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Commentary: Transition from Psoriasis to PsA and New Drug Analyses, June 2024
Recent studies in psoriatic arthritis (PsA) have focused on transition from psoriasis to PsA. Patients with PsA are likely go through preclinical, subclinical, prodromal, and finally overt PsA. Zabotti and colleagues aimed to estimate the probability of developing PsA in patients with subclinical PsA defined as psoriasis and arthralgia. Of the 384 psoriasis patients from two European cohorts included in the study, 311 (80.9%) had subclinical PsA. The incidence rate of new-onset PsA was 7.7 per 100 patients-years in this group; the most predominant presentation was peripheral arthritis (82.1%). The risk for PsA was significantly higher in patients with subclinical PsA vs psoriasis (hazard ratio 11.7; 95% CI 1.57-86.7). In another cross-sectional study, Yao and colleagues compared 75 patients diagnosed with clinical PsA with 345 patients with psoriasis and without PsA, all of whom were aged 18-65 years. The authors demonstrated that at age 40 years or older, nail involvement, increased erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein (CRP) levels were associated with PsA. Moreover, MRI-detected enthesitis and tenosynovitis combined with these risk factors vs the risk factors alone showed better specificity (94.3% vs 69.0%) and similar sensitivity (89.0% vs 84.6%) in distinguishing PsA from psoriasis alone. Thus, psoriasis patients with arthralgia as well as those with nail disease and elevated ESR/CRP levels are at high risk for PsA. These patients should be carefully monitored to detect PsA early. These patients may also be ideal candidates to study interventions intended to prevent transition from psoriasis to PsA.
In regard to treatment, bimekizumab is a new monoclonal antibody that dually targets interleukin (IL)-17A and IL-17F and is highly efficacious for the treatment of psoriasis. In a meta-analysis of four placebo-controlled randomized clinical trials that included 1323 patients with PsA (age 18 years or older), of whom 853 received bimekizumab, Su and colleagues demonstrated that bimekizumab led to a significantly higher response rate for minimal disease activity (risk ratio [RR] 4.188; P < .001) and a 70% or greater improvement in the American College of Rheumatology (ACR) criteria (RR 7.932; P < .0001) when compared with placebo. Bimekizumab was superior to placebo in achieving ACR20/50/70 response at a dose of 160 mg. The risk for treatment-emergent adverse events was modestly higher with bimekizumab vs placebo (RR 1.423; P = .023), whereas the risk for serious cancers, upper respiratory tract infection, injection site reactions, and pharyngitis was similar for both. Thus, bimekizumab is an efficacious agent for the treatment of PsA. Future head-to-head studies will help clinicians determine the role of this drug in the management of PsA.
Not all patients respond equally well to targeted therapies, and the so-called challenging-to-treat patients are being increasingly described. Kivitz and colleagues recently described the efficacy of secukinumab, a monoclonal antibody targeting IL-17A, in these challenging-to-treat patients from the United States. In a post hoc subgroup analysis of four phase 3 studies that included 279 patients, they demonstrated that patients receiving 300 mg secukinumab and 150 mg with a loading dose had a higher rate of achieving the ACR20 response (59.7% and 43.4%, respectively) vs 15.6% for placebo (both P < .0001). The Psoriasis Area and Severity Index 90 response was 47.1% and 22.2%, respectively, vs 5.3% (both P < .05). Thus, secukinumab is efficacious in more challenging-to-treat patients. However, such patients need to be better characterized so that effective treatment strategies to achieve a state of low disease activity may be implemented.
Recent studies in psoriatic arthritis (PsA) have focused on transition from psoriasis to PsA. Patients with PsA are likely go through preclinical, subclinical, prodromal, and finally overt PsA. Zabotti and colleagues aimed to estimate the probability of developing PsA in patients with subclinical PsA defined as psoriasis and arthralgia. Of the 384 psoriasis patients from two European cohorts included in the study, 311 (80.9%) had subclinical PsA. The incidence rate of new-onset PsA was 7.7 per 100 patients-years in this group; the most predominant presentation was peripheral arthritis (82.1%). The risk for PsA was significantly higher in patients with subclinical PsA vs psoriasis (hazard ratio 11.7; 95% CI 1.57-86.7). In another cross-sectional study, Yao and colleagues compared 75 patients diagnosed with clinical PsA with 345 patients with psoriasis and without PsA, all of whom were aged 18-65 years. The authors demonstrated that at age 40 years or older, nail involvement, increased erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein (CRP) levels were associated with PsA. Moreover, MRI-detected enthesitis and tenosynovitis combined with these risk factors vs the risk factors alone showed better specificity (94.3% vs 69.0%) and similar sensitivity (89.0% vs 84.6%) in distinguishing PsA from psoriasis alone. Thus, psoriasis patients with arthralgia as well as those with nail disease and elevated ESR/CRP levels are at high risk for PsA. These patients should be carefully monitored to detect PsA early. These patients may also be ideal candidates to study interventions intended to prevent transition from psoriasis to PsA.
In regard to treatment, bimekizumab is a new monoclonal antibody that dually targets interleukin (IL)-17A and IL-17F and is highly efficacious for the treatment of psoriasis. In a meta-analysis of four placebo-controlled randomized clinical trials that included 1323 patients with PsA (age 18 years or older), of whom 853 received bimekizumab, Su and colleagues demonstrated that bimekizumab led to a significantly higher response rate for minimal disease activity (risk ratio [RR] 4.188; P < .001) and a 70% or greater improvement in the American College of Rheumatology (ACR) criteria (RR 7.932; P < .0001) when compared with placebo. Bimekizumab was superior to placebo in achieving ACR20/50/70 response at a dose of 160 mg. The risk for treatment-emergent adverse events was modestly higher with bimekizumab vs placebo (RR 1.423; P = .023), whereas the risk for serious cancers, upper respiratory tract infection, injection site reactions, and pharyngitis was similar for both. Thus, bimekizumab is an efficacious agent for the treatment of PsA. Future head-to-head studies will help clinicians determine the role of this drug in the management of PsA.
Not all patients respond equally well to targeted therapies, and the so-called challenging-to-treat patients are being increasingly described. Kivitz and colleagues recently described the efficacy of secukinumab, a monoclonal antibody targeting IL-17A, in these challenging-to-treat patients from the United States. In a post hoc subgroup analysis of four phase 3 studies that included 279 patients, they demonstrated that patients receiving 300 mg secukinumab and 150 mg with a loading dose had a higher rate of achieving the ACR20 response (59.7% and 43.4%, respectively) vs 15.6% for placebo (both P < .0001). The Psoriasis Area and Severity Index 90 response was 47.1% and 22.2%, respectively, vs 5.3% (both P < .05). Thus, secukinumab is efficacious in more challenging-to-treat patients. However, such patients need to be better characterized so that effective treatment strategies to achieve a state of low disease activity may be implemented.
Recent studies in psoriatic arthritis (PsA) have focused on transition from psoriasis to PsA. Patients with PsA are likely go through preclinical, subclinical, prodromal, and finally overt PsA. Zabotti and colleagues aimed to estimate the probability of developing PsA in patients with subclinical PsA defined as psoriasis and arthralgia. Of the 384 psoriasis patients from two European cohorts included in the study, 311 (80.9%) had subclinical PsA. The incidence rate of new-onset PsA was 7.7 per 100 patients-years in this group; the most predominant presentation was peripheral arthritis (82.1%). The risk for PsA was significantly higher in patients with subclinical PsA vs psoriasis (hazard ratio 11.7; 95% CI 1.57-86.7). In another cross-sectional study, Yao and colleagues compared 75 patients diagnosed with clinical PsA with 345 patients with psoriasis and without PsA, all of whom were aged 18-65 years. The authors demonstrated that at age 40 years or older, nail involvement, increased erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein (CRP) levels were associated with PsA. Moreover, MRI-detected enthesitis and tenosynovitis combined with these risk factors vs the risk factors alone showed better specificity (94.3% vs 69.0%) and similar sensitivity (89.0% vs 84.6%) in distinguishing PsA from psoriasis alone. Thus, psoriasis patients with arthralgia as well as those with nail disease and elevated ESR/CRP levels are at high risk for PsA. These patients should be carefully monitored to detect PsA early. These patients may also be ideal candidates to study interventions intended to prevent transition from psoriasis to PsA.
In regard to treatment, bimekizumab is a new monoclonal antibody that dually targets interleukin (IL)-17A and IL-17F and is highly efficacious for the treatment of psoriasis. In a meta-analysis of four placebo-controlled randomized clinical trials that included 1323 patients with PsA (age 18 years or older), of whom 853 received bimekizumab, Su and colleagues demonstrated that bimekizumab led to a significantly higher response rate for minimal disease activity (risk ratio [RR] 4.188; P < .001) and a 70% or greater improvement in the American College of Rheumatology (ACR) criteria (RR 7.932; P < .0001) when compared with placebo. Bimekizumab was superior to placebo in achieving ACR20/50/70 response at a dose of 160 mg. The risk for treatment-emergent adverse events was modestly higher with bimekizumab vs placebo (RR 1.423; P = .023), whereas the risk for serious cancers, upper respiratory tract infection, injection site reactions, and pharyngitis was similar for both. Thus, bimekizumab is an efficacious agent for the treatment of PsA. Future head-to-head studies will help clinicians determine the role of this drug in the management of PsA.
Not all patients respond equally well to targeted therapies, and the so-called challenging-to-treat patients are being increasingly described. Kivitz and colleagues recently described the efficacy of secukinumab, a monoclonal antibody targeting IL-17A, in these challenging-to-treat patients from the United States. In a post hoc subgroup analysis of four phase 3 studies that included 279 patients, they demonstrated that patients receiving 300 mg secukinumab and 150 mg with a loading dose had a higher rate of achieving the ACR20 response (59.7% and 43.4%, respectively) vs 15.6% for placebo (both P < .0001). The Psoriasis Area and Severity Index 90 response was 47.1% and 22.2%, respectively, vs 5.3% (both P < .05). Thus, secukinumab is efficacious in more challenging-to-treat patients. However, such patients need to be better characterized so that effective treatment strategies to achieve a state of low disease activity may be implemented.
CGM Aids in Detecting Early Gestational Diabetes
TOPLINE:
In women with gestational diabetes (GD), continuous glucose monitoring (CGM) shows elevated glycemic metrics earlier in pregnancy compared with the standard oral glucose tolerance test (OGTT).
METHODOLOGY:
- Earlier diagnosis and treatment of GDM may mitigate some perinatal risks, but the traditional OGTT at 24-28 weeks’ gestation delivers inconsistent results in early pregnancy, potentially leading to missed cases or overdiagnosis.
- This prospective noninterventional observational study conducted at two US academic-based clinical sites from June 2020 to December 2021 assessed CGM-derived glycemic patterns in 768 participants (mean age, 33 years; 77% White) enrolled prior to 17 weeks’ gestation with singleton pregnancy and an initial A1c level < 6.5%.
- Participants were encouraged to wear a blinded Dexcom G6 Pro CGM System sensor continuously until the day of delivery, with a median CGM wear duration of 67 days prior to OGTT.
- GDM was diagnosed using an OGTT conducted between 24 and 34 weeks’ gestation, which sorted women into those with GDM (n = 58) or without GDM (n = 710).
- CGM-derived glycemic patterns were compared between the participants with and without GDM.
TAKEAWAY:
- Women with GDM had a higher mean glucose (109 ± 13 vs 100 ± 8 mg/dL; P < .001) and greater glucose SD (23 ± 4 vs 19 ± 3; P < .001) than those without GDM throughout the gestational period prior to OGTT.
- Women with GDM spent lesser time in glycemic ranges of 63-140 mg/dL (87% ± 11% vs 94% ± 4%; P < .001) and 63-120 mg/dL (70% ± 17% vs 84% ± 8%; P < .001) throughout gestation than those without GDM prior to OGTT.
- The daytime and overnight mean glucose levels were higher in those with vs without GDM and attributed to increased hyperglycemia rather than decreased hypoglycemia, with those with GDM spending more time > 120 mg/dL and > 140 mg/dL and less time < 63 mg/dL and < 54 mg/dL.
