting CRC screening at 45 years of age,” the authors wrote.

SOURCE:

This study, led by Mohamed Abdallah, MD, Division of Gastroenterology and Hepatology, University of Minnesota Medical Center, Minneapolis, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The inclusion of retrospective studies has an inherent bias. The heterogeneity between studies may limit the generalizability of the findings. Some studies that reported detection rates included individuals at both average and high risk for CRC, so they could not be used to evaluate ADRs in individuals with an average risk for CRC. Data duplication could not be ruled out.

DISCLOSURES:

The study did not receive any funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

For individuals aged 45-49 years at average risk for colorectal cancer (CRC), the adenoma detection rate (ADR) in screening colonoscopies is 28%, which is comparable with rates seen in those aged 50-54 years.

METHODOLOGY:

• The rising incidence of CRC in younger populations prompted most guidelines to recommend screening to start at age 45. The impact of lowering the screening age on adenoma and sessile serrated lesion detection rates remains unclear, however.
• Researchers conducted a systematic review and meta-analysis of 16 studies; all studies were retrospective except one.
• Patients aged 45-49 years undergoing colonoscopy for any indication were included, with a separate analysis of patients in that age group at average CRC risk undergoing screening colonoscopies.
• The primary outcome was the overall detection rates of adenomas and sessile serrated lesions for colonoscopies performed for any indication.

TAKEAWAY:

• Across 15 studies, 41,709 adenomas were detected in 150,436 colonoscopies performed for any indication, resulting in a pooled overall ADR of 23.1%.
• Across six studies, 1162 sessile serrated lesions were reported in 11,457 colonoscopies performed for any indication, with a pooled detection rate of 6.3%.
• Across seven studies, the pooled ADR in screening colonoscopies performed on individuals with average CRC risk was 28.2%, which is comparable with that of 50- to 54-year-old individuals undergoing screening colonoscopy. There was not enough data to calculate the sessile serrated lesion detection rate in average-risk patients.
• The ADR was higher in the United States and Canada (26.1%) compared with studies from Asia (16.9%).

IN PRACTICE:

“The comparable detection rates of precancerous lesions in this age group to those 50 to 54 years old support starting CRC screening at 45 years of age,” the authors wrote.

SOURCE:

This study, led by Mohamed Abdallah, MD, Division of Gastroenterology and Hepatology, University of Minnesota Medical Center, Minneapolis, was published online in The American Journal of Gastroenterology.

LIMITATIONS:

The inclusion of retrospective studies has an inherent bias. The heterogeneity between studies may limit the generalizability of the findings. Some studies that reported detection rates included individuals at both average and high risk for CRC, so they could not be used to evaluate ADRs in individuals with an average risk for CRC. Data duplication could not be ruled out.

DISCLOSURES:

The study did not receive any funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

No significant association was found between the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and thyroid cancer over nearly 4 years.

METHODOLOGY:

• A cohort study using data from nationwide registers in Denmark, Norway, and Sweden between 2007 and 2021 included 145,410 patients who initiated GLP-1 RAs and 291,667 propensity score-matched patients initiating dipeptidyl peptidase 4 (DPP4) inhibitors as active comparators.
• Additional analysis included 111,744 who initiated GLP-1 RAs and 148,179 patients initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors.
• Overall, mean follow-up time was 3.9 years, with 25% followed for more than 6 years.

TAKEAWAY:

• The most common individual GLP-1 RAs were liraglutide (57.3%) and semaglutide (32.9%).
• During follow-up, there were 76 incident thyroid cancer cases among GLP-1 RA users and 184 cases in DPP4 inhibitor users, giving incidence rates per 10,000 of 1.33 and 1.46, respectively, a nonsignificant difference (hazard ratio [HR], 0.93; 95% CI, 0.66-1.31).
• Papillary thyroid cancer was the most common thyroid cancer subtype, followed by follicular and medullary, with no significant increases in risk with GLP-1 RAs by cancer type, although the numbers were small.
• In the SGLT2 inhibitor comparison, there was also no significantly increased thyroid cancer risk for GLP-1 RAs (HR, 1.16; 95% CI, 0.65-2.05).

IN PRACTICE:

“Given the upper limit of the confidence interval, the findings are incompatible with more than a 31% increased relative risk of thyroid cancer. In absolute terms, this translates to no more than 0.36 excess cases per 10 000 person-years, a figure that should be interpreted against the background incidence of 1.46 per 10,000 person-years among the comparator group in the study populations.”

SOURCE:

This study was conducted by Björn Pasternak, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues. It was published online on April 10, 2024, in The BMJ.

LIMITATIONS:

Relatively short follow-up for cancer risk. Risk by individual GLP-1 RA not analyzed. Small event numbers. Observational, with potential for residual confounding and time-release bias.

DISCLOSURES:

The study was supported by grants from the Swedish Cancer Society and the Swedish Research Council. Dr. Pasternak was supported by a consolidator investigator grant from Karolinska Institutet. Some of the coauthors had industry disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

No significant association was found between the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and thyroid cancer over nearly 4 years.

METHODOLOGY:

• A cohort study using data from nationwide registers in Denmark, Norway, and Sweden between 2007 and 2021 included 145,410 patients who initiated GLP-1 RAs and 291,667 propensity score-matched patients initiating dipeptidyl peptidase 4 (DPP4) inhibitors as active comparators.
• Additional analysis included 111,744 who initiated GLP-1 RAs and 148,179 patients initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors.
• Overall, mean follow-up time was 3.9 years, with 25% followed for more than 6 years.

TAKEAWAY:

• The most common individual GLP-1 RAs were liraglutide (57.3%) and semaglutide (32.9%).
• During follow-up, there were 76 incident thyroid cancer cases among GLP-1 RA users and 184 cases in DPP4 inhibitor users, giving incidence rates per 10,000 of 1.33 and 1.46, respectively, a nonsignificant difference (hazard ratio [HR], 0.93; 95% CI, 0.66-1.31).
• Papillary thyroid cancer was the most common thyroid cancer subtype, followed by follicular and medullary, with no significant increases in risk with GLP-1 RAs by cancer type, although the numbers were small.
• In the SGLT2 inhibitor comparison, there was also no significantly increased thyroid cancer risk for GLP-1 RAs (HR, 1.16; 95% CI, 0.65-2.05).

IN PRACTICE:

“Given the upper limit of the confidence interval, the findings are incompatible with more than a 31% increased relative risk of thyroid cancer. In absolute terms, this translates to no more than 0.36 excess cases per 10 000 person-years, a figure that should be interpreted against the background incidence of 1.46 per 10,000 person-years among the comparator group in the study populations.”

SOURCE:

This study was conducted by Björn Pasternak, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues. It was published online on April 10, 2024, in The BMJ.

LIMITATIONS:

Relatively short follow-up for cancer risk. Risk by individual GLP-1 RA not analyzed. Small event numbers. Observational, with potential for residual confounding and time-release bias.

DISCLOSURES:

The study was supported by grants from the Swedish Cancer Society and the Swedish Research Council. Dr. Pasternak was supported by a consolidator investigator grant from Karolinska Institutet. Some of the coauthors had industry disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

No significant association was found between the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and thyroid cancer over nearly 4 years.

METHODOLOGY:

• A cohort study using data from nationwide registers in Denmark, Norway, and Sweden between 2007 and 2021 included 145,410 patients who initiated GLP-1 RAs and 291,667 propensity score-matched patients initiating dipeptidyl peptidase 4 (DPP4) inhibitors as active comparators.
• Additional analysis included 111,744 who initiated GLP-1 RAs and 148,179 patients initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors.
• Overall, mean follow-up time was 3.9 years, with 25% followed for more than 6 years.

TAKEAWAY:

• The most common individual GLP-1 RAs were liraglutide (57.3%) and semaglutide (32.9%).
• During follow-up, there were 76 incident thyroid cancer cases among GLP-1 RA users and 184 cases in DPP4 inhibitor users, giving incidence rates per 10,000 of 1.33 and 1.46, respectively, a nonsignificant difference (hazard ratio [HR], 0.93; 95% CI, 0.66-1.31).
• Papillary thyroid cancer was the most common thyroid cancer subtype, followed by follicular and medullary, with no significant increases in risk with GLP-1 RAs by cancer type, although the numbers were small.
• In the SGLT2 inhibitor comparison, there was also no significantly increased thyroid cancer risk for GLP-1 RAs (HR, 1.16; 95% CI, 0.65-2.05).

IN PRACTICE:

“Given the upper limit of the confidence interval, the findings are incompatible with more than a 31% increased relative risk of thyroid cancer. In absolute terms, this translates to no more than 0.36 excess cases per 10 000 person-years, a figure that should be interpreted against the background incidence of 1.46 per 10,000 person-years among the comparator group in the study populations.”

SOURCE:

This study was conducted by Björn Pasternak, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues. It was published online on April 10, 2024, in The BMJ.

LIMITATIONS:

Relatively short follow-up for cancer risk. Risk by individual GLP-1 RA not analyzed. Small event numbers. Observational, with potential for residual confounding and time-release bias.

DISCLOSURES:

The study was supported by grants from the Swedish Cancer Society and the Swedish Research Council. Dr. Pasternak was supported by a consolidator investigator grant from Karolinska Institutet. Some of the coauthors had industry disclosures.

A version of this article appeared on Medscape.com.

Progressive resistance training (PRT) and neuromuscular exercise (NEMEX) programs result in similar improvements in hip function, pain, and hip-related quality of life (QOL) in people with osteoarthritis (OA), according to the results of a randomized controlled trial.

At the end of the 12-week exercise period, both interventions yielded changes from baseline on the 30-second chair stand test (30s-CST) that were below the threshold for a major clinical effect. 

Mean changes in the Hip Disability and Osteoarthritis Outcome Score (HOOS) pain subscale and HOOS QOL score were also similar among the participants, regardless of which exercise program they had been assigned to.

“The lack of superiority of PRT for increasing muscle strength and power is surprising given the principle of specificity (higher-intensity resistance training yields greater improvements in maximal muscle strength),” according to the Danish researchers who reported the results online today in Annals of Internal Medicine.

“However, the point estimates only showed modest and uncertain superiority of PRT for increasing muscle strength and power and no differences for any functional performance tests or self-reported physical function,” they added.
 

The Power of Exercise

Worldwide, most clinical guidelines recommend exercise as a first-line conservative treatment option in both hip and knee OA. However, there is not much evidence to help guide healthcare practitioners in deciding which type of exercises to use with their patients, Troels Kjeldsen, MSc, the principal investigator for the study, told this news organization.

“Neuromuscular exercise is a very commonly used exercise program in clinical practice, but, to our knowledge, it has never been compared to another type of exercise in hip OA,” observed Mr. Kjeldsen, who is a PhD student in the department of orthopedic surgery at Aarhus University Hospital, Aarhus, Denmark.

“Each year, many thousands of patients are referred to having neuromuscular exercise therapy with a physiotherapist,” Mr. Kjeldsen said. “So, we thought it would be worthwhile to compare it to PRT, another promising exercise type, to see if it really did perform as well as I think most people thought it did,” he added.
 

Comparing the Two Exercise Programs

PRT and NEMEX are two different types of exercise programs. PRT involves using resistance-training machines, and the focus is to maximize the exercise intensity by using as high an exercise load or weight as possible. By contrast, NEMEX consists of exercises that are low to moderate in intensity and emphasizes alignment, control, and stability of the movements.

To compare the two exercise strategies, Mr. Kjeldsen and fellow investigators recruited 160 participants at five hospitals and 10 physiotherapy clinics across three of five healthcare regions in Denmark.

For inclusion in the trial, the participants had to have a clinical diagnosis of hip OA, be older than 45 years, and experience pain during activity in one or both hips that was rated as 3 or higher on a 10-point numerical rating scale. Participants also had to have no or less than 30 minutes of hip joint stiffness in the morning as well as no surgery involving the lower extremities in the previous 6 months. 

