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Mortality increases substantially with fibrosis stage in NAFLD
The risks of all-cause and liver-related mortality increase substantially based on fibrosis stage in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD), according to a study published in Clinical Gastroenterology and Hepatology.
In particular, patients with NAFLD and advanced fibrosis have a threefold higher risk of all-cause mortality and 10-fold higher risk of liver-related mortality, as compared with patients with NAFLD but not advanced fibrosis, Cheng Han Ng, with the National University of Singapore, and colleagues wrote.
they wrote. “In addition, these findings have important implications for clinical trial design and highlight the importance of developing therapeutics.”
Although previous studies have found higher risks of all-cause and liver-related mortality in patients with NAFLD with increasing fibrosis stages, they examined the risk of mortality in reference to stage 0 fibrosis and didn’t include comparisons across different stages of fibrosis. In addition, the studies typically used pooled risk ratios, didn’t account for time-to-event analysis, or incorporate the most recent data.
The study investigators conducted an updated time-to-event meta-analysis to understand the impact of fibrosis stage on all-cause and liver-related mortality in biopsy-confirmed NAFLD. In addition, they pooled the survival estimates of individual fibrosis stages based on reconstructed individual patient data and compared mortality between fibrosis stages.
In 14 included studies, 17,301 patients had biopsy-proven NAFLD, including 6,069 assessed for overall mortality and 3,421 for liver-related mortality. The studies were conducted in the United States, Canada, Sweden, Israel, Japan, and Hong Kong, with four multicenter studies across multiple regions. The median follow-up duration was 7.7 years, and the average age of patients was 50.5.
For nonadvanced fibrosis (F0-F2), the 1-, 3-, 5-, 8-, and 10-year all-cause mortality were 0.1%, 1.9%, 3.3%, 6%, and 7.7%, respectively. For clinically significant fibrosis (F2-F4), the rates were 0.3%, 8.4%, 14%, 23.7%, and 29.3%, respectively. For advanced fibrosis (F3-F4), the rates were 0.3%, 8.8%, 14.9%, 25.5%, and 32.2%, respectively. For cirrhosis (F4), the rates were 0.3%, 13%, 20.6%, 33.3%, and 41.5%, respectively.
Compared with F0 as a reference, there were no statistically significant differences in all-cause mortality for F1. However, the risk significantly increased for F2 (HR, 1.46; 95% confidence interval, 1.08-1.98; P 1⁄4 .01), F3 (HR, 1.96; 95% CI, 1.41-2.72; P < .01), and F4 (HR, 3.66; 95% CI, 2.65-5.05; P < .01). In addition, early fibrosis (F1-F2) resulted in a statistically significant increase in all-cause mortality, as did the presence of clinically significant fibrosis or advanced fibrosis.
Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in a statistically significant increase in mortality (HR, 2.06; 95% CI, 1.52-2.81; P < .01).
Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a significantly increased risk of mortality (HR, 3.32; 95% CI, 2.38-4.65; P < .01).
In a comparison between F3 and F4, F4 resulted in a statistically significant increase in mortality (HR, 2.67; 95% CI, 1.47-4.83; P < .01). In a sensitivity analysis with three studies including nonalcoholic steatohepatitis, patients with NASH had a significantly increased risk of mortality in F4 (HR, 5.08; 95% CI, 2.70-9.55; P < .01).
For liver-related mortality, F1 didn’t result in a statistically significant increase, as compared with F0. However, increased risks were found for F2 (HR, 4.07; 95% CI, 1.44-11.5; P < .01), F3 (HR, 7.59; 95% CI, 2.80-20.5; P < .01), and F4 (HR, 15.1; 95% CI, 5.27-43.4; P < .01). In addition, any fibrosis (F1-F4) resulted in an increased risk of mortality, early fibrosis resulted in a borderline nonsignificant increase, and clinically significant or advanced fibrosis led to an increased risk.
Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in an increase in liver-related mortality (HR, 6.49; 95% CI, 3.30-12.8; P < .01).
Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a statistically significant increase in liver-related mortality (HR, 10.4; 95% CI, 6.18-17.5; P < .01).
In a comparison between F3 and F4, F4 resulted in a significant increase in liver-related mortality (HR, 2.57; 95% CI, 1.22-5.42; P < .01).
Although the presence of F4 leads to the greatest risk of mortality, selection criteria in NASH clinical trials have predominately targeted patients with F0-F3, the authors wrote.
“NASH is currently the fastest growing cause for liver transplant and [transplant] remains the only known curative treatment for cirrhosis,” they wrote. “However, with the global shortage of suitable grafts for transplant and lack of viable treatment, our results highlight that there is an urgent need for an efficacious treatment for patients with NASH and F4.”
The researchers outlined several limitations of their study. The development of hepatocellular carcinoma and its effects on survival were outside the scope of the study, they wrote. Analysis of liver-related mortality by proportion was not conducted because of insufficient studies. Data were insufficient to perform subgroup analyses by gender, age, study design, medication use, and diagnostic modality for fibrosis stage.
The authors reported funding support from several national U.S. grants and disclosed consultant and advisory rules for numerous pharmaceutical companies.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases globally. This meta-analysis shows that all-cause mortality and liver-related mortality increase significantly and exponentially from fibrosis stage F2 onward. The findings have important implications for patients, care providers, health policy, and the NAFLD research agenda.
At the policy level, the significant increase in all-cause mortality even at early stages of NAFLD also highlights gaps in the need for coverage of well-established weight-loss treatments. While provisions of the Affordable Care Act have tried to reduce health disparities and improve access to weight-loss treatment, many health plans continue to limit or deny coverage for medications and bariatric surgery. Finally, the study emphasizes the urgency of conducting more research to establish successful treatments for individuals with advanced fibrosis, specifically those with cirrhosis.
Overall, the study provides valuable insights into mortality risks associated with different stages of fibrosis in NAFLD for all stakeholders in the NAFLD community.
Achita P. Desai, MD is an National Institutes of Health–funded clinician scientist, transplant hepatologist, and assistant professor in the division of gastroenterology and hepatology at Indiana University, Indianapolis. She reported no conflicts of interest.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases globally. This meta-analysis shows that all-cause mortality and liver-related mortality increase significantly and exponentially from fibrosis stage F2 onward. The findings have important implications for patients, care providers, health policy, and the NAFLD research agenda.
At the policy level, the significant increase in all-cause mortality even at early stages of NAFLD also highlights gaps in the need for coverage of well-established weight-loss treatments. While provisions of the Affordable Care Act have tried to reduce health disparities and improve access to weight-loss treatment, many health plans continue to limit or deny coverage for medications and bariatric surgery. Finally, the study emphasizes the urgency of conducting more research to establish successful treatments for individuals with advanced fibrosis, specifically those with cirrhosis.
Overall, the study provides valuable insights into mortality risks associated with different stages of fibrosis in NAFLD for all stakeholders in the NAFLD community.
Achita P. Desai, MD is an National Institutes of Health–funded clinician scientist, transplant hepatologist, and assistant professor in the division of gastroenterology and hepatology at Indiana University, Indianapolis. She reported no conflicts of interest.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases globally. This meta-analysis shows that all-cause mortality and liver-related mortality increase significantly and exponentially from fibrosis stage F2 onward. The findings have important implications for patients, care providers, health policy, and the NAFLD research agenda.
At the policy level, the significant increase in all-cause mortality even at early stages of NAFLD also highlights gaps in the need for coverage of well-established weight-loss treatments. While provisions of the Affordable Care Act have tried to reduce health disparities and improve access to weight-loss treatment, many health plans continue to limit or deny coverage for medications and bariatric surgery. Finally, the study emphasizes the urgency of conducting more research to establish successful treatments for individuals with advanced fibrosis, specifically those with cirrhosis.
Overall, the study provides valuable insights into mortality risks associated with different stages of fibrosis in NAFLD for all stakeholders in the NAFLD community.
Achita P. Desai, MD is an National Institutes of Health–funded clinician scientist, transplant hepatologist, and assistant professor in the division of gastroenterology and hepatology at Indiana University, Indianapolis. She reported no conflicts of interest.
The risks of all-cause and liver-related mortality increase substantially based on fibrosis stage in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD), according to a study published in Clinical Gastroenterology and Hepatology.
In particular, patients with NAFLD and advanced fibrosis have a threefold higher risk of all-cause mortality and 10-fold higher risk of liver-related mortality, as compared with patients with NAFLD but not advanced fibrosis, Cheng Han Ng, with the National University of Singapore, and colleagues wrote.
they wrote. “In addition, these findings have important implications for clinical trial design and highlight the importance of developing therapeutics.”
Although previous studies have found higher risks of all-cause and liver-related mortality in patients with NAFLD with increasing fibrosis stages, they examined the risk of mortality in reference to stage 0 fibrosis and didn’t include comparisons across different stages of fibrosis. In addition, the studies typically used pooled risk ratios, didn’t account for time-to-event analysis, or incorporate the most recent data.
The study investigators conducted an updated time-to-event meta-analysis to understand the impact of fibrosis stage on all-cause and liver-related mortality in biopsy-confirmed NAFLD. In addition, they pooled the survival estimates of individual fibrosis stages based on reconstructed individual patient data and compared mortality between fibrosis stages.
In 14 included studies, 17,301 patients had biopsy-proven NAFLD, including 6,069 assessed for overall mortality and 3,421 for liver-related mortality. The studies were conducted in the United States, Canada, Sweden, Israel, Japan, and Hong Kong, with four multicenter studies across multiple regions. The median follow-up duration was 7.7 years, and the average age of patients was 50.5.
For nonadvanced fibrosis (F0-F2), the 1-, 3-, 5-, 8-, and 10-year all-cause mortality were 0.1%, 1.9%, 3.3%, 6%, and 7.7%, respectively. For clinically significant fibrosis (F2-F4), the rates were 0.3%, 8.4%, 14%, 23.7%, and 29.3%, respectively. For advanced fibrosis (F3-F4), the rates were 0.3%, 8.8%, 14.9%, 25.5%, and 32.2%, respectively. For cirrhosis (F4), the rates were 0.3%, 13%, 20.6%, 33.3%, and 41.5%, respectively.
Compared with F0 as a reference, there were no statistically significant differences in all-cause mortality for F1. However, the risk significantly increased for F2 (HR, 1.46; 95% confidence interval, 1.08-1.98; P 1⁄4 .01), F3 (HR, 1.96; 95% CI, 1.41-2.72; P < .01), and F4 (HR, 3.66; 95% CI, 2.65-5.05; P < .01). In addition, early fibrosis (F1-F2) resulted in a statistically significant increase in all-cause mortality, as did the presence of clinically significant fibrosis or advanced fibrosis.
Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in a statistically significant increase in mortality (HR, 2.06; 95% CI, 1.52-2.81; P < .01).
Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a significantly increased risk of mortality (HR, 3.32; 95% CI, 2.38-4.65; P < .01).
In a comparison between F3 and F4, F4 resulted in a statistically significant increase in mortality (HR, 2.67; 95% CI, 1.47-4.83; P < .01). In a sensitivity analysis with three studies including nonalcoholic steatohepatitis, patients with NASH had a significantly increased risk of mortality in F4 (HR, 5.08; 95% CI, 2.70-9.55; P < .01).
For liver-related mortality, F1 didn’t result in a statistically significant increase, as compared with F0. However, increased risks were found for F2 (HR, 4.07; 95% CI, 1.44-11.5; P < .01), F3 (HR, 7.59; 95% CI, 2.80-20.5; P < .01), and F4 (HR, 15.1; 95% CI, 5.27-43.4; P < .01). In addition, any fibrosis (F1-F4) resulted in an increased risk of mortality, early fibrosis resulted in a borderline nonsignificant increase, and clinically significant or advanced fibrosis led to an increased risk.
Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in an increase in liver-related mortality (HR, 6.49; 95% CI, 3.30-12.8; P < .01).
Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a statistically significant increase in liver-related mortality (HR, 10.4; 95% CI, 6.18-17.5; P < .01).
In a comparison between F3 and F4, F4 resulted in a significant increase in liver-related mortality (HR, 2.57; 95% CI, 1.22-5.42; P < .01).
Although the presence of F4 leads to the greatest risk of mortality, selection criteria in NASH clinical trials have predominately targeted patients with F0-F3, the authors wrote.
“NASH is currently the fastest growing cause for liver transplant and [transplant] remains the only known curative treatment for cirrhosis,” they wrote. “However, with the global shortage of suitable grafts for transplant and lack of viable treatment, our results highlight that there is an urgent need for an efficacious treatment for patients with NASH and F4.”
The researchers outlined several limitations of their study. The development of hepatocellular carcinoma and its effects on survival were outside the scope of the study, they wrote. Analysis of liver-related mortality by proportion was not conducted because of insufficient studies. Data were insufficient to perform subgroup analyses by gender, age, study design, medication use, and diagnostic modality for fibrosis stage.
The authors reported funding support from several national U.S. grants and disclosed consultant and advisory rules for numerous pharmaceutical companies.
The risks of all-cause and liver-related mortality increase substantially based on fibrosis stage in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD), according to a study published in Clinical Gastroenterology and Hepatology.
In particular, patients with NAFLD and advanced fibrosis have a threefold higher risk of all-cause mortality and 10-fold higher risk of liver-related mortality, as compared with patients with NAFLD but not advanced fibrosis, Cheng Han Ng, with the National University of Singapore, and colleagues wrote.
they wrote. “In addition, these findings have important implications for clinical trial design and highlight the importance of developing therapeutics.”
Although previous studies have found higher risks of all-cause and liver-related mortality in patients with NAFLD with increasing fibrosis stages, they examined the risk of mortality in reference to stage 0 fibrosis and didn’t include comparisons across different stages of fibrosis. In addition, the studies typically used pooled risk ratios, didn’t account for time-to-event analysis, or incorporate the most recent data.
The study investigators conducted an updated time-to-event meta-analysis to understand the impact of fibrosis stage on all-cause and liver-related mortality in biopsy-confirmed NAFLD. In addition, they pooled the survival estimates of individual fibrosis stages based on reconstructed individual patient data and compared mortality between fibrosis stages.
In 14 included studies, 17,301 patients had biopsy-proven NAFLD, including 6,069 assessed for overall mortality and 3,421 for liver-related mortality. The studies were conducted in the United States, Canada, Sweden, Israel, Japan, and Hong Kong, with four multicenter studies across multiple regions. The median follow-up duration was 7.7 years, and the average age of patients was 50.5.
For nonadvanced fibrosis (F0-F2), the 1-, 3-, 5-, 8-, and 10-year all-cause mortality were 0.1%, 1.9%, 3.3%, 6%, and 7.7%, respectively. For clinically significant fibrosis (F2-F4), the rates were 0.3%, 8.4%, 14%, 23.7%, and 29.3%, respectively. For advanced fibrosis (F3-F4), the rates were 0.3%, 8.8%, 14.9%, 25.5%, and 32.2%, respectively. For cirrhosis (F4), the rates were 0.3%, 13%, 20.6%, 33.3%, and 41.5%, respectively.
Compared with F0 as a reference, there were no statistically significant differences in all-cause mortality for F1. However, the risk significantly increased for F2 (HR, 1.46; 95% confidence interval, 1.08-1.98; P 1⁄4 .01), F3 (HR, 1.96; 95% CI, 1.41-2.72; P < .01), and F4 (HR, 3.66; 95% CI, 2.65-5.05; P < .01). In addition, early fibrosis (F1-F2) resulted in a statistically significant increase in all-cause mortality, as did the presence of clinically significant fibrosis or advanced fibrosis.
Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in a statistically significant increase in mortality (HR, 2.06; 95% CI, 1.52-2.81; P < .01).
Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a significantly increased risk of mortality (HR, 3.32; 95% CI, 2.38-4.65; P < .01).
In a comparison between F3 and F4, F4 resulted in a statistically significant increase in mortality (HR, 2.67; 95% CI, 1.47-4.83; P < .01). In a sensitivity analysis with three studies including nonalcoholic steatohepatitis, patients with NASH had a significantly increased risk of mortality in F4 (HR, 5.08; 95% CI, 2.70-9.55; P < .01).
For liver-related mortality, F1 didn’t result in a statistically significant increase, as compared with F0. However, increased risks were found for F2 (HR, 4.07; 95% CI, 1.44-11.5; P < .01), F3 (HR, 7.59; 95% CI, 2.80-20.5; P < .01), and F4 (HR, 15.1; 95% CI, 5.27-43.4; P < .01). In addition, any fibrosis (F1-F4) resulted in an increased risk of mortality, early fibrosis resulted in a borderline nonsignificant increase, and clinically significant or advanced fibrosis led to an increased risk.
Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in an increase in liver-related mortality (HR, 6.49; 95% CI, 3.30-12.8; P < .01).
Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a statistically significant increase in liver-related mortality (HR, 10.4; 95% CI, 6.18-17.5; P < .01).
In a comparison between F3 and F4, F4 resulted in a significant increase in liver-related mortality (HR, 2.57; 95% CI, 1.22-5.42; P < .01).
Although the presence of F4 leads to the greatest risk of mortality, selection criteria in NASH clinical trials have predominately targeted patients with F0-F3, the authors wrote.
“NASH is currently the fastest growing cause for liver transplant and [transplant] remains the only known curative treatment for cirrhosis,” they wrote. “However, with the global shortage of suitable grafts for transplant and lack of viable treatment, our results highlight that there is an urgent need for an efficacious treatment for patients with NASH and F4.”
The researchers outlined several limitations of their study. The development of hepatocellular carcinoma and its effects on survival were outside the scope of the study, they wrote. Analysis of liver-related mortality by proportion was not conducted because of insufficient studies. Data were insufficient to perform subgroup analyses by gender, age, study design, medication use, and diagnostic modality for fibrosis stage.