- Mean glucose and percent time in the > 120 mg/dL and > 140 mg/dL ranges were higher in those with GDM as early as 13-14 weeks of gestation, which persisted at each 2-week period prior to OGTT.
IN PRACTICE:
“CGM could be used in addition to or instead of OGTT to screen individuals at risk for hyperglycemia during pregnancy, even as early as the first trimester,” the authors wrote, adding that “CGM could potentially play a pivotal role in providing timely identification of distinct glycemic patterns indicative of early dysglycemia.”
SOURCE:
The study, led by Celeste Durnwald, MD, Maternal-Fetal Medicine Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, was published online in Diabetes Care.
LIMITATIONS:
To include participants with possible early GDM, the study allowed the inclusion of up to 14 days of CGM data after OGTT in the overall gestational period and up to 10 days in the first and second trimesters. A detailed analysis of glycemia at the earliest timepoint of pregnancy could not be conducted as the first trimester data were limited. The findings may not be generalizable to a population with gestational hyperglycemia, as only 58 participants were identified with GDM using OGTT.
DISCLOSURES:
The study was supported by the Leona M. and Harry B. Helmsley Charitable Trust and UnitedHealth Group. Some authors reported performing advisory work, receiving research support and consultancy fees, and being on scientific advisory boards through their employer, while several authors reported that their institution received funds on their behalf from various pharmaceutical, healthcare, and medical device companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
In women with gestational diabetes (GD), continuous glucose monitoring (CGM) shows elevated glycemic metrics earlier in pregnancy compared with the standard oral glucose tolerance test (OGTT).
METHODOLOGY:
- Earlier diagnosis and treatment of GDM may mitigate some perinatal risks, but the traditional OGTT at 24-28 weeks’ gestation delivers inconsistent results in early pregnancy, potentially leading to missed cases or overdiagnosis.
- This prospective noninterventional observational study conducted at two US academic-based clinical sites from June 2020 to December 2021 assessed CGM-derived glycemic patterns in 768 participants (mean age, 33 years; 77% White) enrolled prior to 17 weeks’ gestation with singleton pregnancy and an initial A1c level < 6.5%.
- Participants were encouraged to wear a blinded Dexcom G6 Pro CGM System sensor continuously until the day of delivery, with a median CGM wear duration of 67 days prior to OGTT.
- GDM was diagnosed using an OGTT conducted between 24 and 34 weeks’ gestation, which sorted women into those with GDM (n = 58) or without GDM (n = 710).
- CGM-derived glycemic patterns were compared between the participants with and without GDM.
TAKEAWAY:
- Women with GDM had a higher mean glucose (109 ± 13 vs 100 ± 8 mg/dL; P < .001) and greater glucose SD (23 ± 4 vs 19 ± 3; P < .001) than those without GDM throughout the gestational period prior to OGTT.
- Women with GDM spent lesser time in glycemic ranges of 63-140 mg/dL (87% ± 11% vs 94% ± 4%; P < .001) and 63-120 mg/dL (70% ± 17% vs 84% ± 8%; P < .001) throughout gestation than those without GDM prior to OGTT.
- The daytime and overnight mean glucose levels were higher in those with vs without GDM and attributed to increased hyperglycemia rather than decreased hypoglycemia, with those with GDM spending more time > 120 mg/dL and > 140 mg/dL and less time < 63 mg/dL and < 54 mg/dL.
- Mean glucose and percent time in the > 120 mg/dL and > 140 mg/dL ranges were higher in those with GDM as early as 13-14 weeks of gestation, which persisted at each 2-week period prior to OGTT.
IN PRACTICE:
“CGM could be used in addition to or instead of OGTT to screen individuals at risk for hyperglycemia during pregnancy, even as early as the first trimester,” the authors wrote, adding that “CGM could potentially play a pivotal role in providing timely identification of distinct glycemic patterns indicative of early dysglycemia.”
SOURCE:
The study, led by Celeste Durnwald, MD, Maternal-Fetal Medicine Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, was published online in Diabetes Care.
LIMITATIONS:
To include participants with possible early GDM, the study allowed the inclusion of up to 14 days of CGM data after OGTT in the overall gestational period and up to 10 days in the first and second trimesters. A detailed analysis of glycemia at the earliest timepoint of pregnancy could not be conducted as the first trimester data were limited. The findings may not be generalizable to a population with gestational hyperglycemia, as only 58 participants were identified with GDM using OGTT.
DISCLOSURES:
The study was supported by the Leona M. and Harry B. Helmsley Charitable Trust and UnitedHealth Group. Some authors reported performing advisory work, receiving research support and consultancy fees, and being on scientific advisory boards through their employer, while several authors reported that their institution received funds on their behalf from various pharmaceutical, healthcare, and medical device companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
In women with gestational diabetes (GD), continuous glucose monitoring (CGM) shows elevated glycemic metrics earlier in pregnancy compared with the standard oral glucose tolerance test (OGTT).
METHODOLOGY:
- Earlier diagnosis and treatment of GDM may mitigate some perinatal risks, but the traditional OGTT at 24-28 weeks’ gestation delivers inconsistent results in early pregnancy, potentially leading to missed cases or overdiagnosis.
- This prospective noninterventional observational study conducted at two US academic-based clinical sites from June 2020 to December 2021 assessed CGM-derived glycemic patterns in 768 participants (mean age, 33 years; 77% White) enrolled prior to 17 weeks’ gestation with singleton pregnancy and an initial A1c level < 6.5%.
- Participants were encouraged to wear a blinded Dexcom G6 Pro CGM System sensor continuously until the day of delivery, with a median CGM wear duration of 67 days prior to OGTT.
- GDM was diagnosed using an OGTT conducted between 24 and 34 weeks’ gestation, which sorted women into those with GDM (n = 58) or without GDM (n = 710).
- CGM-derived glycemic patterns were compared between the participants with and without GDM.
TAKEAWAY:
- Women with GDM had a higher mean glucose (109 ± 13 vs 100 ± 8 mg/dL; P < .001) and greater glucose SD (23 ± 4 vs 19 ± 3; P < .001) than those without GDM throughout the gestational period prior to OGTT.
- Women with GDM spent lesser time in glycemic ranges of 63-140 mg/dL (87% ± 11% vs 94% ± 4%; P < .001) and 63-120 mg/dL (70% ± 17% vs 84% ± 8%; P < .001) throughout gestation than those without GDM prior to OGTT.
- The daytime and overnight mean glucose levels were higher in those with vs without GDM and attributed to increased hyperglycemia rather than decreased hypoglycemia, with those with GDM spending more time > 120 mg/dL and > 140 mg/dL and less time < 63 mg/dL and < 54 mg/dL.
- Mean glucose and percent time in the > 120 mg/dL and > 140 mg/dL ranges were higher in those with GDM as early as 13-14 weeks of gestation, which persisted at each 2-week period prior to OGTT.
IN PRACTICE:
“CGM could be used in addition to or instead of OGTT to screen individuals at risk for hyperglycemia during pregnancy, even as early as the first trimester,” the authors wrote, adding that “CGM could potentially play a pivotal role in providing timely identification of distinct glycemic patterns indicative of early dysglycemia.”
SOURCE:
The study, led by Celeste Durnwald, MD, Maternal-Fetal Medicine Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, was published online in Diabetes Care.
LIMITATIONS:
To include participants with possible early GDM, the study allowed the inclusion of up to 14 days of CGM data after OGTT in the overall gestational period and up to 10 days in the first and second trimesters. A detailed analysis of glycemia at the earliest timepoint of pregnancy could not be conducted as the first trimester data were limited. The findings may not be generalizable to a population with gestational hyperglycemia, as only 58 participants were identified with GDM using OGTT.
DISCLOSURES:
The study was supported by the Leona M. and Harry B. Helmsley Charitable Trust and UnitedHealth Group. Some authors reported performing advisory work, receiving research support and consultancy fees, and being on scientific advisory boards through their employer, while several authors reported that their institution received funds on their behalf from various pharmaceutical, healthcare, and medical device companies.
A version of this article first appeared on Medscape.com.
Clinicians Face Hurdles in Caring for the Growing Number of Cancer Survivors
BOSTON — Primary care clinicians face challenges in knowledge and care coordination as they care for a rising number of cancer survivors in the United States, according to panelists who spoke during a workshop at the 2024 annual meeting of the Society of General Internal Medicine.
By the year 2040, an estimated 26 million people will have lived ≥ 5 years after their initial cancer diagnosis, an increase of eight million from 2022, according to the National Cancer Institute. Primary care clinicians must help patients with new health problems that emerge as the result of previous cancer treatments and with side effects that can last for decades.
“It’s a good thing that more people are living longer and living better after cancer, but now that means we have to train an army of primary care doctors to feel empowered to take care of these patients in a general setting,” said Ilana Yurkiewicz, MD, an oncologist, internal medicine physician, and clinical assistant professor at Stanford University, Stanford, California, who co-moderated the workshop.
Dr. Yurkiewicz and her fellow panelists emphasized the high likelihood that every primary care clinician is currently caring for a survivor of cancer.
One of the greatest barriers these clinicians face in caring for survivors is the difficulty in getting screening tests paid for by insurers, according to Regina Jacob, MD, associate professor at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, who co-moderated the session.
“We have a tough time getting surveillance tests [for cancer] covered through insurance” because in some cases physician groups do not provide consensus on which surveillance tools to use or how often people should be screened, Dr. Jacob said.
For instance, the American Gastroenterological Association and the US Preventive Services Task Force — which many insurers use as basis for coverage determinations — offer differing recommendations.
Primary care physicians also face challenges in understanding the complexity of conditions patients may face during and after cancer treatment since conditions that emerge from cancer or treatment may vary among patients.
“Cancer survivorship starts the day of the diagnosis,” said Dr. Yurkiewicz. “It doesn’t necessarily mean someone who has completed cancer treatment.”
During the workshop, participants offered their own recommendations for care based on case studies, which included issues such as long-term effects of cancer and its therapies, which may arise immediately after or even years or decades after treatment.
A common situation for cancer survivors involves new health issues that occur after treatment has ended.
“Who do they turn to in cases where they don’t know if it’s related to the cancer or the cancer treatment or are separate issues? Do they turn to their oncologist? Do they turn to their primary care doctor?” Dr. Yurkiewicz said. “How should I, the primary care doctor, be thinking about the issue?”
She proposed that primary care clinicians give patients a 2-week waiting period at the onset of a symptom before intervening.
Participants also suggested establishing rapport with the treating oncologist and other specialists so that if a question arises, the primary care clinician can ask for advice.
The method physicians choose to communicate and coordinate care should be tailored to the health system in which they work, participants suggested.
“Some people have the luxury of having a unified electronic health record; some people don’t have that luxury,” said Dr. Jacob. “Recognize the institution in which you work, recognize the context in which you work, and develop a communication strategy that closes the gap.”
The moderators reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
BOSTON — Primary care clinicians face challenges in knowledge and care coordination as they care for a rising number of cancer survivors in the United States, according to panelists who spoke during a workshop at the 2024 annual meeting of the Society of General Internal Medicine.
By the year 2040, an estimated 26 million people will have lived ≥ 5 years after their initial cancer diagnosis, an increase of eight million from 2022, according to the National Cancer Institute. Primary care clinicians must help patients with new health problems that emerge as the result of previous cancer treatments and with side effects that can last for decades.
“It’s a good thing that more people are living longer and living better after cancer, but now that means we have to train an army of primary care doctors to feel empowered to take care of these patients in a general setting,” said Ilana Yurkiewicz, MD, an oncologist, internal medicine physician, and clinical assistant professor at Stanford University, Stanford, California, who co-moderated the workshop.
Dr. Yurkiewicz and her fellow panelists emphasized the high likelihood that every primary care clinician is currently caring for a survivor of cancer.
One of the greatest barriers these clinicians face in caring for survivors is the difficulty in getting screening tests paid for by insurers, according to Regina Jacob, MD, associate professor at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, who co-moderated the session.