Participants were then randomized to undertake the PRT (n = 82) or NEMEX (n = 78) program, delivered as two physiotherapist-led group sessions every week for 12 weeks. Exercise sessions were held at least 72 hours apart and consisted of a 10-minute warm-up on an exercise bike and then 50 minutes of PRT or NEMEX. PRT consisted of five generic resistance-based exercises targeting hip and knee joint muscles and NEMEX consisted of 10 exercises that increased in difficulty by varying the number, direction, speed, and surface of the movements performed.
 

Dead Heat Between PRT and NEMEX

The primary endpoint was the 30s-CST, which counted the number of times participants could stand from a seated position in 30 seconds. Participants in the PRT and NEMEX groups were able to do this maneuver a respective 11.3 and 11.6 times at baseline and 12.8 and 13.1 times after completion of the exercise programs. 

Other functional performance tests included a 40-m fast-paced walk, a nine-step timed stair climb, leg extensor power in the affected and unaffected limb, and a unilateral single repetition leg press. None of these showed a statistically significant benefit of PRT over NEMEX, or vice versa.

HOOS pain scores at baseline and 12 weeks for PRT were a respective 57.5 and 66.1, representing an overall 8.6-point increase, and for NEMEX they were 58.9 and 68.2, giving a 9.3-point increase, meaning there was only a -0.7 mean change when comparing the two groups.

Corresponding baseline and 12-week HOOS QOL scores for PRT were 43.7 and 51.7; for NEMEX, they were 47.1 and 52.8 thus giving 8.0- and 5.7-point increases and a 2.3 difference in change between the groups. Again, this wasn’t quite enough to show a clinically meaningful effect.
 

Future Steps

“The effect of exercise seems to be at its highest at 3-4 months when you implement exercise, so we compared the effects of the exercises at the time when they are probably going to be at their highest,” Mr. Kjeldsen explained. He said the research team also plans to look at what happens after 1 year of follow-up.

“The key take home message is that patients can be encouraged to pick the type of exercise that they find the most enjoyable, or the type that is available to them,” Mr. Kjeldsen suggested. 

Stephanie Chang, MD, MPH, who is the Deputy Editor of Annals of Internal Medicine and practices in Rockville, Maryland, commented on the paper to this news organization. “In this small study, we learned that exercises to strengthen lower extremity muscles did not improve pain or function any more than exercises for core stability and balance,” she said.

Dr. Chang pointed out that there was variance in the levels of activity that people already undertook at baseline: 40% of the PRT group and 41% of the NEMEX group already did 150 minutes or more of moderate intensity physical activity. 

“It’s possible that benefit or differences between interventions would be greater in people with different levels of baseline activity or even in those with different osteoarthritis severity,” she said. 

“In the meantime,” Dr. Chang added, “with the findings from this study, I would feel comfortable advising my patients with hip osteoarthritis to engage in whichever type of exercise they prefer — whether that exercise focuses on core strengthening and balance or on specific lower extremity muscle strengthening.”

The trial was funded by the Independent Research Fund Denmark, the Physiotherapy Practice Foundation, the Health Foundation, Aarhus University, Region Zealand, the Association of Danish Physiotherapists, Andelsfonden, and Hede Nielsens Family Foundation. Mr. Kjeldsen and Dr. Chang report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Progressive resistance training (PRT) and neuromuscular exercise (NEMEX) programs result in similar improvements in hip function, pain, and hip-related quality of life (QOL) in people with osteoarthritis (OA), according to the results of a randomized controlled trial.

At the end of the 12-week exercise period, both interventions yielded changes from baseline on the 30-second chair stand test (30s-CST) that were below the threshold for a major clinical effect. 

Mean changes in the Hip Disability and Osteoarthritis Outcome Score (HOOS) pain subscale and HOOS QOL score were also similar among the participants, regardless of which exercise program they had been assigned to.

“The lack of superiority of PRT for increasing muscle strength and power is surprising given the principle of specificity (higher-intensity resistance training yields greater improvements in maximal muscle strength),” according to the Danish researchers who reported the results online today in Annals of Internal Medicine.

“However, the point estimates only showed modest and uncertain superiority of PRT for increasing muscle strength and power and no differences for any functional performance tests or self-reported physical function,” they added.
 

The Power of Exercise

Worldwide, most clinical guidelines recommend exercise as a first-line conservative treatment option in both hip and knee OA. However, there is not much evidence to help guide healthcare practitioners in deciding which type of exercises to use with their patients, Troels Kjeldsen, MSc, the principal investigator for the study, told this news organization.

“Neuromuscular exercise is a very commonly used exercise program in clinical practice, but, to our knowledge, it has never been compared to another type of exercise in hip OA,” observed Mr. Kjeldsen, who is a PhD student in the department of orthopedic surgery at Aarhus University Hospital, Aarhus, Denmark.

“Each year, many thousands of patients are referred to having neuromuscular exercise therapy with a physiotherapist,” Mr. Kjeldsen said. “So, we thought it would be worthwhile to compare it to PRT, another promising exercise type, to see if it really did perform as well as I think most people thought it did,” he added.
 

Comparing the Two Exercise Programs

PRT and NEMEX are two different types of exercise programs. PRT involves using resistance-training machines, and the focus is to maximize the exercise intensity by using as high an exercise load or weight as possible. By contrast, NEMEX consists of exercises that are low to moderate in intensity and emphasizes alignment, control, and stability of the movements.

To compare the two exercise strategies, Mr. Kjeldsen and fellow investigators recruited 160 participants at five hospitals and 10 physiotherapy clinics across three of five healthcare regions in Denmark.

For inclusion in the trial, the participants had to have a clinical diagnosis of hip OA, be older than 45 years, and experience pain during activity in one or both hips that was rated as 3 or higher on a 10-point numerical rating scale. Participants also had to have no or less than 30 minutes of hip joint stiffness in the morning as well as no surgery involving the lower extremities in the previous 6 months. 

Participants were then randomized to undertake the PRT (n = 82) or NEMEX (n = 78) program, delivered as two physiotherapist-led group sessions every week for 12 weeks. Exercise sessions were held at least 72 hours apart and consisted of a 10-minute warm-up on an exercise bike and then 50 minutes of PRT or NEMEX. PRT consisted of five generic resistance-based exercises targeting hip and knee joint muscles and NEMEX consisted of 10 exercises that increased in difficulty by varying the number, direction, speed, and surface of the movements performed.
 

Dead Heat Between PRT and NEMEX

The primary endpoint was the 30s-CST, which counted the number of times participants could stand from a seated position in 30 seconds. Participants in the PRT and NEMEX groups were able to do this maneuver a respective 11.3 and 11.6 times at baseline and 12.8 and 13.1 times after completion of the exercise programs. 

Other functional performance tests included a 40-m fast-paced walk, a nine-step timed stair climb, leg extensor power in the affected and unaffected limb, and a unilateral single repetition leg press. None of these showed a statistically significant benefit of PRT over NEMEX, or vice versa.

HOOS pain scores at baseline and 12 weeks for PRT were a respective 57.5 and 66.1, representing an overall 8.6-point increase, and for NEMEX they were 58.9 and 68.2, giving a 9.3-point increase, meaning there was only a -0.7 mean change when comparing the two groups.

Corresponding baseline and 12-week HOOS QOL scores for PRT were 43.7 and 51.7; for NEMEX, they were 47.1 and 52.8 thus giving 8.0- and 5.7-point increases and a 2.3 difference in change between the groups. Again, this wasn’t quite enough to show a clinically meaningful effect.
 

Future Steps

“The effect of exercise seems to be at its highest at 3-4 months when you implement exercise, so we compared the effects of the exercises at the time when they are probably going to be at their highest,” Mr. Kjeldsen explained. He said the research team also plans to look at what happens after 1 year of follow-up.

“The key take home message is that patients can be encouraged to pick the type of exercise that they find the most enjoyable, or the type that is available to them,” Mr. Kjeldsen suggested. 

Stephanie Chang, MD, MPH, who is the Deputy Editor of Annals of Internal Medicine and practices in Rockville, Maryland, commented on the paper to this news organization. “In this small study, we learned that exercises to strengthen lower extremity muscles did not improve pain or function any more than exercises for core stability and balance,” she said.

Dr. Chang pointed out that there was variance in the levels of activity that people already undertook at baseline: 40% of the PRT group and 41% of the NEMEX group already did 150 minutes or more of moderate intensity physical activity. 

“It’s possible that benefit or differences between interventions would be greater in people with different levels of baseline activity or even in those with different osteoarthritis severity,” she said. 

“In the meantime,” Dr. Chang added, “with the findings from this study, I would feel comfortable advising my patients with hip osteoarthritis to engage in whichever type of exercise they prefer — whether that exercise focuses on core strengthening and balance or on specific lower extremity muscle strengthening.”

The trial was funded by the Independent Research Fund Denmark, the Physiotherapy Practice Foundation, the Health Foundation, Aarhus University, Region Zealand, the Association of Danish Physiotherapists, Andelsfonden, and Hede Nielsens Family Foundation. Mr. Kjeldsen and Dr. Chang report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Progressive resistance training (PRT) and neuromuscular exercise (NEMEX) programs result in similar improvements in hip function, pain, and hip-related quality of life (QOL) in people with osteoarthritis (OA), according to the results of a randomized controlled trial.

At the end of the 12-week exercise period, both interventions yielded changes from baseline on the 30-second chair stand test (30s-CST) that were below the threshold for a major clinical effect. 

Mean changes in the Hip Disability and Osteoarthritis Outcome Score (HOOS) pain subscale and HOOS QOL score were also similar among the participants, regardless of which exercise program they had been assigned to.

“The lack of superiority of PRT for increasing muscle strength and power is surprising given the principle of specificity (higher-intensity resistance training yields greater improvements in maximal muscle strength),” according to the Danish researchers who reported the results online today in Annals of Internal Medicine.

“However, the point estimates only showed modest and uncertain superiority of PRT for increasing muscle strength and power and no differences for any functional performance tests or self-reported physical function,” they added.
 

The Power of Exercise

Worldwide, most clinical guidelines recommend exercise as a first-line conservative treatment option in both hip and knee OA. However, there is not much evidence to help guide healthcare practitioners in deciding which type of exercises to use with their patients, Troels Kjeldsen, MSc, the principal investigator for the study, told this news organization.

“Neuromuscular exercise is a very commonly used exercise program in clinical practice, but, to our knowledge, it has never been compared to another type of exercise in hip OA,” observed Mr. Kjeldsen, who is a PhD student in the department of orthopedic surgery at Aarhus University Hospital, Aarhus, Denmark.

“Each year, many thousands of patients are referred to having neuromuscular exercise therapy with a physiotherapist,” Mr. Kjeldsen said. “So, we thought it would be worthwhile to compare it to PRT, another promising exercise type, to see if it really did perform as well as I think most people thought it did,” he added.
 

Comparing the Two Exercise Programs

PRT and NEMEX are two different types of exercise programs. PRT involves using resistance-training machines, and the focus is to maximize the exercise intensity by using as high an exercise load or weight as possible. By contrast, NEMEX consists of exercises that are low to moderate in intensity and emphasizes alignment, control, and stability of the movements.

To compare the two exercise strategies, Mr. Kjeldsen and fellow investigators recruited 160 participants at five hospitals and 10 physiotherapy clinics across three of five healthcare regions in Denmark.

For inclusion in the trial, the participants had to have a clinical diagnosis of hip OA, be older than 45 years, and experience pain during activity in one or both hips that was rated as 3 or higher on a 10-point numerical rating scale. Participants also had to have no or less than 30 minutes of hip joint stiffness in the morning as well as no surgery involving the lower extremities in the previous 6 months. 