The authors reported funding support from several national U.S. grants and disclosed consultant and advisory rules for numerous pharmaceutical companies.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Digital therapeutics could help patients with IBS
, according to a new review of available products.
These tools aren’t widely used by gastroenterologists yet, but the market is expected to grow broadly during the next decade.
“Digital therapeutics make so much sense and solve so many access issues,” coauthor William Chey, MD, chief of gastroenterology at the University of Michigan, Ann Arbor, said in an interview. “Because of this, their promise could easily outstrip their substance. We need to hold digital therapeutics companies accountable for proper evidence of benefit, so patients and doctors don’t end up chasing the latest shiny object.”
The review was published online in The American Journal of Gastroenterology.
Understanding the apps
IBS is most effectively treated with a combination of medications, diet changes, and behavioral interventions that are specific to the patient, the authors write. Cognitive behavioral therapy (CBT) and gut-directed hypnotherapy (GDH) have been effective at modifying behaviors and thought patterns, they add.
However, many gastroenterologists and their patients with IBS don’t have easy access to the mental health services component of integrated gastrointestinal (GI) care. DTx may offer a solution.
The review by Dr. Chey and colleagues is intended to serve as a primer for gastroenterologists about the current generation of DTx that provide virtual behavioral health interventions. For each product, they include a description of its services, evidence supporting its use, and other key information.
Mahana IBS, made by Mahana Therapeutics, is an FDA-approved, prescription-only CBT program for adults with IBS. The maximum out-of-pocket cost is $90. The product includes 10 sessions over 12 weeks.
Available as a mobile app or Web-based platform, Mahana IBS was validated in a randomized comparative effectiveness trial in a group of 558 patients, divided into three groups who received Web-based CBT, phone-based CBT, or treatment as usual. Before treatment, the mean IBS Symptom Severity Score for the entire group was 265.
At 12 weeks, the control group had an average reduction of 52.9 points, while the phone-based therapy group had a reduction of 133.3 points, and the Web-based therapy group had a reduction of 101.2 points. The average Work and Social Adjustment Scale (WSAS) decreased by an additional 3.5 points in the phone-based group and 3 points in the Web-based group, compared with the control group.
Zemedy, made by Bold Health, is a mobile app that provides virtual CBT through a chat bot for patients with IBS. It costs $19.49 per month or $154.99 per year. The app isn’t FDA-approved and doesn’t require a prescription.
The program includes six weekly psychoeducational modules with information about IBS and CBT, followed by CBT training modules. Users can chat with an automated system that provides computer-generated responses for support. A “flare module” supports patients when symptoms worsen.
Zemedy was evaluated in a crossover randomized controlled trial with 62 people in an active treatment group and 59 people in a wait-list control group. The app improved several measures, including self-reported IBS-quality of life, GI symptoms on the IBS rating scale, the Fear of Food Questionnaire, the Visceral Sensitivity Index, and the Depression Anxiety Stress Scale.
A larger clinical trial to validate the results is ongoing.
Regulora, made by metaMe Health, is an FDA-approved, prescription-only GDH program aimed at addressing abdominal pain related to IBS. The maximum out-of-pocket cost is $75. The protocols were developed by GI behavioral health researchers at the University of North Carolina at Chapel Hill. Available on a Web-based platform or as a mobile app, the program includes seven sessions of 30 minutes each over 12 weeks.
Regulora was evaluated in a randomized comparative effectiveness trial of 362 patients who used either this program or an app focused on muscle relaxation. The primary endpoint was the proportion of patients with a 30% or more reduction in abdominal pain intensity, and although the researchers found no significant difference between them, there was some relief. In the GDH group, 31% of participants reported a 30% or greater reduction in abdominal pain intensity, and 45% experienced a 30% or greater improvement in the proportion of stools with normal consistency.
The complete results of the trial still need to receive formal peer review and publication in a scientific journal.
Nerva, made by Mindset Health, is a GDH program delivered by mobile app or Web browser that costs $79.99 for 3 months. It isn’t FDA-approved and doesn’t require a prescription. The protocols were developed in collaboration with researchers from Monash University in Melbourne. The program features 6 weeks of daily sessions, psychoeducation readings, and breathing techniques.
Nerva was evaluated in an observational cohort study of 190 patients who completed all 42 sessions, typically within 2 months. About 64% responded to the program, with a 20 mm or greater symptom reduction on the Visual Analog Scale and median improvement of 33 mm. Participants also reported improvements in abdominal pain, bloating, dissatisfaction with stool consistency, flatulence, and nausea.
Results were reported as an abstract, and full findings from a formal randomized controlled trial aren’t yet available.
Patient and provider benefits
Although DTx tools are still in the early stages of development and validation, they can improve patient care and add value to a gastroenterologist’s practice, the authors write.
The products should undergo the same level of scientific rigor as pharmaceutical therapies, including randomized controlled trials in diverse patient groups, and patient data handling must be secure and transparent, the authors write. Cost analyses will be an important factor in clinical integration and adoption, they add.
“Change is inevitable, and the right change will bring benefits to providers and their patients,” Dr. Chey said. “Don’t be afraid of it, but do your due diligence before you embrace it. Our primer is intended to help providers conduct that due diligence.”
While behavioral health care is essential for many patients with IBS, there aren’t enough therapists with GI knowledge to meet the demand, Melissa Hunt, PhD, associate director of clinical training in psychology at the University of Pennsylvania, Philadelphia, said in an interview. The population prevalence of IBS is 6%, which means about 18 million people in the United States need guidance, she said.
Dr. Hunt, who wasn’t involved with this paper, has evaluated DTx options for patients with IBS, including the randomized controlled trial of Zemedy. Her research suggests that about 50% of IBS patients could benefit from self-help DTx.
“I get two to three new patient referrals a week and have a 6-month wait-list for my private practice,” Dr. Hunt said. “DTx is a cutting edge, evidence-based way to address the gaps in service and meet the needs of this population.”
The study didn’t receive any funding. The authors disclosed research, consultant, and leadership relationships with several companies not related to this report. Dr. Hunt declared no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
, according to a new review of available products.
These tools aren’t widely used by gastroenterologists yet, but the market is expected to grow broadly during the next decade.
“Digital therapeutics make so much sense and solve so many access issues,” coauthor William Chey, MD, chief of gastroenterology at the University of Michigan, Ann Arbor, said in an interview. “Because of this, their promise could easily outstrip their substance. We need to hold digital therapeutics companies accountable for proper evidence of benefit, so patients and doctors don’t end up chasing the latest shiny object.”
The review was published online in The American Journal of Gastroenterology.
Understanding the apps
IBS is most effectively treated with a combination of medications, diet changes, and behavioral interventions that are specific to the patient, the authors write. Cognitive behavioral therapy (CBT) and gut-directed hypnotherapy (GDH) have been effective at modifying behaviors and thought patterns, they add.
However, many gastroenterologists and their patients with IBS don’t have easy access to the mental health services component of integrated gastrointestinal (GI) care. DTx may offer a solution.
The review by Dr. Chey and colleagues is intended to serve as a primer for gastroenterologists about the current generation of DTx that provide virtual behavioral health interventions. For each product, they include a description of its services, evidence supporting its use, and other key information.
Mahana IBS, made by Mahana Therapeutics, is an FDA-approved, prescription-only CBT program for adults with IBS. The maximum out-of-pocket cost is $90. The product includes 10 sessions over 12 weeks.
Available as a mobile app or Web-based platform, Mahana IBS was validated in a randomized comparative effectiveness trial in a group of 558 patients, divided into three groups who received Web-based CBT, phone-based CBT, or treatment as usual. Before treatment, the mean IBS Symptom Severity Score for the entire group was 265.
At 12 weeks, the control group had an average reduction of 52.9 points, while the phone-based therapy group had a reduction of 133.3 points, and the Web-based therapy group had a reduction of 101.2 points. The average Work and Social Adjustment Scale (WSAS) decreased by an additional 3.5 points in the phone-based group and 3 points in the Web-based group, compared with the control group.
Zemedy, made by Bold Health, is a mobile app that provides virtual CBT through a chat bot for patients with IBS. It costs $19.49 per month or $154.99 per year. The app isn’t FDA-approved and doesn’t require a prescription.
The program includes six weekly psychoeducational modules with information about IBS and CBT, followed by CBT training modules. Users can chat with an automated system that provides computer-generated responses for support. A “flare module” supports patients when symptoms worsen.
Zemedy was evaluated in a crossover randomized controlled trial with 62 people in an active treatment group and 59 people in a wait-list control group. The app improved several measures, including self-reported IBS-quality of life, GI symptoms on the IBS rating scale, the Fear of Food Questionnaire, the Visceral Sensitivity Index, and the Depression Anxiety Stress Scale.
A larger clinical trial to validate the results is ongoing.
Regulora, made by metaMe Health, is an FDA-approved, prescription-only GDH program aimed at addressing abdominal pain related to IBS. The maximum out-of-pocket cost is $75. The protocols were developed by GI behavioral health researchers at the University of North Carolina at Chapel Hill. Available on a Web-based platform or as a mobile app, the program includes seven sessions of 30 minutes each over 12 weeks.
Regulora was evaluated in a randomized comparative effectiveness trial of 362 patients who used either this program or an app focused on muscle relaxation. The primary endpoint was the proportion of patients with a 30% or more reduction in abdominal pain intensity, and although the researchers found no significant difference between them, there was some relief. In the GDH group, 31% of participants reported a 30% or greater reduction in abdominal pain intensity, and 45% experienced a 30% or greater improvement in the proportion of stools with normal consistency.
The complete results of the trial still need to receive formal peer review and publication in a scientific journal.
Nerva, made by Mindset Health, is a GDH program delivered by mobile app or Web browser that costs $79.99 for 3 months. It isn’t FDA-approved and doesn’t require a prescription. The protocols were developed in collaboration with researchers from Monash University in Melbourne. The program features 6 weeks of daily sessions, psychoeducation readings, and breathing techniques.
Nerva was evaluated in an observational cohort study of 190 patients who completed all 42 sessions, typically within 2 months. About 64% responded to the program, with a 20 mm or greater symptom reduction on the Visual Analog Scale and median improvement of 33 mm. Participants also reported improvements in abdominal pain, bloating, dissatisfaction with stool consistency, flatulence, and nausea.
Results were reported as an abstract, and full findings from a formal randomized controlled trial aren’t yet available.
Patient and provider benefits
Although DTx tools are still in the early stages of development and validation, they can improve patient care and add value to a gastroenterologist’s practice, the authors write.
The products should undergo the same level of scientific rigor as pharmaceutical therapies, including randomized controlled trials in diverse patient groups, and patient data handling must be secure and transparent, the authors write. Cost analyses will be an important factor in clinical integration and adoption, they add.
“Change is inevitable, and the right change will bring benefits to providers and their patients,” Dr. Chey said. “Don’t be afraid of it, but do your due diligence before you embrace it. Our primer is intended to help providers conduct that due diligence.”
While behavioral health care is essential for many patients with IBS, there aren’t enough therapists with GI knowledge to meet the demand, Melissa Hunt, PhD, associate director of clinical training in psychology at the University of Pennsylvania, Philadelphia, said in an interview. The population prevalence of IBS is 6%, which means about 18 million people in the United States need guidance, she said.
Dr. Hunt, who wasn’t involved with this paper, has evaluated DTx options for patients with IBS, including the randomized controlled trial of Zemedy. Her research suggests that about 50% of IBS patients could benefit from self-help DTx.
“I get two to three new patient referrals a week and have a 6-month wait-list for my private practice,” Dr. Hunt said. “DTx is a cutting edge, evidence-based way to address the gaps in service and meet the needs of this population.”
The study didn’t receive any funding. The authors disclosed research, consultant, and leadership relationships with several companies not related to this report. Dr. Hunt declared no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
, according to a new review of available products.
These tools aren’t widely used by gastroenterologists yet, but the market is expected to grow broadly during the next decade.
“Digital therapeutics make so much sense and solve so many access issues,” coauthor William Chey, MD, chief of gastroenterology at the University of Michigan, Ann Arbor, said in an interview. “Because of this, their promise could easily outstrip their substance. We need to hold digital therapeutics companies accountable for proper evidence of benefit, so patients and doctors don’t end up chasing the latest shiny object.”
The review was published online in The American Journal of Gastroenterology.
Understanding the apps
IBS is most effectively treated with a combination of medications, diet changes, and behavioral interventions that are specific to the patient, the authors write. Cognitive behavioral therapy (CBT) and gut-directed hypnotherapy (GDH) have been effective at modifying behaviors and thought patterns, they add.
However, many gastroenterologists and their patients with IBS don’t have easy access to the mental health services component of integrated gastrointestinal (GI) care. DTx may offer a solution.
The review by Dr. Chey and colleagues is intended to serve as a primer for gastroenterologists about the current generation of DTx that provide virtual behavioral health interventions. For each product, they include a description of its services, evidence supporting its use, and other key information.
Mahana IBS, made by Mahana Therapeutics, is an FDA-approved, prescription-only CBT program for adults with IBS. The maximum out-of-pocket cost is $90. The product includes 10 sessions over 12 weeks.
Available as a mobile app or Web-based platform, Mahana IBS was validated in a randomized comparative effectiveness trial in a group of 558 patients, divided into three groups who received Web-based CBT, phone-based CBT, or treatment as usual. Before treatment, the mean IBS Symptom Severity Score for the entire group was 265.
At 12 weeks, the control group had an average reduction of 52.9 points, while the phone-based therapy group had a reduction of 133.3 points, and the Web-based therapy group had a reduction of 101.2 points. The average Work and Social Adjustment Scale (WSAS) decreased by an additional 3.5 points in the phone-based group and 3 points in the Web-based group, compared with the control group.
Zemedy, made by Bold Health, is a mobile app that provides virtual CBT through a chat bot for patients with IBS. It costs $19.49 per month or $154.99 per year. The app isn’t FDA-approved and doesn’t require a prescription.
The program includes six weekly psychoeducational modules with information about IBS and CBT, followed by CBT training modules. Users can chat with an automated system that provides computer-generated responses for support. A “flare module” supports patients when symptoms worsen.
Zemedy was evaluated in a crossover randomized controlled trial with 62 people in an active treatment group and 59 people in a wait-list control group. The app improved several measures, including self-reported IBS-quality of life, GI symptoms on the IBS rating scale, the Fear of Food Questionnaire, the Visceral Sensitivity Index, and the Depression Anxiety Stress Scale.
A larger clinical trial to validate the results is ongoing.
Regulora, made by metaMe Health, is an FDA-approved, prescription-only GDH program aimed at addressing abdominal pain related to IBS. The maximum out-of-pocket cost is $75. The protocols were developed by GI behavioral health researchers at the University of North Carolina at Chapel Hill. Available on a Web-based platform or as a mobile app, the program includes seven sessions of 30 minutes each over 12 weeks.
Regulora was evaluated in a randomized comparative effectiveness trial of 362 patients who used either this program or an app focused on muscle relaxation. The primary endpoint was the proportion of patients with a 30% or more reduction in abdominal pain intensity, and although the researchers found no significant difference between them, there was some relief. In the GDH group, 31% of participants reported a 30% or greater reduction in abdominal pain intensity, and 45% experienced a 30% or greater improvement in the proportion of stools with normal consistency.
The complete results of the trial still need to receive formal peer review and publication in a scientific journal.
Nerva, made by Mindset Health, is a GDH program delivered by mobile app or Web browser that costs $79.99 for 3 months. It isn’t FDA-approved and doesn’t require a prescription. The protocols were developed in collaboration with researchers from Monash University in Melbourne. The program features 6 weeks of daily sessions, psychoeducation readings, and breathing techniques.
Nerva was evaluated in an observational cohort study of 190 patients who completed all 42 sessions, typically within 2 months. About 64% responded to the program, with a 20 mm or greater symptom reduction on the Visual Analog Scale and median improvement of 33 mm. Participants also reported improvements in abdominal pain, bloating, dissatisfaction with stool consistency, flatulence, and nausea.
Results were reported as an abstract, and full findings from a formal randomized controlled trial aren’t yet available.
Patient and provider benefits
Although DTx tools are still in the early stages of development and validation, they can improve patient care and add value to a gastroenterologist’s practice, the authors write.
The products should undergo the same level of scientific rigor as pharmaceutical therapies, including randomized controlled trials in diverse patient groups, and patient data handling must be secure and transparent, the authors write. Cost analyses will be an important factor in clinical integration and adoption, they add.
“Change is inevitable, and the right change will bring benefits to providers and their patients,” Dr. Chey said. “Don’t be afraid of it, but do your due diligence before you embrace it. Our primer is intended to help providers conduct that due diligence.”
While behavioral health care is essential for many patients with IBS, there aren’t enough therapists with GI knowledge to meet the demand, Melissa Hunt, PhD, associate director of clinical training in psychology at the University of Pennsylvania, Philadelphia, said in an interview. The population prevalence of IBS is 6%, which means about 18 million people in the United States need guidance, she said.
Dr. Hunt, who wasn’t involved with this paper, has evaluated DTx options for patients with IBS, including the randomized controlled trial of Zemedy. Her research suggests that about 50% of IBS patients could benefit from self-help DTx.
“I get two to three new patient referrals a week and have a 6-month wait-list for my private practice,” Dr. Hunt said. “DTx is a cutting edge, evidence-based way to address the gaps in service and meet the needs of this population.”
The study didn’t receive any funding. The authors disclosed research, consultant, and leadership relationships with several companies not related to this report. Dr. Hunt declared no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY
Pancreatic cancer incidence increases among young women in U.S.