“We have a tough time getting surveillance tests [for cancer] covered through insurance” because in some cases physician groups do not provide consensus on which surveillance tools to use or how often people should be screened, Dr. Jacob said.
For instance, the American Gastroenterological Association and the US Preventive Services Task Force — which many insurers use as basis for coverage determinations — offer differing recommendations.
Primary care physicians also face challenges in understanding the complexity of conditions patients may face during and after cancer treatment since conditions that emerge from cancer or treatment may vary among patients.
“Cancer survivorship starts the day of the diagnosis,” said Dr. Yurkiewicz. “It doesn’t necessarily mean someone who has completed cancer treatment.”
During the workshop, participants offered their own recommendations for care based on case studies, which included issues such as long-term effects of cancer and its therapies, which may arise immediately after or even years or decades after treatment.
A common situation for cancer survivors involves new health issues that occur after treatment has ended.
“Who do they turn to in cases where they don’t know if it’s related to the cancer or the cancer treatment or are separate issues? Do they turn to their oncologist? Do they turn to their primary care doctor?” Dr. Yurkiewicz said. “How should I, the primary care doctor, be thinking about the issue?”
She proposed that primary care clinicians give patients a 2-week waiting period at the onset of a symptom before intervening.
Participants also suggested establishing rapport with the treating oncologist and other specialists so that if a question arises, the primary care clinician can ask for advice.
The method physicians choose to communicate and coordinate care should be tailored to the health system in which they work, participants suggested.
“Some people have the luxury of having a unified electronic health record; some people don’t have that luxury,” said Dr. Jacob. “Recognize the institution in which you work, recognize the context in which you work, and develop a communication strategy that closes the gap.”
The moderators reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
BOSTON — Primary care clinicians face challenges in knowledge and care coordination as they care for a rising number of cancer survivors in the United States, according to panelists who spoke during a workshop at the 2024 annual meeting of the Society of General Internal Medicine.
By the year 2040, an estimated 26 million people will have lived ≥ 5 years after their initial cancer diagnosis, an increase of eight million from 2022, according to the National Cancer Institute. Primary care clinicians must help patients with new health problems that emerge as the result of previous cancer treatments and with side effects that can last for decades.
“It’s a good thing that more people are living longer and living better after cancer, but now that means we have to train an army of primary care doctors to feel empowered to take care of these patients in a general setting,” said Ilana Yurkiewicz, MD, an oncologist, internal medicine physician, and clinical assistant professor at Stanford University, Stanford, California, who co-moderated the workshop.
Dr. Yurkiewicz and her fellow panelists emphasized the high likelihood that every primary care clinician is currently caring for a survivor of cancer.
One of the greatest barriers these clinicians face in caring for survivors is the difficulty in getting screening tests paid for by insurers, according to Regina Jacob, MD, associate professor at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, who co-moderated the session.
“We have a tough time getting surveillance tests [for cancer] covered through insurance” because in some cases physician groups do not provide consensus on which surveillance tools to use or how often people should be screened, Dr. Jacob said.
For instance, the American Gastroenterological Association and the US Preventive Services Task Force — which many insurers use as basis for coverage determinations — offer differing recommendations.
Primary care physicians also face challenges in understanding the complexity of conditions patients may face during and after cancer treatment since conditions that emerge from cancer or treatment may vary among patients.
“Cancer survivorship starts the day of the diagnosis,” said Dr. Yurkiewicz. “It doesn’t necessarily mean someone who has completed cancer treatment.”
During the workshop, participants offered their own recommendations for care based on case studies, which included issues such as long-term effects of cancer and its therapies, which may arise immediately after or even years or decades after treatment.
A common situation for cancer survivors involves new health issues that occur after treatment has ended.
“Who do they turn to in cases where they don’t know if it’s related to the cancer or the cancer treatment or are separate issues? Do they turn to their oncologist? Do they turn to their primary care doctor?” Dr. Yurkiewicz said. “How should I, the primary care doctor, be thinking about the issue?”
She proposed that primary care clinicians give patients a 2-week waiting period at the onset of a symptom before intervening.
Participants also suggested establishing rapport with the treating oncologist and other specialists so that if a question arises, the primary care clinician can ask for advice.
The method physicians choose to communicate and coordinate care should be tailored to the health system in which they work, participants suggested.
“Some people have the luxury of having a unified electronic health record; some people don’t have that luxury,” said Dr. Jacob. “Recognize the institution in which you work, recognize the context in which you work, and develop a communication strategy that closes the gap.”
The moderators reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM SGIM 2024
Is Mental Illness ‘Transmissible’?
Teens with classmates who have a mental illness have a significantly greater risk for a psychiatric diagnosis later in life, even after controlling for parents’ mental health history and other factors, a new study suggested.
The research provides new evidence that adolescents within a specific peer network may possibly “transmit” mental disorders such as depression and anxiety to each other, the investigators noted.
The study is said to the be the largest to date on the topic, including data on more than 700,000 ninth graders in Finland who were followed for up to 18 years.
At least one expert noted that the numbers are higher than he would have expected, but the investigators were quick to caution the study doesn’t prove having a classmate with a mental illness leads to later psychiatric diagnosis among peers.
“The associations observed in the study are not necessarily causal,” lead investigator Jussi Alho, PhD, a postdoctoral researcher at the University of Helsinki, Finland, told this news organization. “The study did not investigate the mechanisms that explain the observed associations.”
The results were published online on May 22 in JAMA Psychiatry.
Few Data
Previous studies have reported a clustering of mood symptoms, eating disorders, and other psychiatric illnesses among adolescent and adult social networks. But most involve self-selected peer groups.
“Investigating the transmission of mental disorders is especially important in childhood and adolescence,” the authors noted. “Yet, despite a few survey studies reporting that adolescents may experience increased mental health symptoms when exposed to friends or peers with mental health problems, large-scale studies on the potential peer influences of mental disorders in youth are lacking,” the authors wrote.
Researchers used a database of 713,809 students in the ninth grade, about half boys and half girls. All were born between January 1, 1985, and December 31, 1997. About 47,000 were excluded as they had a mental disorder diagnosis before the study began.
Some 666,000 students in 860 schools were followed from ninth grade until the first diagnosed mental disorder, death, emigration, or the end of the study in 2019. Median follow-up was 11.4 years.
Diagnoses were gathered from Finnish registries for inpatient, outpatient, and primary care and included ICD-9 and ICD-10 diagnoses for substance misuse disorders, schizophrenia spectrum disorders, mood disorders, anxiety disorders, eating disorders, emotional and social-functioning disorders, and hyperkinetic and conduct disorders.
The authors adjusted for sex, birth year, school and ninth-grade class size, area-level urbanicity, area-level morbidity, area-level education, area-level employment rate, parental educational level, and parental mental health, with a random intercept per school.
Dose-Response Relationship
Overall, a quarter (167,227) of the students were diagnosed with a mental disorder.
The risk of being diagnosed with any mental disorder was 3% higher during the entire follow-up period (hazard ratio [HR], 1.03; 95% CI, 1.02-1.04). Risk was highest in the first year of follow-up (HR, 1.13; 95% CI, 1.08-1.18) and then rose again in years 4 and 5, when the risk was 5% higher with one diagnosed classmate and 10% higher with more than one diagnosed classmate.
The risk was significantly increased for mood, anxiety, and eating disorders in each follow-up time window. Investigators also noted a dose-response relationship: The more classmates with a psychiatric illness, the greater the risk for later mental illness.
“These findings suggest that mental disorders may be transmitted within adolescent peer networks,” the authors wrote.
The researchers chose to describe the spread of mental disorders among peer classmates as “transmission” in part because it has been previously used in the literature, Dr. Alho said.
Alho said the researchers also believe that transmission is an accurate term to describe the potential mechanisms by which mental disorders may spread.
The authors hypothesized that more students might be diagnosed when disorders are normalized, through increased awareness and receptivity to diagnosis and treatment.
Conversely, the rate of disorders might also have increased — especially in the first year of follow-up — if there were no students in the peer network who had been diagnosed, the authors added. Without an example, it might discourage a student to seek help.
The authors also noted that it’s “conceivable that long-term exposure to a depressive individual could lead to gradual development of depressive symptoms through the well-established neural mechanisms of emotional contagion.”
New Direction for Treatment?
Commenting on the findings, Madhukar H. Trivedi, MD, the Betty Jo Hay Distinguished Chair in Mental Health at UT Southwestern Medical School, Dallas, said that the theory that having classmates with psychiatric illness could normalize these conditions has merit.
Once someone is diagnosed or receives treatment, “their peers kind of get implicit permission to be able to then express their own symptoms or express their own problems, which they may have been hiding or not recognized,” he said.
However, Dr. Trivedi disagreed with the authors’ suggestion that the rate of disorders might also have increased if no classmates had received a psychiatric diagnosis, noting that it was unlikely that a student would not have been exposed to depression, anxiety, or another mood disorder — through a peer or family member — given how common those illnesses are.
“The numbers are slightly higher than I would have expected,” Dr. Trivedi said, adding that peer influence having that type of impact “is something that has not been shown before.”
The study is notable for its use of comprehensive registries, which helped solidify the data integrity, Trivedi said, and the results offer some potential new directions for treatment, such as adding peer support. That has been found useful in adult treatment but has been less utilized with adolescents, he said.
The study was funded by the European Union and the Academy of Finland. The authors reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Teens with classmates who have a mental illness have a significantly greater risk for a psychiatric diagnosis later in life, even after controlling for parents’ mental health history and other factors, a new study suggested.
The research provides new evidence that adolescents within a specific peer network may possibly “transmit” mental disorders such as depression and anxiety to each other, the investigators noted.
The study is said to the be the largest to date on the topic, including data on more than 700,000 ninth graders in Finland who were followed for up to 18 years.
At least one expert noted that the numbers are higher than he would have expected, but the investigators were quick to caution the study doesn’t prove having a classmate with a mental illness leads to later psychiatric diagnosis among peers.
“The associations observed in the study are not necessarily causal,” lead investigator Jussi Alho, PhD, a postdoctoral researcher at the University of Helsinki, Finland, told this news organization. “The study did not investigate the mechanisms that explain the observed associations.”
The results were published online on May 22 in JAMA Psychiatry.
Few Data
Previous studies have reported a clustering of mood symptoms, eating disorders, and other psychiatric illnesses among adolescent and adult social networks. But most involve self-selected peer groups.
“Investigating the transmission of mental disorders is especially important in childhood and adolescence,” the authors noted. “Yet, despite a few survey studies reporting that adolescents may experience increased mental health symptoms when exposed to friends or peers with mental health problems, large-scale studies on the potential peer influences of mental disorders in youth are lacking,” the authors wrote.
Researchers used a database of 713,809 students in the ninth grade, about half boys and half girls. All were born between January 1, 1985, and December 31, 1997. About 47,000 were excluded as they had a mental disorder diagnosis before the study began.
Some 666,000 students in 860 schools were followed from ninth grade until the first diagnosed mental disorder, death, emigration, or the end of the study in 2019. Median follow-up was 11.4 years.
Diagnoses were gathered from Finnish registries for inpatient, outpatient, and primary care and included ICD-9 and ICD-10 diagnoses for substance misuse disorders, schizophrenia spectrum disorders, mood disorders, anxiety disorders, eating disorders, emotional and social-functioning disorders, and hyperkinetic and conduct disorders.
The authors adjusted for sex, birth year, school and ninth-grade class size, area-level urbanicity, area-level morbidity, area-level education, area-level employment rate, parental educational level, and parental mental health, with a random intercept per school.
Dose-Response Relationship
Overall, a quarter (167,227) of the students were diagnosed with a mental disorder.
The risk of being diagnosed with any mental disorder was 3% higher during the entire follow-up period (hazard ratio [HR], 1.03; 95% CI, 1.02-1.04). Risk was highest in the first year of follow-up (HR, 1.13; 95% CI, 1.08-1.18) and then rose again in years 4 and 5, when the risk was 5% higher with one diagnosed classmate and 10% higher with more than one diagnosed classmate.
The risk was significantly increased for mood, anxiety, and eating disorders in each follow-up time window. Investigators also noted a dose-response relationship: The more classmates with a psychiatric illness, the greater the risk for later mental illness.