Participants were then randomized to undertake the PRT (n = 82) or NEMEX (n = 78) program, delivered as two physiotherapist-led group sessions every week for 12 weeks. Exercise sessions were held at least 72 hours apart and consisted of a 10-minute warm-up on an exercise bike and then 50 minutes of PRT or NEMEX. PRT consisted of five generic resistance-based exercises targeting hip and knee joint muscles and NEMEX consisted of 10 exercises that increased in difficulty by varying the number, direction, speed, and surface of the movements performed.
 

Dead Heat Between PRT and NEMEX

The primary endpoint was the 30s-CST, which counted the number of times participants could stand from a seated position in 30 seconds. Participants in the PRT and NEMEX groups were able to do this maneuver a respective 11.3 and 11.6 times at baseline and 12.8 and 13.1 times after completion of the exercise programs. 

Other functional performance tests included a 40-m fast-paced walk, a nine-step timed stair climb, leg extensor power in the affected and unaffected limb, and a unilateral single repetition leg press. None of these showed a statistically significant benefit of PRT over NEMEX, or vice versa.

HOOS pain scores at baseline and 12 weeks for PRT were a respective 57.5 and 66.1, representing an overall 8.6-point increase, and for NEMEX they were 58.9 and 68.2, giving a 9.3-point increase, meaning there was only a -0.7 mean change when comparing the two groups.

Corresponding baseline and 12-week HOOS QOL scores for PRT were 43.7 and 51.7; for NEMEX, they were 47.1 and 52.8 thus giving 8.0- and 5.7-point increases and a 2.3 difference in change between the groups. Again, this wasn’t quite enough to show a clinically meaningful effect.
 

Future Steps

“The effect of exercise seems to be at its highest at 3-4 months when you implement exercise, so we compared the effects of the exercises at the time when they are probably going to be at their highest,” Mr. Kjeldsen explained. He said the research team also plans to look at what happens after 1 year of follow-up.

“The key take home message is that patients can be encouraged to pick the type of exercise that they find the most enjoyable, or the type that is available to them,” Mr. Kjeldsen suggested. 

Stephanie Chang, MD, MPH, who is the Deputy Editor of Annals of Internal Medicine and practices in Rockville, Maryland, commented on the paper to this news organization. “In this small study, we learned that exercises to strengthen lower extremity muscles did not improve pain or function any more than exercises for core stability and balance,” she said.

Dr. Chang pointed out that there was variance in the levels of activity that people already undertook at baseline: 40% of the PRT group and 41% of the NEMEX group already did 150 minutes or more of moderate intensity physical activity. 

“It’s possible that benefit or differences between interventions would be greater in people with different levels of baseline activity or even in those with different osteoarthritis severity,” she said. 

“In the meantime,” Dr. Chang added, “with the findings from this study, I would feel comfortable advising my patients with hip osteoarthritis to engage in whichever type of exercise they prefer — whether that exercise focuses on core strengthening and balance or on specific lower extremity muscle strengthening.”

The trial was funded by the Independent Research Fund Denmark, the Physiotherapy Practice Foundation, the Health Foundation, Aarhus University, Region Zealand, the Association of Danish Physiotherapists, Andelsfonden, and Hede Nielsens Family Foundation. Mr. Kjeldsen and Dr. Chang report no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Both labial and parotid salivary glands can be used for the diagnosis of Sjögren syndrome (SjS), as their biopsies show largely similar histopathologic features in patients with sicca complaints suspected of having SjS.

METHODOLOGY:

• While a labial gland biopsy is the conventional method for diagnosing SjS, a biopsy of the parotid gland is preferable, as it allows for repeat measurements and increases the possibility of finding a mucosa-associated lymphoid tissue lymphoma.
• In this prospective study, researchers compared the focus score (FS) and other histopathologic features of SjS between paired labial and parotid salivary gland biopsies in a diagnostic cohort of patients with sicca suspected of having SjS.
• Labial and parotid gland biopsies were simultaneously obtained under local infiltration anesthesia in 99 patients with oral and/or ocular sicca complaints at the University Medical Center Groningen, Groningen, the Netherlands, between 2014 and 2017.
• FS is defined as the number of foci per 4 mm2 of salivary gland tissue. An FS ≥ 1 indicates a positive diagnosis of SjS.
• On the basis of an expert opinion of three experienced rheumatologists, 36 patients were diagnosed with SjS, and 63 were diagnosed with non-SjS sicca.

TAKEAWAY:

• The absolute agreement of various histopathologic features was high between labial and parotid biopsies, with values being 80% for FS, 89% for germinal centers, 84% for the immunoglobulin (Ig) A/IgG plasma cell shift, and 93% for pre-lymphoepithelial lesions.
• However, an FS ≥ 1 was more frequently seen in labial glands than in parotid glands (P = .012) in both the SjS and non-SjS sicca populations, indicating that labial gland biopsies show more inflammation irrespective of the presence of SjS.
• In patients with SjS, the absolute B-lymphocyte count, the number of germinal centers per mm², and the severity of pre-lymphoepithelial lesions were higher in parotid glands than in labial glands, revealing evident histopathologic signs of B-lymphocyte hyperactivity.

IN PRACTICE:

“The results of this study offer novel insights into the pathophysiology of pSS [primary Sjögren syndrome] and can be incorporated into guidelines for the histopathological analysis of salivary gland biopsies,” the authors wrote.

SOURCE:

This study, led by Uzma Nakshbandi, MD, Department of Reumatology & Clinical Immunology, University Medical Center Groningen, Groningen, the Netherlands, was published online in Rheumatology (Oxford).

LIMITATIONS:

This study did not discuss any limitations.

DISCLOSURES:

This study was funded by the National Institutes of Health. One of the authors disclosed serving as a consultant and scientific advisory board member for several pharmaceutical companies, as well as receiving speaker’s fees from some of them.

A version of this article appeared on Medscape.com.

TOPLINE:

Both labial and parotid salivary glands can be used for the diagnosis of Sjögren syndrome (SjS), as their biopsies show largely similar histopathologic features in patients with sicca complaints suspected of having SjS.

METHODOLOGY:

• While a labial gland biopsy is the conventional method for diagnosing SjS, a biopsy of the parotid gland is preferable, as it allows for repeat measurements and increases the possibility of finding a mucosa-associated lymphoid tissue lymphoma.
• In this prospective study, researchers compared the focus score (FS) and other histopathologic features of SjS between paired labial and parotid salivary gland biopsies in a diagnostic cohort of patients with sicca suspected of having SjS.
• Labial and parotid gland biopsies were simultaneously obtained under local infiltration anesthesia in 99 patients with oral and/or ocular sicca complaints at the University Medical Center Groningen, Groningen, the Netherlands, between 2014 and 2017.
• FS is defined as the number of foci per 4 mm2 of salivary gland tissue. An FS ≥ 1 indicates a positive diagnosis of SjS.
• On the basis of an expert opinion of three experienced rheumatologists, 36 patients were diagnosed with SjS, and 63 were diagnosed with non-SjS sicca.

TAKEAWAY:

• The absolute agreement of various histopathologic features was high between labial and parotid biopsies, with values being 80% for FS, 89% for germinal centers, 84% for the immunoglobulin (Ig) A/IgG plasma cell shift, and 93% for pre-lymphoepithelial lesions.
• However, an FS ≥ 1 was more frequently seen in labial glands than in parotid glands (P = .012) in both the SjS and non-SjS sicca populations, indicating that labial gland biopsies show more inflammation irrespective of the presence of SjS.
• In patients with SjS, the absolute B-lymphocyte count, the number of germinal centers per mm², and the severity of pre-lymphoepithelial lesions were higher in parotid glands than in labial glands, revealing evident histopathologic signs of B-lymphocyte hyperactivity.

IN PRACTICE:

“The results of this study offer novel insights into the pathophysiology of pSS [primary Sjögren syndrome] and can be incorporated into guidelines for the histopathological analysis of salivary gland biopsies,” the authors wrote.

SOURCE:

This study, led by Uzma Nakshbandi, MD, Department of Reumatology & Clinical Immunology, University Medical Center Groningen, Groningen, the Netherlands, was published online in Rheumatology (Oxford).

LIMITATIONS:

This study did not discuss any limitations.

DISCLOSURES:

This study was funded by the National Institutes of Health. One of the authors disclosed serving as a consultant and scientific advisory board member for several pharmaceutical companies, as well as receiving speaker’s fees from some of them.

A version of this article appeared on Medscape.com.

TOPLINE:

Both labial and parotid salivary glands can be used for the diagnosis of Sjögren syndrome (SjS), as their biopsies show largely similar histopathologic features in patients with sicca complaints suspected of having SjS.

METHODOLOGY:

• While a labial gland biopsy is the conventional method for diagnosing SjS, a biopsy of the parotid gland is preferable, as it allows for repeat measurements and increases the possibility of finding a mucosa-associated lymphoid tissue lymphoma.
• In this prospective study, researchers compared the focus score (FS) and other histopathologic features of SjS between paired labial and parotid salivary gland biopsies in a diagnostic cohort of patients with sicca suspected of having SjS.
• Labial and parotid gland biopsies were simultaneously obtained under local infiltration anesthesia in 99 patients with oral and/or ocular sicca complaints at the University Medical Center Groningen, Groningen, the Netherlands, between 2014 and 2017.
• FS is defined as the number of foci per 4 mm2 of salivary gland tissue. An FS ≥ 1 indicates a positive diagnosis of SjS.
• On the basis of an expert opinion of three experienced rheumatologists, 36 patients were diagnosed with SjS, and 63 were diagnosed with non-SjS sicca.

TAKEAWAY:

• The absolute agreement of various histopathologic features was high between labial and parotid biopsies, with values being 80% for FS, 89% for germinal centers, 84% for the immunoglobulin (Ig) A/IgG plasma cell shift, and 93% for pre-lymphoepithelial lesions.
• However, an FS ≥ 1 was more frequently seen in labial glands than in parotid glands (P = .012) in both the SjS and non-SjS sicca populations, indicating that labial gland biopsies show more inflammation irrespective of the presence of SjS.
• In patients with SjS, the absolute B-lymphocyte count, the number of germinal centers per mm², and the severity of pre-lymphoepithelial lesions were higher in parotid glands than in labial glands, revealing evident histopathologic signs of B-lymphocyte hyperactivity.

IN PRACTICE:

“The results of this study offer novel insights into the pathophysiology of pSS [primary Sjögren syndrome] and can be incorporated into guidelines for the histopathological analysis of salivary gland biopsies,” the authors wrote.

SOURCE:

This study, led by Uzma Nakshbandi, MD, Department of Reumatology & Clinical Immunology, University Medical Center Groningen, Groningen, the Netherlands, was published online in Rheumatology (Oxford).

LIMITATIONS:

This study did not discuss any limitations.

DISCLOSURES:

This study was funded by the National Institutes of Health. One of the authors disclosed serving as a consultant and scientific advisory board member for several pharmaceutical companies, as well as receiving speaker’s fees from some of them.

A version of this article appeared on Medscape.com.

You are what you eat, as the adage goes. But a growing body of evidence indicates that it’s not just what and how much you eat that influence your health. How fast and when you eat also play a role.

Research now indicates that these two factors may affect the risk for gastrointestinal problems, obesity, and type 2 diabetes (T2D). Because meal timing and speed of consumption are modifiable, they present new opportunities to change patient behavior to help prevent and perhaps address these conditions.

Not So Fast

Most people are well acquainted with the short-term gastrointestinal effects of eating too quickly, which include indigestion, gas, bloating, and nausea. But regularly eating too fast can cause long-term consequences.

Obtaining a sense of fullness is key to staving off overeating and excess caloric intake. However, it takes approximately 20 minutes for the stomach to alert the brain to feelings of fullness. Eat too quickly and the fullness signaling might not set in until you’ve consumed more calories than intended. Research links this habit to excess body weight.

The practice also can lead to gastrointestinal diseases over the long term because overeating causes food to remain in the stomach longer, thus prolonging the time that the gastric mucosa is exposed to gastric acids.