Between 2001 and 2018, there was a greater than 200% difference in the incidence trend between men and women for ages 15-34, wrote Yazan Abboud, MD, a postdoctoral research fellow in the pancreaticobiliary department of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai Medical Center, Los Angeles, and colleagues.
“The exact cause of the trend among younger women is unclear and may be driven by sex-based disproportional exposure or response to known or yet-to-be-explored risk factors,” they wrote. “Future efforts should aim to elucidate the causes of such a trend with the goal to formulate possible preventive measures.”
Although previous studies have found increasing pancreatic cancer incidence rates, especially in younger women, the data haven’t been externally validated outside of the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) data, they wrote. In addition, there are limited data about the contributing factors, such as race, histopathological subtype, tumor location, and stage at diagnosis.
Using SEER-excluded data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR), Dr. Abboud and colleagues conducted a population-based time-trend analysis of pancreatic cancer incidence rates from 2001 to 2018 in younger adults under age 55, including the role of demographics and tumor characteristics. They analyzed age-adjusted incidence rates (aIR), mortality rates, annual percentage change (APC), and average annual percentage change (AAPC) for ages 55 and older and ages 55 and younger. In addition, the research team evaluated the impact of incidence trends on sex-specific mortality trends in younger adults using the CDC’s National Center of Health Statistics database.
Between 2001 and 2018, 748,132 patients were diagnosed with pancreatic cancer. After excluding SEER data, 454,611 patients met the inclusion criteria. About 48.9% were women.
The overall aIR of pancreatic cancer during that time was 12.18 per 100,000 people. Women had a significantly lower aIR, at 10.69 per 100,000, compared with men at 13.95 per 100,000.
In general, pancreatic cancer aIR significantly increased during that time (AAPC = 1.17%). Sex-specific trends increased among both women (AAPC = 1.27%) and men (AAPC = 1.14%), though they showed no significant difference and were parallel.
In ages 55 and older, 401,419 patients (49.7% women) were diagnosed with pancreatic cancer. The aIR significantly increased during the study period (AAPC = 1.11%), with sex-specific aIR increasing in both women (AAPC = 1.11%) and men (AAPC = 1.17%), without a significant difference.
However, a difference appeared in the 53,051 patients (42.9% women) who were ages 55 and younger. The aIR relatively increased (AAPC = 1.29%), with faster jumps in women (AAPC = 2.36%), compared with men (AAPC = .62%). There was an absolute significant difference of 1.74%.
The trends continued in breakdowns by age. For 50,599 patients (42.2% women) between ages 35 and 54, the aIR relatively increased (AAPC = 1.10%). Sex-specific aIR increased among women (AAPC = 2.09%) but remained stable among men (AAPC = 0.54%), with an absolute significant difference of 1.55%.
In the youngest cohort of 2,452 patients (57.3% women) between ages 15 and 34, aIR relatively increased (AAPC = 4.93). Sex-specific aIR also increased in both women (AAPC = 6.45%) and men (AAPC = 2.97%), with an absolute significant difference of 3.48%.
By race, although White women under age 55 experienced increasing aIR at a greater rate than men (AAPC difference = 1.59%), an even more dramatic increase was seen in Black women, as compared to counterpart men (AAPC difference = 2.23%). Sex-specific trends in people of other races were parallel.
Based on tumor characteristics in ages 55 and younger, the pancreatic ductal adenocarcinoma histopathological subtype had an AAPC difference of 0.89%, and a tumor location in the head-of-pancreas had an AAPC difference of 1.64%.
When evaluating tumors based on stage-at-diagnosis, the AAPC difference was nonsignificant in all subgroups. However, sex-specific trends differed in tumors diagnosed at localized stages, suggesting that aIR in women may be increasing at a greater rate than in men (AAPC difference = 1.64%).
Among 64,239 patients (39.3% women) who died from pancreatic cancer under age 55, the mortality rates were unchanged in women (AAPC = –0.09%) but declined in men (AAPC = –0.64%), with an absolute significant AAPC difference of 0.54%.
“Pancreatic cancer has a very poor overall survival, accounting for 7% of cancer-related deaths. The incidence of cancers, in general, is expected to rise as life expectancy increases in the United States,” said Danny Issa, MD, a gastroenterologist at the University of California, Los Angeles, who wasn’t involved with this study.
“Recently, noncomparative studies showed a possible increase in the incidence of pancreatic cancer in younger White women and in older White men and women. These reports had limitations,” he said. “The findings of this study are monumental as they confirmed that age-adjusted incidence rates have been increasing at a higher rate in younger women compared to younger men.”
In addition, Dr. Issa said, the significant increases among Black women for adenocarcinoma and for cancers located in the head of the pancreas are notable and should be studied further.
“Over the past few decades, research studies have helped improve cancer treatment by uncovering risk factors and identifying the most affected (or protected) population,” he said. “Therefore, epidemiologic studies are crucial, especially for hard-to-treat cancers such as pancreatic cancer.”
The study was supported in part by a philanthropic grant from The Widjaja Family Fund for Pancreatic Cancer Research. The authors disclosed no conflicts of interest. Dr. Issa reported no relevant disclosures.
Between 2001 and 2018, there was a greater than 200% difference in the incidence trend between men and women for ages 15-34, wrote Yazan Abboud, MD, a postdoctoral research fellow in the pancreaticobiliary department of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai Medical Center, Los Angeles, and colleagues.
“The exact cause of the trend among younger women is unclear and may be driven by sex-based disproportional exposure or response to known or yet-to-be-explored risk factors,” they wrote. “Future efforts should aim to elucidate the causes of such a trend with the goal to formulate possible preventive measures.”
Although previous studies have found increasing pancreatic cancer incidence rates, especially in younger women, the data haven’t been externally validated outside of the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) data, they wrote. In addition, there are limited data about the contributing factors, such as race, histopathological subtype, tumor location, and stage at diagnosis.
Using SEER-excluded data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR), Dr. Abboud and colleagues conducted a population-based time-trend analysis of pancreatic cancer incidence rates from 2001 to 2018 in younger adults under age 55, including the role of demographics and tumor characteristics. They analyzed age-adjusted incidence rates (aIR), mortality rates, annual percentage change (APC), and average annual percentage change (AAPC) for ages 55 and older and ages 55 and younger. In addition, the research team evaluated the impact of incidence trends on sex-specific mortality trends in younger adults using the CDC’s National Center of Health Statistics database.
Between 2001 and 2018, 748,132 patients were diagnosed with pancreatic cancer. After excluding SEER data, 454,611 patients met the inclusion criteria. About 48.9% were women.
The overall aIR of pancreatic cancer during that time was 12.18 per 100,000 people. Women had a significantly lower aIR, at 10.69 per 100,000, compared with men at 13.95 per 100,000.
In general, pancreatic cancer aIR significantly increased during that time (AAPC = 1.17%). Sex-specific trends increased among both women (AAPC = 1.27%) and men (AAPC = 1.14%), though they showed no significant difference and were parallel.
In ages 55 and older, 401,419 patients (49.7% women) were diagnosed with pancreatic cancer. The aIR significantly increased during the study period (AAPC = 1.11%), with sex-specific aIR increasing in both women (AAPC = 1.11%) and men (AAPC = 1.17%), without a significant difference.
However, a difference appeared in the 53,051 patients (42.9% women) who were ages 55 and younger. The aIR relatively increased (AAPC = 1.29%), with faster jumps in women (AAPC = 2.36%), compared with men (AAPC = .62%). There was an absolute significant difference of 1.74%.
The trends continued in breakdowns by age. For 50,599 patients (42.2% women) between ages 35 and 54, the aIR relatively increased (AAPC = 1.10%). Sex-specific aIR increased among women (AAPC = 2.09%) but remained stable among men (AAPC = 0.54%), with an absolute significant difference of 1.55%.
In the youngest cohort of 2,452 patients (57.3% women) between ages 15 and 34, aIR relatively increased (AAPC = 4.93). Sex-specific aIR also increased in both women (AAPC = 6.45%) and men (AAPC = 2.97%), with an absolute significant difference of 3.48%.
By race, although White women under age 55 experienced increasing aIR at a greater rate than men (AAPC difference = 1.59%), an even more dramatic increase was seen in Black women, as compared to counterpart men (AAPC difference = 2.23%). Sex-specific trends in people of other races were parallel.
Based on tumor characteristics in ages 55 and younger, the pancreatic ductal adenocarcinoma histopathological subtype had an AAPC difference of 0.89%, and a tumor location in the head-of-pancreas had an AAPC difference of 1.64%.
When evaluating tumors based on stage-at-diagnosis, the AAPC difference was nonsignificant in all subgroups. However, sex-specific trends differed in tumors diagnosed at localized stages, suggesting that aIR in women may be increasing at a greater rate than in men (AAPC difference = 1.64%).
Among 64,239 patients (39.3% women) who died from pancreatic cancer under age 55, the mortality rates were unchanged in women (AAPC = –0.09%) but declined in men (AAPC = –0.64%), with an absolute significant AAPC difference of 0.54%.
“Pancreatic cancer has a very poor overall survival, accounting for 7% of cancer-related deaths. The incidence of cancers, in general, is expected to rise as life expectancy increases in the United States,” said Danny Issa, MD, a gastroenterologist at the University of California, Los Angeles, who wasn’t involved with this study.
“Recently, noncomparative studies showed a possible increase in the incidence of pancreatic cancer in younger White women and in older White men and women. These reports had limitations,” he said. “The findings of this study are monumental as they confirmed that age-adjusted incidence rates have been increasing at a higher rate in younger women compared to younger men.”
In addition, Dr. Issa said, the significant increases among Black women for adenocarcinoma and for cancers located in the head of the pancreas are notable and should be studied further.
“Over the past few decades, research studies have helped improve cancer treatment by uncovering risk factors and identifying the most affected (or protected) population,” he said. “Therefore, epidemiologic studies are crucial, especially for hard-to-treat cancers such as pancreatic cancer.”
The study was supported in part by a philanthropic grant from The Widjaja Family Fund for Pancreatic Cancer Research. The authors disclosed no conflicts of interest. Dr. Issa reported no relevant disclosures.
Between 2001 and 2018, there was a greater than 200% difference in the incidence trend between men and women for ages 15-34, wrote Yazan Abboud, MD, a postdoctoral research fellow in the pancreaticobiliary department of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai Medical Center, Los Angeles, and colleagues.
“The exact cause of the trend among younger women is unclear and may be driven by sex-based disproportional exposure or response to known or yet-to-be-explored risk factors,” they wrote. “Future efforts should aim to elucidate the causes of such a trend with the goal to formulate possible preventive measures.”
Although previous studies have found increasing pancreatic cancer incidence rates, especially in younger women, the data haven’t been externally validated outside of the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) data, they wrote. In addition, there are limited data about the contributing factors, such as race, histopathological subtype, tumor location, and stage at diagnosis.
Using SEER-excluded data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR), Dr. Abboud and colleagues conducted a population-based time-trend analysis of pancreatic cancer incidence rates from 2001 to 2018 in younger adults under age 55, including the role of demographics and tumor characteristics. They analyzed age-adjusted incidence rates (aIR), mortality rates, annual percentage change (APC), and average annual percentage change (AAPC) for ages 55 and older and ages 55 and younger. In addition, the research team evaluated the impact of incidence trends on sex-specific mortality trends in younger adults using the CDC’s National Center of Health Statistics database.
Between 2001 and 2018, 748,132 patients were diagnosed with pancreatic cancer. After excluding SEER data, 454,611 patients met the inclusion criteria. About 48.9% were women.
The overall aIR of pancreatic cancer during that time was 12.18 per 100,000 people. Women had a significantly lower aIR, at 10.69 per 100,000, compared with men at 13.95 per 100,000.
In general, pancreatic cancer aIR significantly increased during that time (AAPC = 1.17%). Sex-specific trends increased among both women (AAPC = 1.27%) and men (AAPC = 1.14%), though they showed no significant difference and were parallel.
In ages 55 and older, 401,419 patients (49.7% women) were diagnosed with pancreatic cancer. The aIR significantly increased during the study period (AAPC = 1.11%), with sex-specific aIR increasing in both women (AAPC = 1.11%) and men (AAPC = 1.17%), without a significant difference.
However, a difference appeared in the 53,051 patients (42.9% women) who were ages 55 and younger. The aIR relatively increased (AAPC = 1.29%), with faster jumps in women (AAPC = 2.36%), compared with men (AAPC = .62%). There was an absolute significant difference of 1.74%.
The trends continued in breakdowns by age. For 50,599 patients (42.2% women) between ages 35 and 54, the aIR relatively increased (AAPC = 1.10%). Sex-specific aIR increased among women (AAPC = 2.09%) but remained stable among men (AAPC = 0.54%), with an absolute significant difference of 1.55%.
In the youngest cohort of 2,452 patients (57.3% women) between ages 15 and 34, aIR relatively increased (AAPC = 4.93). Sex-specific aIR also increased in both women (AAPC = 6.45%) and men (AAPC = 2.97%), with an absolute significant difference of 3.48%.
By race, although White women under age 55 experienced increasing aIR at a greater rate than men (AAPC difference = 1.59%), an even more dramatic increase was seen in Black women, as compared to counterpart men (AAPC difference = 2.23%). Sex-specific trends in people of other races were parallel.
Based on tumor characteristics in ages 55 and younger, the pancreatic ductal adenocarcinoma histopathological subtype had an AAPC difference of 0.89%, and a tumor location in the head-of-pancreas had an AAPC difference of 1.64%.
When evaluating tumors based on stage-at-diagnosis, the AAPC difference was nonsignificant in all subgroups. However, sex-specific trends differed in tumors diagnosed at localized stages, suggesting that aIR in women may be increasing at a greater rate than in men (AAPC difference = 1.64%).
Among 64,239 patients (39.3% women) who died from pancreatic cancer under age 55, the mortality rates were unchanged in women (AAPC = –0.09%) but declined in men (AAPC = –0.64%), with an absolute significant AAPC difference of 0.54%.
“Pancreatic cancer has a very poor overall survival, accounting for 7% of cancer-related deaths. The incidence of cancers, in general, is expected to rise as life expectancy increases in the United States,” said Danny Issa, MD, a gastroenterologist at the University of California, Los Angeles, who wasn’t involved with this study.
“Recently, noncomparative studies showed a possible increase in the incidence of pancreatic cancer in younger White women and in older White men and women. These reports had limitations,” he said. “The findings of this study are monumental as they confirmed that age-adjusted incidence rates have been increasing at a higher rate in younger women compared to younger men.”
In addition, Dr. Issa said, the significant increases among Black women for adenocarcinoma and for cancers located in the head of the pancreas are notable and should be studied further.
“Over the past few decades, research studies have helped improve cancer treatment by uncovering risk factors and identifying the most affected (or protected) population,” he said. “Therefore, epidemiologic studies are crucial, especially for hard-to-treat cancers such as pancreatic cancer.”
The study was supported in part by a philanthropic grant from The Widjaja Family Fund for Pancreatic Cancer Research. The authors disclosed no conflicts of interest. Dr. Issa reported no relevant disclosures.
FROM GASTROENTEROLOGY
Irregular sleep tied to markers of atherosclerosis
a new report suggests.
In particular, variation in sleep duration of more than 2 hours per night in the same week was tied to higher rates of atherosclerosis.
“Poor sleep is linked with several cardiovascular conditions, including heart disease, hypertension, and type 2 diabetes,” lead author Kelsie M. Full, PhD, MPH, assistant professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.
“Overall, we found that participants who slept varying amounts of hours throughout the week (meaning that one night they slept less, one night they slept more) were more likely to have atherosclerosis than participants who slept about the same amount of time each night,” she said.
The study was published online in the Journal of the American Heart Association.
Analyzing associations
Dr. Full and colleagues examined data from 2032 participants in the Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study, which included adults aged between 45 and 84 years in six U.S. communities who completed 7-day wrist actigraphy assessment and kept a sleep diary between 2010 and 2013.
For subclinical markers of cardiovascular disease, participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and ankle-brachial index.
The research team assessed sleep duration, or the total number of minutes of sleep in a night, and sleep timing regularity, which was determined on the basis of the time someone initially fell asleep each night. They adjusted for cardiovascular disease risk factors and sleep characteristics, such as obstructive sleep apnea, sleep duration, and sleep fragmentation.
The average age of the participants was 68.6 years, and 53.6% were women. About 37.9% identified as White, 27.6% as Black or African American, 23.4% as Hispanic American, and 11.1% as Chinese American.
During the 7-day period, about 38% of participants experienced a change in sleep duration of more than 90 minutes, and 18% experienced a sleep duration change of more than 120 minutes. Those who had irregular sleep were more likely to be non-White, current smokers, have lower average annual incomes, have work shift schedules or did not work, and have a higher average body mass index.
For the study, sleep duration irregularity was defined as a standard deviation of more than 120 minutes. Those participants who had a greater degree of sleep irregularity were more likely to have high coronary artery calcium burden than those whose sleep duration was more more regular, defined as an SD of 60 minutes or less (> 300; prevalence ratio, 1.33; 95% confidence interval, 1.03-1.71), as well as abnormal ankle-brachial index (< 0.9, prevalence ratio, 1.75;95% CI, 1.03-2.95).
Further, those with irregular sleep timing (SD > 90 minutes) were more likely to have a high coronary artery calcium burden (prevalence ratio, 1.39; 95% CI, 1.07-1.82) in comparison with those with more regular sleep timing (SD < 30 minutes).