“These findings suggest that mental disorders may be transmitted within adolescent peer networks,” the authors wrote.
The researchers chose to describe the spread of mental disorders among peer classmates as “transmission” in part because it has been previously used in the literature, Dr. Alho said.
Alho said the researchers also believe that transmission is an accurate term to describe the potential mechanisms by which mental disorders may spread.
The authors hypothesized that more students might be diagnosed when disorders are normalized, through increased awareness and receptivity to diagnosis and treatment.
Conversely, the rate of disorders might also have increased — especially in the first year of follow-up — if there were no students in the peer network who had been diagnosed, the authors added. Without an example, it might discourage a student to seek help.
The authors also noted that it’s “conceivable that long-term exposure to a depressive individual could lead to gradual development of depressive symptoms through the well-established neural mechanisms of emotional contagion.”
New Direction for Treatment?
Commenting on the findings, Madhukar H. Trivedi, MD, the Betty Jo Hay Distinguished Chair in Mental Health at UT Southwestern Medical School, Dallas, said that the theory that having classmates with psychiatric illness could normalize these conditions has merit.
Once someone is diagnosed or receives treatment, “their peers kind of get implicit permission to be able to then express their own symptoms or express their own problems, which they may have been hiding or not recognized,” he said.
However, Dr. Trivedi disagreed with the authors’ suggestion that the rate of disorders might also have increased if no classmates had received a psychiatric diagnosis, noting that it was unlikely that a student would not have been exposed to depression, anxiety, or another mood disorder — through a peer or family member — given how common those illnesses are.
“The numbers are slightly higher than I would have expected,” Dr. Trivedi said, adding that peer influence having that type of impact “is something that has not been shown before.”
The study is notable for its use of comprehensive registries, which helped solidify the data integrity, Trivedi said, and the results offer some potential new directions for treatment, such as adding peer support. That has been found useful in adult treatment but has been less utilized with adolescents, he said.
The study was funded by the European Union and the Academy of Finland. The authors reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Teens with classmates who have a mental illness have a significantly greater risk for a psychiatric diagnosis later in life, even after controlling for parents’ mental health history and other factors, a new study suggested.
The research provides new evidence that adolescents within a specific peer network may possibly “transmit” mental disorders such as depression and anxiety to each other, the investigators noted.
The study is said to the be the largest to date on the topic, including data on more than 700,000 ninth graders in Finland who were followed for up to 18 years.
At least one expert noted that the numbers are higher than he would have expected, but the investigators were quick to caution the study doesn’t prove having a classmate with a mental illness leads to later psychiatric diagnosis among peers.
“The associations observed in the study are not necessarily causal,” lead investigator Jussi Alho, PhD, a postdoctoral researcher at the University of Helsinki, Finland, told this news organization. “The study did not investigate the mechanisms that explain the observed associations.”
The results were published online on May 22 in JAMA Psychiatry.
Few Data
Previous studies have reported a clustering of mood symptoms, eating disorders, and other psychiatric illnesses among adolescent and adult social networks. But most involve self-selected peer groups.
“Investigating the transmission of mental disorders is especially important in childhood and adolescence,” the authors noted. “Yet, despite a few survey studies reporting that adolescents may experience increased mental health symptoms when exposed to friends or peers with mental health problems, large-scale studies on the potential peer influences of mental disorders in youth are lacking,” the authors wrote.
Researchers used a database of 713,809 students in the ninth grade, about half boys and half girls. All were born between January 1, 1985, and December 31, 1997. About 47,000 were excluded as they had a mental disorder diagnosis before the study began.
Some 666,000 students in 860 schools were followed from ninth grade until the first diagnosed mental disorder, death, emigration, or the end of the study in 2019. Median follow-up was 11.4 years.
Diagnoses were gathered from Finnish registries for inpatient, outpatient, and primary care and included ICD-9 and ICD-10 diagnoses for substance misuse disorders, schizophrenia spectrum disorders, mood disorders, anxiety disorders, eating disorders, emotional and social-functioning disorders, and hyperkinetic and conduct disorders.
The authors adjusted for sex, birth year, school and ninth-grade class size, area-level urbanicity, area-level morbidity, area-level education, area-level employment rate, parental educational level, and parental mental health, with a random intercept per school.
Dose-Response Relationship
Overall, a quarter (167,227) of the students were diagnosed with a mental disorder.
The risk of being diagnosed with any mental disorder was 3% higher during the entire follow-up period (hazard ratio [HR], 1.03; 95% CI, 1.02-1.04). Risk was highest in the first year of follow-up (HR, 1.13; 95% CI, 1.08-1.18) and then rose again in years 4 and 5, when the risk was 5% higher with one diagnosed classmate and 10% higher with more than one diagnosed classmate.
The risk was significantly increased for mood, anxiety, and eating disorders in each follow-up time window. Investigators also noted a dose-response relationship: The more classmates with a psychiatric illness, the greater the risk for later mental illness.
“These findings suggest that mental disorders may be transmitted within adolescent peer networks,” the authors wrote.
The researchers chose to describe the spread of mental disorders among peer classmates as “transmission” in part because it has been previously used in the literature, Dr. Alho said.
Alho said the researchers also believe that transmission is an accurate term to describe the potential mechanisms by which mental disorders may spread.
The authors hypothesized that more students might be diagnosed when disorders are normalized, through increased awareness and receptivity to diagnosis and treatment.
Conversely, the rate of disorders might also have increased — especially in the first year of follow-up — if there were no students in the peer network who had been diagnosed, the authors added. Without an example, it might discourage a student to seek help.
The authors also noted that it’s “conceivable that long-term exposure to a depressive individual could lead to gradual development of depressive symptoms through the well-established neural mechanisms of emotional contagion.”
New Direction for Treatment?
Commenting on the findings, Madhukar H. Trivedi, MD, the Betty Jo Hay Distinguished Chair in Mental Health at UT Southwestern Medical School, Dallas, said that the theory that having classmates with psychiatric illness could normalize these conditions has merit.
Once someone is diagnosed or receives treatment, “their peers kind of get implicit permission to be able to then express their own symptoms or express their own problems, which they may have been hiding or not recognized,” he said.
However, Dr. Trivedi disagreed with the authors’ suggestion that the rate of disorders might also have increased if no classmates had received a psychiatric diagnosis, noting that it was unlikely that a student would not have been exposed to depression, anxiety, or another mood disorder — through a peer or family member — given how common those illnesses are.
“The numbers are slightly higher than I would have expected,” Dr. Trivedi said, adding that peer influence having that type of impact “is something that has not been shown before.”
The study is notable for its use of comprehensive registries, which helped solidify the data integrity, Trivedi said, and the results offer some potential new directions for treatment, such as adding peer support. That has been found useful in adult treatment but has been less utilized with adolescents, he said.
The study was funded by the European Union and the Academy of Finland. The authors reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Losing Muscle with GLP-1 RAs? There May be a Drug for That
NEW ORLEANS — Medications in development would preserve muscle mass and augment fat loss when used in combination with glucagon-like peptide 1 (GLP-1) receptor agonists taken for weight loss.
As drugs such as semaglutide (Wegovy) and the dual agonist glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide (Zepbound) are producing unprecedented degrees of weight loss in increasing numbers of people, concern has arisen about the proportion of the lost weight, approximately 30%-50%, that is beneficial lean body mass vs fat mass. While some loss of muscle mass is expected with any rapid overall weight loss, it’s not clear what long-term effect that may have on physical function, bone density, and longevity, particularly in older adults with sarcopenic obesity who are at risk for muscle atrophy and frailty.
Trials now underway will need to show improved function — not just increased muscle — and also establish safety, experts told this news organization.
One such agent is Veru Inc.’s oral selective androgen receptor modulator (SARM) enobosarm, currently in a phase 2b clinical trial for use with semaglutide in people who are at risk for muscle atrophy and weakness.
Also in a phase 2b trial for use with semaglutide is the antimyostatin intravenous agent bimagrumab. In July 2023, Eli Lilly purchased Versanis, the company that was developing that drug. Previous phase 2 data on bimagrumab alone vs placebo in people with obesity and type 2 diabetes showed improvement in muscle mass with greater fat loss but also produced a signal for pancreatitis requiring further evaluation.
Scholar Rock’s intravenous antimyostatin apitegromab is also now in a phase 2 trial and Biohaven Pharmaceuticals is expected to launch a phase 2 trial of its subcutaneous antimyostatin taldefgrobep alfa later this year.
Most of these and other similar agents have also been under investigation for use in one or more other muscle-losing conditions including spinal muscular atrophy, sarcopenia, and cancer.
“Wouldn’t it be nice if there was a drug that built up muscle mass?”
Data presented in two late-breaking posters at the annual meeting of the American Association of Clinical Endocrinology meeting held May 9-11, 2024, laid the groundwork for the subsequent phase 2 studies of enobosarm in combination with a GLP-1 RA. One showed increases in total lean mass and decreases in total fat mass with 3 mg enobosarm for 14 days compared with placebo in both healthy young men and older men (≥ 60 years), with the greatest benefit seen in the older men who had lower lean mass and higher fat mass at baseline.
The other was a post hoc analysis of a phase 3 clinical trial of 3 mg/d oral enobosarm for the treatment of muscle wasting in advanced lung cancer. Here, a subset of participants who were aged ≥ 60 years and had obesity also showed reductions in fat mass and preservation of lean body mass with the drug compared with placebo, leading to “high-quality weight loss.”
Endocrinologist Adrian Dobs, MD, professor of medicine and oncology at Johns Hopkins University Medical School, Baltimore, an investigator on both of the Veru-sponsored studies, told Medscape Medical News, “The wishful thinking about these drugs has been around for quite a while, particularly in the cancer population or ... in a frail population. The hope was, wouldn’t it be nice if there was a drug that built up muscle mass? Certainly, we know that going into the gym does that but looking for some medication had been the goal. The thought was this class of medication would have a muscle-building effect, an anabolic effect without an androgenic effect causing masculinization.”
The problem with those studies in terms of regulatory approval, Dr. Dobs said, was defining the endpoints. “The [US Food and Drug Administration] is very interested in functional status. You can show that there is an increase in muscle mass. But to take that leap and show that a person can walk upstairs, carry groceries, and be more functionally able is hard to prove.”
And she noted that bringing frail elderly people into clinical trials isn’t easy. But now, “this is an interesting new avenue of scientific pursuit, looking at this particular population that is losing weight due to GLP-1 [agonists]. Now we’re dealing with high numbers of patients who are easy to identify because they’re taking those medications.”
“We have to also focus on ‘first, do no harm’”
Asked to comment, Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center, Boston, expressed caution. “We have to remember that it is not all about muscle mass. Maintaining muscle mass with weight loss is obviously important, but even today, with 30% of the weight loss coming from lean mass, which is not the same as muscle, there are huge benefits from fat loss, including cardiovascular and cancer risk reduction, increased life increased life expectancy, and diabetes remission.”
Moreover, Dr. Fitch pointed out, SARMs have been linked to increased cardiovascular events and blood clots.
“So, we have to also focus on ‘first, do no harm’. A lot of these muscle-promoting medications have been associated with increased risk of other things. So, it is going to take a lot of time and testing to be sure they are safe. While I am supportive of research to look into these risks vs benefits, we have to be mindful of the risks and recognize that in most cases of weight loss in people with obesity losing some lean mass is acceptable and the benefits of fat loss outweigh the risks of lean loss, especially if people are doing resistance exercise and maintaining strength.”
“Wherever the GLP-1s go, we go”
In an investor call held on May 8, 2024, Veru’s Chairman, CEO, and President Mitchell Steiner, MD, said that the current phase 2b study of enobosarm with semaglutide is only examining people aged ≥ 60 years to maximize the functional outcome benefit. But phase 3, he anticipates, will be “all comers, for sure. And then we’ll embed special populations.” The thinking, he said, is “Wherever the GLP-1s go, we go.”
Fitch has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. Dobs had no disclosures beyond conducting research for Veru.
A version of this article appeared on Medscape.com.