A study of 10,893 adults in Korea reported that those with the fastest eating speed (< 5 min/meal) had a 1.7 times greater likelihood of endoscopic erosive gastritis than those with the slowest times (≥ 15 min/meal). Faster eating also was linked to increased risk for functional dyspepsia in a study involving 89 young-adult female military cadets in Korea with relatively controlled eating patterns.

On the extreme end of the spectrum, researchers who performed an assessment of a competitive speed eater speculated that the observed physiological accommodation required for the role (expanding the stomach to form a large flaccid sac) makes speed eaters vulnerable to morbid obesity, gastroparesis, intractable nausea and vomiting, and the need for gastrectomy.

The risk for metabolic changes and eventual development of T2D also appear to be linked to how quickly food is consumed.

Two clinical studies conducted in Japan — a cohort study of 2050 male factory workers and a nationwide study with 197,825 participants — identified a significant association between faster eating and T2D and insulin resistance. A case-control study involving 234 patients with new onset T2D and 468 controls from Lithuania linked faster eating to a greater than twofold risk for T2D. And a Chinese cross-sectional study of 7972 adults indicated that faster eating significantly increased the risk for metabolic syndrome, elevated blood pressure, and central obesity in adults.

Various hypotheses have been proposed to explain why fast eating may upset metabolic processes, including a delayed sense of fullness contributing to spiking postprandial glucose levels, lack of time for mastication causing higher glucose concentrations, and the triggering of specific cytokines (eg, interleukin-1 beta and interleukin-6) that lead to insulin resistance. It is also possible that the association is the result of people who eat quickly having relatively higher body weights, which translates to a higher risk for T2D.

However, there’s an opportunity in the association of rapid meal consumption with gastrointestinal and metabolic diseases, as people can slow the speed at which they eat so they feel full before they overeat.

A 2019 study in which 21 participants were instructed to eat a 600-kcal meal at a “normal” or “slow” pace (6 minutes or 24 minutes) found that the latter group reported feeling fuller while consuming fewer calories.

This approach may not work for all patients, however. There’s evidence to suggest that tactics to slow down eating may not limit the energy intake of those who are already overweight or obese.

Patients with obesity may physiologically differ in their processing of food, according to Michael Camilleri, MD, consultant in the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester, Minnesota.

“We have demonstrated that about 20%-25% of people with obesity actually have rapid gastric emptying,” he told this news organization. “As a result, they don’t feel full after they eat a meal and that might impact the total volume of food that they eat before they really feel full.”

The Ideal Time to Eat

It’s not only the speed at which individuals eat that may influence outcomes but when they take their meals. Research indicates that eating earlier in the day to align meals with the body’s circadian rhythms in metabolism offers health benefits.

“The focus would be to eat a meal that syncs during those daytime hours,” Collin Popp, PhD, MS, RD, a research scientist at the NYU Grossman School of Medicine in New York, told this news organization. “I typically suggest patients have their largest meal in the morning, whether that’s a large or medium-sized breakfast, or a big lunch.”

A recent cross-sectional study of 2050 participants found that having the largest meal at lunch protected against obesity (odds ratio [OR], 0.71), whereas having it at dinner increased the risk for obesity (OR, 1.67) and led to higher body mass index.

Consuming the majority of calories in meals earlier in the day may have metabolic health benefits, as well.

A 2015 randomized controlled trial involving 18 adults with obesity and T2D found that eating a high-energy breakfast and a low-energy dinner leads to reduced hyperglycemia throughout the day compared with eating a low-energy breakfast and a high-energy dinner.

Time-restricted eating (TRE), a form of intermittent fasting, also can improve metabolic health depending on the time of day.

A 2023 meta-analysis found that TRE was more effective at reducing fasting glucose levels in participants who were overweight and obese if done earlier rather than later in the day. Similarly, a 2022 study involving 82 healthy patients without diabetes or obesity found that early TRE was more effective than mid-day TRE at improving insulin sensitivity and that it improved fasting glucose and reduced total body mass and adiposity, while mid-day TRE did not.

A study that analyzed the effects of TRE in eight adult men with overweight and prediabetes found “better insulin resistance when the window of food consumption was earlier in the day,» noted endocrinologist Beverly Tchang, MD, an assistant professor of clinical medicine at Weill Cornell Medicine with a focus on obesity medication.

Patients May Benefit From Behavioral Interventions

Patients potentially negatively affected by eating too quickly or at late hours may benefit from adopting behavioral interventions to address these tendencies. To determine if a patient is a candidate for such interventions, Dr. Popp recommends starting with a simple conversation.

“When I first meet patients, I always ask them to describe to me a typical day for how they eat — when they’re eating, what they’re eating, the food quality, who are they with — to see if there’s social aspects to it. Then try and make the recommendations based on that,” said Dr. Popp, whose work focuses on biobehavioral interventions for the treatment and prevention of obesity, T2D, and other cardiometabolic outcomes.

Dr. Tchang said she encourages her patients to be mindful of hunger and fullness cues.

“Eat if you’re hungry; don’t force yourself to eat if you’re not hungry,” she said. “If you’re not sure whether you’re hungry or not, speak to a doctor because this points to an abnormality in your appetite-regulation system, which can be helped with GLP-1 [glucagon-like peptide 1] receptor agonists.”

Adjusting what patients eat can help them improve their meal timing.

“For example, we know that a high-fiber diet or a diet that has a large amount of fat in it tends to empty from the stomach slower,” Dr. Camilleri said. “That might give a sensation of fullness that lasts longer and that might prevent, for instance, the ingestion of the next meal.”

Those trying to eat more slowly are advised to seek out foods that are hard in texture and minimally processed.

A study involving 50 patients with healthy weights found that hard foods are consumed more slowly than soft foods and that energy intake is lowest with hard, minimally processed foods. Combining hard-textured foods with explicit instructions to reduce eating speed has also been shown to be an effective strategy. For those inclined to seek out technology-based solution, evidence suggests that a self-monitoring wearable device can slow the eating rate.

Although the evidence is mounting that the timing and duration of meals have an impact on certain chronic diseases, clinicians should remember that these two factors are far from the most important contributors, Dr. Popp said.

“We also have to consider total caloric intake, food quality, sleep, alcohol use, smoking, and physical activity,” he said. “Meal timing should be considered as under the umbrella of health that is important for a lot of folks.”

A version of this article appeared on Medscape.com.

You are what you eat, as the adage goes. But a growing body of evidence indicates that it’s not just what and how much you eat that influence your health. How fast and when you eat also play a role.

Research now indicates that these two factors may affect the risk for gastrointestinal problems, obesity, and type 2 diabetes (T2D). Because meal timing and speed of consumption are modifiable, they present new opportunities to change patient behavior to help prevent and perhaps address these conditions.

Not So Fast

Most people are well acquainted with the short-term gastrointestinal effects of eating too quickly, which include indigestion, gas, bloating, and nausea. But regularly eating too fast can cause long-term consequences.

Obtaining a sense of fullness is key to staving off overeating and excess caloric intake. However, it takes approximately 20 minutes for the stomach to alert the brain to feelings of fullness. Eat too quickly and the fullness signaling might not set in until you’ve consumed more calories than intended. Research links this habit to excess body weight.

The practice also can lead to gastrointestinal diseases over the long term because overeating causes food to remain in the stomach longer, thus prolonging the time that the gastric mucosa is exposed to gastric acids.

A study of 10,893 adults in Korea reported that those with the fastest eating speed (< 5 min/meal) had a 1.7 times greater likelihood of endoscopic erosive gastritis than those with the slowest times (≥ 15 min/meal). Faster eating also was linked to increased risk for functional dyspepsia in a study involving 89 young-adult female military cadets in Korea with relatively controlled eating patterns.

On the extreme end of the spectrum, researchers who performed an assessment of a competitive speed eater speculated that the observed physiological accommodation required for the role (expanding the stomach to form a large flaccid sac) makes speed eaters vulnerable to morbid obesity, gastroparesis, intractable nausea and vomiting, and the need for gastrectomy.

The risk for metabolic changes and eventual development of T2D also appear to be linked to how quickly food is consumed.

Two clinical studies conducted in Japan — a cohort study of 2050 male factory workers and a nationwide study with 197,825 participants — identified a significant association between faster eating and T2D and insulin resistance. A case-control study involving 234 patients with new onset T2D and 468 controls from Lithuania linked faster eating to a greater than twofold risk for T2D. And a Chinese cross-sectional study of 7972 adults indicated that faster eating significantly increased the risk for metabolic syndrome, elevated blood pressure, and central obesity in adults.

Various hypotheses have been proposed to explain why fast eating may upset metabolic processes, including a delayed sense of fullness contributing to spiking postprandial glucose levels, lack of time for mastication causing higher glucose concentrations, and the triggering of specific cytokines (eg, interleukin-1 beta and interleukin-6) that lead to insulin resistance. It is also possible that the association is the result of people who eat quickly having relatively higher body weights, which translates to a higher risk for T2D.

However, there’s an opportunity in the association of rapid meal consumption with gastrointestinal and metabolic diseases, as people can slow the speed at which they eat so they feel full before they overeat.

A 2019 study in which 21 participants were instructed to eat a 600-kcal meal at a “normal” or “slow” pace (6 minutes or 24 minutes) found that the latter group reported feeling fuller while consuming fewer calories.

This approach may not work for all patients, however. There’s evidence to suggest that tactics to slow down eating may not limit the energy intake of those who are already overweight or obese.

Patients with obesity may physiologically differ in their processing of food, according to Michael Camilleri, MD, consultant in the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester, Minnesota.

“We have demonstrated that about 20%-25% of people with obesity actually have rapid gastric emptying,” he told this news organization. “As a result, they don’t feel full after they eat a meal and that might impact the total volume of food that they eat before they really feel full.”

The Ideal Time to Eat

It’s not only the speed at which individuals eat that may influence outcomes but when they take their meals. Research indicates that eating earlier in the day to align meals with the body’s circadian rhythms in metabolism offers health benefits.

“The focus would be to eat a meal that syncs during those daytime hours,” Collin Popp, PhD, MS, RD, a research scientist at the NYU Grossman School of Medicine in New York, told this news organization. “I typically suggest patients have their largest meal in the morning, whether that’s a large or medium-sized breakfast, or a big lunch.”

A recent cross-sectional study of 2050 participants found that having the largest meal at lunch protected against obesity (odds ratio [OR], 0.71), whereas having it at dinner increased the risk for obesity (OR, 1.67) and led to higher body mass index.

Consuming the majority of calories in meals earlier in the day may have metabolic health benefits, as well.

A 2015 randomized controlled trial involving 18 adults with obesity and T2D found that eating a high-energy breakfast and a low-energy dinner leads to reduced hyperglycemia throughout the day compared with eating a low-energy breakfast and a high-energy dinner.

Time-restricted eating (TRE), a form of intermittent fasting, also can improve metabolic health depending on the time of day.

A 2023 meta-analysis found that TRE was more effective at reducing fasting glucose levels in participants who were overweight and obese if done earlier rather than later in the day. Similarly, a 2022 study involving 82 healthy patients without diabetes or obesity found that early TRE was more effective than mid-day TRE at improving insulin sensitivity and that it improved fasting glucose and reduced total body mass and adiposity, while mid-day TRE did not.

A study that analyzed the effects of TRE in eight adult men with overweight and prediabetes found “better insulin resistance when the window of food consumption was earlier in the day,» noted endocrinologist Beverly Tchang, MD, an assistant professor of clinical medicine at Weill Cornell Medicine with a focus on obesity medication.

Patients May Benefit From Behavioral Interventions

Patients potentially negatively affected by eating too quickly or at late hours may benefit from adopting behavioral interventions to address these tendencies. To determine if a patient is a candidate for such interventions, Dr. Popp recommends starting with a simple conversation.