“The biggest surprise to me was that 30% of the participants in the study had total sleep times that varied by more than 90 minutes over the course of the week,” Dr. Full said. “This is consistent with prior studies that suggest that a large proportion of the general public have irregular sleep patterns, not just shift workers.”
Investigating next steps
In additional analyses, Dr. Full and colleagues found that sleep duration regularity continued to be associated with high coronary artery calcium burden and abnormal ankle-brachial index when accounting for severe obstructive sleep apnea, average nightly sleep duration, and average sleep fragmentation.
Notably, when sleep duration was added, all participants with more irregular sleep durations (SD > 60 minutes) were more likely to have a high coronary artery calcium burden, compared with those with regular sleep durations (SD < 60 minutes). The results remained when participants who reported shift work, including night shift work, were excluded.
Additional studies are needed to understand the mechanisms, the study authors wrote. Night-to-night variability in sleep duration and sleep timing can cause desynchronization in the sleep-wake timing and circadian disruption.
“A key issue highlighted in this study is that sleep irregularity itself, independent of how much sleep people were getting, was related to heart health. Sleep is a naturally recurring phenomenon, and maintaining regularity helps provide stability and predictability to the body,” Michael Grandner, PhD, associate professor of psychiatry and director of the sleep and health research program at the University of Arizona, Tucson, said in an interview.
Dr. Grandner, who wasn’t involved with this study, has researched sleep irregularity and associations with cardiovascular disease, diabetes, obesity, and many other adverse outcomes.
“When people have very irregular sleep schedules, it may make it harder for the body to optimally make good use of the sleep it is getting, since it such a moving target,” he said. “The unique angle here is the ability to focus on regularity of sleep.”
The study was supported by the National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health. One author received grants and consulting fees from pharmaceutical companies unrelated to the research. The other authors and Dr. Grandner disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
a new report suggests.
In particular, variation in sleep duration of more than 2 hours per night in the same week was tied to higher rates of atherosclerosis.
“Poor sleep is linked with several cardiovascular conditions, including heart disease, hypertension, and type 2 diabetes,” lead author Kelsie M. Full, PhD, MPH, assistant professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.
“Overall, we found that participants who slept varying amounts of hours throughout the week (meaning that one night they slept less, one night they slept more) were more likely to have atherosclerosis than participants who slept about the same amount of time each night,” she said.
The study was published online in the Journal of the American Heart Association.
Analyzing associations
Dr. Full and colleagues examined data from 2032 participants in the Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study, which included adults aged between 45 and 84 years in six U.S. communities who completed 7-day wrist actigraphy assessment and kept a sleep diary between 2010 and 2013.
For subclinical markers of cardiovascular disease, participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and ankle-brachial index.
The research team assessed sleep duration, or the total number of minutes of sleep in a night, and sleep timing regularity, which was determined on the basis of the time someone initially fell asleep each night. They adjusted for cardiovascular disease risk factors and sleep characteristics, such as obstructive sleep apnea, sleep duration, and sleep fragmentation.
The average age of the participants was 68.6 years, and 53.6% were women. About 37.9% identified as White, 27.6% as Black or African American, 23.4% as Hispanic American, and 11.1% as Chinese American.
During the 7-day period, about 38% of participants experienced a change in sleep duration of more than 90 minutes, and 18% experienced a sleep duration change of more than 120 minutes. Those who had irregular sleep were more likely to be non-White, current smokers, have lower average annual incomes, have work shift schedules or did not work, and have a higher average body mass index.
For the study, sleep duration irregularity was defined as a standard deviation of more than 120 minutes. Those participants who had a greater degree of sleep irregularity were more likely to have high coronary artery calcium burden than those whose sleep duration was more more regular, defined as an SD of 60 minutes or less (> 300; prevalence ratio, 1.33; 95% confidence interval, 1.03-1.71), as well as abnormal ankle-brachial index (< 0.9, prevalence ratio, 1.75;95% CI, 1.03-2.95).
Further, those with irregular sleep timing (SD > 90 minutes) were more likely to have a high coronary artery calcium burden (prevalence ratio, 1.39; 95% CI, 1.07-1.82) in comparison with those with more regular sleep timing (SD < 30 minutes).
“The biggest surprise to me was that 30% of the participants in the study had total sleep times that varied by more than 90 minutes over the course of the week,” Dr. Full said. “This is consistent with prior studies that suggest that a large proportion of the general public have irregular sleep patterns, not just shift workers.”
Investigating next steps
In additional analyses, Dr. Full and colleagues found that sleep duration regularity continued to be associated with high coronary artery calcium burden and abnormal ankle-brachial index when accounting for severe obstructive sleep apnea, average nightly sleep duration, and average sleep fragmentation.
Notably, when sleep duration was added, all participants with more irregular sleep durations (SD > 60 minutes) were more likely to have a high coronary artery calcium burden, compared with those with regular sleep durations (SD < 60 minutes). The results remained when participants who reported shift work, including night shift work, were excluded.
Additional studies are needed to understand the mechanisms, the study authors wrote. Night-to-night variability in sleep duration and sleep timing can cause desynchronization in the sleep-wake timing and circadian disruption.
“A key issue highlighted in this study is that sleep irregularity itself, independent of how much sleep people were getting, was related to heart health. Sleep is a naturally recurring phenomenon, and maintaining regularity helps provide stability and predictability to the body,” Michael Grandner, PhD, associate professor of psychiatry and director of the sleep and health research program at the University of Arizona, Tucson, said in an interview.
Dr. Grandner, who wasn’t involved with this study, has researched sleep irregularity and associations with cardiovascular disease, diabetes, obesity, and many other adverse outcomes.
“When people have very irregular sleep schedules, it may make it harder for the body to optimally make good use of the sleep it is getting, since it such a moving target,” he said. “The unique angle here is the ability to focus on regularity of sleep.”
The study was supported by the National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health. One author received grants and consulting fees from pharmaceutical companies unrelated to the research. The other authors and Dr. Grandner disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
a new report suggests.
In particular, variation in sleep duration of more than 2 hours per night in the same week was tied to higher rates of atherosclerosis.
“Poor sleep is linked with several cardiovascular conditions, including heart disease, hypertension, and type 2 diabetes,” lead author Kelsie M. Full, PhD, MPH, assistant professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.
“Overall, we found that participants who slept varying amounts of hours throughout the week (meaning that one night they slept less, one night they slept more) were more likely to have atherosclerosis than participants who slept about the same amount of time each night,” she said.
The study was published online in the Journal of the American Heart Association.
Analyzing associations
Dr. Full and colleagues examined data from 2032 participants in the Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study, which included adults aged between 45 and 84 years in six U.S. communities who completed 7-day wrist actigraphy assessment and kept a sleep diary between 2010 and 2013.
For subclinical markers of cardiovascular disease, participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and ankle-brachial index.
The research team assessed sleep duration, or the total number of minutes of sleep in a night, and sleep timing regularity, which was determined on the basis of the time someone initially fell asleep each night. They adjusted for cardiovascular disease risk factors and sleep characteristics, such as obstructive sleep apnea, sleep duration, and sleep fragmentation.
The average age of the participants was 68.6 years, and 53.6% were women. About 37.9% identified as White, 27.6% as Black or African American, 23.4% as Hispanic American, and 11.1% as Chinese American.
During the 7-day period, about 38% of participants experienced a change in sleep duration of more than 90 minutes, and 18% experienced a sleep duration change of more than 120 minutes. Those who had irregular sleep were more likely to be non-White, current smokers, have lower average annual incomes, have work shift schedules or did not work, and have a higher average body mass index.
For the study, sleep duration irregularity was defined as a standard deviation of more than 120 minutes. Those participants who had a greater degree of sleep irregularity were more likely to have high coronary artery calcium burden than those whose sleep duration was more more regular, defined as an SD of 60 minutes or less (> 300; prevalence ratio, 1.33; 95% confidence interval, 1.03-1.71), as well as abnormal ankle-brachial index (< 0.9, prevalence ratio, 1.75;95% CI, 1.03-2.95).
Further, those with irregular sleep timing (SD > 90 minutes) were more likely to have a high coronary artery calcium burden (prevalence ratio, 1.39; 95% CI, 1.07-1.82) in comparison with those with more regular sleep timing (SD < 30 minutes).
“The biggest surprise to me was that 30% of the participants in the study had total sleep times that varied by more than 90 minutes over the course of the week,” Dr. Full said. “This is consistent with prior studies that suggest that a large proportion of the general public have irregular sleep patterns, not just shift workers.”
Investigating next steps
In additional analyses, Dr. Full and colleagues found that sleep duration regularity continued to be associated with high coronary artery calcium burden and abnormal ankle-brachial index when accounting for severe obstructive sleep apnea, average nightly sleep duration, and average sleep fragmentation.
Notably, when sleep duration was added, all participants with more irregular sleep durations (SD > 60 minutes) were more likely to have a high coronary artery calcium burden, compared with those with regular sleep durations (SD < 60 minutes). The results remained when participants who reported shift work, including night shift work, were excluded.
Additional studies are needed to understand the mechanisms, the study authors wrote. Night-to-night variability in sleep duration and sleep timing can cause desynchronization in the sleep-wake timing and circadian disruption.
“A key issue highlighted in this study is that sleep irregularity itself, independent of how much sleep people were getting, was related to heart health. Sleep is a naturally recurring phenomenon, and maintaining regularity helps provide stability and predictability to the body,” Michael Grandner, PhD, associate professor of psychiatry and director of the sleep and health research program at the University of Arizona, Tucson, said in an interview.
Dr. Grandner, who wasn’t involved with this study, has researched sleep irregularity and associations with cardiovascular disease, diabetes, obesity, and many other adverse outcomes.
“When people have very irregular sleep schedules, it may make it harder for the body to optimally make good use of the sleep it is getting, since it such a moving target,” he said. “The unique angle here is the ability to focus on regularity of sleep.”
The study was supported by the National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health. One author received grants and consulting fees from pharmaceutical companies unrelated to the research. The other authors and Dr. Grandner disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN HEART ASSOCIATION
Advanced imaging technology could help predict lung cancer progression after surgery
, according to new data.
The technology, known as highly multiplexed imaging mass cytometry (IMC), can provide cellular-level detail of the tumor immune microenvironment, which may allow clinicians to identify patients who need additional treatment, as well as those who don’t.
“It is well known that the frequency of certain cell populations within the tumor microenvironment correlates with clinical outcomes. These observations help us understand the biology underlying cancer progression,” senior author Logan Walsh, PhD, assistant professor of human genetics and the Rosalind Goodman Chair in Lung Cancer Research at McGill University’s Rosalind and Morris Goodman Cancer Institute, Montreal, said in an interview.
“We wanted to test whether using completely unbiased AI could find and use the spatial topography of the tumor microenvironment from IMC data to predict clinical outcomes,” he said. “It turns out the answer is yes! AI can predict clinical outcomes when combined with IMC with extremely high accuracy from a single 1-mm2 tumor core.”
The study was published on in Nature.
The immune landscape
Lung cancer is the leading cause of cancer-related death in Canada, surpassing breast, colon, and prostate cancer deaths combined, the study authors write.
Lung adenocarcinoma, a non–small cell lung cancer, is the most common subtype and is characterized by distinct cellular and molecular features. The tumor immune microenvironment influences disease progression and therapy response, the authors write. Understanding the spatial landscape of the microenvironment could provide insight into disease progression, therapeutic vulnerabilities, and biomarkers of response to existing treatments.
In a collaborative study, Dr. Walsh and colleagues from McGill University and Université Laval profiled the cellular composition and spatial organization of the tumor immune microenvironment in tumors from 416 patients with lung adenocarcinoma across five histologic patterns. They used IMC to assess at samples from the universities’ biobanks that patients had provided for research purposes.
The research team detected more than 1.6 million cells, which allowed spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. They used a supervised lineage assignment approach to classify 14 distinct immune cell populations, along with tumor cells and endothelial cells.
High-grade solid tumors had the greatest immune infiltrate (44.6%), compared with micropapillary (37%), acinar (39.7%), papillary (32.8%), and lepidic architectures (32.7%). Macrophages were the most frequent cell population in the tumor immune microenvironment, representing 12.3% of total cells and 34.1% of immune cells.
The prevalence of CD163+ macrophages was strongly correlated with FOXP3+ immunoregulatory T cells in the solid pattern. This relationship was less pronounced in low-grade lepidic and papillary architectures. This finding could suggest an interplay between macrophage and T-cell populations in the tumor immune microenvironment across lung adenocarcinoma patterns.
Using a deep neural network model, the researchers also analyzed the relationship between immune populations and clinical or pathologic variables by examining the frequency of individual cell types as a percentage of total cells in each image. Each image was cross-referenced with clinical data from patients, including sex, age, body mass index, smoking status, stage, progression, survival, and histologic subtype.
Overall, the researchers found that various clinical outcomes, including cancer progression, could be predicted with high accuracy using a single 1-mm2 tumor core. For instance, they could predict progression in stage IA and IB resected lung cancer with 95.9% accuracy.
Additional applications
“We were not surprised that AI was able to predict clinical outcomes, but we were surprised that it was able to do so with such high accuracy and precision,” said Dr. Walsh. “We were also surprised to learn that our predictions were equally accurate using only six-plex data, compared with 35-plex. This hinted to us that we could potentially scale down the number of markers to a practical number that would be amenable to technologies available in routine pathology labs.”
Dr. Walsh and colleagues are now validating the predictive tool using a lower-plex technology. In addition, they are investigating the immune landscapes of primary and metastatic brain tumors.
“This study is important, as it helps us to understand and appreciate the biological and mechanistic factors that may influence treatment outcomes. Our standard clinical predictors for predicting risk of recurrence and probability of response to therapy are not optimal,” Yee Ung, MD, an associate professor of radiation oncology at Sunnybrook Health Sciences Centre, Toronto, said in an interview.
Dr. Ung, who wasn’t involved with this study, has researched noninvasive hypoxia imaging and targeting in lung cancer. Ideally, he said, future studies should incorporate the use of noninvasive imaging predictive factors, in addition to the tumor immune microenvironment and clinical factors, to predict outcomes and provide personalized treatment.
“As we begin to investigate and understand more about cancer biology down to the cellular and molecular level, we need to strategically use AI methodologies in the processing and analysis of data,” he said.
The study was supported by the McGill Interdisciplinary Initiative in Infection and Immunity, the Brain Tumour Funders’ Collaborative, the Canadian Institutes of Health Research, and the Canadian Foundation for Innovation. Dr. Walsh and Dr. Ung have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to new data.
The technology, known as highly multiplexed imaging mass cytometry (IMC), can provide cellular-level detail of the tumor immune microenvironment, which may allow clinicians to identify patients who need additional treatment, as well as those who don’t.
“It is well known that the frequency of certain cell populations within the tumor microenvironment correlates with clinical outcomes. These observations help us understand the biology underlying cancer progression,” senior author Logan Walsh, PhD, assistant professor of human genetics and the Rosalind Goodman Chair in Lung Cancer Research at McGill University’s Rosalind and Morris Goodman Cancer Institute, Montreal, said in an interview.
“We wanted to test whether using completely unbiased AI could find and use the spatial topography of the tumor microenvironment from IMC data to predict clinical outcomes,” he said. “It turns out the answer is yes! AI can predict clinical outcomes when combined with IMC with extremely high accuracy from a single 1-mm2 tumor core.”
The study was published on in Nature.
The immune landscape
Lung cancer is the leading cause of cancer-related death in Canada, surpassing breast, colon, and prostate cancer deaths combined, the study authors write.
Lung adenocarcinoma, a non–small cell lung cancer, is the most common subtype and is characterized by distinct cellular and molecular features. The tumor immune microenvironment influences disease progression and therapy response, the authors write. Understanding the spatial landscape of the microenvironment could provide insight into disease progression, therapeutic vulnerabilities, and biomarkers of response to existing treatments.
In a collaborative study, Dr. Walsh and colleagues from McGill University and Université Laval profiled the cellular composition and spatial organization of the tumor immune microenvironment in tumors from 416 patients with lung adenocarcinoma across five histologic patterns. They used IMC to assess at samples from the universities’ biobanks that patients had provided for research purposes.
The research team detected more than 1.6 million cells, which allowed spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. They used a supervised lineage assignment approach to classify 14 distinct immune cell populations, along with tumor cells and endothelial cells.
High-grade solid tumors had the greatest immune infiltrate (44.6%), compared with micropapillary (37%), acinar (39.7%), papillary (32.8%), and lepidic architectures (32.7%). Macrophages were the most frequent cell population in the tumor immune microenvironment, representing 12.3% of total cells and 34.1% of immune cells.
The prevalence of CD163+ macrophages was strongly correlated with FOXP3+ immunoregulatory T cells in the solid pattern. This relationship was less pronounced in low-grade lepidic and papillary architectures. This finding could suggest an interplay between macrophage and T-cell populations in the tumor immune microenvironment across lung adenocarcinoma patterns.
Using a deep neural network model, the researchers also analyzed the relationship between immune populations and clinical or pathologic variables by examining the frequency of individual cell types as a percentage of total cells in each image. Each image was cross-referenced with clinical data from patients, including sex, age, body mass index, smoking status, stage, progression, survival, and histologic subtype.
Overall, the researchers found that various clinical outcomes, including cancer progression, could be predicted with high accuracy using a single 1-mm2 tumor core. For instance, they could predict progression in stage IA and IB resected lung cancer with 95.9% accuracy.
Additional applications
“We were not surprised that AI was able to predict clinical outcomes, but we were surprised that it was able to do so with such high accuracy and precision,” said Dr. Walsh. “We were also surprised to learn that our predictions were equally accurate using only six-plex data, compared with 35-plex. This hinted to us that we could potentially scale down the number of markers to a practical number that would be amenable to technologies available in routine pathology labs.”