NEW ORLEANS — Medications in development would preserve muscle mass and augment fat loss when used in combination with glucagon-like peptide 1 (GLP-1) receptor agonists taken for weight loss.
As drugs such as semaglutide (Wegovy) and the dual agonist glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide (Zepbound) are producing unprecedented degrees of weight loss in increasing numbers of people, concern has arisen about the proportion of the lost weight, approximately 30%-50%, that is beneficial lean body mass vs fat mass. While some loss of muscle mass is expected with any rapid overall weight loss, it’s not clear what long-term effect that may have on physical function, bone density, and longevity, particularly in older adults with sarcopenic obesity who are at risk for muscle atrophy and frailty.
Trials now underway will need to show improved function — not just increased muscle — and also establish safety, experts told this news organization.
One such agent is Veru Inc.’s oral selective androgen receptor modulator (SARM) enobosarm, currently in a phase 2b clinical trial for use with semaglutide in people who are at risk for muscle atrophy and weakness.
Also in a phase 2b trial for use with semaglutide is the antimyostatin intravenous agent bimagrumab. In July 2023, Eli Lilly purchased Versanis, the company that was developing that drug. Previous phase 2 data on bimagrumab alone vs placebo in people with obesity and type 2 diabetes showed improvement in muscle mass with greater fat loss but also produced a signal for pancreatitis requiring further evaluation.
Scholar Rock’s intravenous antimyostatin apitegromab is also now in a phase 2 trial and Biohaven Pharmaceuticals is expected to launch a phase 2 trial of its subcutaneous antimyostatin taldefgrobep alfa later this year.
Most of these and other similar agents have also been under investigation for use in one or more other muscle-losing conditions including spinal muscular atrophy, sarcopenia, and cancer.
“Wouldn’t it be nice if there was a drug that built up muscle mass?”
Data presented in two late-breaking posters at the annual meeting of the American Association of Clinical Endocrinology meeting held May 9-11, 2024, laid the groundwork for the subsequent phase 2 studies of enobosarm in combination with a GLP-1 RA. One showed increases in total lean mass and decreases in total fat mass with 3 mg enobosarm for 14 days compared with placebo in both healthy young men and older men (≥ 60 years), with the greatest benefit seen in the older men who had lower lean mass and higher fat mass at baseline.
The other was a post hoc analysis of a phase 3 clinical trial of 3 mg/d oral enobosarm for the treatment of muscle wasting in advanced lung cancer. Here, a subset of participants who were aged ≥ 60 years and had obesity also showed reductions in fat mass and preservation of lean body mass with the drug compared with placebo, leading to “high-quality weight loss.”
Endocrinologist Adrian Dobs, MD, professor of medicine and oncology at Johns Hopkins University Medical School, Baltimore, an investigator on both of the Veru-sponsored studies, told Medscape Medical News, “The wishful thinking about these drugs has been around for quite a while, particularly in the cancer population or ... in a frail population. The hope was, wouldn’t it be nice if there was a drug that built up muscle mass? Certainly, we know that going into the gym does that but looking for some medication had been the goal. The thought was this class of medication would have a muscle-building effect, an anabolic effect without an androgenic effect causing masculinization.”
The problem with those studies in terms of regulatory approval, Dr. Dobs said, was defining the endpoints. “The [US Food and Drug Administration] is very interested in functional status. You can show that there is an increase in muscle mass. But to take that leap and show that a person can walk upstairs, carry groceries, and be more functionally able is hard to prove.”
And she noted that bringing frail elderly people into clinical trials isn’t easy. But now, “this is an interesting new avenue of scientific pursuit, looking at this particular population that is losing weight due to GLP-1 [agonists]. Now we’re dealing with high numbers of patients who are easy to identify because they’re taking those medications.”
“We have to also focus on ‘first, do no harm’”
Asked to comment, Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center, Boston, expressed caution. “We have to remember that it is not all about muscle mass. Maintaining muscle mass with weight loss is obviously important, but even today, with 30% of the weight loss coming from lean mass, which is not the same as muscle, there are huge benefits from fat loss, including cardiovascular and cancer risk reduction, increased life increased life expectancy, and diabetes remission.”
Moreover, Dr. Fitch pointed out, SARMs have been linked to increased cardiovascular events and blood clots.
“So, we have to also focus on ‘first, do no harm’. A lot of these muscle-promoting medications have been associated with increased risk of other things. So, it is going to take a lot of time and testing to be sure they are safe. While I am supportive of research to look into these risks vs benefits, we have to be mindful of the risks and recognize that in most cases of weight loss in people with obesity losing some lean mass is acceptable and the benefits of fat loss outweigh the risks of lean loss, especially if people are doing resistance exercise and maintaining strength.”
“Wherever the GLP-1s go, we go”
In an investor call held on May 8, 2024, Veru’s Chairman, CEO, and President Mitchell Steiner, MD, said that the current phase 2b study of enobosarm with semaglutide is only examining people aged ≥ 60 years to maximize the functional outcome benefit. But phase 3, he anticipates, will be “all comers, for sure. And then we’ll embed special populations.” The thinking, he said, is “Wherever the GLP-1s go, we go.”
Fitch has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. Dobs had no disclosures beyond conducting research for Veru.
A version of this article appeared on Medscape.com.
NEW ORLEANS — Medications in development would preserve muscle mass and augment fat loss when used in combination with glucagon-like peptide 1 (GLP-1) receptor agonists taken for weight loss.
As drugs such as semaglutide (Wegovy) and the dual agonist glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide (Zepbound) are producing unprecedented degrees of weight loss in increasing numbers of people, concern has arisen about the proportion of the lost weight, approximately 30%-50%, that is beneficial lean body mass vs fat mass. While some loss of muscle mass is expected with any rapid overall weight loss, it’s not clear what long-term effect that may have on physical function, bone density, and longevity, particularly in older adults with sarcopenic obesity who are at risk for muscle atrophy and frailty.
Trials now underway will need to show improved function — not just increased muscle — and also establish safety, experts told this news organization.
One such agent is Veru Inc.’s oral selective androgen receptor modulator (SARM) enobosarm, currently in a phase 2b clinical trial for use with semaglutide in people who are at risk for muscle atrophy and weakness.
Also in a phase 2b trial for use with semaglutide is the antimyostatin intravenous agent bimagrumab. In July 2023, Eli Lilly purchased Versanis, the company that was developing that drug. Previous phase 2 data on bimagrumab alone vs placebo in people with obesity and type 2 diabetes showed improvement in muscle mass with greater fat loss but also produced a signal for pancreatitis requiring further evaluation.
Scholar Rock’s intravenous antimyostatin apitegromab is also now in a phase 2 trial and Biohaven Pharmaceuticals is expected to launch a phase 2 trial of its subcutaneous antimyostatin taldefgrobep alfa later this year.
Most of these and other similar agents have also been under investigation for use in one or more other muscle-losing conditions including spinal muscular atrophy, sarcopenia, and cancer.
“Wouldn’t it be nice if there was a drug that built up muscle mass?”
Data presented in two late-breaking posters at the annual meeting of the American Association of Clinical Endocrinology meeting held May 9-11, 2024, laid the groundwork for the subsequent phase 2 studies of enobosarm in combination with a GLP-1 RA. One showed increases in total lean mass and decreases in total fat mass with 3 mg enobosarm for 14 days compared with placebo in both healthy young men and older men (≥ 60 years), with the greatest benefit seen in the older men who had lower lean mass and higher fat mass at baseline.
The other was a post hoc analysis of a phase 3 clinical trial of 3 mg/d oral enobosarm for the treatment of muscle wasting in advanced lung cancer. Here, a subset of participants who were aged ≥ 60 years and had obesity also showed reductions in fat mass and preservation of lean body mass with the drug compared with placebo, leading to “high-quality weight loss.”
Endocrinologist Adrian Dobs, MD, professor of medicine and oncology at Johns Hopkins University Medical School, Baltimore, an investigator on both of the Veru-sponsored studies, told Medscape Medical News, “The wishful thinking about these drugs has been around for quite a while, particularly in the cancer population or ... in a frail population. The hope was, wouldn’t it be nice if there was a drug that built up muscle mass? Certainly, we know that going into the gym does that but looking for some medication had been the goal. The thought was this class of medication would have a muscle-building effect, an anabolic effect without an androgenic effect causing masculinization.”
The problem with those studies in terms of regulatory approval, Dr. Dobs said, was defining the endpoints. “The [US Food and Drug Administration] is very interested in functional status. You can show that there is an increase in muscle mass. But to take that leap and show that a person can walk upstairs, carry groceries, and be more functionally able is hard to prove.”
And she noted that bringing frail elderly people into clinical trials isn’t easy. But now, “this is an interesting new avenue of scientific pursuit, looking at this particular population that is losing weight due to GLP-1 [agonists]. Now we’re dealing with high numbers of patients who are easy to identify because they’re taking those medications.”
“We have to also focus on ‘first, do no harm’”
Asked to comment, Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center, Boston, expressed caution. “We have to remember that it is not all about muscle mass. Maintaining muscle mass with weight loss is obviously important, but even today, with 30% of the weight loss coming from lean mass, which is not the same as muscle, there are huge benefits from fat loss, including cardiovascular and cancer risk reduction, increased life increased life expectancy, and diabetes remission.”
Moreover, Dr. Fitch pointed out, SARMs have been linked to increased cardiovascular events and blood clots.
“So, we have to also focus on ‘first, do no harm’. A lot of these muscle-promoting medications have been associated with increased risk of other things. So, it is going to take a lot of time and testing to be sure they are safe. While I am supportive of research to look into these risks vs benefits, we have to be mindful of the risks and recognize that in most cases of weight loss in people with obesity losing some lean mass is acceptable and the benefits of fat loss outweigh the risks of lean loss, especially if people are doing resistance exercise and maintaining strength.”
“Wherever the GLP-1s go, we go”
In an investor call held on May 8, 2024, Veru’s Chairman, CEO, and President Mitchell Steiner, MD, said that the current phase 2b study of enobosarm with semaglutide is only examining people aged ≥ 60 years to maximize the functional outcome benefit. But phase 3, he anticipates, will be “all comers, for sure. And then we’ll embed special populations.” The thinking, he said, is “Wherever the GLP-1s go, we go.”
Fitch has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. Dobs had no disclosures beyond conducting research for Veru.
A version of this article appeared on Medscape.com.
FROM AACE 2024
AI-Assessed Bowel Prep Helps Ensure Successful Screening Colonoscopy
TOPLINE:
The adenoma missed rate (AMR), including lesions > 5 mm, was lower in patients whose precolonoscopy bowel preparation was deemed suitable using an artificial intelligence (AI)–guided assessment.
METHODOLOGY:
- Individuals with inappropriate bowel preparation before a colonoscopy face a higher lesion miss rate and may need to repeat the procedure.
- This prospective single-center study analyzed the screening colonoscopies of 393 individuals (mean age, 55 years; 50% men) using assessments made by endoscopists and AI.
- The AI-based method was the e-Boston Bowel Preparation Scale (e-BBPS), in which a score of 3 is the threshold to guarantee an adenoma detection rate of > 25%. Patients with an e-BBPS score of ≤ 3 or > 3 were considered by the AI as being qualified or unqualified, respectively.
- If the bowel preparation was considered adequate by the endoscopists and qualified by AI, individuals immediately underwent a repeat colonoscopy to assess for any missed lesions; otherwise, they underwent bowel recleansing before a repeat colonoscopy.
- The primary outcome was a > 5-mm AMR.
TAKEAWAY:
- The > 5-mm AMR was higher in individuals whose bowel preparation was deemed unqualified vs qualified by AI (35.71% vs 13.19%), particularly in the cecum (50.00% vs 25.00%), ascending colon (25.00% vs 9.09%), transverse colon (58.82% vs 14.71%), and descending colon (40.00% vs 21.43%).
- Similarly, any AMR (50.89% vs 20.79%), > 5-mm polyp miss rate (35.82% vs 19.48%), and any polyp miss rate (43.05% vs 25.51%) were higher in the unqualified AI vs qualified AI individuals.