“When I first meet patients, I always ask them to describe to me a typical day for how they eat — when they’re eating, what they’re eating, the food quality, who are they with — to see if there’s social aspects to it. Then try and make the recommendations based on that,” said Dr. Popp, whose work focuses on biobehavioral interventions for the treatment and prevention of obesity, T2D, and other cardiometabolic outcomes.

Dr. Tchang said she encourages her patients to be mindful of hunger and fullness cues.

“Eat if you’re hungry; don’t force yourself to eat if you’re not hungry,” she said. “If you’re not sure whether you’re hungry or not, speak to a doctor because this points to an abnormality in your appetite-regulation system, which can be helped with GLP-1 [glucagon-like peptide 1] receptor agonists.”

Adjusting what patients eat can help them improve their meal timing.

“For example, we know that a high-fiber diet or a diet that has a large amount of fat in it tends to empty from the stomach slower,” Dr. Camilleri said. “That might give a sensation of fullness that lasts longer and that might prevent, for instance, the ingestion of the next meal.”

Those trying to eat more slowly are advised to seek out foods that are hard in texture and minimally processed.

A study involving 50 patients with healthy weights found that hard foods are consumed more slowly than soft foods and that energy intake is lowest with hard, minimally processed foods. Combining hard-textured foods with explicit instructions to reduce eating speed has also been shown to be an effective strategy. For those inclined to seek out technology-based solution, evidence suggests that a self-monitoring wearable device can slow the eating rate.

Although the evidence is mounting that the timing and duration of meals have an impact on certain chronic diseases, clinicians should remember that these two factors are far from the most important contributors, Dr. Popp said.

“We also have to consider total caloric intake, food quality, sleep, alcohol use, smoking, and physical activity,” he said. “Meal timing should be considered as under the umbrella of health that is important for a lot of folks.”

A version of this article appeared on Medscape.com.

You are what you eat, as the adage goes. But a growing body of evidence indicates that it’s not just what and how much you eat that influence your health. How fast and when you eat also play a role.

Research now indicates that these two factors may affect the risk for gastrointestinal problems, obesity, and type 2 diabetes (T2D). Because meal timing and speed of consumption are modifiable, they present new opportunities to change patient behavior to help prevent and perhaps address these conditions.

Not So Fast

Most people are well acquainted with the short-term gastrointestinal effects of eating too quickly, which include indigestion, gas, bloating, and nausea. But regularly eating too fast can cause long-term consequences.

Obtaining a sense of fullness is key to staving off overeating and excess caloric intake. However, it takes approximately 20 minutes for the stomach to alert the brain to feelings of fullness. Eat too quickly and the fullness signaling might not set in until you’ve consumed more calories than intended. Research links this habit to excess body weight.

The practice also can lead to gastrointestinal diseases over the long term because overeating causes food to remain in the stomach longer, thus prolonging the time that the gastric mucosa is exposed to gastric acids.

A study of 10,893 adults in Korea reported that those with the fastest eating speed (< 5 min/meal) had a 1.7 times greater likelihood of endoscopic erosive gastritis than those with the slowest times (≥ 15 min/meal). Faster eating also was linked to increased risk for functional dyspepsia in a study involving 89 young-adult female military cadets in Korea with relatively controlled eating patterns.

On the extreme end of the spectrum, researchers who performed an assessment of a competitive speed eater speculated that the observed physiological accommodation required for the role (expanding the stomach to form a large flaccid sac) makes speed eaters vulnerable to morbid obesity, gastroparesis, intractable nausea and vomiting, and the need for gastrectomy.

The risk for metabolic changes and eventual development of T2D also appear to be linked to how quickly food is consumed.

Two clinical studies conducted in Japan — a cohort study of 2050 male factory workers and a nationwide study with 197,825 participants — identified a significant association between faster eating and T2D and insulin resistance. A case-control study involving 234 patients with new onset T2D and 468 controls from Lithuania linked faster eating to a greater than twofold risk for T2D. And a Chinese cross-sectional study of 7972 adults indicated that faster eating significantly increased the risk for metabolic syndrome, elevated blood pressure, and central obesity in adults.

Various hypotheses have been proposed to explain why fast eating may upset metabolic processes, including a delayed sense of fullness contributing to spiking postprandial glucose levels, lack of time for mastication causing higher glucose concentrations, and the triggering of specific cytokines (eg, interleukin-1 beta and interleukin-6) that lead to insulin resistance. It is also possible that the association is the result of people who eat quickly having relatively higher body weights, which translates to a higher risk for T2D.

However, there’s an opportunity in the association of rapid meal consumption with gastrointestinal and metabolic diseases, as people can slow the speed at which they eat so they feel full before they overeat.

A 2019 study in which 21 participants were instructed to eat a 600-kcal meal at a “normal” or “slow” pace (6 minutes or 24 minutes) found that the latter group reported feeling fuller while consuming fewer calories.

This approach may not work for all patients, however. There’s evidence to suggest that tactics to slow down eating may not limit the energy intake of those who are already overweight or obese.

Patients with obesity may physiologically differ in their processing of food, according to Michael Camilleri, MD, consultant in the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester, Minnesota.

“We have demonstrated that about 20%-25% of people with obesity actually have rapid gastric emptying,” he told this news organization. “As a result, they don’t feel full after they eat a meal and that might impact the total volume of food that they eat before they really feel full.”

The Ideal Time to Eat

It’s not only the speed at which individuals eat that may influence outcomes but when they take their meals. Research indicates that eating earlier in the day to align meals with the body’s circadian rhythms in metabolism offers health benefits.

“The focus would be to eat a meal that syncs during those daytime hours,” Collin Popp, PhD, MS, RD, a research scientist at the NYU Grossman School of Medicine in New York, told this news organization. “I typically suggest patients have their largest meal in the morning, whether that’s a large or medium-sized breakfast, or a big lunch.”

A recent cross-sectional study of 2050 participants found that having the largest meal at lunch protected against obesity (odds ratio [OR], 0.71), whereas having it at dinner increased the risk for obesity (OR, 1.67) and led to higher body mass index.

Consuming the majority of calories in meals earlier in the day may have metabolic health benefits, as well.

A 2015 randomized controlled trial involving 18 adults with obesity and T2D found that eating a high-energy breakfast and a low-energy dinner leads to reduced hyperglycemia throughout the day compared with eating a low-energy breakfast and a high-energy dinner.

Time-restricted eating (TRE), a form of intermittent fasting, also can improve metabolic health depending on the time of day.

A 2023 meta-analysis found that TRE was more effective at reducing fasting glucose levels in participants who were overweight and obese if done earlier rather than later in the day. Similarly, a 2022 study involving 82 healthy patients without diabetes or obesity found that early TRE was more effective than mid-day TRE at improving insulin sensitivity and that it improved fasting glucose and reduced total body mass and adiposity, while mid-day TRE did not.

A study that analyzed the effects of TRE in eight adult men with overweight and prediabetes found “better insulin resistance when the window of food consumption was earlier in the day,» noted endocrinologist Beverly Tchang, MD, an assistant professor of clinical medicine at Weill Cornell Medicine with a focus on obesity medication.

Patients May Benefit From Behavioral Interventions

Patients potentially negatively affected by eating too quickly or at late hours may benefit from adopting behavioral interventions to address these tendencies. To determine if a patient is a candidate for such interventions, Dr. Popp recommends starting with a simple conversation.

“When I first meet patients, I always ask them to describe to me a typical day for how they eat — when they’re eating, what they’re eating, the food quality, who are they with — to see if there’s social aspects to it. Then try and make the recommendations based on that,” said Dr. Popp, whose work focuses on biobehavioral interventions for the treatment and prevention of obesity, T2D, and other cardiometabolic outcomes.

Dr. Tchang said she encourages her patients to be mindful of hunger and fullness cues.

“Eat if you’re hungry; don’t force yourself to eat if you’re not hungry,” she said. “If you’re not sure whether you’re hungry or not, speak to a doctor because this points to an abnormality in your appetite-regulation system, which can be helped with GLP-1 [glucagon-like peptide 1] receptor agonists.”

Adjusting what patients eat can help them improve their meal timing.

“For example, we know that a high-fiber diet or a diet that has a large amount of fat in it tends to empty from the stomach slower,” Dr. Camilleri said. “That might give a sensation of fullness that lasts longer and that might prevent, for instance, the ingestion of the next meal.”

Those trying to eat more slowly are advised to seek out foods that are hard in texture and minimally processed.

A study involving 50 patients with healthy weights found that hard foods are consumed more slowly than soft foods and that energy intake is lowest with hard, minimally processed foods. Combining hard-textured foods with explicit instructions to reduce eating speed has also been shown to be an effective strategy. For those inclined to seek out technology-based solution, evidence suggests that a self-monitoring wearable device can slow the eating rate.

Although the evidence is mounting that the timing and duration of meals have an impact on certain chronic diseases, clinicians should remember that these two factors are far from the most important contributors, Dr. Popp said.

“We also have to consider total caloric intake, food quality, sleep, alcohol use, smoking, and physical activity,” he said. “Meal timing should be considered as under the umbrella of health that is important for a lot of folks.”

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the launch of the first clinical trial for chimeric antigen receptor (CAR) T-cell therapy in children with systemic lupus erythematosus.

The trial, called Reversing Autoimmunity through Cell Therapy (REACT-01), will take place at Seattle Children’s Hospital in Washington State and is expected to begin this summer.

The CAR-T therapy will target CD19 positive B-cells, an approach that has had promising results in a small number of adult patients. While the FDA has approved a number of clinical trials using CAR-T therapy to treat autoimmune diseases in adults, this is the first authorization for a CAR T-cell therapy trial to treat autoimmune disease in children.

REACT-01 will enroll 12 individuals under 18 years of age, Shaun W. Jackson, MD, PhD, the principal investigator of the trial and attending physician in Pediatric Nephrology and Pediatric Rheumatology at Seattle Children’s Hospital, told this news organization. 

The trial will be initiated in separate phases, using three age cohorts. The first phase will enroll three individuals aged at least 17 years, before moving to the second phase and enrolling three individuals aged 12-17 years. Then, phase 3 will also include children aged 5-12 years.

To be eligible for the trial, participants must have failed at least two standard immunosuppressive therapies as well as have evidence of active lupus disease affecting a major organ system, such as the heart, lungs, and kidneys.

“Seattle Children’s Hospital will be the only site for this study, although patients can travel to Seattle to receive the therapy and then return back to their primary center for ongoing care,” Dr. Jackson said. 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the launch of the first clinical trial for chimeric antigen receptor (CAR) T-cell therapy in children with systemic lupus erythematosus.

The trial, called Reversing Autoimmunity through Cell Therapy (REACT-01), will take place at Seattle Children’s Hospital in Washington State and is expected to begin this summer.

The CAR-T therapy will target CD19 positive B-cells, an approach that has had promising results in a small number of adult patients. While the FDA has approved a number of clinical trials using CAR-T therapy to treat autoimmune diseases in adults, this is the first authorization for a CAR T-cell therapy trial to treat autoimmune disease in children.

REACT-01 will enroll 12 individuals under 18 years of age, Shaun W. Jackson, MD, PhD, the principal investigator of the trial and attending physician in Pediatric Nephrology and Pediatric Rheumatology at Seattle Children’s Hospital, told this news organization. 

The trial will be initiated in separate phases, using three age cohorts. The first phase will enroll three individuals aged at least 17 years, before moving to the second phase and enrolling three individuals aged 12-17 years. Then, phase 3 will also include children aged 5-12 years.

To be eligible for the trial, participants must have failed at least two standard immunosuppressive therapies as well as have evidence of active lupus disease affecting a major organ system, such as the heart, lungs, and kidneys.

“Seattle Children’s Hospital will be the only site for this study, although patients can travel to Seattle to receive the therapy and then return back to their primary center for ongoing care,” Dr. Jackson said. 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the launch of the first clinical trial for chimeric antigen receptor (CAR) T-cell therapy in children with systemic lupus erythematosus.