Dr. Walsh and colleagues are now validating the predictive tool using a lower-plex technology. In addition, they are investigating the immune landscapes of primary and metastatic brain tumors.
“This study is important, as it helps us to understand and appreciate the biological and mechanistic factors that may influence treatment outcomes. Our standard clinical predictors for predicting risk of recurrence and probability of response to therapy are not optimal,” Yee Ung, MD, an associate professor of radiation oncology at Sunnybrook Health Sciences Centre, Toronto, said in an interview.
Dr. Ung, who wasn’t involved with this study, has researched noninvasive hypoxia imaging and targeting in lung cancer. Ideally, he said, future studies should incorporate the use of noninvasive imaging predictive factors, in addition to the tumor immune microenvironment and clinical factors, to predict outcomes and provide personalized treatment.
“As we begin to investigate and understand more about cancer biology down to the cellular and molecular level, we need to strategically use AI methodologies in the processing and analysis of data,” he said.
The study was supported by the McGill Interdisciplinary Initiative in Infection and Immunity, the Brain Tumour Funders’ Collaborative, the Canadian Institutes of Health Research, and the Canadian Foundation for Innovation. Dr. Walsh and Dr. Ung have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to new data.
The technology, known as highly multiplexed imaging mass cytometry (IMC), can provide cellular-level detail of the tumor immune microenvironment, which may allow clinicians to identify patients who need additional treatment, as well as those who don’t.
“It is well known that the frequency of certain cell populations within the tumor microenvironment correlates with clinical outcomes. These observations help us understand the biology underlying cancer progression,” senior author Logan Walsh, PhD, assistant professor of human genetics and the Rosalind Goodman Chair in Lung Cancer Research at McGill University’s Rosalind and Morris Goodman Cancer Institute, Montreal, said in an interview.
“We wanted to test whether using completely unbiased AI could find and use the spatial topography of the tumor microenvironment from IMC data to predict clinical outcomes,” he said. “It turns out the answer is yes! AI can predict clinical outcomes when combined with IMC with extremely high accuracy from a single 1-mm2 tumor core.”
The study was published on in Nature.
The immune landscape
Lung cancer is the leading cause of cancer-related death in Canada, surpassing breast, colon, and prostate cancer deaths combined, the study authors write.
Lung adenocarcinoma, a non–small cell lung cancer, is the most common subtype and is characterized by distinct cellular and molecular features. The tumor immune microenvironment influences disease progression and therapy response, the authors write. Understanding the spatial landscape of the microenvironment could provide insight into disease progression, therapeutic vulnerabilities, and biomarkers of response to existing treatments.
In a collaborative study, Dr. Walsh and colleagues from McGill University and Université Laval profiled the cellular composition and spatial organization of the tumor immune microenvironment in tumors from 416 patients with lung adenocarcinoma across five histologic patterns. They used IMC to assess at samples from the universities’ biobanks that patients had provided for research purposes.
The research team detected more than 1.6 million cells, which allowed spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. They used a supervised lineage assignment approach to classify 14 distinct immune cell populations, along with tumor cells and endothelial cells.
High-grade solid tumors had the greatest immune infiltrate (44.6%), compared with micropapillary (37%), acinar (39.7%), papillary (32.8%), and lepidic architectures (32.7%). Macrophages were the most frequent cell population in the tumor immune microenvironment, representing 12.3% of total cells and 34.1% of immune cells.
The prevalence of CD163+ macrophages was strongly correlated with FOXP3+ immunoregulatory T cells in the solid pattern. This relationship was less pronounced in low-grade lepidic and papillary architectures. This finding could suggest an interplay between macrophage and T-cell populations in the tumor immune microenvironment across lung adenocarcinoma patterns.
Using a deep neural network model, the researchers also analyzed the relationship between immune populations and clinical or pathologic variables by examining the frequency of individual cell types as a percentage of total cells in each image. Each image was cross-referenced with clinical data from patients, including sex, age, body mass index, smoking status, stage, progression, survival, and histologic subtype.
Overall, the researchers found that various clinical outcomes, including cancer progression, could be predicted with high accuracy using a single 1-mm2 tumor core. For instance, they could predict progression in stage IA and IB resected lung cancer with 95.9% accuracy.
Additional applications
“We were not surprised that AI was able to predict clinical outcomes, but we were surprised that it was able to do so with such high accuracy and precision,” said Dr. Walsh. “We were also surprised to learn that our predictions were equally accurate using only six-plex data, compared with 35-plex. This hinted to us that we could potentially scale down the number of markers to a practical number that would be amenable to technologies available in routine pathology labs.”
Dr. Walsh and colleagues are now validating the predictive tool using a lower-plex technology. In addition, they are investigating the immune landscapes of primary and metastatic brain tumors.
“This study is important, as it helps us to understand and appreciate the biological and mechanistic factors that may influence treatment outcomes. Our standard clinical predictors for predicting risk of recurrence and probability of response to therapy are not optimal,” Yee Ung, MD, an associate professor of radiation oncology at Sunnybrook Health Sciences Centre, Toronto, said in an interview.
Dr. Ung, who wasn’t involved with this study, has researched noninvasive hypoxia imaging and targeting in lung cancer. Ideally, he said, future studies should incorporate the use of noninvasive imaging predictive factors, in addition to the tumor immune microenvironment and clinical factors, to predict outcomes and provide personalized treatment.
“As we begin to investigate and understand more about cancer biology down to the cellular and molecular level, we need to strategically use AI methodologies in the processing and analysis of data,” he said.
The study was supported by the McGill Interdisciplinary Initiative in Infection and Immunity, the Brain Tumour Funders’ Collaborative, the Canadian Institutes of Health Research, and the Canadian Foundation for Innovation. Dr. Walsh and Dr. Ung have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NATURE
Novel celery seed–derived drug may improve stroke outcomes
a new report suggests.
Patients treated with butylphthalide had fewer severe neurologic symptoms and better function 90 days after the stroke, compared with those receiving placebo.
Butylphthalide is approved and available for use in China, where the study was conducted. However, the medication hasn’t been approved for use by the U.S. Food and Drug Administration.
“Patients who received butylphthalide had less severe neurological symptoms and a better living status at 90 days post stroke, compared to those who received the placebo,” said coauthor Baixue Jia, MD, an attending physician in interventional neuroradiology at the Beijing Tiantan Hospital of Capital Medical University and a faculty member at the China National Clinical Research Center for Neurological Diseases in Beijing. “If the results are confirmed in other trials, this may lead to more options to treat strokes caused by clots.”
The study was presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
Studying stroke outcomes
The researchers described butylphthalide as a cerebroprotective drug that was originally extracted from seeds of Apium graveolens. In China, previous studies have shown that the drug has cerebroprotective effects in animal models of ischemia-reperfusion, they noted.
In this randomized, double-blind, placebo-controlled trial, Dr. Jia and colleagues evaluated whether treatment with butylphthalide could improve 90-day outcomes for adults with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (tPA), endovascular treatment, or both.
The participants were treated at one of 59 medical centers in China between July 2018 and February 2022. Those who had minimal stroke symptoms on their initial exam, defined as a score of 0-3 on the National Institutes of Health Stroke Scale, or had severe stroke symptoms, defined as having a score of 26 or higher on the NIHSS, were excluded from the study.
Along with an initial revascularization intervention chosen by their physician, participants were randomly selected to receive either butylphthalide or a placebo daily for 90 days. The drug was administered through daily intravenous injections for the first 14 days, after which patients received oral capsules for 76 days.
The research team defined the outcomes as “favorable” if a patient fell into one of the following categories 90 days after the stroke: an initially mild to moderate stroke (NIHSS, 4-7) and no symptoms after treatment, defined as a score of 0 on the Modified Rankin Scale (mRS), which measures disability and dependence; an initially moderate to serious stroke (NIHSS, 8-14) and no residual symptoms or mild symptoms that don’t impair the ability to perform routine activities of daily living without assistance (mRS, 0-1); or an initially serious to severe stroke (NIHSS, 15-25) and no remaining symptoms or a slight disability that impairs some activities but allows one to conduct daily living without assistance (mRS, 0-2).
Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke, and mortality.
Among the 1,216 participants, 607 were assigned to the treatment group, and 609 were assigned to the placebo group. The average age was 66 years, and 68% were men.
Overall, participants in the butylphthalide group were 70% more likely to have a favorable 90-day outcome, compared with the placebo group. Favorable outcomes occurred in 344 patients (56.7%) in the butylphthalide group, compared with 268 patients (44%) in the placebo group (odds ratio, 1.70; 95% confidence interval, 1.35-2.14; P < .001).
In addition, butylphthalide improved function equally well for the patients who initially received tPA, those who received endovascular treatment, and those who received both tPA and endovascular treatment.
Secondary events, such as recurrent stroke and intracranial hemorrhage, weren’t significantly different between the butylphthalide and placebo groups.
Ongoing questions
Dr. Jia and colleagues noted the need to understand how butylphthalide works in the brain. Animal studies have suggested several possible mechanisms, but it remains unclear.
“The next step should be investigating the exact mechanisms of butylphthalide in humans,” Dr. Jia said.
Additional research should assess the medication in other populations, the authors noted, particularly because the study involved participants who received initial treatment with tPA, endovascular treatment, or both. The results may not be generalizable to stroke patients who receive other treatments or to populations outside of China.
“While these are interesting results, this is only one relatively small study on a fairly select population in China. Butylphthalide, a medication initially compounded from celery seed, is not ready for use in standard stroke treatment,” said Daniel Lackland, DrPH, professor of neurology and director of the division of translational neurosciences and population studies at the Medical University of South Carolina, Charleston.
Dr. Lackland, who wasn’t involved with the study, is a member of the American Stroke Association’s Stroke Council. Although butylphthalide was originally extracted from seeds, he noted, it’s not what patients would find commercially available.
“The medication used in this study is not the same as celery seed or celery seed extract supplements,” he said. “Stroke survivors should always consult with their neurologist or healthcare professional regarding diet after a stroke.”
The study was funded by the National Key Technology Research and Development Program of the Ministry of Science and Technology of the People’s Republic of China and Shijiazhuang Pharmaceutical Group dl-3-butylphthalide Pharmaceutical. Several authors are employed with Beijing Tiantan Hospital and the Beijing Institute of Brain Disorders. Dr. Lackland reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
a new report suggests.
Patients treated with butylphthalide had fewer severe neurologic symptoms and better function 90 days after the stroke, compared with those receiving placebo.
Butylphthalide is approved and available for use in China, where the study was conducted. However, the medication hasn’t been approved for use by the U.S. Food and Drug Administration.
“Patients who received butylphthalide had less severe neurological symptoms and a better living status at 90 days post stroke, compared to those who received the placebo,” said coauthor Baixue Jia, MD, an attending physician in interventional neuroradiology at the Beijing Tiantan Hospital of Capital Medical University and a faculty member at the China National Clinical Research Center for Neurological Diseases in Beijing. “If the results are confirmed in other trials, this may lead to more options to treat strokes caused by clots.”
The study was presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
Studying stroke outcomes
The researchers described butylphthalide as a cerebroprotective drug that was originally extracted from seeds of Apium graveolens. In China, previous studies have shown that the drug has cerebroprotective effects in animal models of ischemia-reperfusion, they noted.
In this randomized, double-blind, placebo-controlled trial, Dr. Jia and colleagues evaluated whether treatment with butylphthalide could improve 90-day outcomes for adults with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (tPA), endovascular treatment, or both.
The participants were treated at one of 59 medical centers in China between July 2018 and February 2022. Those who had minimal stroke symptoms on their initial exam, defined as a score of 0-3 on the National Institutes of Health Stroke Scale, or had severe stroke symptoms, defined as having a score of 26 or higher on the NIHSS, were excluded from the study.
Along with an initial revascularization intervention chosen by their physician, participants were randomly selected to receive either butylphthalide or a placebo daily for 90 days. The drug was administered through daily intravenous injections for the first 14 days, after which patients received oral capsules for 76 days.
The research team defined the outcomes as “favorable” if a patient fell into one of the following categories 90 days after the stroke: an initially mild to moderate stroke (NIHSS, 4-7) and no symptoms after treatment, defined as a score of 0 on the Modified Rankin Scale (mRS), which measures disability and dependence; an initially moderate to serious stroke (NIHSS, 8-14) and no residual symptoms or mild symptoms that don’t impair the ability to perform routine activities of daily living without assistance (mRS, 0-1); or an initially serious to severe stroke (NIHSS, 15-25) and no remaining symptoms or a slight disability that impairs some activities but allows one to conduct daily living without assistance (mRS, 0-2).
Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke, and mortality.
Among the 1,216 participants, 607 were assigned to the treatment group, and 609 were assigned to the placebo group. The average age was 66 years, and 68% were men.
Overall, participants in the butylphthalide group were 70% more likely to have a favorable 90-day outcome, compared with the placebo group. Favorable outcomes occurred in 344 patients (56.7%) in the butylphthalide group, compared with 268 patients (44%) in the placebo group (odds ratio, 1.70; 95% confidence interval, 1.35-2.14; P < .001).
In addition, butylphthalide improved function equally well for the patients who initially received tPA, those who received endovascular treatment, and those who received both tPA and endovascular treatment.
Secondary events, such as recurrent stroke and intracranial hemorrhage, weren’t significantly different between the butylphthalide and placebo groups.
Ongoing questions
Dr. Jia and colleagues noted the need to understand how butylphthalide works in the brain. Animal studies have suggested several possible mechanisms, but it remains unclear.
“The next step should be investigating the exact mechanisms of butylphthalide in humans,” Dr. Jia said.
Additional research should assess the medication in other populations, the authors noted, particularly because the study involved participants who received initial treatment with tPA, endovascular treatment, or both. The results may not be generalizable to stroke patients who receive other treatments or to populations outside of China.
“While these are interesting results, this is only one relatively small study on a fairly select population in China. Butylphthalide, a medication initially compounded from celery seed, is not ready for use in standard stroke treatment,” said Daniel Lackland, DrPH, professor of neurology and director of the division of translational neurosciences and population studies at the Medical University of South Carolina, Charleston.
Dr. Lackland, who wasn’t involved with the study, is a member of the American Stroke Association’s Stroke Council. Although butylphthalide was originally extracted from seeds, he noted, it’s not what patients would find commercially available.
“The medication used in this study is not the same as celery seed or celery seed extract supplements,” he said. “Stroke survivors should always consult with their neurologist or healthcare professional regarding diet after a stroke.”
The study was funded by the National Key Technology Research and Development Program of the Ministry of Science and Technology of the People’s Republic of China and Shijiazhuang Pharmaceutical Group dl-3-butylphthalide Pharmaceutical. Several authors are employed with Beijing Tiantan Hospital and the Beijing Institute of Brain Disorders. Dr. Lackland reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
a new report suggests.
Patients treated with butylphthalide had fewer severe neurologic symptoms and better function 90 days after the stroke, compared with those receiving placebo.
Butylphthalide is approved and available for use in China, where the study was conducted. However, the medication hasn’t been approved for use by the U.S. Food and Drug Administration.
“Patients who received butylphthalide had less severe neurological symptoms and a better living status at 90 days post stroke, compared to those who received the placebo,” said coauthor Baixue Jia, MD, an attending physician in interventional neuroradiology at the Beijing Tiantan Hospital of Capital Medical University and a faculty member at the China National Clinical Research Center for Neurological Diseases in Beijing. “If the results are confirmed in other trials, this may lead to more options to treat strokes caused by clots.”
The study was presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
Studying stroke outcomes
The researchers described butylphthalide as a cerebroprotective drug that was originally extracted from seeds of Apium graveolens. In China, previous studies have shown that the drug has cerebroprotective effects in animal models of ischemia-reperfusion, they noted.
In this randomized, double-blind, placebo-controlled trial, Dr. Jia and colleagues evaluated whether treatment with butylphthalide could improve 90-day outcomes for adults with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (tPA), endovascular treatment, or both.
The participants were treated at one of 59 medical centers in China between July 2018 and February 2022. Those who had minimal stroke symptoms on their initial exam, defined as a score of 0-3 on the National Institutes of Health Stroke Scale, or had severe stroke symptoms, defined as having a score of 26 or higher on the NIHSS, were excluded from the study.
Along with an initial revascularization intervention chosen by their physician, participants were randomly selected to receive either butylphthalide or a placebo daily for 90 days. The drug was administered through daily intravenous injections for the first 14 days, after which patients received oral capsules for 76 days.
The research team defined the outcomes as “favorable” if a patient fell into one of the following categories 90 days after the stroke: an initially mild to moderate stroke (NIHSS, 4-7) and no symptoms after treatment, defined as a score of 0 on the Modified Rankin Scale (mRS), which measures disability and dependence; an initially moderate to serious stroke (NIHSS, 8-14) and no residual symptoms or mild symptoms that don’t impair the ability to perform routine activities of daily living without assistance (mRS, 0-1); or an initially serious to severe stroke (NIHSS, 15-25) and no remaining symptoms or a slight disability that impairs some activities but allows one to conduct daily living without assistance (mRS, 0-2).
Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke, and mortality.
Among the 1,216 participants, 607 were assigned to the treatment group, and 609 were assigned to the placebo group. The average age was 66 years, and 68% were men.
Overall, participants in the butylphthalide group were 70% more likely to have a favorable 90-day outcome, compared with the placebo group. Favorable outcomes occurred in 344 patients (56.7%) in the butylphthalide group, compared with 268 patients (44%) in the placebo group (odds ratio, 1.70; 95% confidence interval, 1.35-2.14; P < .001).