- The rate of detection of adenomas > 5 mm (2.88% vs 11.25%) or any adenoma (15.97% vs 46.25%) was lower among the qualified AI vs unqualified AI individuals during the repeat colonoscopy.
- The e-BBPS also showed a high pairwise agreement with the analysis of expert endoscopists and moderate pairwise agreement with that of general endoscopists.
IN PRACTICE:
“The use of AI in bowel preparation assessment can relieve endoscopists’ workload, enabling them to concentrate more on detecting lesions during colonoscopy without being distracted by preparation evaluation, thus enhancing both efficiency and overall medical quality,” the authors wrote.
SOURCE:
The study, led by Liwen Yao, PhD, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China, was published online in Gastrointestinal Endoscopy.
LIMITATIONS:
Limitations included the study’s lack of external validity, including Western populations. Different bowel preparation regimens were not compared; therefore, conclusions about their efficacy cannot be deduced. The use of AI in the assessment of bowel preparation may lead to ethical issues, such as increased colonoscopy costs due to the technology and whether patients are fully informed.
DISCLOSURES:
This study was funded by the Science and Technology Achievement Transformation Platform Construction Project of Ministry of Education and Public Health Research Project of Futian District, Shenzhen. The authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
The adenoma missed rate (AMR), including lesions > 5 mm, was lower in patients whose precolonoscopy bowel preparation was deemed suitable using an artificial intelligence (AI)–guided assessment.
METHODOLOGY:
- Individuals with inappropriate bowel preparation before a colonoscopy face a higher lesion miss rate and may need to repeat the procedure.
- This prospective single-center study analyzed the screening colonoscopies of 393 individuals (mean age, 55 years; 50% men) using assessments made by endoscopists and AI.
- The AI-based method was the e-Boston Bowel Preparation Scale (e-BBPS), in which a score of 3 is the threshold to guarantee an adenoma detection rate of > 25%. Patients with an e-BBPS score of ≤ 3 or > 3 were considered by the AI as being qualified or unqualified, respectively.
- If the bowel preparation was considered adequate by the endoscopists and qualified by AI, individuals immediately underwent a repeat colonoscopy to assess for any missed lesions; otherwise, they underwent bowel recleansing before a repeat colonoscopy.
- The primary outcome was a > 5-mm AMR.
TAKEAWAY:
- The > 5-mm AMR was higher in individuals whose bowel preparation was deemed unqualified vs qualified by AI (35.71% vs 13.19%), particularly in the cecum (50.00% vs 25.00%), ascending colon (25.00% vs 9.09%), transverse colon (58.82% vs 14.71%), and descending colon (40.00% vs 21.43%).
- Similarly, any AMR (50.89% vs 20.79%), > 5-mm polyp miss rate (35.82% vs 19.48%), and any polyp miss rate (43.05% vs 25.51%) were higher in the unqualified AI vs qualified AI individuals.
- The rate of detection of adenomas > 5 mm (2.88% vs 11.25%) or any adenoma (15.97% vs 46.25%) was lower among the qualified AI vs unqualified AI individuals during the repeat colonoscopy.
- The e-BBPS also showed a high pairwise agreement with the analysis of expert endoscopists and moderate pairwise agreement with that of general endoscopists.
IN PRACTICE:
“The use of AI in bowel preparation assessment can relieve endoscopists’ workload, enabling them to concentrate more on detecting lesions during colonoscopy without being distracted by preparation evaluation, thus enhancing both efficiency and overall medical quality,” the authors wrote.
SOURCE:
The study, led by Liwen Yao, PhD, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China, was published online in Gastrointestinal Endoscopy.
LIMITATIONS:
Limitations included the study’s lack of external validity, including Western populations. Different bowel preparation regimens were not compared; therefore, conclusions about their efficacy cannot be deduced. The use of AI in the assessment of bowel preparation may lead to ethical issues, such as increased colonoscopy costs due to the technology and whether patients are fully informed.
DISCLOSURES:
This study was funded by the Science and Technology Achievement Transformation Platform Construction Project of Ministry of Education and Public Health Research Project of Futian District, Shenzhen. The authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
The adenoma missed rate (AMR), including lesions > 5 mm, was lower in patients whose precolonoscopy bowel preparation was deemed suitable using an artificial intelligence (AI)–guided assessment.
METHODOLOGY:
- Individuals with inappropriate bowel preparation before a colonoscopy face a higher lesion miss rate and may need to repeat the procedure.
- This prospective single-center study analyzed the screening colonoscopies of 393 individuals (mean age, 55 years; 50% men) using assessments made by endoscopists and AI.
- The AI-based method was the e-Boston Bowel Preparation Scale (e-BBPS), in which a score of 3 is the threshold to guarantee an adenoma detection rate of > 25%. Patients with an e-BBPS score of ≤ 3 or > 3 were considered by the AI as being qualified or unqualified, respectively.
- If the bowel preparation was considered adequate by the endoscopists and qualified by AI, individuals immediately underwent a repeat colonoscopy to assess for any missed lesions; otherwise, they underwent bowel recleansing before a repeat colonoscopy.
- The primary outcome was a > 5-mm AMR.
TAKEAWAY:
- The > 5-mm AMR was higher in individuals whose bowel preparation was deemed unqualified vs qualified by AI (35.71% vs 13.19%), particularly in the cecum (50.00% vs 25.00%), ascending colon (25.00% vs 9.09%), transverse colon (58.82% vs 14.71%), and descending colon (40.00% vs 21.43%).
- Similarly, any AMR (50.89% vs 20.79%), > 5-mm polyp miss rate (35.82% vs 19.48%), and any polyp miss rate (43.05% vs 25.51%) were higher in the unqualified AI vs qualified AI individuals.
- The rate of detection of adenomas > 5 mm (2.88% vs 11.25%) or any adenoma (15.97% vs 46.25%) was lower among the qualified AI vs unqualified AI individuals during the repeat colonoscopy.
- The e-BBPS also showed a high pairwise agreement with the analysis of expert endoscopists and moderate pairwise agreement with that of general endoscopists.
IN PRACTICE:
“The use of AI in bowel preparation assessment can relieve endoscopists’ workload, enabling them to concentrate more on detecting lesions during colonoscopy without being distracted by preparation evaluation, thus enhancing both efficiency and overall medical quality,” the authors wrote.
SOURCE:
The study, led by Liwen Yao, PhD, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China, was published online in Gastrointestinal Endoscopy.
LIMITATIONS:
Limitations included the study’s lack of external validity, including Western populations. Different bowel preparation regimens were not compared; therefore, conclusions about their efficacy cannot be deduced. The use of AI in the assessment of bowel preparation may lead to ethical issues, such as increased colonoscopy costs due to the technology and whether patients are fully informed.
DISCLOSURES:
This study was funded by the Science and Technology Achievement Transformation Platform Construction Project of Ministry of Education and Public Health Research Project of Futian District, Shenzhen. The authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
Recently Incarcerated Account for Nearly 20% of US Suicides
Nearly one-fifth of suicides in the United States occur in people who were incarcerated in the previous year, a new study showed.
An analysis of more than seven million recently incarcerated US adults revealed a nearly ninefold increased risk for suicide within 1 year after release and an almost sevenfold higher risk during the 2 years following release compared with nonincarcerated people.
The findings suggest that recent incarceration should be considered a risk factor for suicide, investigators said.
“Suicide prevention efforts should focus on people who have spent at least 1 night in jail in the past year,” investigator Ted R. Miller, PhD, of the Pacific Institute for Research and Evaluation, Beltsville, Maryland, and Curtin University School of Public Health, Silver Spring, Maryland, and colleagues wrote. “Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.”
The study was published online on May 10, 2024, in JAMA Network Open.
To address the lack of data on suicide risk after recent incarceration, researchers used estimates from meta-analyses and jail census counts.
In 2019, a little more than seven million people (77% male), or 2.8% of the US adult population, were released from US jails at least once, typically after brief pretrial stays. Of those, 9121 died by suicide.
Compared with suicide risk in people who had never been incarcerated, risk was nearly nine times higher within 1 year of release (relative risk [RR], 8.95; 95% CI, 7.21-10.69) and nearly seven times higher during the second year after release (RR, 6.98; 95% CI, 4.21-9.76), researchers found.
Over a quarter (27%) of all adult suicides in the United States occurred in formerly incarcerated people within 2 years of jail release, and one fifth occurred within 1 year of release.
“The results suggest that better integration of suicide risk detection and prevention across health and criminal justice systems is critical to advancing population-level suicide-prevention efforts,” the authors wrote.
High volumes of jail admissions and discharges, short jail stays, and understaffing limit the capacity of many jails to coordinate care with outside health agencies, researchers acknowledged.
“The suicide rate after the return to the community after jail stay is higher than the suicide rate in jail, but local jails have limited capacity to coordinate postrelease health activities,” authors wrote. “Thus, a comprehensive approach to reducing the population-level US suicide rate would include health systems screening their subscribers or patients for recent arrest or police involvement and reaching out to those recently released to prevent suicide.”
In an accompanying editorial, Stuart A. Kinner, PhD, and Rohan Borschmann, PhD, both with the Melbourne School of Population and Global Health, University of Melbourne, Australia, noted that people who experience incarceration “are distinguished by complex health problems that necessitate coordinated, multisectoral care.”
“Miller and colleagues’ findings provide further evidence that incarceration serves as an important marker for disease vulnerability and risk,” Dr. Kinner and Borschmann wrote. “Yet, all too often, the health care provided to these individuals before, during, and after incarceration is underresourced, interrupted, and fragmented.”
Coordinating care for recently incarcerated individuals will require a coordinated effort by all stakeholders, including those in the criminal justice system, they argued.
“The systems that incarcerate 7.1 million people in the United States each year should not be given a get-out-of-jail-free card,” they wrote.
This study was supported by grants from the National Institutes of Mental Health (NIMH)/National Institutes of Health (NIH) and from the National Center for Health and Justice Integration for Suicide Prevention. Dr. Miller reported receiving grants from the NIMH/NIH with his employer as a subcontractor during the conduct of the study and a contract from government plaintiffs in Opioid Litigation: Epidemiology/Abatement Planning outside the submitted work. The other authors’ disclosures are listed on the original paper. Dr. Kinner and Borschmann declared no relevant financial relationships.
A version of this article appeared on Medscape.com.
Nearly one-fifth of suicides in the United States occur in people who were incarcerated in the previous year, a new study showed.
An analysis of more than seven million recently incarcerated US adults revealed a nearly ninefold increased risk for suicide within 1 year after release and an almost sevenfold higher risk during the 2 years following release compared with nonincarcerated people.
The findings suggest that recent incarceration should be considered a risk factor for suicide, investigators said.
“Suicide prevention efforts should focus on people who have spent at least 1 night in jail in the past year,” investigator Ted R. Miller, PhD, of the Pacific Institute for Research and Evaluation, Beltsville, Maryland, and Curtin University School of Public Health, Silver Spring, Maryland, and colleagues wrote. “Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.”
The study was published online on May 10, 2024, in JAMA Network Open.
To address the lack of data on suicide risk after recent incarceration, researchers used estimates from meta-analyses and jail census counts.
In 2019, a little more than seven million people (77% male), or 2.8% of the US adult population, were released from US jails at least once, typically after brief pretrial stays. Of those, 9121 died by suicide.
Compared with suicide risk in people who had never been incarcerated, risk was nearly nine times higher within 1 year of release (relative risk [RR], 8.95; 95% CI, 7.21-10.69) and nearly seven times higher during the second year after release (RR, 6.98; 95% CI, 4.21-9.76), researchers found.
Over a quarter (27%) of all adult suicides in the United States occurred in formerly incarcerated people within 2 years of jail release, and one fifth occurred within 1 year of release.
“The results suggest that better integration of suicide risk detection and prevention across health and criminal justice systems is critical to advancing population-level suicide-prevention efforts,” the authors wrote.
High volumes of jail admissions and discharges, short jail stays, and understaffing limit the capacity of many jails to coordinate care with outside health agencies, researchers acknowledged.