The trial, called Reversing Autoimmunity through Cell Therapy (REACT-01), will take place at Seattle Children’s Hospital in Washington State and is expected to begin this summer.

The CAR-T therapy will target CD19 positive B-cells, an approach that has had promising results in a small number of adult patients. While the FDA has approved a number of clinical trials using CAR-T therapy to treat autoimmune diseases in adults, this is the first authorization for a CAR T-cell therapy trial to treat autoimmune disease in children.

REACT-01 will enroll 12 individuals under 18 years of age, Shaun W. Jackson, MD, PhD, the principal investigator of the trial and attending physician in Pediatric Nephrology and Pediatric Rheumatology at Seattle Children’s Hospital, told this news organization. 

The trial will be initiated in separate phases, using three age cohorts. The first phase will enroll three individuals aged at least 17 years, before moving to the second phase and enrolling three individuals aged 12-17 years. Then, phase 3 will also include children aged 5-12 years.

To be eligible for the trial, participants must have failed at least two standard immunosuppressive therapies as well as have evidence of active lupus disease affecting a major organ system, such as the heart, lungs, and kidneys.

“Seattle Children’s Hospital will be the only site for this study, although patients can travel to Seattle to receive the therapy and then return back to their primary center for ongoing care,” Dr. Jackson said. 

A version of this article appeared on Medscape.com.

Multitarget stool-based tests are showing promise for colorectal cancer (CRC) screening in average-risk individuals and could edge out the current standard fecal immunochemical test (FIT).

These new tests aren’t radical departures from the standard FIT. Like the standard test, the multitarget FIT uses antibodies to test for hemoglobin in stool samples. But these multitarget approaches take the standard FIT a step further by testing for additional DNA, RNA, or protein biomarkers associated with CRC to help improve early detection.

Currently, the US Preventive Services Task Force (USPSTF) recommends two FIT tests — standard FIT and stool FIT-DNA — as well as a third noninvasive CRC screening test, guaiac fecal occult blood test (gFOBT). gFOBT detects heme, a component of hemoglobin, through a chemical reaction.

But both standard FIT and stool FIT-DNA come with caveats. Compared to the standard test, FIT-DNA tends to be better at detecting traces of blood in the stool, and thus can uncover more instances of CRC or other advanced lesions. The flipside is that the DNA test also often leads to more false-positive findings.

In fact, the American College of Physicians does not recommend stool FIT-DNA for screening, citing issues such as cost — more than $600 per test vs about $30 for standard FIT — and the greater likelihood of false-positives compared with both standard FIT and gFOBT.

Given these trade-offs with current noninvasive screening options, developing a FIT option that can improve early detection of CRC and advanced precancerous lesions without increasing false-positives could make a big difference in outcomes. 

Three new noninvasive multitarget tests under investigation — an updated DNA-based test, Cologuard 2.0 (Exact Sciences; Madison, WI); an RNA-based test, ColoSense (Geneoscopy; St Louis, MO); and a protein-based test from CRCbioscreen (Amsterdam, the Netherlands) — may be able to do just that. 
 

Cologuard 2.0: Multitarget Stool DNA-Based Test

An updated version of the stool FIT-DNA is currently under development. Dubbed Next Generation Cologuard, or Cologuard 2.0, this multitarget test detects three novel methylated DNA markers along with fecal hemoglobin.

In a recent trial comparing Cologuard 2.0 vs standard FIT, 20,176 participants aged 40 years or older were screened with Cologuard 2.0 as well as standard FIT before they all also received a colonoscopy. The researchers compared findings with Cologuard 2.0 and standard FIT, which used a positivity cutoff ≥ 20 mcg hemoglobin/g feces. 

The researchers then assessed Cologuard 2.0’s sensitivity (a gauge of how well it detects disease that is truly present) and specificity (a measure of how well a test indicates the absence of disease when no disease is present) compared with standard FIT and the original Cologuard test.

Overall, Cologuard 2.0 demonstrated better sensitivity for CRC than did standard FIT (93.9% vs 67.3%, respectively) and for advanced precancerous lesions (43.4% vs 23.3%). The next-generation test, for instance, identified 92 of 98 participants with colonoscopy-confirmed CRC diagnoses vs 66 cases using standard FIT.

Compared with the original Cologuard, Cologuard 2.0’s sensitivity improved slightly for CRC, from 92% to 93.9%,; for advanced precancerous lesions, from 42% to 43.4%; and for high-grade dysplasia, from 69% to 75%. Specificity also improved with the latest version, from 87% to 90.6%. 

However, Cologuard 2.0’s specificity for advanced neoplasia was worse than that of standard FIT (90.6% vs 94.8%, respectively), which would increase the likelihood of false-positive findings.

Despite its lower specificity compared with standard FIT, Cologuard 2.0 has several advantages. The test can identify more people with CRC and advanced precancerous lesions than the standard test and can lead to fewer false-positives than the original Cologuard test.

Cologuard maker Exact Sciences has submitted trial data to the US Food and Drug Administration (FDA) for approval.
 

Multitarget Stool RNA-Based Test

ColoSense, an RNA-based stool test, looks for eight RNA biomarkers associated with CRC. 

The company says that RNA-based testing has an advantage over DNA biomarker assays, such as the currently marketed Cologuard test, because it isn›t subject to the age-related changes in DNA methylation that can throw off the results from DNA assays. 

Like Cologuard 2.0, Geneoscopy’s Colosense test is under review by the FDA.

The data Geneoscopy submitted to the FDA came from the CRC-PREVENT trial, which included 8920 participants who were screened with both ColoSense and standard FIT before all had a colonoscopy. The participants ranged in age from 45 to 90 years, with 22% between 45 and 50 years old, a population recently added to the USPSTF screening recommendations. 

ColoSense showed higher sensitivity than standard FIT for the presence of CRC (94% vs 78%, respectively) and advanced adenomas (46% vs 29%). In the group aged 45-50 years, the RNA-based test had a sensitivity of 100% for CRC, correctly identifying all five people with colonoscopy-confirmed CRC, and 45% for advanced adenomas.

However, ColoSense was less specific than standard FIT compared with negative colonoscopy findings (88% vs 96%, respectively) and negative findings for advanced lesions or CRC (85.5% vs 94.9%); thus, it was more likely to lead to false-positive results.

Overall, the investigators said ColoSense is comparable to Cologuard — its chief market rival — in terms of sensitivity for CRC and advanced adenomas but has higher sensitivity for colorectal neoplasia in people aged 50 years or younger.
 

Multitarget Protein-Based Test

The multitarget protein-based FIT uses antibodies to test for two additional proteins: calprotectin, an inflammatory marker associated with CRC, and serpin family F member 2, a protease inhibitor thought to be upregulated in colon cancer. 

A 2021 study of 1284 patients found that the sensitivity of the multitarget protein-based test was 42.9% for advanced neoplasias compared with 37.3% with standard FIT. Its specificity was similar to that of standard FIT, at 96.6% for advanced neoplasias. 

In a more recent report published in The Lancet Oncology, the team modeled three scenarios comparing the two FIT tests. These scenarios used different cutoff values for a test to be positive for CRC or an advanced lesion.

Overall, the analysis included stool samples from 13,187 patients aged 55-75 years who were in the Netherlands’ national CRC screening program. Stool samples were evaluated with both the multitarget test and the standard FIT, using a positivity cutoff ≥ 47 mcg hemoglobin/g feces. Colonoscopy data were available for only 1270 participants. 

In scenario 1, the multitarget test had a lower threshold for a positive test and consequently identified more precancerous lesions than the standard FIT (828 vs 354, respectively). The multitarget FIT identified a few more CRC cases: Of 29 colonoscopy-confirmed CRC cases, the multitarget FIT identified 26 vs 23 with standard FIT. 

But the multitarget FIT also had more than double the number of false-positives than the standard FIT (347 vs 161, respectively).

Perhaps the most telling comparison occurred in scenario 2, with both tests set at the same low positivity threshold to minimize false-positives.

As expected, the two tests had similar positivity rates for advanced lesions, with the multitarget test correctly identifying 22 of 29 people with CRC, one fewer than the standard test. The protein-based test identified slightly more people with advanced lesions (156 vs 136 with the standard test), leading to a higher sensitivity for advanced lesions. 

Most notably, the protein-based test resulted in fewer false-positives than did the standard test (295 vs 311, respectively) , resulting in a slightly higher specificity.

In this scenario, “a single screening round might not have the biggest impact on cancer incidence and mortality,” the authors said, but the higher detection rate would still accumulate over 20 years of testing. The authors estimated that, under this scenario, substituting the multitarget FIT for the standard test in the Netherlands’ CRC screening program could reduce CRC incidence by 5% and CRC mortality by 4%.

Gerrit Meijer, MD, PhD, a pathologist at the Netherlands Cancer Institute, and colleagues recently launched a company called CRCbioscreen to commercialize this multitarget FIT for large-scale programs. The company›s priority is to develop and validate a clinical-grade test to sell to federal governments with national screening programs, such as those throughout Europe, Australia, and Asia, Dr. Meijer told this news organization. Dr. Meijer expects this process will take about 4 years.

The test will be developed for the US market, but with no nationwide screening program in the United States, future availability will depend on interest from providers and institutions, noted Dr. Meijer, who is also chief scientific officer at CRCbioscreen.

Overall, these three new multitarget stool-based CRC screening tests could help catch more cancers and advanced precancerous lesions. And, if the tests have a high enough specificity, a negative test result could also allow people to forgo screening colonoscopy. 

Still, people with a positive FIT finding would require follow-up colonoscopy, but about 10% of patients decline colonoscopy following an abnormal FIT, Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Health in Murray, Utah, told this news organization last year. That means that even if precancerous lesions and CRC are being caught earlier, treatment can’t be started unless people follow through with colonoscopy.

A version of this article appeared on Medscape.com.

Multitarget stool-based tests are showing promise for colorectal cancer (CRC) screening in average-risk individuals and could edge out the current standard fecal immunochemical test (FIT).

These new tests aren’t radical departures from the standard FIT. Like the standard test, the multitarget FIT uses antibodies to test for hemoglobin in stool samples. But these multitarget approaches take the standard FIT a step further by testing for additional DNA, RNA, or protein biomarkers associated with CRC to help improve early detection.

Currently, the US Preventive Services Task Force (USPSTF) recommends two FIT tests — standard FIT and stool FIT-DNA — as well as a third noninvasive CRC screening test, guaiac fecal occult blood test (gFOBT). gFOBT detects heme, a component of hemoglobin, through a chemical reaction.

But both standard FIT and stool FIT-DNA come with caveats. Compared to the standard test, FIT-DNA tends to be better at detecting traces of blood in the stool, and thus can uncover more instances of CRC or other advanced lesions. The flipside is that the DNA test also often leads to more false-positive findings.

In fact, the American College of Physicians does not recommend stool FIT-DNA for screening, citing issues such as cost — more than $600 per test vs about $30 for standard FIT — and the greater likelihood of false-positives compared with both standard FIT and gFOBT.

Given these trade-offs with current noninvasive screening options, developing a FIT option that can improve early detection of CRC and advanced precancerous lesions without increasing false-positives could make a big difference in outcomes. 

Three new noninvasive multitarget tests under investigation — an updated DNA-based test, Cologuard 2.0 (Exact Sciences; Madison, WI); an RNA-based test, ColoSense (Geneoscopy; St Louis, MO); and a protein-based test from CRCbioscreen (Amsterdam, the Netherlands) — may be able to do just that. 
 

Cologuard 2.0: Multitarget Stool DNA-Based Test

An updated version of the stool FIT-DNA is currently under development. Dubbed Next Generation Cologuard, or Cologuard 2.0, this multitarget test detects three novel methylated DNA markers along with fecal hemoglobin.