In addition, butylphthalide improved function equally well for the patients who initially received tPA, those who received endovascular treatment, and those who received both tPA and endovascular treatment.
Secondary events, such as recurrent stroke and intracranial hemorrhage, weren’t significantly different between the butylphthalide and placebo groups.
Ongoing questions
Dr. Jia and colleagues noted the need to understand how butylphthalide works in the brain. Animal studies have suggested several possible mechanisms, but it remains unclear.
“The next step should be investigating the exact mechanisms of butylphthalide in humans,” Dr. Jia said.
Additional research should assess the medication in other populations, the authors noted, particularly because the study involved participants who received initial treatment with tPA, endovascular treatment, or both. The results may not be generalizable to stroke patients who receive other treatments or to populations outside of China.
“While these are interesting results, this is only one relatively small study on a fairly select population in China. Butylphthalide, a medication initially compounded from celery seed, is not ready for use in standard stroke treatment,” said Daniel Lackland, DrPH, professor of neurology and director of the division of translational neurosciences and population studies at the Medical University of South Carolina, Charleston.
Dr. Lackland, who wasn’t involved with the study, is a member of the American Stroke Association’s Stroke Council. Although butylphthalide was originally extracted from seeds, he noted, it’s not what patients would find commercially available.
“The medication used in this study is not the same as celery seed or celery seed extract supplements,” he said. “Stroke survivors should always consult with their neurologist or healthcare professional regarding diet after a stroke.”
The study was funded by the National Key Technology Research and Development Program of the Ministry of Science and Technology of the People’s Republic of China and Shijiazhuang Pharmaceutical Group dl-3-butylphthalide Pharmaceutical. Several authors are employed with Beijing Tiantan Hospital and the Beijing Institute of Brain Disorders. Dr. Lackland reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ISC 2023
Exercise training reduces liver fat in patients with NAFLD, even without weight loss
(NAFLD), according to a new systematic review and meta-analysis.
An exercise dose of 750 metabolic equivalents of task (MET)–minutes per week – or 150 minutes per week of brisk walking – was required to achieve a treatment response, independently of weight loss.
“In the absence of a regulatory agency–approved drug treatment or a cure, lifestyle modification with dietary change and increased exercise is recommended for all patients with NAFLD,” first author Jonathan Stine, MD, an associate professor of medicine and public health sciences and director of the fatty liver program at the Penn State Health Milton S. Hershey Medical Center, Hershey, said in an interview.
“With that said, there are many key unanswered questions about how to best prescribe exercise as medicine to our patients with NAFLD, including whether the liver-specific benefit of exercise can be seen without any body weight loss,” Dr. Stine said. “And if found, what dose of exercise is required in order to achieve clinically meaningful benefit?” He noted that this analysis is a step toward helping to answer these questions.
The study by Dr. Stine and colleagues was published online in The American Journal of Gastroenterology.
Analyzing studies
Exercise training, which includes planned and structured physical activity intended to improve physical fitness, has been shown to provide multiple benefits for patients with NAFLD, the study authors wrote. The gains include improvements in liver fat, physical fitness, body composition, vascular biology, and health-related quality of life.
However, it has been unclear whether exercise training achieves a 30% or more relative reduction in liver fat, which is considered the minimal clinically important difference and is a surrogate for histologic response or improvement in liver fibrosis.
In their systematic review and meta-analysis, Dr. Stine and colleagues analyzed the evidence for MRI-measured liver reduction in response to exercise training across different doses, with a 30% or more relative reduction serving as the primary outcome. They included randomized controlled trials in adults with NAFLD who participated in exercise training programs.
The 14 studies included a total of 551 participants. The average age of the participants was 53 years, and the average body mass index was 31 kg/mg2. The duration of the interventions ranged from 4 to 52 weeks and included different types of exercise, such as aerobic, high-intensity interval, resistance, and aerobic plus resistance training.
No study yielded the clinically significant weight loss required for histologic response (7%-10%). The average weight loss was about 2.8% among those who participated in exercise training.
Overall, seven studies with 152 participants had data for the 30% or more relative reduction in MRI-measured liver fat. The pooled rate was 34% for exercise training and 13% for the control condition.
In general, those who participated in exercise training were 3.5 times more likely to achieve a 30% or more relative reduction in MRI-measured liver fat than those in the control condition.
Among all participants, the mean change in absolute liver fat was –6.7% for the 338 participants enrolled in exercise training, compared with –0.8% for the 213 participants under the control condition. The pooled mean difference in absolute change in MRI-measured liver fat for exercise training versus the control was –5.8%.
For relative change in MRI-measured liver fat, researchers analyzed nine studies with 195 participants – 118 participants in exercise training, and 77 control participants. The mean relative change was –24.1% among the exercise training group and 7.3% among the control group. The pooled mean difference in relative change for exercise training versus the control was –26.4%.
For all 14 studies, an exercise dose of 750 or more MET-minutes per week resulted in a significant treatment response. This equates to 150 minutes per week of moderate-intensity exercise, such as brisk walking, or 75 minutes per week of vigorous-intensity exercise, such as jogging or cycling.
Among participants who had 750 MET-minutes per week, there was a –8% absolute and –28.9% relative mean difference in MRI-measured liver fat, compared with –4.1% and –22.8%, respectively, among those who had fewer than 750 MET-minutes per week.
An exercise dose of 750 or more MET-minutes per week led to a 30% or more relative reduction in MRI-measured liver fat in 39.3% of participants, compared with 25.7% who had fewer than that threshold.
The treatment response was independent of clinically significant body weight loss of more than 5%.
“Prior to our study, it was felt that body weight loss of at least 5% was required in order to significantly improve liver histology,” Dr. Stine said. “Our findings challenge this thought in that exercise training achieved rates of clinically significant liver fat reduction.”
Ongoing research
Dr. Stine and colleagues are continuing their research and are directly comparing exercise doses of 750 MET-minutes per week and 1,000 MET-minutes per week to standard clinical care in adults with biopsy-proven nonalcoholic steatohepatitis, or the progressive type of NAFLD.
“Importantly, this new study we’re undertaking is designed to mimic a real-world setting in which people’s daily schedules are highly variable,” he said. “Our experienced team of exercise professionals may vary frequency and time of exercise in a week so long as our study participant achieves the prescribed dose of exercise.”
Currently, leading professional societies have not reached consensus regarding the optimal physical activity program for patients with NAFLD, the study authors wrote. However, most clinical guidelines support at least 150 minutes per week of moderate-intensity aerobic activity.
Although more head-to-head clinical trials are needed, exercise training appears to reduce liver fat and provides other benefits, such as cardiorespiratory fitness, body composition changes, and improvements in vascular biology, they wrote.
“The important piece here is that this review shows that there does not have to be weight loss for improvements in fatty liver,” Jill Kanaley, PhD, a professor of nutrition and exercise physiology at University of Missouri–Columbia, said in an interview.
Dr. Kanaley, who wasn’t involved with this study, has researched exercise training among patients with NAFLD. She and her colleagues have found that moderate-and high-intensity exercise can decrease intrahepatic lipid content and NAFLD risk factors, independently of abdominal fat or body mass reductions.
“So often, people get frustrated with exercise if they do not see weight loss,” she said. “But in this case, there seems to be benefits of the exercise, even without weight loss.”
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have received research funding and have had consultant roles with numerous pharmaceutical companies. Dr. Kanaley reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(NAFLD), according to a new systematic review and meta-analysis.
An exercise dose of 750 metabolic equivalents of task (MET)–minutes per week – or 150 minutes per week of brisk walking – was required to achieve a treatment response, independently of weight loss.
“In the absence of a regulatory agency–approved drug treatment or a cure, lifestyle modification with dietary change and increased exercise is recommended for all patients with NAFLD,” first author Jonathan Stine, MD, an associate professor of medicine and public health sciences and director of the fatty liver program at the Penn State Health Milton S. Hershey Medical Center, Hershey, said in an interview.
“With that said, there are many key unanswered questions about how to best prescribe exercise as medicine to our patients with NAFLD, including whether the liver-specific benefit of exercise can be seen without any body weight loss,” Dr. Stine said. “And if found, what dose of exercise is required in order to achieve clinically meaningful benefit?” He noted that this analysis is a step toward helping to answer these questions.
The study by Dr. Stine and colleagues was published online in The American Journal of Gastroenterology.
Analyzing studies
Exercise training, which includes planned and structured physical activity intended to improve physical fitness, has been shown to provide multiple benefits for patients with NAFLD, the study authors wrote. The gains include improvements in liver fat, physical fitness, body composition, vascular biology, and health-related quality of life.
However, it has been unclear whether exercise training achieves a 30% or more relative reduction in liver fat, which is considered the minimal clinically important difference and is a surrogate for histologic response or improvement in liver fibrosis.
In their systematic review and meta-analysis, Dr. Stine and colleagues analyzed the evidence for MRI-measured liver reduction in response to exercise training across different doses, with a 30% or more relative reduction serving as the primary outcome. They included randomized controlled trials in adults with NAFLD who participated in exercise training programs.
The 14 studies included a total of 551 participants. The average age of the participants was 53 years, and the average body mass index was 31 kg/mg2. The duration of the interventions ranged from 4 to 52 weeks and included different types of exercise, such as aerobic, high-intensity interval, resistance, and aerobic plus resistance training.
No study yielded the clinically significant weight loss required for histologic response (7%-10%). The average weight loss was about 2.8% among those who participated in exercise training.
Overall, seven studies with 152 participants had data for the 30% or more relative reduction in MRI-measured liver fat. The pooled rate was 34% for exercise training and 13% for the control condition.
In general, those who participated in exercise training were 3.5 times more likely to achieve a 30% or more relative reduction in MRI-measured liver fat than those in the control condition.
Among all participants, the mean change in absolute liver fat was –6.7% for the 338 participants enrolled in exercise training, compared with –0.8% for the 213 participants under the control condition. The pooled mean difference in absolute change in MRI-measured liver fat for exercise training versus the control was –5.8%.
For relative change in MRI-measured liver fat, researchers analyzed nine studies with 195 participants – 118 participants in exercise training, and 77 control participants. The mean relative change was –24.1% among the exercise training group and 7.3% among the control group. The pooled mean difference in relative change for exercise training versus the control was –26.4%.
For all 14 studies, an exercise dose of 750 or more MET-minutes per week resulted in a significant treatment response. This equates to 150 minutes per week of moderate-intensity exercise, such as brisk walking, or 75 minutes per week of vigorous-intensity exercise, such as jogging or cycling.
Among participants who had 750 MET-minutes per week, there was a –8% absolute and –28.9% relative mean difference in MRI-measured liver fat, compared with –4.1% and –22.8%, respectively, among those who had fewer than 750 MET-minutes per week.
An exercise dose of 750 or more MET-minutes per week led to a 30% or more relative reduction in MRI-measured liver fat in 39.3% of participants, compared with 25.7% who had fewer than that threshold.
The treatment response was independent of clinically significant body weight loss of more than 5%.
“Prior to our study, it was felt that body weight loss of at least 5% was required in order to significantly improve liver histology,” Dr. Stine said. “Our findings challenge this thought in that exercise training achieved rates of clinically significant liver fat reduction.”
Ongoing research
Dr. Stine and colleagues are continuing their research and are directly comparing exercise doses of 750 MET-minutes per week and 1,000 MET-minutes per week to standard clinical care in adults with biopsy-proven nonalcoholic steatohepatitis, or the progressive type of NAFLD.
“Importantly, this new study we’re undertaking is designed to mimic a real-world setting in which people’s daily schedules are highly variable,” he said. “Our experienced team of exercise professionals may vary frequency and time of exercise in a week so long as our study participant achieves the prescribed dose of exercise.”
Currently, leading professional societies have not reached consensus regarding the optimal physical activity program for patients with NAFLD, the study authors wrote. However, most clinical guidelines support at least 150 minutes per week of moderate-intensity aerobic activity.
Although more head-to-head clinical trials are needed, exercise training appears to reduce liver fat and provides other benefits, such as cardiorespiratory fitness, body composition changes, and improvements in vascular biology, they wrote.
“The important piece here is that this review shows that there does not have to be weight loss for improvements in fatty liver,” Jill Kanaley, PhD, a professor of nutrition and exercise physiology at University of Missouri–Columbia, said in an interview.
Dr. Kanaley, who wasn’t involved with this study, has researched exercise training among patients with NAFLD. She and her colleagues have found that moderate-and high-intensity exercise can decrease intrahepatic lipid content and NAFLD risk factors, independently of abdominal fat or body mass reductions.
“So often, people get frustrated with exercise if they do not see weight loss,” she said. “But in this case, there seems to be benefits of the exercise, even without weight loss.”
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have received research funding and have had consultant roles with numerous pharmaceutical companies. Dr. Kanaley reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(NAFLD), according to a new systematic review and meta-analysis.
An exercise dose of 750 metabolic equivalents of task (MET)–minutes per week – or 150 minutes per week of brisk walking – was required to achieve a treatment response, independently of weight loss.
“In the absence of a regulatory agency–approved drug treatment or a cure, lifestyle modification with dietary change and increased exercise is recommended for all patients with NAFLD,” first author Jonathan Stine, MD, an associate professor of medicine and public health sciences and director of the fatty liver program at the Penn State Health Milton S. Hershey Medical Center, Hershey, said in an interview.
“With that said, there are many key unanswered questions about how to best prescribe exercise as medicine to our patients with NAFLD, including whether the liver-specific benefit of exercise can be seen without any body weight loss,” Dr. Stine said. “And if found, what dose of exercise is required in order to achieve clinically meaningful benefit?” He noted that this analysis is a step toward helping to answer these questions.
The study by Dr. Stine and colleagues was published online in The American Journal of Gastroenterology.
Analyzing studies
Exercise training, which includes planned and structured physical activity intended to improve physical fitness, has been shown to provide multiple benefits for patients with NAFLD, the study authors wrote. The gains include improvements in liver fat, physical fitness, body composition, vascular biology, and health-related quality of life.
However, it has been unclear whether exercise training achieves a 30% or more relative reduction in liver fat, which is considered the minimal clinically important difference and is a surrogate for histologic response or improvement in liver fibrosis.
In their systematic review and meta-analysis, Dr. Stine and colleagues analyzed the evidence for MRI-measured liver reduction in response to exercise training across different doses, with a 30% or more relative reduction serving as the primary outcome. They included randomized controlled trials in adults with NAFLD who participated in exercise training programs.
The 14 studies included a total of 551 participants. The average age of the participants was 53 years, and the average body mass index was 31 kg/mg2. The duration of the interventions ranged from 4 to 52 weeks and included different types of exercise, such as aerobic, high-intensity interval, resistance, and aerobic plus resistance training.
No study yielded the clinically significant weight loss required for histologic response (7%-10%). The average weight loss was about 2.8% among those who participated in exercise training.
Overall, seven studies with 152 participants had data for the 30% or more relative reduction in MRI-measured liver fat. The pooled rate was 34% for exercise training and 13% for the control condition.
In general, those who participated in exercise training were 3.5 times more likely to achieve a 30% or more relative reduction in MRI-measured liver fat than those in the control condition.
Among all participants, the mean change in absolute liver fat was –6.7% for the 338 participants enrolled in exercise training, compared with –0.8% for the 213 participants under the control condition. The pooled mean difference in absolute change in MRI-measured liver fat for exercise training versus the control was –5.8%.
For relative change in MRI-measured liver fat, researchers analyzed nine studies with 195 participants – 118 participants in exercise training, and 77 control participants. The mean relative change was –24.1% among the exercise training group and 7.3% among the control group. The pooled mean difference in relative change for exercise training versus the control was –26.4%.
For all 14 studies, an exercise dose of 750 or more MET-minutes per week resulted in a significant treatment response. This equates to 150 minutes per week of moderate-intensity exercise, such as brisk walking, or 75 minutes per week of vigorous-intensity exercise, such as jogging or cycling.
Among participants who had 750 MET-minutes per week, there was a –8% absolute and –28.9% relative mean difference in MRI-measured liver fat, compared with –4.1% and –22.8%, respectively, among those who had fewer than 750 MET-minutes per week.
An exercise dose of 750 or more MET-minutes per week led to a 30% or more relative reduction in MRI-measured liver fat in 39.3% of participants, compared with 25.7% who had fewer than that threshold.
The treatment response was independent of clinically significant body weight loss of more than 5%.
“Prior to our study, it was felt that body weight loss of at least 5% was required in order to significantly improve liver histology,” Dr. Stine said. “Our findings challenge this thought in that exercise training achieved rates of clinically significant liver fat reduction.”
Ongoing research
Dr. Stine and colleagues are continuing their research and are directly comparing exercise doses of 750 MET-minutes per week and 1,000 MET-minutes per week to standard clinical care in adults with biopsy-proven nonalcoholic steatohepatitis, or the progressive type of NAFLD.
“Importantly, this new study we’re undertaking is designed to mimic a real-world setting in which people’s daily schedules are highly variable,” he said. “Our experienced team of exercise professionals may vary frequency and time of exercise in a week so long as our study participant achieves the prescribed dose of exercise.”
Currently, leading professional societies have not reached consensus regarding the optimal physical activity program for patients with NAFLD, the study authors wrote. However, most clinical guidelines support at least 150 minutes per week of moderate-intensity aerobic activity.
Although more head-to-head clinical trials are needed, exercise training appears to reduce liver fat and provides other benefits, such as cardiorespiratory fitness, body composition changes, and improvements in vascular biology, they wrote.
“The important piece here is that this review shows that there does not have to be weight loss for improvements in fatty liver,” Jill Kanaley, PhD, a professor of nutrition and exercise physiology at University of Missouri–Columbia, said in an interview.