“The suicide rate after the return to the community after jail stay is higher than the suicide rate in jail, but local jails have limited capacity to coordinate postrelease health activities,” authors wrote. “Thus, a comprehensive approach to reducing the population-level US suicide rate would include health systems screening their subscribers or patients for recent arrest or police involvement and reaching out to those recently released to prevent suicide.”
In an accompanying editorial, Stuart A. Kinner, PhD, and Rohan Borschmann, PhD, both with the Melbourne School of Population and Global Health, University of Melbourne, Australia, noted that people who experience incarceration “are distinguished by complex health problems that necessitate coordinated, multisectoral care.”
“Miller and colleagues’ findings provide further evidence that incarceration serves as an important marker for disease vulnerability and risk,” Dr. Kinner and Borschmann wrote. “Yet, all too often, the health care provided to these individuals before, during, and after incarceration is underresourced, interrupted, and fragmented.”
Coordinating care for recently incarcerated individuals will require a coordinated effort by all stakeholders, including those in the criminal justice system, they argued.
“The systems that incarcerate 7.1 million people in the United States each year should not be given a get-out-of-jail-free card,” they wrote.
This study was supported by grants from the National Institutes of Mental Health (NIMH)/National Institutes of Health (NIH) and from the National Center for Health and Justice Integration for Suicide Prevention. Dr. Miller reported receiving grants from the NIMH/NIH with his employer as a subcontractor during the conduct of the study and a contract from government plaintiffs in Opioid Litigation: Epidemiology/Abatement Planning outside the submitted work. The other authors’ disclosures are listed on the original paper. Dr. Kinner and Borschmann declared no relevant financial relationships.
A version of this article appeared on Medscape.com.
Nearly one-fifth of suicides in the United States occur in people who were incarcerated in the previous year, a new study showed.
An analysis of more than seven million recently incarcerated US adults revealed a nearly ninefold increased risk for suicide within 1 year after release and an almost sevenfold higher risk during the 2 years following release compared with nonincarcerated people.
The findings suggest that recent incarceration should be considered a risk factor for suicide, investigators said.
“Suicide prevention efforts should focus on people who have spent at least 1 night in jail in the past year,” investigator Ted R. Miller, PhD, of the Pacific Institute for Research and Evaluation, Beltsville, Maryland, and Curtin University School of Public Health, Silver Spring, Maryland, and colleagues wrote. “Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.”
The study was published online on May 10, 2024, in JAMA Network Open.
To address the lack of data on suicide risk after recent incarceration, researchers used estimates from meta-analyses and jail census counts.
In 2019, a little more than seven million people (77% male), or 2.8% of the US adult population, were released from US jails at least once, typically after brief pretrial stays. Of those, 9121 died by suicide.
Compared with suicide risk in people who had never been incarcerated, risk was nearly nine times higher within 1 year of release (relative risk [RR], 8.95; 95% CI, 7.21-10.69) and nearly seven times higher during the second year after release (RR, 6.98; 95% CI, 4.21-9.76), researchers found.
Over a quarter (27%) of all adult suicides in the United States occurred in formerly incarcerated people within 2 years of jail release, and one fifth occurred within 1 year of release.
“The results suggest that better integration of suicide risk detection and prevention across health and criminal justice systems is critical to advancing population-level suicide-prevention efforts,” the authors wrote.
High volumes of jail admissions and discharges, short jail stays, and understaffing limit the capacity of many jails to coordinate care with outside health agencies, researchers acknowledged.
“The suicide rate after the return to the community after jail stay is higher than the suicide rate in jail, but local jails have limited capacity to coordinate postrelease health activities,” authors wrote. “Thus, a comprehensive approach to reducing the population-level US suicide rate would include health systems screening their subscribers or patients for recent arrest or police involvement and reaching out to those recently released to prevent suicide.”
In an accompanying editorial, Stuart A. Kinner, PhD, and Rohan Borschmann, PhD, both with the Melbourne School of Population and Global Health, University of Melbourne, Australia, noted that people who experience incarceration “are distinguished by complex health problems that necessitate coordinated, multisectoral care.”
“Miller and colleagues’ findings provide further evidence that incarceration serves as an important marker for disease vulnerability and risk,” Dr. Kinner and Borschmann wrote. “Yet, all too often, the health care provided to these individuals before, during, and after incarceration is underresourced, interrupted, and fragmented.”
Coordinating care for recently incarcerated individuals will require a coordinated effort by all stakeholders, including those in the criminal justice system, they argued.
“The systems that incarcerate 7.1 million people in the United States each year should not be given a get-out-of-jail-free card,” they wrote.
This study was supported by grants from the National Institutes of Mental Health (NIMH)/National Institutes of Health (NIH) and from the National Center for Health and Justice Integration for Suicide Prevention. Dr. Miller reported receiving grants from the NIMH/NIH with his employer as a subcontractor during the conduct of the study and a contract from government plaintiffs in Opioid Litigation: Epidemiology/Abatement Planning outside the submitted work. The other authors’ disclosures are listed on the original paper. Dr. Kinner and Borschmann declared no relevant financial relationships.
A version of this article appeared on Medscape.com.
Late-Night Eaters May Have Increased Risk for Colorectal Cancer
WASHINGTON —
, according to the results of research presented at the annual Digestive Disease Week® (DDW).Investigators in a new study questioned 664 people getting a colonoscopy to screen for cancer, and 42% said they were late eaters. This group was 46% more likely than non–late eaters to have an adenoma found during colonoscopy. An estimated 5% to 10% of them become cancerous over time.
“A lot of other studies are about what we eat but not when we eat,” said Edena Khoshaba, lead investigator and a medical student at Rush University Medical College in Chicago. “The common advice includes not eating red meat, eating more fruits and vegetables — which is great, of course — but we wanted to see if the timing affects us at all.”
Ms. Khoshaba and colleagues found it did. Late eaters were 5.5 times more likely to have three or more tubular adenomas compared to non–late eaters, even after adjusting for what people were eating. Tubular adenomas are the most common type of polyp found in the colon.
So, what’s the possible connection between late eating and the risk for colorectal cancer?
Resetting Your Internal Clock
Eating close to bedtime could be throwing off the body’s circadian rhythm. But in this case, it’s not the central circadian center located in the brain — the one that releases melatonin. Instead, late eating could disrupt the peripheral circadian rhythm, part of which is found in the GI tract. For example, if a person is eating late at night, the brain thinks it is nighttime while the gut thinks it is daytime, Ms. Khoshaba said in an interview.
This is an interesting study, said Amy Bragagnini, MS, RD, spokesperson for the Academy of Nutrition and Dietetics, when asked to comment on the research. “It is true that eating later at night can disrupt your circadian rhythm.”
“In addition, many of my patients have told me that when they do eat later at night, they don’t always make the healthiest food choices,” Ms. Bragagnini said. “Their late-night food choices are generally higher in added sugar and fat. This may cause them to consume far more calories than their body needs.” So, eating late at night can also lead to unwanted weight gain.
An unanswered question is if late eating is connected in any way at all to increasing rates of colorectal cancer seen in younger patients.
This was an observational study, and another possible limitation, Ms. Khoshaba said, is that people were asked to recall their diets over 24 hours, which may not always be accurate.
Some of the organisms in the gut have their own internal clocks that follow a daily rhythm, and what someone eat determines how many different kinds of these organisms are active, Ms. Bragagnini said.
“So, if your late-night eating consists of foods high in sugar and fat, you may be negatively impacting your microbiome.” she said.
The next step for Ms. Khoshaba and colleagues is a study examining the peripheral circadian rhythm, changes in the gut microbiome, and the risk for developing metabolic syndrome. Ms. Khoshaba and Ms. Bragagnini had no relevant disclosures.
A version of this article appeared on Medscape.com.
WASHINGTON —
, according to the results of research presented at the annual Digestive Disease Week® (DDW).Investigators in a new study questioned 664 people getting a colonoscopy to screen for cancer, and 42% said they were late eaters. This group was 46% more likely than non–late eaters to have an adenoma found during colonoscopy. An estimated 5% to 10% of them become cancerous over time.
“A lot of other studies are about what we eat but not when we eat,” said Edena Khoshaba, lead investigator and a medical student at Rush University Medical College in Chicago. “The common advice includes not eating red meat, eating more fruits and vegetables — which is great, of course — but we wanted to see if the timing affects us at all.”
Ms. Khoshaba and colleagues found it did. Late eaters were 5.5 times more likely to have three or more tubular adenomas compared to non–late eaters, even after adjusting for what people were eating. Tubular adenomas are the most common type of polyp found in the colon.
So, what’s the possible connection between late eating and the risk for colorectal cancer?
Resetting Your Internal Clock
Eating close to bedtime could be throwing off the body’s circadian rhythm. But in this case, it’s not the central circadian center located in the brain — the one that releases melatonin. Instead, late eating could disrupt the peripheral circadian rhythm, part of which is found in the GI tract. For example, if a person is eating late at night, the brain thinks it is nighttime while the gut thinks it is daytime, Ms. Khoshaba said in an interview.
This is an interesting study, said Amy Bragagnini, MS, RD, spokesperson for the Academy of Nutrition and Dietetics, when asked to comment on the research. “It is true that eating later at night can disrupt your circadian rhythm.”
“In addition, many of my patients have told me that when they do eat later at night, they don’t always make the healthiest food choices,” Ms. Bragagnini said. “Their late-night food choices are generally higher in added sugar and fat. This may cause them to consume far more calories than their body needs.” So, eating late at night can also lead to unwanted weight gain.
An unanswered question is if late eating is connected in any way at all to increasing rates of colorectal cancer seen in younger patients.
This was an observational study, and another possible limitation, Ms. Khoshaba said, is that people were asked to recall their diets over 24 hours, which may not always be accurate.
Some of the organisms in the gut have their own internal clocks that follow a daily rhythm, and what someone eat determines how many different kinds of these organisms are active, Ms. Bragagnini said.
“So, if your late-night eating consists of foods high in sugar and fat, you may be negatively impacting your microbiome.” she said.
The next step for Ms. Khoshaba and colleagues is a study examining the peripheral circadian rhythm, changes in the gut microbiome, and the risk for developing metabolic syndrome. Ms. Khoshaba and Ms. Bragagnini had no relevant disclosures.
A version of this article appeared on Medscape.com.
WASHINGTON —
, according to the results of research presented at the annual Digestive Disease Week® (DDW).Investigators in a new study questioned 664 people getting a colonoscopy to screen for cancer, and 42% said they were late eaters. This group was 46% more likely than non–late eaters to have an adenoma found during colonoscopy. An estimated 5% to 10% of them become cancerous over time.
“A lot of other studies are about what we eat but not when we eat,” said Edena Khoshaba, lead investigator and a medical student at Rush University Medical College in Chicago. “The common advice includes not eating red meat, eating more fruits and vegetables — which is great, of course — but we wanted to see if the timing affects us at all.”
Ms. Khoshaba and colleagues found it did. Late eaters were 5.5 times more likely to have three or more tubular adenomas compared to non–late eaters, even after adjusting for what people were eating. Tubular adenomas are the most common type of polyp found in the colon.
So, what’s the possible connection between late eating and the risk for colorectal cancer?
Resetting Your Internal Clock
Eating close to bedtime could be throwing off the body’s circadian rhythm. But in this case, it’s not the central circadian center located in the brain — the one that releases melatonin. Instead, late eating could disrupt the peripheral circadian rhythm, part of which is found in the GI tract. For example, if a person is eating late at night, the brain thinks it is nighttime while the gut thinks it is daytime, Ms. Khoshaba said in an interview.
This is an interesting study, said Amy Bragagnini, MS, RD, spokesperson for the Academy of Nutrition and Dietetics, when asked to comment on the research. “It is true that eating later at night can disrupt your circadian rhythm.”
“In addition, many of my patients have told me that when they do eat later at night, they don’t always make the healthiest food choices,” Ms. Bragagnini said. “Their late-night food choices are generally higher in added sugar and fat. This may cause them to consume far more calories than their body needs.” So, eating late at night can also lead to unwanted weight gain.
An unanswered question is if late eating is connected in any way at all to increasing rates of colorectal cancer seen in younger patients.
This was an observational study, and another possible limitation, Ms. Khoshaba said, is that people were asked to recall their diets over 24 hours, which may not always be accurate.
Some of the organisms in the gut have their own internal clocks that follow a daily rhythm, and what someone eat determines how many different kinds of these organisms are active, Ms. Bragagnini said.
“So, if your late-night eating consists of foods high in sugar and fat, you may be negatively impacting your microbiome.” she said.
The next step for Ms. Khoshaba and colleagues is a study examining the peripheral circadian rhythm, changes in the gut microbiome, and the risk for developing metabolic syndrome. Ms. Khoshaba and Ms. Bragagnini had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM DDW 2024
Obesity and Cancer: Untangling a Complex Web
According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.
The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers.
Is obesity the new smoking? Not exactly.
While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.
Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?
There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?
When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.
A Consistent but Complicated Relationship
Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.
Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.
“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.
In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.
That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.
At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes.
It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.
Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.
One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells.
But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.
That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.
How Big Is the Effect?
While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably.
Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.
With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.
A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).
Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.
Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.
CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.
Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.
When Do Extra Pounds Matter?
When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?
Some evidence suggests there’s no “safe” time for putting on excess pounds.
A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years.
The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.
Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers.
An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.
There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.
But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.
“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”
Does Weight Loss Help?
With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.
Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.
Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers.
A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.
But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.
Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”
“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”
Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations.
People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week.
“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.
A version of this article appeared on Medscape.com.
According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.
The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers.
Is obesity the new smoking? Not exactly.
While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.
Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?
There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?
When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.
A Consistent but Complicated Relationship
Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.
Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.
“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.
In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.
That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.
At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes.
It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.
Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.
One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells.
But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.
That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.
How Big Is the Effect?
While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably.
Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.
With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.
A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).
Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.
Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.
CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.
Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.
When Do Extra Pounds Matter?
When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?
Some evidence suggests there’s no “safe” time for putting on excess pounds.
A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years.
The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.
Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers.
An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.
There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.
But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.
“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”
Does Weight Loss Help?
With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.
Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.
Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers.
A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.
But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.
Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”
“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”
Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations.
People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week.
“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.
A version of this article appeared on Medscape.com.
According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.
The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers.
Is obesity the new smoking? Not exactly.
While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.
Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?
There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?
When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.
A Consistent but Complicated Relationship
Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.
Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.
“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.
In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.
That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.
At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes.
It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.
Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.
One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells.
But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.
That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.
How Big Is the Effect?
While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably.
Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.
With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.
A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).
Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.
Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.
CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.
Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.
When Do Extra Pounds Matter?
When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?
Some evidence suggests there’s no “safe” time for putting on excess pounds.
A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years.
The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.
Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers.
An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.
There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.
But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.
“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”
Does Weight Loss Help?
With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.
Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.
Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers.
A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.
But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.
Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”
“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”
Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations.
People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week.
“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.
A version of this article appeared on Medscape.com.
Failed IOL Promotes Poor Maternal and Fetal Outcomes for Mothers With Diabetes
Approximately one-quarter of mothers with diabetes failed induction of labor, and this failure was associated with a range of adverse outcomes for mothers and infants, based on data from more than 2,000 individuals.
Uncontrolled diabetes remains a risk factor for cesarean delivery, Ali Alhousseini, MD, of Corewell Health East, Dearborn, Michigan, and colleagues wrote in a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
“Identifying and stratifying associated risk factors for failed induction of labor [IOL] may improve counseling and intrapartum care,” the researchers wrote in their abstract.
The researchers reviewed data from 2,172 mothers with diabetes who underwent IOL at a single university medical center between January 2013 and December 2021. They examined a range of maternal characteristics including age, ethnicity, gestational age, medical comorbidities, insulin administration, parity, and health insurance.
A total of 567 mothers with diabetes (26.1%) failed IOL and underwent cesarean delivery.
Overall, failed IOL was significantly associated with nulliparity (P = .0001), as well as preexisting diabetes compared with gestational diabetes, diabetes control with insulin, maternal essential hypertension, preeclampsia, and polyhydramnios (P = .001 for all). Other factors significantly associated with failed IOL included prenatal diagnosis of fetal growth restriction (P = .008), and placental abnormalities (P = .027).
Neonatal factors of weight, large for gestational age, head circumference, and height were not significantly associated with failed IOL (P > .05 for all).
As for neonatal outcomes, failed IOL was significantly associated with admission to neonatal intensive care unit, hyperbilirubinemia, and longer hospital stay (P = .001 for all). Failed IOL was significantly associated with lower 1-minute APGAR scores, but not with lower 5-minute APGAR scores, the researchers noted (P = .033 for 1-minute score). No association was noted between failed IOL and neonatal readmission, lower umbilical cord pH value, or maternal ethnicity.
The findings were limited by the retrospective design, but data analysis is ongoing, Dr. Alhousseini said. The researchers are continuing to assess the roles not only of optimal glucose control, but other maternal factors in improving maternal and neonatal outcomes, he said.
Data Add to Awareness of Risk Factors
The current study is important because of the increasing incidence of diabetes and the need to examine associated risk factors in pregnancy, Michael Richley, MD, a maternal fetal medicine physician at the University of Washington, Seattle, said in an interview. “The average age of onset of diabetes is becoming younger and type 2 diabetes in pregnancy is an increasingly common diagnosis,” said Dr. Richley, who was not involved in the study.
The increase in both maternal and neonatal adverse outcomes is expected given the risk factors identified in the study, said Dr. Richley. “The patients with diabetes also were sicker at baseline, with hypertensive disorders, growth restriction, and pregestational diabetes,” he noted.
The study findings support data from previous research, Dr. Richley said. The message to clinicians is that patients with diabetes not only have an increased risk of needing a cesarean delivery but also have an increased risk of poor outcomes if a cesarean delivery is needed, he said.
Although a prospective study would be useful to show causality as opposed to just an association, such a study is challenging in this patient population given the limitations of conducting research on labor and delivery, he said.
The study received no outside funding. The researchers and Dr. Richley had no financial conflicts to disclose.
Approximately one-quarter of mothers with diabetes failed induction of labor, and this failure was associated with a range of adverse outcomes for mothers and infants, based on data from more than 2,000 individuals.
Uncontrolled diabetes remains a risk factor for cesarean delivery, Ali Alhousseini, MD, of Corewell Health East, Dearborn, Michigan, and colleagues wrote in a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
“Identifying and stratifying associated risk factors for failed induction of labor [IOL] may improve counseling and intrapartum care,” the researchers wrote in their abstract.
The researchers reviewed data from 2,172 mothers with diabetes who underwent IOL at a single university medical center between January 2013 and December 2021. They examined a range of maternal characteristics including age, ethnicity, gestational age, medical comorbidities, insulin administration, parity, and health insurance.
A total of 567 mothers with diabetes (26.1%) failed IOL and underwent cesarean delivery.
Overall, failed IOL was significantly associated with nulliparity (P = .0001), as well as preexisting diabetes compared with gestational diabetes, diabetes control with insulin, maternal essential hypertension, preeclampsia, and polyhydramnios (P = .001 for all). Other factors significantly associated with failed IOL included prenatal diagnosis of fetal growth restriction (P = .008), and placental abnormalities (P = .027).
Neonatal factors of weight, large for gestational age, head circumference, and height were not significantly associated with failed IOL (P > .05 for all).
As for neonatal outcomes, failed IOL was significantly associated with admission to neonatal intensive care unit, hyperbilirubinemia, and longer hospital stay (P = .001 for all). Failed IOL was significantly associated with lower 1-minute APGAR scores, but not with lower 5-minute APGAR scores, the researchers noted (P = .033 for 1-minute score). No association was noted between failed IOL and neonatal readmission, lower umbilical cord pH value, or maternal ethnicity.
The findings were limited by the retrospective design, but data analysis is ongoing, Dr. Alhousseini said. The researchers are continuing to assess the roles not only of optimal glucose control, but other maternal factors in improving maternal and neonatal outcomes, he said.
Data Add to Awareness of Risk Factors
The current study is important because of the increasing incidence of diabetes and the need to examine associated risk factors in pregnancy, Michael Richley, MD, a maternal fetal medicine physician at the University of Washington, Seattle, said in an interview. “The average age of onset of diabetes is becoming younger and type 2 diabetes in pregnancy is an increasingly common diagnosis,” said Dr. Richley, who was not involved in the study.
The increase in both maternal and neonatal adverse outcomes is expected given the risk factors identified in the study, said Dr. Richley. “The patients with diabetes also were sicker at baseline, with hypertensive disorders, growth restriction, and pregestational diabetes,” he noted.
The study findings support data from previous research, Dr. Richley said. The message to clinicians is that patients with diabetes not only have an increased risk of needing a cesarean delivery but also have an increased risk of poor outcomes if a cesarean delivery is needed, he said.
Although a prospective study would be useful to show causality as opposed to just an association, such a study is challenging in this patient population given the limitations of conducting research on labor and delivery, he said.
The study received no outside funding. The researchers and Dr. Richley had no financial conflicts to disclose.
Approximately one-quarter of mothers with diabetes failed induction of labor, and this failure was associated with a range of adverse outcomes for mothers and infants, based on data from more than 2,000 individuals.
Uncontrolled diabetes remains a risk factor for cesarean delivery, Ali Alhousseini, MD, of Corewell Health East, Dearborn, Michigan, and colleagues wrote in a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
“Identifying and stratifying associated risk factors for failed induction of labor [IOL] may improve counseling and intrapartum care,” the researchers wrote in their abstract.
The researchers reviewed data from 2,172 mothers with diabetes who underwent IOL at a single university medical center between January 2013 and December 2021. They examined a range of maternal characteristics including age, ethnicity, gestational age, medical comorbidities, insulin administration, parity, and health insurance.
A total of 567 mothers with diabetes (26.1%) failed IOL and underwent cesarean delivery.
Overall, failed IOL was significantly associated with nulliparity (P = .0001), as well as preexisting diabetes compared with gestational diabetes, diabetes control with insulin, maternal essential hypertension, preeclampsia, and polyhydramnios (P = .001 for all). Other factors significantly associated with failed IOL included prenatal diagnosis of fetal growth restriction (P = .008), and placental abnormalities (P = .027).
Neonatal factors of weight, large for gestational age, head circumference, and height were not significantly associated with failed IOL (P > .05 for all).
As for neonatal outcomes, failed IOL was significantly associated with admission to neonatal intensive care unit, hyperbilirubinemia, and longer hospital stay (P = .001 for all). Failed IOL was significantly associated with lower 1-minute APGAR scores, but not with lower 5-minute APGAR scores, the researchers noted (P = .033 for 1-minute score). No association was noted between failed IOL and neonatal readmission, lower umbilical cord pH value, or maternal ethnicity.
The findings were limited by the retrospective design, but data analysis is ongoing, Dr. Alhousseini said. The researchers are continuing to assess the roles not only of optimal glucose control, but other maternal factors in improving maternal and neonatal outcomes, he said.
Data Add to Awareness of Risk Factors
The current study is important because of the increasing incidence of diabetes and the need to examine associated risk factors in pregnancy, Michael Richley, MD, a maternal fetal medicine physician at the University of Washington, Seattle, said in an interview. “The average age of onset of diabetes is becoming younger and type 2 diabetes in pregnancy is an increasingly common diagnosis,” said Dr. Richley, who was not involved in the study.
The increase in both maternal and neonatal adverse outcomes is expected given the risk factors identified in the study, said Dr. Richley. “The patients with diabetes also were sicker at baseline, with hypertensive disorders, growth restriction, and pregestational diabetes,” he noted.
The study findings support data from previous research, Dr. Richley said. The message to clinicians is that patients with diabetes not only have an increased risk of needing a cesarean delivery but also have an increased risk of poor outcomes if a cesarean delivery is needed, he said.
Although a prospective study would be useful to show causality as opposed to just an association, such a study is challenging in this patient population given the limitations of conducting research on labor and delivery, he said.
The study received no outside funding. The researchers and Dr. Richley had no financial conflicts to disclose.
FROM ACOG 2024