In a recent trial comparing Cologuard 2.0 vs standard FIT, 20,176 participants aged 40 years or older were screened with Cologuard 2.0 as well as standard FIT before they all also received a colonoscopy. The researchers compared findings with Cologuard 2.0 and standard FIT, which used a positivity cutoff ≥ 20 mcg hemoglobin/g feces. 

The researchers then assessed Cologuard 2.0’s sensitivity (a gauge of how well it detects disease that is truly present) and specificity (a measure of how well a test indicates the absence of disease when no disease is present) compared with standard FIT and the original Cologuard test.

Overall, Cologuard 2.0 demonstrated better sensitivity for CRC than did standard FIT (93.9% vs 67.3%, respectively) and for advanced precancerous lesions (43.4% vs 23.3%). The next-generation test, for instance, identified 92 of 98 participants with colonoscopy-confirmed CRC diagnoses vs 66 cases using standard FIT.

Compared with the original Cologuard, Cologuard 2.0’s sensitivity improved slightly for CRC, from 92% to 93.9%,; for advanced precancerous lesions, from 42% to 43.4%; and for high-grade dysplasia, from 69% to 75%. Specificity also improved with the latest version, from 87% to 90.6%. 

However, Cologuard 2.0’s specificity for advanced neoplasia was worse than that of standard FIT (90.6% vs 94.8%, respectively), which would increase the likelihood of false-positive findings.

Despite its lower specificity compared with standard FIT, Cologuard 2.0 has several advantages. The test can identify more people with CRC and advanced precancerous lesions than the standard test and can lead to fewer false-positives than the original Cologuard test.

Cologuard maker Exact Sciences has submitted trial data to the US Food and Drug Administration (FDA) for approval.
 

Multitarget Stool RNA-Based Test

ColoSense, an RNA-based stool test, looks for eight RNA biomarkers associated with CRC. 

The company says that RNA-based testing has an advantage over DNA biomarker assays, such as the currently marketed Cologuard test, because it isn›t subject to the age-related changes in DNA methylation that can throw off the results from DNA assays. 

Like Cologuard 2.0, Geneoscopy’s Colosense test is under review by the FDA.

The data Geneoscopy submitted to the FDA came from the CRC-PREVENT trial, which included 8920 participants who were screened with both ColoSense and standard FIT before all had a colonoscopy. The participants ranged in age from 45 to 90 years, with 22% between 45 and 50 years old, a population recently added to the USPSTF screening recommendations. 

ColoSense showed higher sensitivity than standard FIT for the presence of CRC (94% vs 78%, respectively) and advanced adenomas (46% vs 29%). In the group aged 45-50 years, the RNA-based test had a sensitivity of 100% for CRC, correctly identifying all five people with colonoscopy-confirmed CRC, and 45% for advanced adenomas.

However, ColoSense was less specific than standard FIT compared with negative colonoscopy findings (88% vs 96%, respectively) and negative findings for advanced lesions or CRC (85.5% vs 94.9%); thus, it was more likely to lead to false-positive results.

Overall, the investigators said ColoSense is comparable to Cologuard — its chief market rival — in terms of sensitivity for CRC and advanced adenomas but has higher sensitivity for colorectal neoplasia in people aged 50 years or younger.
 

Multitarget Protein-Based Test

The multitarget protein-based FIT uses antibodies to test for two additional proteins: calprotectin, an inflammatory marker associated with CRC, and serpin family F member 2, a protease inhibitor thought to be upregulated in colon cancer. 

A 2021 study of 1284 patients found that the sensitivity of the multitarget protein-based test was 42.9% for advanced neoplasias compared with 37.3% with standard FIT. Its specificity was similar to that of standard FIT, at 96.6% for advanced neoplasias. 

In a more recent report published in The Lancet Oncology, the team modeled three scenarios comparing the two FIT tests. These scenarios used different cutoff values for a test to be positive for CRC or an advanced lesion.

Overall, the analysis included stool samples from 13,187 patients aged 55-75 years who were in the Netherlands’ national CRC screening program. Stool samples were evaluated with both the multitarget test and the standard FIT, using a positivity cutoff ≥ 47 mcg hemoglobin/g feces. Colonoscopy data were available for only 1270 participants. 

In scenario 1, the multitarget test had a lower threshold for a positive test and consequently identified more precancerous lesions than the standard FIT (828 vs 354, respectively). The multitarget FIT identified a few more CRC cases: Of 29 colonoscopy-confirmed CRC cases, the multitarget FIT identified 26 vs 23 with standard FIT. 

But the multitarget FIT also had more than double the number of false-positives than the standard FIT (347 vs 161, respectively).

Perhaps the most telling comparison occurred in scenario 2, with both tests set at the same low positivity threshold to minimize false-positives.

As expected, the two tests had similar positivity rates for advanced lesions, with the multitarget test correctly identifying 22 of 29 people with CRC, one fewer than the standard test. The protein-based test identified slightly more people with advanced lesions (156 vs 136 with the standard test), leading to a higher sensitivity for advanced lesions. 

Most notably, the protein-based test resulted in fewer false-positives than did the standard test (295 vs 311, respectively) , resulting in a slightly higher specificity.

In this scenario, “a single screening round might not have the biggest impact on cancer incidence and mortality,” the authors said, but the higher detection rate would still accumulate over 20 years of testing. The authors estimated that, under this scenario, substituting the multitarget FIT for the standard test in the Netherlands’ CRC screening program could reduce CRC incidence by 5% and CRC mortality by 4%.

Gerrit Meijer, MD, PhD, a pathologist at the Netherlands Cancer Institute, and colleagues recently launched a company called CRCbioscreen to commercialize this multitarget FIT for large-scale programs. The company›s priority is to develop and validate a clinical-grade test to sell to federal governments with national screening programs, such as those throughout Europe, Australia, and Asia, Dr. Meijer told this news organization. Dr. Meijer expects this process will take about 4 years.

The test will be developed for the US market, but with no nationwide screening program in the United States, future availability will depend on interest from providers and institutions, noted Dr. Meijer, who is also chief scientific officer at CRCbioscreen.

Overall, these three new multitarget stool-based CRC screening tests could help catch more cancers and advanced precancerous lesions. And, if the tests have a high enough specificity, a negative test result could also allow people to forgo screening colonoscopy. 

Still, people with a positive FIT finding would require follow-up colonoscopy, but about 10% of patients decline colonoscopy following an abnormal FIT, Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Health in Murray, Utah, told this news organization last year. That means that even if precancerous lesions and CRC are being caught earlier, treatment can’t be started unless people follow through with colonoscopy.

A version of this article appeared on Medscape.com.

Multitarget stool-based tests are showing promise for colorectal cancer (CRC) screening in average-risk individuals and could edge out the current standard fecal immunochemical test (FIT).

These new tests aren’t radical departures from the standard FIT. Like the standard test, the multitarget FIT uses antibodies to test for hemoglobin in stool samples. But these multitarget approaches take the standard FIT a step further by testing for additional DNA, RNA, or protein biomarkers associated with CRC to help improve early detection.

Currently, the US Preventive Services Task Force (USPSTF) recommends two FIT tests — standard FIT and stool FIT-DNA — as well as a third noninvasive CRC screening test, guaiac fecal occult blood test (gFOBT). gFOBT detects heme, a component of hemoglobin, through a chemical reaction.

But both standard FIT and stool FIT-DNA come with caveats. Compared to the standard test, FIT-DNA tends to be better at detecting traces of blood in the stool, and thus can uncover more instances of CRC or other advanced lesions. The flipside is that the DNA test also often leads to more false-positive findings.

In fact, the American College of Physicians does not recommend stool FIT-DNA for screening, citing issues such as cost — more than $600 per test vs about $30 for standard FIT — and the greater likelihood of false-positives compared with both standard FIT and gFOBT.

Given these trade-offs with current noninvasive screening options, developing a FIT option that can improve early detection of CRC and advanced precancerous lesions without increasing false-positives could make a big difference in outcomes. 

Three new noninvasive multitarget tests under investigation — an updated DNA-based test, Cologuard 2.0 (Exact Sciences; Madison, WI); an RNA-based test, ColoSense (Geneoscopy; St Louis, MO); and a protein-based test from CRCbioscreen (Amsterdam, the Netherlands) — may be able to do just that. 
 

Cologuard 2.0: Multitarget Stool DNA-Based Test

An updated version of the stool FIT-DNA is currently under development. Dubbed Next Generation Cologuard, or Cologuard 2.0, this multitarget test detects three novel methylated DNA markers along with fecal hemoglobin.

In a recent trial comparing Cologuard 2.0 vs standard FIT, 20,176 participants aged 40 years or older were screened with Cologuard 2.0 as well as standard FIT before they all also received a colonoscopy. The researchers compared findings with Cologuard 2.0 and standard FIT, which used a positivity cutoff ≥ 20 mcg hemoglobin/g feces. 

The researchers then assessed Cologuard 2.0’s sensitivity (a gauge of how well it detects disease that is truly present) and specificity (a measure of how well a test indicates the absence of disease when no disease is present) compared with standard FIT and the original Cologuard test.

Overall, Cologuard 2.0 demonstrated better sensitivity for CRC than did standard FIT (93.9% vs 67.3%, respectively) and for advanced precancerous lesions (43.4% vs 23.3%). The next-generation test, for instance, identified 92 of 98 participants with colonoscopy-confirmed CRC diagnoses vs 66 cases using standard FIT.

Compared with the original Cologuard, Cologuard 2.0’s sensitivity improved slightly for CRC, from 92% to 93.9%,; for advanced precancerous lesions, from 42% to 43.4%; and for high-grade dysplasia, from 69% to 75%. Specificity also improved with the latest version, from 87% to 90.6%. 

However, Cologuard 2.0’s specificity for advanced neoplasia was worse than that of standard FIT (90.6% vs 94.8%, respectively), which would increase the likelihood of false-positive findings.

Despite its lower specificity compared with standard FIT, Cologuard 2.0 has several advantages. The test can identify more people with CRC and advanced precancerous lesions than the standard test and can lead to fewer false-positives than the original Cologuard test.

Cologuard maker Exact Sciences has submitted trial data to the US Food and Drug Administration (FDA) for approval.
 

Multitarget Stool RNA-Based Test

ColoSense, an RNA-based stool test, looks for eight RNA biomarkers associated with CRC. 

The company says that RNA-based testing has an advantage over DNA biomarker assays, such as the currently marketed Cologuard test, because it isn›t subject to the age-related changes in DNA methylation that can throw off the results from DNA assays. 

Like Cologuard 2.0, Geneoscopy’s Colosense test is under review by the FDA.

The data Geneoscopy submitted to the FDA came from the CRC-PREVENT trial, which included 8920 participants who were screened with both ColoSense and standard FIT before all had a colonoscopy. The participants ranged in age from 45 to 90 years, with 22% between 45 and 50 years old, a population recently added to the USPSTF screening recommendations. 

ColoSense showed higher sensitivity than standard FIT for the presence of CRC (94% vs 78%, respectively) and advanced adenomas (46% vs 29%). In the group aged 45-50 years, the RNA-based test had a sensitivity of 100% for CRC, correctly identifying all five people with colonoscopy-confirmed CRC, and 45% for advanced adenomas.

However, ColoSense was less specific than standard FIT compared with negative colonoscopy findings (88% vs 96%, respectively) and negative findings for advanced lesions or CRC (85.5% vs 94.9%); thus, it was more likely to lead to false-positive results.

Overall, the investigators said ColoSense is comparable to Cologuard — its chief market rival — in terms of sensitivity for CRC and advanced adenomas but has higher sensitivity for colorectal neoplasia in people aged 50 years or younger.
 

Multitarget Protein-Based Test

The multitarget protein-based FIT uses antibodies to test for two additional proteins: calprotectin, an inflammatory marker associated with CRC, and serpin family F member 2, a protease inhibitor thought to be upregulated in colon cancer. 