Dr. Kanaley, who wasn’t involved with this study, has researched exercise training among patients with NAFLD. She and her colleagues have found that moderate-and high-intensity exercise can decrease intrahepatic lipid content and NAFLD risk factors, independently of abdominal fat or body mass reductions.
“So often, people get frustrated with exercise if they do not see weight loss,” she said. “But in this case, there seems to be benefits of the exercise, even without weight loss.”
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have received research funding and have had consultant roles with numerous pharmaceutical companies. Dr. Kanaley reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY
Be aware of hepatic encephalopathy, dementia overlap in older patients with cirrhosis
, according to a new study involving U.S. veterans.
The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.
“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.
“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.
“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.
The study was published online in The American Journal of Gastroenterology.
Analyzing associations
HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.
Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.
Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.
Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.
In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.
In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.
When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.
“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.
“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
Additional research needed
Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.
“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.
Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.
The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.
Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.
“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”
The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”
Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.
“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”
The study received no financial support. The authors reported no potential competing interests.
A version of this article first appeared on Medscape.com.
, according to a new study involving U.S. veterans.
The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.
“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.
“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.
“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.
The study was published online in The American Journal of Gastroenterology.
Analyzing associations
HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.
Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.
Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.
Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.
In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.
In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.
When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.
“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.
“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
Additional research needed
Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.
“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.
Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.
The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.
Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.
“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”
The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”
Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.
“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”
The study received no financial support. The authors reported no potential competing interests.
A version of this article first appeared on Medscape.com.
, according to a new study involving U.S. veterans.
The overlap between dementia and HE was also independent of alcohol use, brain injury, age, and other metabolic risk factors.
“The aging of patients with cirrhosis leads us to encounter several individuals who may be prone to both of these diseases,” senior author Jasmohan Bajaj, MD, a professor of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University Medical Center and GI section of the Central Virginia Veterans Healthcare System in Richmond, said in an interview.
“Given the epidemic of metabolic syndrome and alcohol, consider excluding cirrhosis in your patient [for] whom the presumptive diagnosis is dementia, since they could have concomitant HE,” he said.
“On the flip side, in those with HE who have predominant long-term memory issues and persistent cognitive changes, consider consulting a neuropsychiatrist or neurologist to ensure there is a resolution of the underlying disease process,” Dr. Bajaj added.
The study was published online in The American Journal of Gastroenterology.
Analyzing associations
HE is a common decompensating event in patients with cirrhosis. Because of the aging population of patients with cirrhosis, however, it’s important to differentiate HE from nonhepatic etiologies of cognitive impairment, such as dementia, the authors note.
Using data from the VA Corporate Data Warehouse, Dr. Bajaj and colleagues identified veterans with cirrhosis who received VA care between October 2019 and September 2021 and compared baseline characteristics between the cohorts based on the presence or absence of dementia. The research team then evaluated factors associated with having a diagnosis of dementia, adjusting for demographics, comorbid illnesses, cirrhosis etiology, and cirrhosis complications.
Investigators identified 71,522 veterans with diagnostic codes for cirrhosis who were engaged in VA care in 2019. They were mostly men (96.2%) and had a median age of 66. The most common etiologies of cirrhosis were alcohol and hepatitis C, followed by nonalcoholic steatohepatitis (NASH). The group also included veterans with predominantly compensated cirrhosis and a median MELD-Na score of 9. The MELD-Na score gauges the severity of chronic liver disease using values such as serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time and sodium to predict survival.
Among those with cirrhosis, 5,647 (7.9%) also had dementia diagnosis codes. This rate is higher than the prevalence of dementia in the general population and equivalent to the rate of dementia in veterans without cirrhosis who are older than 65, the authors note.
In general, veterans with dementia tended to be older, to be White, to live in an urban area, and to have higher MELD-Na scores, and they were more frequently diagnosed with alcohol-related cirrhosis, alcohol and tobacco use disorder, diabetes, chronic kidney disease, chronic heart failure, brain trauma, and cerebrovascular disease.
In a multivariable analysis, the presence of any decompensating event was significantly associated with dementia. In subsequent analyses of individual decompensating events, however, the strongest association was with HE, while ascites or variceal bleeding did not add to the risk.
When HE was defined as patients who filled prescriptions for lactulose or rifaximin, the frequency of patients with HE decreased from 13.7% to 10.9%. In an analysis with HE as the decompensating event, the association between HE and dementia remained significant compared to when HE was defined by diagnostic codes alone.
“We were surprised by the high proportion of patients with dementia who also had cirrhosis, and given the genuine difficulty that clinicians have with defining HE vs. dementia, we were not very surprised at that overlap,” Dr. Bajaj said.
“We were also surprised at the specificity of this overlap only with HE and not with other decompensating events, which was also independent of head injury, alcohol use, and PTSD,” he added.
Additional research needed
Future research should look at the characteristics of HE, including the number of episodes or breakthrough episodes, and should focus on objective biomarkers to differentiate dementia and HE, the study authors write.
“The distinction and study of potential overlapping features among HE and dementia is important because HE is often treatable with medications and reverses after liver transplant, while this does not occur with dementia,” they add.
Dr. Bajaj and colleagues call for a greater awareness of disease processes and complications in older patients with cirrhosis, particularly since diagnostic imprecision can lead to patient and family confusion, distrust, and ineffective treatment.
The study will help physicians better understand the important overlap between dementia and HE, said Eric Orman, MD, an associate professor of medicine at Indiana University, Indianapolis.
Dr. Orman, who wasn’t involved with this study, has researched recent trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis and has found that the proportion of older adults has increased, as well as those with alcoholic cirrhosis and NASH, which has implications for future patient care.
“It is important to recognize that both dementia and HE can occur either separately or concurrently in individuals with cirrhosis,” Dr. Orman told this news organization. “When seeing patients with cognitive impairment, having a high index of suspicion for both conditions is critical to ensure appropriate diagnosis and treatment.”
The study’s findings “represent the tip of the iceberg,” Neal Parikh, MD, an assistant professor of neurology and neuroscience at Weill Cornell Medicine in New York, said in an interview. “There is a tremendous amount left to be discovered regarding the role of the liver in brain health.”
Dr. Parikh, who wasn’t associated with this study, has researched the impact of chronic liver conditions on cognitive impairment and dementia. He is working on a project that addresses HE in detail.
“There is growing recognition of a so-called ‘liver-brain axis,’ with several researchers, including my group, showing that a range of chronic liver conditions may detrimentally impact cognitive function and increase the risk of dementia,” he said. “Studying the specific contributions of cirrhosis is critical for understanding the role of hepatic encephalopathy in age-related cognitive decline.”
The study received no financial support. The authors reported no potential competing interests.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY
USPSTF backs screening for hypertensive disorders of pregnancy
The U.S. Preventive Services Task Force (USPSTF) recommends that clinicians screen for hypertensive disorders of pregnancy, which can cause serious and fatal complications, according to a new draft statement.
All pregnant people should have their blood pressure measured at each prenatal visit to identify and prevent serious health problems. The grade B recommendation expands on the task force’s 2017 recommendation on screening for preeclampsia to include all hypertensive disorders of pregnancy.
“Hypertensive disorders of pregnancy are some of the leading causes of serious complications and death for pregnant people,” Esa Davis, MD, a USPSTF member and associate professor of medicine and clinical and translational science at the University of Pittsburgh School of Medicine, told this news organization.
In the U.S., the rate of hypertensive disorders of pregnancy has increased in recent decades, jumping from about 500 cases per 10,000 deliveries in the early 1990s to more than 1,000 cases per 10,000 deliveries in the mid-2010s.
“The U.S. Preventive Services Task Force wants to help save the lives of pregnant people and their babies by ensuring that clinicians have the most up-to-date guidance on how to find these conditions early,” she said.
The draft recommendation statement was published online .
Screening recommendation
Hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, eclampsia, and chronic hypertension with and without superimposed preeclampsia, are marked by elevated blood pressure during pregnancy.
The disorders can lead to complications for the pregnant person, such as stroke, retinal detachment, organ damage or failure, and seizures, as well as for the baby, including restricted growth, low birth weight, and stillbirth. Many complications can lead to early induction of labor, cesarean delivery, and preterm birth.
After commissioning a systematic evidence review, the USPSTF provided a grade B recommendation for clinicians to offer or provide screening for hypertensive disorders of pregnancy. The recommendation concludes with “moderate certainty” that screening with blood pressure measurements has “substantial net benefit.”
The task force notes that it is “essential” for all pregnant women and pregnant people of all genders to be screened and that those who screen positive receive evidence-based management of their condition.
Risk factors include a history of eclampsia or preeclampsia, a family history of preeclampsia, a previous adverse pregnancy outcome, having gestational diabetes or chronic hypertension, being pregnant with more than one baby, having a first pregnancy, having a high body mass index prior to pregnancy, and being 35 years of age or older.
In addition, Black, American Indian, and Alaska Native people face higher risks and are more likely both to have and to die from a hypertensive disorder of pregnancy. In particular, Black people experience higher rates of maternal and infant morbidity and perinatal mortality than other racial and ethnic groups, and hypertensive disorders of pregnancy account for a larger proportion of these outcomes.
Although measuring blood pressure throughout pregnancy is an important first step, it’s not enough to improve inequities in health outcomes, the task force notes. Identifying hypertensive disorders of pregnancy requires adequate prenatal follow-up visits, surveillance, and evidence-based care, which can be a barrier for some pregnant people.
Follow-up visits with health care providers such as nurses, nurse midwives, pediatricians, and lactation consultants could help, as well as screening and monitoring during the postpartum period. Other approaches include telehealth, connections to community resources during the perinatal period, collaborative care provided in medical homes, and multilevel interventions to address underlying health inequities that increase health risks during pregnancy.
“Since screening is not enough to address the health disparities experienced by Black, American Indian, and Alaska Native people, health care professionals should also do what they can to help address these inequities,” Dr. Davis said. “For example, the task force identified a few promising approaches, including using standardized clinical bundles of best practices for disease management to help ensure that all pregnant persons receive appropriate, equitable care.”
Additional considerations
The USPSTF looked at the evidence on additional methods of screening but continued to find that measuring blood pressure at each prenatal visit is the best approach. Other evaluations, such as testing for proteinuria when preeclampsia is suspected, have low accuracy for detecting proteinuria in pregnancy.
Although there is no currently available treatment for preeclampsia except delivery, management strategies for diagnosed hypertensive disorders of pregnancy include close fetal and maternal monitoring, antihypertension medications, and magnesium sulfate for seizure prophylaxis when indicated.
Previously, the USPSTF also recommended that pregnant Black people be considered for treatment with low-dose aspirin to prevent preeclampsia, with aspirin use recommended for those with at least one additional moderate risk factor. Clinicians should also be aware of the complications of poor health outcomes among populations who face higher risks.
The USPSTF noted several gaps for future research, including the best approaches for blood pressure monitoring during pregnancy and the postpartum period, how to address health inequities through multilevel interventions, how to increase access to care through telehealth services, and how to mitigate cardiovascular complications later in life in patients diagnosed with hypertensive disorders of pregnancy.
“Continued research is needed in these promising areas,” Dr. Davis said. “We hope all clinicians will join us in helping ensure that all parents and babies have access to the care they need to be as healthy as possible.”
The draft recommendation statement and draft evidence review were posted for public comment on the USPSTF website. Comments can be submitted until March 6.
No relevant financial relationships have been disclosed.
A version of this article originally appeared on Medscape.com.
The U.S. Preventive Services Task Force (USPSTF) recommends that clinicians screen for hypertensive disorders of pregnancy, which can cause serious and fatal complications, according to a new draft statement.
All pregnant people should have their blood pressure measured at each prenatal visit to identify and prevent serious health problems. The grade B recommendation expands on the task force’s 2017 recommendation on screening for preeclampsia to include all hypertensive disorders of pregnancy.
“Hypertensive disorders of pregnancy are some of the leading causes of serious complications and death for pregnant people,” Esa Davis, MD, a USPSTF member and associate professor of medicine and clinical and translational science at the University of Pittsburgh School of Medicine, told this news organization.
In the U.S., the rate of hypertensive disorders of pregnancy has increased in recent decades, jumping from about 500 cases per 10,000 deliveries in the early 1990s to more than 1,000 cases per 10,000 deliveries in the mid-2010s.
“The U.S. Preventive Services Task Force wants to help save the lives of pregnant people and their babies by ensuring that clinicians have the most up-to-date guidance on how to find these conditions early,” she said.
The draft recommendation statement was published online .
Screening recommendation
Hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, eclampsia, and chronic hypertension with and without superimposed preeclampsia, are marked by elevated blood pressure during pregnancy.
The disorders can lead to complications for the pregnant person, such as stroke, retinal detachment, organ damage or failure, and seizures, as well as for the baby, including restricted growth, low birth weight, and stillbirth. Many complications can lead to early induction of labor, cesarean delivery, and preterm birth.
After commissioning a systematic evidence review, the USPSTF provided a grade B recommendation for clinicians to offer or provide screening for hypertensive disorders of pregnancy. The recommendation concludes with “moderate certainty” that screening with blood pressure measurements has “substantial net benefit.”
The task force notes that it is “essential” for all pregnant women and pregnant people of all genders to be screened and that those who screen positive receive evidence-based management of their condition.
Risk factors include a history of eclampsia or preeclampsia, a family history of preeclampsia, a previous adverse pregnancy outcome, having gestational diabetes or chronic hypertension, being pregnant with more than one baby, having a first pregnancy, having a high body mass index prior to pregnancy, and being 35 years of age or older.
In addition, Black, American Indian, and Alaska Native people face higher risks and are more likely both to have and to die from a hypertensive disorder of pregnancy. In particular, Black people experience higher rates of maternal and infant morbidity and perinatal mortality than other racial and ethnic groups, and hypertensive disorders of pregnancy account for a larger proportion of these outcomes.
Although measuring blood pressure throughout pregnancy is an important first step, it’s not enough to improve inequities in health outcomes, the task force notes. Identifying hypertensive disorders of pregnancy requires adequate prenatal follow-up visits, surveillance, and evidence-based care, which can be a barrier for some pregnant people.
Follow-up visits with health care providers such as nurses, nurse midwives, pediatricians, and lactation consultants could help, as well as screening and monitoring during the postpartum period. Other approaches include telehealth, connections to community resources during the perinatal period, collaborative care provided in medical homes, and multilevel interventions to address underlying health inequities that increase health risks during pregnancy.
“Since screening is not enough to address the health disparities experienced by Black, American Indian, and Alaska Native people, health care professionals should also do what they can to help address these inequities,” Dr. Davis said. “For example, the task force identified a few promising approaches, including using standardized clinical bundles of best practices for disease management to help ensure that all pregnant persons receive appropriate, equitable care.”
Additional considerations
The USPSTF looked at the evidence on additional methods of screening but continued to find that measuring blood pressure at each prenatal visit is the best approach. Other evaluations, such as testing for proteinuria when preeclampsia is suspected, have low accuracy for detecting proteinuria in pregnancy.
Although there is no currently available treatment for preeclampsia except delivery, management strategies for diagnosed hypertensive disorders of pregnancy include close fetal and maternal monitoring, antihypertension medications, and magnesium sulfate for seizure prophylaxis when indicated.
Previously, the USPSTF also recommended that pregnant Black people be considered for treatment with low-dose aspirin to prevent preeclampsia, with aspirin use recommended for those with at least one additional moderate risk factor. Clinicians should also be aware of the complications of poor health outcomes among populations who face higher risks.
The USPSTF noted several gaps for future research, including the best approaches for blood pressure monitoring during pregnancy and the postpartum period, how to address health inequities through multilevel interventions, how to increase access to care through telehealth services, and how to mitigate cardiovascular complications later in life in patients diagnosed with hypertensive disorders of pregnancy.
“Continued research is needed in these promising areas,” Dr. Davis said. “We hope all clinicians will join us in helping ensure that all parents and babies have access to the care they need to be as healthy as possible.”
The draft recommendation statement and draft evidence review were posted for public comment on the USPSTF website. Comments can be submitted until March 6.
No relevant financial relationships have been disclosed.
A version of this article originally appeared on Medscape.com.
The U.S. Preventive Services Task Force (USPSTF) recommends that clinicians screen for hypertensive disorders of pregnancy, which can cause serious and fatal complications, according to a new draft statement.
All pregnant people should have their blood pressure measured at each prenatal visit to identify and prevent serious health problems. The grade B recommendation expands on the task force’s 2017 recommendation on screening for preeclampsia to include all hypertensive disorders of pregnancy.
“Hypertensive disorders of pregnancy are some of the leading causes of serious complications and death for pregnant people,” Esa Davis, MD, a USPSTF member and associate professor of medicine and clinical and translational science at the University of Pittsburgh School of Medicine, told this news organization.
In the U.S., the rate of hypertensive disorders of pregnancy has increased in recent decades, jumping from about 500 cases per 10,000 deliveries in the early 1990s to more than 1,000 cases per 10,000 deliveries in the mid-2010s.
“The U.S. Preventive Services Task Force wants to help save the lives of pregnant people and their babies by ensuring that clinicians have the most up-to-date guidance on how to find these conditions early,” she said.
The draft recommendation statement was published online .
Screening recommendation
Hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, eclampsia, and chronic hypertension with and without superimposed preeclampsia, are marked by elevated blood pressure during pregnancy.
The disorders can lead to complications for the pregnant person, such as stroke, retinal detachment, organ damage or failure, and seizures, as well as for the baby, including restricted growth, low birth weight, and stillbirth. Many complications can lead to early induction of labor, cesarean delivery, and preterm birth.