A 2021 study of 1284 patients found that the sensitivity of the multitarget protein-based test was 42.9% for advanced neoplasias compared with 37.3% with standard FIT. Its specificity was similar to that of standard FIT, at 96.6% for advanced neoplasias. 

In a more recent report published in The Lancet Oncology, the team modeled three scenarios comparing the two FIT tests. These scenarios used different cutoff values for a test to be positive for CRC or an advanced lesion.

Overall, the analysis included stool samples from 13,187 patients aged 55-75 years who were in the Netherlands’ national CRC screening program. Stool samples were evaluated with both the multitarget test and the standard FIT, using a positivity cutoff ≥ 47 mcg hemoglobin/g feces. Colonoscopy data were available for only 1270 participants. 

In scenario 1, the multitarget test had a lower threshold for a positive test and consequently identified more precancerous lesions than the standard FIT (828 vs 354, respectively). The multitarget FIT identified a few more CRC cases: Of 29 colonoscopy-confirmed CRC cases, the multitarget FIT identified 26 vs 23 with standard FIT. 

But the multitarget FIT also had more than double the number of false-positives than the standard FIT (347 vs 161, respectively).

Perhaps the most telling comparison occurred in scenario 2, with both tests set at the same low positivity threshold to minimize false-positives.

As expected, the two tests had similar positivity rates for advanced lesions, with the multitarget test correctly identifying 22 of 29 people with CRC, one fewer than the standard test. The protein-based test identified slightly more people with advanced lesions (156 vs 136 with the standard test), leading to a higher sensitivity for advanced lesions. 

Most notably, the protein-based test resulted in fewer false-positives than did the standard test (295 vs 311, respectively) , resulting in a slightly higher specificity.

In this scenario, “a single screening round might not have the biggest impact on cancer incidence and mortality,” the authors said, but the higher detection rate would still accumulate over 20 years of testing. The authors estimated that, under this scenario, substituting the multitarget FIT for the standard test in the Netherlands’ CRC screening program could reduce CRC incidence by 5% and CRC mortality by 4%.

Gerrit Meijer, MD, PhD, a pathologist at the Netherlands Cancer Institute, and colleagues recently launched a company called CRCbioscreen to commercialize this multitarget FIT for large-scale programs. The company›s priority is to develop and validate a clinical-grade test to sell to federal governments with national screening programs, such as those throughout Europe, Australia, and Asia, Dr. Meijer told this news organization. Dr. Meijer expects this process will take about 4 years.

The test will be developed for the US market, but with no nationwide screening program in the United States, future availability will depend on interest from providers and institutions, noted Dr. Meijer, who is also chief scientific officer at CRCbioscreen.

Overall, these three new multitarget stool-based CRC screening tests could help catch more cancers and advanced precancerous lesions. And, if the tests have a high enough specificity, a negative test result could also allow people to forgo screening colonoscopy. 

Still, people with a positive FIT finding would require follow-up colonoscopy, but about 10% of patients decline colonoscopy following an abnormal FIT, Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Health in Murray, Utah, told this news organization last year. That means that even if precancerous lesions and CRC are being caught earlier, treatment can’t be started unless people follow through with colonoscopy.

A version of this article appeared on Medscape.com.

In recent years, innovative use of bispecific antibodies and CAR T-cell therapy has ushered in an era when many patients with relapsed/refractory acute lymphoblastic leukemia (ALL) — who once had prognoses of 6 months or less — now survive for multiple years with the malignancy, and some are cured.

The comparative benefits and limitations of these two treatments for r/r ALL were a topic for discussion at the Great Debates & Updates Hematological Malignancies conference, held April 5-6 in New York City.

“Every single patient with ALL should benefit from bispecific antibodies before getting CAR-T cells, and I want to make the case that everybody should get CAR T as well. But they should get blinatumomab before they get CAR T,” said Elias Jabbour, MD, of the MD Anderson Cancer Center at The University of Texas in Houston, whose presentation focused on the merits of bispecific antibodies.

MD Anderson Cancer Center

His argument was based on data indicating that patients have better chances of long-term remission with the use of bispecific antibodies when they are administered in an earlier round of salvage treatment — and the fact that patients who are not cured with these drugs can still achieve a lower disease burden and perform better on CAR T-cell therapy than those who don’t receive the drugs.

“When blinatumomab is used as a consolidation during the first salvage treatment and spaces out transplantation, 3-year overall survival increases in the relapse setting, deepening responses and reducing the rate of VOD (veno-occlusive disease). The safety and efficacy of CAR T depends on a disease burden. If you have a minimal residual disease (MRD), you have a safer outcome and a better outcome in the long run,” Dr. Jabbour explained.

This point of view is supported by data from the treatment of patients r/r ALL with low intensity chemotherapy + inotuzumab ozogamicin (Besponsa; Pfizer) +/- blinatumomab (Blincyto; Amgen), knows as Mini-HCVD + Ino +/-Blina. Trial members achieved a median overall survival (OS) rate of 17 months, a 3-year survival rate of 42%, and an overall MRD negativity rate of 85%.

Dr. Jabbour noted that blinatumomab has its limitations. Generally, this treatment is administered intravenously every few weeks and can be cumbersome for patients who must travel to an infusion center. However, data from a phase 1b trial of single agent subcutaneous blinatumomab for advanced ALL has demonstrated that this formulation can be effective and can lead to MRD negativity, possibly paving the way for easier administration of the drug.

Aditi Shastri, MD, a leukemia specialist at New York’s Montefiore Medical Center who attended the debate, agreed that the data presented did support Dr. Jabbour’s contention that subcutaneous blinatumomab could make treatment available to even more people with r/r ALL. “It’s easier to administer than the blina pump and could act as a bridge to curative therapies like AlloHSCT,” she said.

Jae Park, MD, a leukemia and cellular therapy specialist at Memorial Sloan Kettering Cancer Center in New York City, argued that CAR T is the most potent therapy for r/r ALL. Dr. Park agreed that inotuzumab and blinatumomab have yielded tremendous progress in the treatment of patients with r/r ALL, but he noted that bispecific antibodies lack some of the advantages of CAR T.

Memorial Sloan Kettering Cancer Center

In recent years, innovative use of bispecific antibodies and CAR T-cell therapy has ushered in an era when many patients with relapsed/refractory acute lymphoblastic leukemia (ALL) — who once had prognoses of 6 months or less — now survive for multiple years with the malignancy, and some are cured.

The comparative benefits and limitations of these two treatments for r/r ALL were a topic for discussion at the Great Debates & Updates Hematological Malignancies conference, held April 5-6 in New York City.

“Every single patient with ALL should benefit from bispecific antibodies before getting CAR-T cells, and I want to make the case that everybody should get CAR T as well. But they should get blinatumomab before they get CAR T,” said Elias Jabbour, MD, of the MD Anderson Cancer Center at The University of Texas in Houston, whose presentation focused on the merits of bispecific antibodies.

MD Anderson Cancer Center

His argument was based on data indicating that patients have better chances of long-term remission with the use of bispecific antibodies when they are administered in an earlier round of salvage treatment — and the fact that patients who are not cured with these drugs can still achieve a lower disease burden and perform better on CAR T-cell therapy than those who don’t receive the drugs.

“When blinatumomab is used as a consolidation during the first salvage treatment and spaces out transplantation, 3-year overall survival increases in the relapse setting, deepening responses and reducing the rate of VOD (veno-occlusive disease). The safety and efficacy of CAR T depends on a disease burden. If you have a minimal residual disease (MRD), you have a safer outcome and a better outcome in the long run,” Dr. Jabbour explained.

This point of view is supported by data from the treatment of patients r/r ALL with low intensity chemotherapy + inotuzumab ozogamicin (Besponsa; Pfizer) +/- blinatumomab (Blincyto; Amgen), knows as Mini-HCVD + Ino +/-Blina. Trial members achieved a median overall survival (OS) rate of 17 months, a 3-year survival rate of 42%, and an overall MRD negativity rate of 85%.

Dr. Jabbour noted that blinatumomab has its limitations. Generally, this treatment is administered intravenously every few weeks and can be cumbersome for patients who must travel to an infusion center. However, data from a phase 1b trial of single agent subcutaneous blinatumomab for advanced ALL has demonstrated that this formulation can be effective and can lead to MRD negativity, possibly paving the way for easier administration of the drug.

Aditi Shastri, MD, a leukemia specialist at New York’s Montefiore Medical Center who attended the debate, agreed that the data presented did support Dr. Jabbour’s contention that subcutaneous blinatumomab could make treatment available to even more people with r/r ALL. “It’s easier to administer than the blina pump and could act as a bridge to curative therapies like AlloHSCT,” she said.

Jae Park, MD, a leukemia and cellular therapy specialist at Memorial Sloan Kettering Cancer Center in New York City, argued that CAR T is the most potent therapy for r/r ALL. Dr. Park agreed that inotuzumab and blinatumomab have yielded tremendous progress in the treatment of patients with r/r ALL, but he noted that bispecific antibodies lack some of the advantages of CAR T.

Memorial Sloan Kettering Cancer Center

In recent years, innovative use of bispecific antibodies and CAR T-cell therapy has ushered in an era when many patients with relapsed/refractory acute lymphoblastic leukemia (ALL) — who once had prognoses of 6 months or less — now survive for multiple years with the malignancy, and some are cured.

The comparative benefits and limitations of these two treatments for r/r ALL were a topic for discussion at the Great Debates & Updates Hematological Malignancies conference, held April 5-6 in New York City.

“Every single patient with ALL should benefit from bispecific antibodies before getting CAR-T cells, and I want to make the case that everybody should get CAR T as well. But they should get blinatumomab before they get CAR T,” said Elias Jabbour, MD, of the MD Anderson Cancer Center at The University of Texas in Houston, whose presentation focused on the merits of bispecific antibodies.

MD Anderson Cancer Center

His argument was based on data indicating that patients have better chances of long-term remission with the use of bispecific antibodies when they are administered in an earlier round of salvage treatment — and the fact that patients who are not cured with these drugs can still achieve a lower disease burden and perform better on CAR T-cell therapy than those who don’t receive the drugs.

“When blinatumomab is used as a consolidation during the first salvage treatment and spaces out transplantation, 3-year overall survival increases in the relapse setting, deepening responses and reducing the rate of VOD (veno-occlusive disease). The safety and efficacy of CAR T depends on a disease burden. If you have a minimal residual disease (MRD), you have a safer outcome and a better outcome in the long run,” Dr. Jabbour explained.

This point of view is supported by data from the treatment of patients r/r ALL with low intensity chemotherapy + inotuzumab ozogamicin (Besponsa; Pfizer) +/- blinatumomab (Blincyto; Amgen), knows as Mini-HCVD + Ino +/-Blina. Trial members achieved a median overall survival (OS) rate of 17 months, a 3-year survival rate of 42%, and an overall MRD negativity rate of 85%.

Dr. Jabbour noted that blinatumomab has its limitations. Generally, this treatment is administered intravenously every few weeks and can be cumbersome for patients who must travel to an infusion center. However, data from a phase 1b trial of single agent subcutaneous blinatumomab for advanced ALL has demonstrated that this formulation can be effective and can lead to MRD negativity, possibly paving the way for easier administration of the drug.

Aditi Shastri, MD, a leukemia specialist at New York’s Montefiore Medical Center who attended the debate, agreed that the data presented did support Dr. Jabbour’s contention that subcutaneous blinatumomab could make treatment available to even more people with r/r ALL. “It’s easier to administer than the blina pump and could act as a bridge to curative therapies like AlloHSCT,” she said.

Jae Park, MD, a leukemia and cellular therapy specialist at Memorial Sloan Kettering Cancer Center in New York City, argued that CAR T is the most potent therapy for r/r ALL. Dr. Park agreed that inotuzumab and blinatumomab have yielded tremendous progress in the treatment of patients with r/r ALL, but he noted that bispecific antibodies lack some of the advantages of CAR T.

Memorial Sloan Kettering Cancer Center