After commissioning a systematic evidence review, the USPSTF provided a grade B recommendation for clinicians to offer or provide screening for hypertensive disorders of pregnancy. The recommendation concludes with “moderate certainty” that screening with blood pressure measurements has “substantial net benefit.”
The task force notes that it is “essential” for all pregnant women and pregnant people of all genders to be screened and that those who screen positive receive evidence-based management of their condition.
Risk factors include a history of eclampsia or preeclampsia, a family history of preeclampsia, a previous adverse pregnancy outcome, having gestational diabetes or chronic hypertension, being pregnant with more than one baby, having a first pregnancy, having a high body mass index prior to pregnancy, and being 35 years of age or older.
In addition, Black, American Indian, and Alaska Native people face higher risks and are more likely both to have and to die from a hypertensive disorder of pregnancy. In particular, Black people experience higher rates of maternal and infant morbidity and perinatal mortality than other racial and ethnic groups, and hypertensive disorders of pregnancy account for a larger proportion of these outcomes.
Although measuring blood pressure throughout pregnancy is an important first step, it’s not enough to improve inequities in health outcomes, the task force notes. Identifying hypertensive disorders of pregnancy requires adequate prenatal follow-up visits, surveillance, and evidence-based care, which can be a barrier for some pregnant people.
Follow-up visits with health care providers such as nurses, nurse midwives, pediatricians, and lactation consultants could help, as well as screening and monitoring during the postpartum period. Other approaches include telehealth, connections to community resources during the perinatal period, collaborative care provided in medical homes, and multilevel interventions to address underlying health inequities that increase health risks during pregnancy.
“Since screening is not enough to address the health disparities experienced by Black, American Indian, and Alaska Native people, health care professionals should also do what they can to help address these inequities,” Dr. Davis said. “For example, the task force identified a few promising approaches, including using standardized clinical bundles of best practices for disease management to help ensure that all pregnant persons receive appropriate, equitable care.”
Additional considerations
The USPSTF looked at the evidence on additional methods of screening but continued to find that measuring blood pressure at each prenatal visit is the best approach. Other evaluations, such as testing for proteinuria when preeclampsia is suspected, have low accuracy for detecting proteinuria in pregnancy.
Although there is no currently available treatment for preeclampsia except delivery, management strategies for diagnosed hypertensive disorders of pregnancy include close fetal and maternal monitoring, antihypertension medications, and magnesium sulfate for seizure prophylaxis when indicated.
Previously, the USPSTF also recommended that pregnant Black people be considered for treatment with low-dose aspirin to prevent preeclampsia, with aspirin use recommended for those with at least one additional moderate risk factor. Clinicians should also be aware of the complications of poor health outcomes among populations who face higher risks.
The USPSTF noted several gaps for future research, including the best approaches for blood pressure monitoring during pregnancy and the postpartum period, how to address health inequities through multilevel interventions, how to increase access to care through telehealth services, and how to mitigate cardiovascular complications later in life in patients diagnosed with hypertensive disorders of pregnancy.
“Continued research is needed in these promising areas,” Dr. Davis said. “We hope all clinicians will join us in helping ensure that all parents and babies have access to the care they need to be as healthy as possible.”
The draft recommendation statement and draft evidence review were posted for public comment on the USPSTF website. Comments can be submitted until March 6.
No relevant financial relationships have been disclosed.
A version of this article originally appeared on Medscape.com.
Physician opinions vary on surveillance colonoscopies in older adults with prior adenomas, survey finds
Physician recommendations for surveillance colonoscopies in older adults with prior adenomas vary based on several factors, including patient age, health, adenoma risk, and physician specialty, according to a national survey.
In general, physicians were more likely to recommend surveillance for patients at a younger age, with better health, and with prior high-risk adenomas. Additionally, a large proportion of physicians reported uncertainty about whether the benefits of continued surveillance outweighed the risk of harm in older adults.
“There are no existing surveillance colonoscopy guidelines that integrate patient age, health, and adenoma risk, and physicians report significant decisional uncertainty,” Nancy Schoenborn, MD, MHS, associate professor of medicine at Johns Hopkins University, Baltimore, and colleagues wrote.
“Developing the evidence base to evaluate the risks and benefits of surveillance colonoscopy in older adults and decisional support tools that help physicians and patients incorporate available data and weigh risks and benefits are needed to address current gaps in care for older adults with prior adenomas,” the authors wrote.
The study was published online in the American Journal of Gastroenterology.
Surveying physicians
National guidelines recommend surveillance colonoscopy after adenoma removal at more frequent intervals than screening colonoscopy because of a higher risk of colorectal cancer among patients with adenomas. The high quality of screening colonoscopies coupled with an aging population means that many older adults have a history of adenomas and continue to undergo surveillance colonoscopies, the authors wrote.
they wrote.
Dr. Schoenborn and colleagues conducted a national cross-sectional survey of 1,800 primary care physicians and 600 gastroenterologists between April and November 2021. The primary care group included internal medicine, family medicine, general practice, and geriatric medicine physicians.
The research team asked whether physicians would recommend surveillance colonoscopy in a series of 12 vignettes that varied by patient age (75 or 85), patient health (good, medium, or poor), and prior adenoma risk (low or high).
Good health was described as well-controlled hypertension and living independently, whereas moderate health was described as moderate heart failure and has difficulty walking, and poor health was described as severe chronic obstructive pulmonary disease on oxygenand requires help with self-care.
For prior adenomas, high risk involved five tubular adenomas, one of which was 15 mm, and low risk involved two tubular adenomas, both of which were less than 10 mm. The survey also noted that the recommended surveillance intervals were 3 years in the high-risk scenario and 7 years in the low-risk scenario.
Researchers mailed 2,400 surveys and received 1,040 responses. They included 874 in the analysis because the physician respondents provided care to patients ages 65 and older and spent time seeing patients in clinic. Decisions about surveillance colonoscopies for adenomas in the absence of symptoms almost always occur in the outpatient setting, rather than acute or urgent care, the authors wrote.
Large variations found
Overall, physicians were less likely to recommend surveillance colonoscopies if the patient was older, had poor health, and had lower-risk adenomas. Patient age and health had larger effects on decision-making than adenoma risk, with health status having the largest effect.
About 20.6% of physicians recommended surveillance if the patient was 85, compared with 49.8% if the patient was 75. In addition, 7.1% of physicians recommended surveillance if the patient was in poor health, compared with 28.8% for those in moderate health, and 67.7% for patients in good health.
If the prior adenoma was low risk, 29.7% of physicians recommended surveillance, compared with 41.6% if the prior adenoma was high risk.
In general, family medicine and general practice physicians were most likely to recommend surveillance, at 40%, and gastroenterologists were least likely to recommend surveillance, at 30.9%. Patient age and health had larger effects among gastroenterologists than among primary care physicians, and adenoma risk had similar effects between the two groups.
“The importance of patient age and health status found in our study mirrors study results on physician decision-making regarding screening colonoscopies in older adults and makes intuitive sense,” the authors wrote. “Whether the priorities reflected in our findings are supported by evidence is not clear, and our results highlight important knowledge gaps in the field that warrant future research.”
Physician uncertainty
Additional guidance would be helpful, the authors wrote. In the survey, about 52.3% of primary care physicians and 35.4% of gastroenterologists reported uncertainty about the benefit–harm balance of surveillance in older adults.
“Current guidelines on surveillance colonoscopies are solely based on prior adenoma characteristics,” the authors wrote. “Guidelines need to incorporate guidance that considers patient age and health status, as well as adenoma risk, and explicitly considers when surveillance should stop in older adults.”
In addition, most physicians in the survey – 85.9% of primary care physicians and 77% of gastroenterologists – said they would find a decision support tool helpful. At the same time, 32.8% of primary care physicians and 71.5% of gastroenterologists perceived it as the gastroenterologist’s role to decide about surveillance colonoscopies.
“Developing patient-facing materials, communication tools for clinicians, and tools to support shared decision-making about surveillance colonoscopies that engage both physicians and patients are all important next steps,” the authors wrote. “To our knowledge, there is no existing patient decision aid about surveillance colonoscopies; developing such a tool may be valuable.”
The study was supported by Dr. Schoenborn’s career development award from the National Institute on Aging. The authors reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
Physician recommendations for surveillance colonoscopies in older adults with prior adenomas vary based on several factors, including patient age, health, adenoma risk, and physician specialty, according to a national survey.
In general, physicians were more likely to recommend surveillance for patients at a younger age, with better health, and with prior high-risk adenomas. Additionally, a large proportion of physicians reported uncertainty about whether the benefits of continued surveillance outweighed the risk of harm in older adults.
“There are no existing surveillance colonoscopy guidelines that integrate patient age, health, and adenoma risk, and physicians report significant decisional uncertainty,” Nancy Schoenborn, MD, MHS, associate professor of medicine at Johns Hopkins University, Baltimore, and colleagues wrote.
“Developing the evidence base to evaluate the risks and benefits of surveillance colonoscopy in older adults and decisional support tools that help physicians and patients incorporate available data and weigh risks and benefits are needed to address current gaps in care for older adults with prior adenomas,” the authors wrote.
The study was published online in the American Journal of Gastroenterology.
Surveying physicians
National guidelines recommend surveillance colonoscopy after adenoma removal at more frequent intervals than screening colonoscopy because of a higher risk of colorectal cancer among patients with adenomas. The high quality of screening colonoscopies coupled with an aging population means that many older adults have a history of adenomas and continue to undergo surveillance colonoscopies, the authors wrote.
they wrote.
Dr. Schoenborn and colleagues conducted a national cross-sectional survey of 1,800 primary care physicians and 600 gastroenterologists between April and November 2021. The primary care group included internal medicine, family medicine, general practice, and geriatric medicine physicians.
The research team asked whether physicians would recommend surveillance colonoscopy in a series of 12 vignettes that varied by patient age (75 or 85), patient health (good, medium, or poor), and prior adenoma risk (low or high).
Good health was described as well-controlled hypertension and living independently, whereas moderate health was described as moderate heart failure and has difficulty walking, and poor health was described as severe chronic obstructive pulmonary disease on oxygenand requires help with self-care.
For prior adenomas, high risk involved five tubular adenomas, one of which was 15 mm, and low risk involved two tubular adenomas, both of which were less than 10 mm. The survey also noted that the recommended surveillance intervals were 3 years in the high-risk scenario and 7 years in the low-risk scenario.
Researchers mailed 2,400 surveys and received 1,040 responses. They included 874 in the analysis because the physician respondents provided care to patients ages 65 and older and spent time seeing patients in clinic. Decisions about surveillance colonoscopies for adenomas in the absence of symptoms almost always occur in the outpatient setting, rather than acute or urgent care, the authors wrote.
Large variations found
Overall, physicians were less likely to recommend surveillance colonoscopies if the patient was older, had poor health, and had lower-risk adenomas. Patient age and health had larger effects on decision-making than adenoma risk, with health status having the largest effect.
About 20.6% of physicians recommended surveillance if the patient was 85, compared with 49.8% if the patient was 75. In addition, 7.1% of physicians recommended surveillance if the patient was in poor health, compared with 28.8% for those in moderate health, and 67.7% for patients in good health.
If the prior adenoma was low risk, 29.7% of physicians recommended surveillance, compared with 41.6% if the prior adenoma was high risk.
In general, family medicine and general practice physicians were most likely to recommend surveillance, at 40%, and gastroenterologists were least likely to recommend surveillance, at 30.9%. Patient age and health had larger effects among gastroenterologists than among primary care physicians, and adenoma risk had similar effects between the two groups.
“The importance of patient age and health status found in our study mirrors study results on physician decision-making regarding screening colonoscopies in older adults and makes intuitive sense,” the authors wrote. “Whether the priorities reflected in our findings are supported by evidence is not clear, and our results highlight important knowledge gaps in the field that warrant future research.”
Physician uncertainty
Additional guidance would be helpful, the authors wrote. In the survey, about 52.3% of primary care physicians and 35.4% of gastroenterologists reported uncertainty about the benefit–harm balance of surveillance in older adults.
“Current guidelines on surveillance colonoscopies are solely based on prior adenoma characteristics,” the authors wrote. “Guidelines need to incorporate guidance that considers patient age and health status, as well as adenoma risk, and explicitly considers when surveillance should stop in older adults.”
In addition, most physicians in the survey – 85.9% of primary care physicians and 77% of gastroenterologists – said they would find a decision support tool helpful. At the same time, 32.8% of primary care physicians and 71.5% of gastroenterologists perceived it as the gastroenterologist’s role to decide about surveillance colonoscopies.
“Developing patient-facing materials, communication tools for clinicians, and tools to support shared decision-making about surveillance colonoscopies that engage both physicians and patients are all important next steps,” the authors wrote. “To our knowledge, there is no existing patient decision aid about surveillance colonoscopies; developing such a tool may be valuable.”
The study was supported by Dr. Schoenborn’s career development award from the National Institute on Aging. The authors reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
Physician recommendations for surveillance colonoscopies in older adults with prior adenomas vary based on several factors, including patient age, health, adenoma risk, and physician specialty, according to a national survey.
In general, physicians were more likely to recommend surveillance for patients at a younger age, with better health, and with prior high-risk adenomas. Additionally, a large proportion of physicians reported uncertainty about whether the benefits of continued surveillance outweighed the risk of harm in older adults.
“There are no existing surveillance colonoscopy guidelines that integrate patient age, health, and adenoma risk, and physicians report significant decisional uncertainty,” Nancy Schoenborn, MD, MHS, associate professor of medicine at Johns Hopkins University, Baltimore, and colleagues wrote.
“Developing the evidence base to evaluate the risks and benefits of surveillance colonoscopy in older adults and decisional support tools that help physicians and patients incorporate available data and weigh risks and benefits are needed to address current gaps in care for older adults with prior adenomas,” the authors wrote.
The study was published online in the American Journal of Gastroenterology.
Surveying physicians
National guidelines recommend surveillance colonoscopy after adenoma removal at more frequent intervals than screening colonoscopy because of a higher risk of colorectal cancer among patients with adenomas. The high quality of screening colonoscopies coupled with an aging population means that many older adults have a history of adenomas and continue to undergo surveillance colonoscopies, the authors wrote.
they wrote.
Dr. Schoenborn and colleagues conducted a national cross-sectional survey of 1,800 primary care physicians and 600 gastroenterologists between April and November 2021. The primary care group included internal medicine, family medicine, general practice, and geriatric medicine physicians.
The research team asked whether physicians would recommend surveillance colonoscopy in a series of 12 vignettes that varied by patient age (75 or 85), patient health (good, medium, or poor), and prior adenoma risk (low or high).
Good health was described as well-controlled hypertension and living independently, whereas moderate health was described as moderate heart failure and has difficulty walking, and poor health was described as severe chronic obstructive pulmonary disease on oxygenand requires help with self-care.
For prior adenomas, high risk involved five tubular adenomas, one of which was 15 mm, and low risk involved two tubular adenomas, both of which were less than 10 mm. The survey also noted that the recommended surveillance intervals were 3 years in the high-risk scenario and 7 years in the low-risk scenario.
Researchers mailed 2,400 surveys and received 1,040 responses. They included 874 in the analysis because the physician respondents provided care to patients ages 65 and older and spent time seeing patients in clinic. Decisions about surveillance colonoscopies for adenomas in the absence of symptoms almost always occur in the outpatient setting, rather than acute or urgent care, the authors wrote.
Large variations found
Overall, physicians were less likely to recommend surveillance colonoscopies if the patient was older, had poor health, and had lower-risk adenomas. Patient age and health had larger effects on decision-making than adenoma risk, with health status having the largest effect.
About 20.6% of physicians recommended surveillance if the patient was 85, compared with 49.8% if the patient was 75. In addition, 7.1% of physicians recommended surveillance if the patient was in poor health, compared with 28.8% for those in moderate health, and 67.7% for patients in good health.
If the prior adenoma was low risk, 29.7% of physicians recommended surveillance, compared with 41.6% if the prior adenoma was high risk.
In general, family medicine and general practice physicians were most likely to recommend surveillance, at 40%, and gastroenterologists were least likely to recommend surveillance, at 30.9%. Patient age and health had larger effects among gastroenterologists than among primary care physicians, and adenoma risk had similar effects between the two groups.
“The importance of patient age and health status found in our study mirrors study results on physician decision-making regarding screening colonoscopies in older adults and makes intuitive sense,” the authors wrote. “Whether the priorities reflected in our findings are supported by evidence is not clear, and our results highlight important knowledge gaps in the field that warrant future research.”
Physician uncertainty
Additional guidance would be helpful, the authors wrote. In the survey, about 52.3% of primary care physicians and 35.4% of gastroenterologists reported uncertainty about the benefit–harm balance of surveillance in older adults.
“Current guidelines on surveillance colonoscopies are solely based on prior adenoma characteristics,” the authors wrote. “Guidelines need to incorporate guidance that considers patient age and health status, as well as adenoma risk, and explicitly considers when surveillance should stop in older adults.”
In addition, most physicians in the survey – 85.9% of primary care physicians and 77% of gastroenterologists – said they would find a decision support tool helpful. At the same time, 32.8% of primary care physicians and 71.5% of gastroenterologists perceived it as the gastroenterologist’s role to decide about surveillance colonoscopies.
“Developing patient-facing materials, communication tools for clinicians, and tools to support shared decision-making about surveillance colonoscopies that engage both physicians and patients are all important next steps,” the authors wrote. “To our knowledge, there is no existing patient decision aid about surveillance colonoscopies; developing such a tool may be valuable.”
The study was supported by Dr. Schoenborn’s career development award from the National Institute on Aging. The authors reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY