The American Gastroenterological Association announced the association’s venture capital fund, GI Opportunity Fund 1, invested in EvoEndo,, a medical device company developing platforms for unsedated transnasal endoscopy (TNE).

“AGA is proud to support EvoEndo® and its innovative technology that has the potential to improve care, save time, resources, and cost for hospitals and the GI community at large,” said Michael L. Kochman, MD, AGAF, MASGE, Wilmott Family Professor of Medicine and Surgery, Center for Endoscopic Innovation, Research and Training, gastroenterology division, University of Pennsylvania Health System; fund manager and adviser, AGA GI Opportunity Fund.

The EvoEndo® Single-Use Endoscopy System received FDA 510(k) clearance in February 2022. The EvoEndo System includes a sterile, single-use, flexible gastroscope designed for unsedated transnasal upper endoscopy and a small portable video controller. The EvoEndo Comfort Kit (not part of the cleared EvoEndo System) includes virtual reality (VR) goggles for patient distraction during the unsedated transnasal endoscopy procedure. Unsedated TNE can be used to evaluate and diagnose a wide range of upper GI conditions that may require frequent monitoring, including eosinophilic esophagitis (EoE), dysphagia, celiac disease, gastroesophageal reflux disease, Barrett’s esophagus, malabsorption, and abdominal pain.

“We are grateful for the support of the AGA, which is a testament to our ongoing commitment to improving GI outcomes with our technology,” said Jonathan T. Hartmann, CEO at EvoEndo. “The AGA has always been at the forefront of improving GI care. Our team could not be more excited that they have recognized EvoEndo, and we look forward to continuing to expand adoption of our technology to the GI community, its physicians, and their patients.”

TNE enabled by EvoEndo’s Single-Use Endoscopy System allows hospitals to move endoscopy procedures from an ambulatory procedural suite to an office-based environment and allows the “traditional” sedation procedure rooms to be used for more complex, therapeutic cases.

“Expanding our fund’s portfolio to include technologies that can transform the pediatric GI landscape is particularly exciting for Varia Ventures,” said Andrea Vossler, cofounder and managing director at Varia Ventures. “EvoEndo® has made significant progress in the TNE category, and we are excited for what’s to come in the future.”

The EvoEndo® Model LE Gastroscope is intended for the visualization of the upper digestive tract in adults and pediatric patients, specifically for the observation, diagnosis, and endoscopic treatment of the esophagus, stomach, and duodenal bulb in patients over the age of five. The gastroscope is a sterile, single-use device and can be inserted orally or transnasally. The EvoEndo® Controller is intended for use with an EvoEndo® Endoscope for endoscopic diagnosis, treatment, and video observation. The EvoEndo System is only intended for use by medical professionals. Physicians and other medical providers interested in learning more about EvoEndo’s TNE system or scheduling demonstrations and training can contact the company here.

The American Gastroenterological Association announced the association’s venture capital fund, GI Opportunity Fund 1, invested in EvoEndo,, a medical device company developing platforms for unsedated transnasal endoscopy (TNE).

“AGA is proud to support EvoEndo® and its innovative technology that has the potential to improve care, save time, resources, and cost for hospitals and the GI community at large,” said Michael L. Kochman, MD, AGAF, MASGE, Wilmott Family Professor of Medicine and Surgery, Center for Endoscopic Innovation, Research and Training, gastroenterology division, University of Pennsylvania Health System; fund manager and adviser, AGA GI Opportunity Fund.

The EvoEndo® Single-Use Endoscopy System received FDA 510(k) clearance in February 2022. The EvoEndo System includes a sterile, single-use, flexible gastroscope designed for unsedated transnasal upper endoscopy and a small portable video controller. The EvoEndo Comfort Kit (not part of the cleared EvoEndo System) includes virtual reality (VR) goggles for patient distraction during the unsedated transnasal endoscopy procedure. Unsedated TNE can be used to evaluate and diagnose a wide range of upper GI conditions that may require frequent monitoring, including eosinophilic esophagitis (EoE), dysphagia, celiac disease, gastroesophageal reflux disease, Barrett’s esophagus, malabsorption, and abdominal pain.

“We are grateful for the support of the AGA, which is a testament to our ongoing commitment to improving GI outcomes with our technology,” said Jonathan T. Hartmann, CEO at EvoEndo. “The AGA has always been at the forefront of improving GI care. Our team could not be more excited that they have recognized EvoEndo, and we look forward to continuing to expand adoption of our technology to the GI community, its physicians, and their patients.”

TNE enabled by EvoEndo’s Single-Use Endoscopy System allows hospitals to move endoscopy procedures from an ambulatory procedural suite to an office-based environment and allows the “traditional” sedation procedure rooms to be used for more complex, therapeutic cases.

“Expanding our fund’s portfolio to include technologies that can transform the pediatric GI landscape is particularly exciting for Varia Ventures,” said Andrea Vossler, cofounder and managing director at Varia Ventures. “EvoEndo® has made significant progress in the TNE category, and we are excited for what’s to come in the future.”

The EvoEndo® Model LE Gastroscope is intended for the visualization of the upper digestive tract in adults and pediatric patients, specifically for the observation, diagnosis, and endoscopic treatment of the esophagus, stomach, and duodenal bulb in patients over the age of five. The gastroscope is a sterile, single-use device and can be inserted orally or transnasally. The EvoEndo® Controller is intended for use with an EvoEndo® Endoscope for endoscopic diagnosis, treatment, and video observation. The EvoEndo System is only intended for use by medical professionals. Physicians and other medical providers interested in learning more about EvoEndo’s TNE system or scheduling demonstrations and training can contact the company here.

The American Gastroenterological Association announced the association’s venture capital fund, GI Opportunity Fund 1, invested in EvoEndo,, a medical device company developing platforms for unsedated transnasal endoscopy (TNE).

“AGA is proud to support EvoEndo® and its innovative technology that has the potential to improve care, save time, resources, and cost for hospitals and the GI community at large,” said Michael L. Kochman, MD, AGAF, MASGE, Wilmott Family Professor of Medicine and Surgery, Center for Endoscopic Innovation, Research and Training, gastroenterology division, University of Pennsylvania Health System; fund manager and adviser, AGA GI Opportunity Fund.

The EvoEndo® Single-Use Endoscopy System received FDA 510(k) clearance in February 2022. The EvoEndo System includes a sterile, single-use, flexible gastroscope designed for unsedated transnasal upper endoscopy and a small portable video controller. The EvoEndo Comfort Kit (not part of the cleared EvoEndo System) includes virtual reality (VR) goggles for patient distraction during the unsedated transnasal endoscopy procedure. Unsedated TNE can be used to evaluate and diagnose a wide range of upper GI conditions that may require frequent monitoring, including eosinophilic esophagitis (EoE), dysphagia, celiac disease, gastroesophageal reflux disease, Barrett’s esophagus, malabsorption, and abdominal pain.

“We are grateful for the support of the AGA, which is a testament to our ongoing commitment to improving GI outcomes with our technology,” said Jonathan T. Hartmann, CEO at EvoEndo. “The AGA has always been at the forefront of improving GI care. Our team could not be more excited that they have recognized EvoEndo, and we look forward to continuing to expand adoption of our technology to the GI community, its physicians, and their patients.”

TNE enabled by EvoEndo’s Single-Use Endoscopy System allows hospitals to move endoscopy procedures from an ambulatory procedural suite to an office-based environment and allows the “traditional” sedation procedure rooms to be used for more complex, therapeutic cases.

“Expanding our fund’s portfolio to include technologies that can transform the pediatric GI landscape is particularly exciting for Varia Ventures,” said Andrea Vossler, cofounder and managing director at Varia Ventures. “EvoEndo® has made significant progress in the TNE category, and we are excited for what’s to come in the future.”

The EvoEndo® Model LE Gastroscope is intended for the visualization of the upper digestive tract in adults and pediatric patients, specifically for the observation, diagnosis, and endoscopic treatment of the esophagus, stomach, and duodenal bulb in patients over the age of five. The gastroscope is a sterile, single-use device and can be inserted orally or transnasally. The EvoEndo® Controller is intended for use with an EvoEndo® Endoscope for endoscopic diagnosis, treatment, and video observation. The EvoEndo System is only intended for use by medical professionals. Physicians and other medical providers interested in learning more about EvoEndo’s TNE system or scheduling demonstrations and training can contact the company here.

Venetoclax combinations – especially a novel combination of venetoclax, ibrutinib, and obinutuzumab – outperform first-line chemoimmunotherapy for chronic lymphocytic leukemia in otherwise fit adults with few comorbidities, according to a phase 3 trial published in the New England Journal of Medicine.

The trial, dubbed GAIA–CLL13, “is a remarkable demonstration of the quality of fixed-duration therapies for younger, fit patients, and it challenges us to continue to work to develop therapeutic strategies that will ultimately cure patients with CLL,” two hematologic cancer specialists said in an accompanying editorial.

In short, “venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib were superior to chemoimmunotherapy with respect to both the minimal residual disease end point and progression-free survival, but venetoclax-rituximab was not,” Jennifer Woyach, MD, of Ohio State University, Columbus, and John Byrd, MD, University of Cincinnati, said in their commentary.

Noting that randomized trials involving venetoclax combinations in fit CLL patients “have been lacking,” the investigators compared 6 cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) with 12 cycles of venetoclax plus the anti-CD20 antibody rituximab, venetoclax plus the third generation anti-CD20 antibody obinutuzumab, and venetoclax combined with both obinutuzumab and the Bruton’s tyrosine kinase inhibitor ibrutinib in a novel triple-therapy regimen.

The 926 patients in the study were a mean of 61 years old and split about evenly among the four treatment arms. Ibrutinib was discontinued after two consecutive measurements if patients had undetectable minimal residual disease (uMRD). Subjects did not have TP53 aberrations, a marker of poor prognosis in CLL.

At 15 months, the percentage of patients with uMRD was significantly higher in the triple-therapy arm (92.2%) and the venetoclax-obinutuzumab group (86.5%) than in the chemoimmunotherapy group (52.0%), but there was no statistical difference with venetoclax-rituximab (57%, P = .32).

The three-year progression-free survival (PFS) was 90.5% in the triple-therapy arm versus 87.7% with venetoclax-obinutuzumab. The 3-year PFS with venetoclax-rituximab (80.8%) was again not statistically different than the 75.5% with chemoimmunotherapy (P = .18).
 

Not ready for prime time

The benefits of triple therapy and venetoclax-obinutuzumab held only in patients with unmutated IgVH. “The high efficacy of the fludarabine, cyclophosphamide, and rituximab regimen in young, fit patients with mutated IgVH may be difficult to improve on,” noted the investigators, led by Barbara Eichhorst, MD, a hematologic malignancy specialist at the University of Cologne (Germany).

Also, although triple-therapy results were impressive, some of the benefits “are neutralized by the need for dose reductions and early treatment discontinuation owing to adverse events,” they said.

For instance, triple therapy had the highest incidence of both grade 3 and 4 infections (21.2%) and atrial fibrillation (7.8%).

The editorialists noted that there has been “a flurry of interest” in trials combining ibrutinib and venetoclax – as was done in the triple-therapy arm – since both emerged as powerful tools against CLL in recent years. However, even with the study results, they said “the use of triplet therapy should be viewed as investigational.”

For one thing, rates of uMRD were not “dramatically different” between triple therapy and venetoclax-obinutuzumab, and longer follow-up is better gauge differences in PFS and long-term toxicities.

Also, ibrutinib is being eclipsed by the second-generation Bruton’s tyrosine kinase inhibitors acalabrutinib and zanubrutinib, because they have better safety profiles, and they are being assessed in CLL combination trials. For now, there are too many unknowns for routine use of triple therapy in fit CLL patients, they said.

The investigators and editorialists both noted that improved uMRD in the study translated into superior PFS, raising the possibility that uMRD might be a valid alternative endpoint to PFS in CLL trials.

With “median remissions in CLL lasting far in excess of 5 years, designing studies that take 8-10 years” to reach a PFS endpoint is simply too slow. Moving to an alternative endpoint such a uMRD would preserve “the momentum that has been generated” with recent advances, Dr. Woyach and Dr. Byrd said.

The work was funded by the companies that market venetoclax, ibrutinib, and obinutuzumab: AbbVie, Janssen, and Roche. Dr. Eichhorst is a consultant and/or speaker for the companies and also reported grants from them. Dr. Byrd is a consultant/adviser for Eilean Therapeutics, Kurome Therapeutics, Newave, and Orbimed. Dr. Woyach disclosed ties with AbbVie, AstraZeneca, Lilly, and other companies.

Venetoclax combinations – especially a novel combination of venetoclax, ibrutinib, and obinutuzumab – outperform first-line chemoimmunotherapy for chronic lymphocytic leukemia in otherwise fit adults with few comorbidities, according to a phase 3 trial published in the New England Journal of Medicine.

The trial, dubbed GAIA–CLL13, “is a remarkable demonstration of the quality of fixed-duration therapies for younger, fit patients, and it challenges us to continue to work to develop therapeutic strategies that will ultimately cure patients with CLL,” two hematologic cancer specialists said in an accompanying editorial.

In short, “venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib were superior to chemoimmunotherapy with respect to both the minimal residual disease end point and progression-free survival, but venetoclax-rituximab was not,” Jennifer Woyach, MD, of Ohio State University, Columbus, and John Byrd, MD, University of Cincinnati, said in their commentary.

Noting that randomized trials involving venetoclax combinations in fit CLL patients “have been lacking,” the investigators compared 6 cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) with 12 cycles of venetoclax plus the anti-CD20 antibody rituximab, venetoclax plus the third generation anti-CD20 antibody obinutuzumab, and venetoclax combined with both obinutuzumab and the Bruton’s tyrosine kinase inhibitor ibrutinib in a novel triple-therapy regimen.

The 926 patients in the study were a mean of 61 years old and split about evenly among the four treatment arms. Ibrutinib was discontinued after two consecutive measurements if patients had undetectable minimal residual disease (uMRD). Subjects did not have TP53 aberrations, a marker of poor prognosis in CLL.

At 15 months, the percentage of patients with uMRD was significantly higher in the triple-therapy arm (92.2%) and the venetoclax-obinutuzumab group (86.5%) than in the chemoimmunotherapy group (52.0%), but there was no statistical difference with venetoclax-rituximab (57%, P = .32).

The three-year progression-free survival (PFS) was 90.5% in the triple-therapy arm versus 87.7% with venetoclax-obinutuzumab. The 3-year PFS with venetoclax-rituximab (80.8%) was again not statistically different than the 75.5% with chemoimmunotherapy (P = .18).
 

Not ready for prime time

The benefits of triple therapy and venetoclax-obinutuzumab held only in patients with unmutated IgVH. “The high efficacy of the fludarabine, cyclophosphamide, and rituximab regimen in young, fit patients with mutated IgVH may be difficult to improve on,” noted the investigators, led by Barbara Eichhorst, MD, a hematologic malignancy specialist at the University of Cologne (Germany).

Also, although triple-therapy results were impressive, some of the benefits “are neutralized by the need for dose reductions and early treatment discontinuation owing to adverse events,” they said.

For instance, triple therapy had the highest incidence of both grade 3 and 4 infections (21.2%) and atrial fibrillation (7.8%).

The editorialists noted that there has been “a flurry of interest” in trials combining ibrutinib and venetoclax – as was done in the triple-therapy arm – since both emerged as powerful tools against CLL in recent years. However, even with the study results, they said “the use of triplet therapy should be viewed as investigational.”

For one thing, rates of uMRD were not “dramatically different” between triple therapy and venetoclax-obinutuzumab, and longer follow-up is better gauge differences in PFS and long-term toxicities.

Also, ibrutinib is being eclipsed by the second-generation Bruton’s tyrosine kinase inhibitors acalabrutinib and zanubrutinib, because they have better safety profiles, and they are being assessed in CLL combination trials. For now, there are too many unknowns for routine use of triple therapy in fit CLL patients, they said.

The investigators and editorialists both noted that improved uMRD in the study translated into superior PFS, raising the possibility that uMRD might be a valid alternative endpoint to PFS in CLL trials.

With “median remissions in CLL lasting far in excess of 5 years, designing studies that take 8-10 years” to reach a PFS endpoint is simply too slow. Moving to an alternative endpoint such a uMRD would preserve “the momentum that has been generated” with recent advances, Dr. Woyach and Dr. Byrd said.

The work was funded by the companies that market venetoclax, ibrutinib, and obinutuzumab: AbbVie, Janssen, and Roche. Dr. Eichhorst is a consultant and/or speaker for the companies and also reported grants from them. Dr. Byrd is a consultant/adviser for Eilean Therapeutics, Kurome Therapeutics, Newave, and Orbimed. Dr. Woyach disclosed ties with AbbVie, AstraZeneca, Lilly, and other companies.

Venetoclax combinations – especially a novel combination of venetoclax, ibrutinib, and obinutuzumab – outperform first-line chemoimmunotherapy for chronic lymphocytic leukemia in otherwise fit adults with few comorbidities, according to a phase 3 trial published in the New England Journal of Medicine.

The trial, dubbed GAIA–CLL13, “is a remarkable demonstration of the quality of fixed-duration therapies for younger, fit patients, and it challenges us to continue to work to develop therapeutic strategies that will ultimately cure patients with CLL,” two hematologic cancer specialists said in an accompanying editorial.

In short, “venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib were superior to chemoimmunotherapy with respect to both the minimal residual disease end point and progression-free survival, but venetoclax-rituximab was not,” Jennifer Woyach, MD, of Ohio State University, Columbus, and John Byrd, MD, University of Cincinnati, said in their commentary.

Noting that randomized trials involving venetoclax combinations in fit CLL patients “have been lacking,” the investigators compared 6 cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) with 12 cycles of venetoclax plus the anti-CD20 antibody rituximab, venetoclax plus the third generation anti-CD20 antibody obinutuzumab, and venetoclax combined with both obinutuzumab and the Bruton’s tyrosine kinase inhibitor ibrutinib in a novel triple-therapy regimen.

The 926 patients in the study were a mean of 61 years old and split about evenly among the four treatment arms. Ibrutinib was discontinued after two consecutive measurements if patients had undetectable minimal residual disease (uMRD). Subjects did not have TP53 aberrations, a marker of poor prognosis in CLL.

At 15 months, the percentage of patients with uMRD was significantly higher in the triple-therapy arm (92.2%) and the venetoclax-obinutuzumab group (86.5%) than in the chemoimmunotherapy group (52.0%), but there was no statistical difference with venetoclax-rituximab (57%, P = .32).

The three-year progression-free survival (PFS) was 90.5% in the triple-therapy arm versus 87.7% with venetoclax-obinutuzumab. The 3-year PFS with venetoclax-rituximab (80.8%) was again not statistically different than the 75.5% with chemoimmunotherapy (P = .18).
 

Not ready for prime time

The benefits of triple therapy and venetoclax-obinutuzumab held only in patients with unmutated IgVH. “The high efficacy of the fludarabine, cyclophosphamide, and rituximab regimen in young, fit patients with mutated IgVH may be difficult to improve on,” noted the investigators, led by Barbara Eichhorst, MD, a hematologic malignancy specialist at the University of Cologne (Germany).

Also, although triple-therapy results were impressive, some of the benefits “are neutralized by the need for dose reductions and early treatment discontinuation owing to adverse events,” they said.

For instance, triple therapy had the highest incidence of both grade 3 and 4 infections (21.2%) and atrial fibrillation (7.8%).

The editorialists noted that there has been “a flurry of interest” in trials combining ibrutinib and venetoclax – as was done in the triple-therapy arm – since both emerged as powerful tools against CLL in recent years. However, even with the study results, they said “the use of triplet therapy should be viewed as investigational.”

For one thing, rates of uMRD were not “dramatically different” between triple therapy and venetoclax-obinutuzumab, and longer follow-up is better gauge differences in PFS and long-term toxicities.

Also, ibrutinib is being eclipsed by the second-generation Bruton’s tyrosine kinase inhibitors acalabrutinib and zanubrutinib, because they have better safety profiles, and they are being assessed in CLL combination trials. For now, there are too many unknowns for routine use of triple therapy in fit CLL patients, they said.

The investigators and editorialists both noted that improved uMRD in the study translated into superior PFS, raising the possibility that uMRD might be a valid alternative endpoint to PFS in CLL trials.

With “median remissions in CLL lasting far in excess of 5 years, designing studies that take 8-10 years” to reach a PFS endpoint is simply too slow. Moving to an alternative endpoint such a uMRD would preserve “the momentum that has been generated” with recent advances, Dr. Woyach and Dr. Byrd said.

The work was funded by the companies that market venetoclax, ibrutinib, and obinutuzumab: AbbVie, Janssen, and Roche. Dr. Eichhorst is a consultant and/or speaker for the companies and also reported grants from them. Dr. Byrd is a consultant/adviser for Eilean Therapeutics, Kurome Therapeutics, Newave, and Orbimed. Dr. Woyach disclosed ties with AbbVie, AstraZeneca, Lilly, and other companies.

CHICAGO – Antiobesity medications and endoscopic sleeve gastroplasty (ESG) are popular strategies for weight loss on their own. Now researchers are looking at what happens when you combine them.

In a study presented at the annual Digestive Disease Week® (DDW), they found ESG followed by an antiobesity medication led to more total weight loss than ESG alone.

Starting medication within 6 months of ESG was more ideal than other timing intervals. Initiating medical therapy more than 6 months before ESG was associated with less weight loss.

In the single-center, retrospective study, 224 patients were enrolled, of whom 34% were on monotherapy (ESG alone), 31% had combination therapy (medication prescribed within 6 months prior to or after ESG), and 35% had sequential therapy (medication more than 6 months prior to or after ESG).

Most patients were female, ranging from 74% to 95% of each group, and baseline BMI ranged from a mean 37.5 kg/m² to 40.1 kg/m².

The medications involved in the study were phentermine, phentermine/topiramate extended release (Qsymia), orlistat (Xenical, Alli), bupropion/naltrexone ER (Contrave), or the glucagonlike peptide–1 receptor agonist (GLP-1RA) liraglutide (Saxenda, Victoza) or semaglutide (Ozempic, Wegovy, Rybelsus). Of the patients who underwent combination therapy, 30% were prescribed a regimen that included a GLP-1RA. Of the patients who underwent sequential therapy, 81% were prescribed a medication first and 19% underwent ESG first.

At 1 year, the greatest total weight loss was a mean 23.7% with the combination of ESG and a GLP-1RA. Total weight loss was 18% with ESG plus a non–GLP-1RA medication. ESG alone led to 17.3%. Sequential therapy that began with ESG yielded 14.7% total weight loss, whereas sequential therapy that began with medication first resulted in 12% weight loss.

Different study, similar result

In a second study, also presented at DDW 2023, investigators looked at timing of liraglutide for weight loss in a randomized controlled trial. They found that administration of GLP-1RA right after transoral outlet reduction endoscopy (TORe) in people with a history of Roux-en-Y gastric bypass extended weight loss longer than a placebo injection. This strategy was also favorable versus waiting to give liraglutide 1 year later.

The researchers randomly assigned 51 people to get weekly subcutaneous liraglutide injections following TORe for 12 months, then placebo injections for 12 months. They assigned 58 patients to receive weekly placebo injections following TORe for 12 months, then liraglutide injections for 12 months.

At 12 months following the procedure, total body weight loss (TBWL) among participants receiving liraglutide was about 22%, compared with about 14% among patients receiving placebo. At 24 months following the procedure (12 months after crossover), TBWL among patients in the liraglutide-first group was almost 35%, compared with about 24% in the placebo-first/liraglutide-second group.

There was a durable effect associated with liraglutide even after switching to placebo, said Ali Lahooti, lead study author and second-year medical student at Weill Cornell Medicine, New York.

“There did seem to be a better benefit of starting on it for the first year and then stopping it,” Dr. Austin noted.

These two studies come at a time when the debate over the timing of different obesity interventions continues. Some experts believe weight loss medications can help with the rebound in weight that some people experience months after bariatric surgery, for example.
 

‘Wave of the future’

The study by Dr. Jirapinyo and colleagues is “really exciting and interesting,” said Linda S. Lee, MD, medical director of endoscopy, Brigham and Women’s Hospital, Boston, when asked to comment.

Medication begun within 6 months of the endoscopic procedure “led to superior outcomes, compared to just endoscopy alone,” Dr. Lee said. “I think that’s really the wave of the future as far as treating patients with obesity issues. We clearly know that diet and exercise alone for most people is not good enough. Of course, we have surgery, but we also realize that with surgery sometimes the weight starts to creep back up over time.”

Dr. Lee noted that the study was limited because it was retrospective. Ideally, it would be good if future, prospective research randomly assigns people to endoscopy alone or endoscopy plus medication.

Dr. Lee also noted there is a limited number of bariatric endoscopists. By the time people with obesity get to a specialist, they’ve likely tried diet and exercise and “probably have seen all the commercials for these different medications. I think the reality is that most people will ask their primary care physicians about antiobesity medication.

“From my point of view, as long as the medicine is safe and not harming them, then let’s do both of them together,” Dr. Lee added.

Dr. Lee also mentioned another study (Abstract Mo1898) presented at DDW 2023 that showed total weight loss with endoscopic sleeve gastroplasty was durable over 10 years. Follow-up was with only seven patients, however.

Larger numbers are needed to confirm the finding, but it’s “exciting,” she said.

Dr. Jirapinyo receives grant/research support from Apollo Endosurgery, Fractyl, and USGI Medical, and is a consultant for ERBE, GI Dynamics, and Spatz Medical. Dr. Lahooti, Dr. Austin, and Dr. Lee reported no relevant financial relationships.

The meeting is sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

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

CHICAGO – Antiobesity medications and endoscopic sleeve gastroplasty (ESG) are popular strategies for weight loss on their own. Now researchers are looking at what happens when you combine them.

In a study presented at the annual Digestive Disease Week® (DDW), they found ESG followed by an antiobesity medication led to more total weight loss than ESG alone.

Starting medication within 6 months of ESG was more ideal than other timing intervals. Initiating medical therapy more than 6 months before ESG was associated with less weight loss.

In the single-center, retrospective study, 224 patients were enrolled, of whom 34% were on monotherapy (ESG alone), 31% had combination therapy (medication prescribed within 6 months prior to or after ESG), and 35% had sequential therapy (medication more than 6 months prior to or after ESG).

Most patients were female, ranging from 74% to 95% of each group, and baseline BMI ranged from a mean 37.5 kg/m² to 40.1 kg/m².

The medications involved in the study were phentermine, phentermine/topiramate extended release (Qsymia), orlistat (Xenical, Alli), bupropion/naltrexone ER (Contrave), or the glucagonlike peptide–1 receptor agonist (GLP-1RA) liraglutide (Saxenda, Victoza) or semaglutide (Ozempic, Wegovy, Rybelsus). Of the patients who underwent combination therapy, 30% were prescribed a regimen that included a GLP-1RA. Of the patients who underwent sequential therapy, 81% were prescribed a medication first and 19% underwent ESG first.

At 1 year, the greatest total weight loss was a mean 23.7% with the combination of ESG and a GLP-1RA. Total weight loss was 18% with ESG plus a non–GLP-1RA medication. ESG alone led to 17.3%. Sequential therapy that began with ESG yielded 14.7% total weight loss, whereas sequential therapy that began with medication first resulted in 12% weight loss.

Different study, similar result

In a second study, also presented at DDW 2023, investigators looked at timing of liraglutide for weight loss in a randomized controlled trial. They found that administration of GLP-1RA right after transoral outlet reduction endoscopy (TORe) in people with a history of Roux-en-Y gastric bypass extended weight loss longer than a placebo injection. This strategy was also favorable versus waiting to give liraglutide 1 year later.

The researchers randomly assigned 51 people to get weekly subcutaneous liraglutide injections following TORe for 12 months, then placebo injections for 12 months. They assigned 58 patients to receive weekly placebo injections following TORe for 12 months, then liraglutide injections for 12 months.

At 12 months following the procedure, total body weight loss (TBWL) among participants receiving liraglutide was about 22%, compared with about 14% among patients receiving placebo. At 24 months following the procedure (12 months after crossover), TBWL among patients in the liraglutide-first group was almost 35%, compared with about 24% in the placebo-first/liraglutide-second group.

There was a durable effect associated with liraglutide even after switching to placebo, said Ali Lahooti, lead study author and second-year medical student at Weill Cornell Medicine, New York.

“There did seem to be a better benefit of starting on it for the first year and then stopping it,” Dr. Austin noted.

These two studies come at a time when the debate over the timing of different obesity interventions continues. Some experts believe weight loss medications can help with the rebound in weight that some people experience months after bariatric surgery, for example.
 

‘Wave of the future’

The study by Dr. Jirapinyo and colleagues is “really exciting and interesting,” said Linda S. Lee, MD, medical director of endoscopy, Brigham and Women’s Hospital, Boston, when asked to comment.

Medication begun within 6 months of the endoscopic procedure “led to superior outcomes, compared to just endoscopy alone,” Dr. Lee said. “I think that’s really the wave of the future as far as treating patients with obesity issues. We clearly know that diet and exercise alone for most people is not good enough. Of course, we have surgery, but we also realize that with surgery sometimes the weight starts to creep back up over time.”

Dr. Lee noted that the study was limited because it was retrospective. Ideally, it would be good if future, prospective research randomly assigns people to endoscopy alone or endoscopy plus medication.

Dr. Lee also noted there is a limited number of bariatric endoscopists. By the time people with obesity get to a specialist, they’ve likely tried diet and exercise and “probably have seen all the commercials for these different medications. I think the reality is that most people will ask their primary care physicians about antiobesity medication.

“From my point of view, as long as the medicine is safe and not harming them, then let’s do both of them together,” Dr. Lee added.

Dr. Lee also mentioned another study (Abstract Mo1898) presented at DDW 2023 that showed total weight loss with endoscopic sleeve gastroplasty was durable over 10 years. Follow-up was with only seven patients, however.

Larger numbers are needed to confirm the finding, but it’s “exciting,” she said.

Dr. Jirapinyo receives grant/research support from Apollo Endosurgery, Fractyl, and USGI Medical, and is a consultant for ERBE, GI Dynamics, and Spatz Medical. Dr. Lahooti, Dr. Austin, and Dr. Lee reported no relevant financial relationships.

The meeting is sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

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

CHICAGO – Antiobesity medications and endoscopic sleeve gastroplasty (ESG) are popular strategies for weight loss on their own. Now researchers are looking at what happens when you combine them.

In a study presented at the annual Digestive Disease Week® (DDW), they found ESG followed by an antiobesity medication led to more total weight loss than ESG alone.

Starting medication within 6 months of ESG was more ideal than other timing intervals. Initiating medical therapy more than 6 months before ESG was associated with less weight loss.

In the single-center, retrospective study, 224 patients were enrolled, of whom 34% were on monotherapy (ESG alone), 31% had combination therapy (medication prescribed within 6 months prior to or after ESG), and 35% had sequential therapy (medication more than 6 months prior to or after ESG).

Most patients were female, ranging from 74% to 95% of each group, and baseline BMI ranged from a mean 37.5 kg/m² to 40.1 kg/m².

The medications involved in the study were phentermine, phentermine/topiramate extended release (Qsymia), orlistat (Xenical, Alli), bupropion/naltrexone ER (Contrave), or the glucagonlike peptide–1 receptor agonist (GLP-1RA) liraglutide (Saxenda, Victoza) or semaglutide (Ozempic, Wegovy, Rybelsus). Of the patients who underwent combination therapy, 30% were prescribed a regimen that included a GLP-1RA. Of the patients who underwent sequential therapy, 81% were prescribed a medication first and 19% underwent ESG first.

At 1 year, the greatest total weight loss was a mean 23.7% with the combination of ESG and a GLP-1RA. Total weight loss was 18% with ESG plus a non–GLP-1RA medication. ESG alone led to 17.3%. Sequential therapy that began with ESG yielded 14.7% total weight loss, whereas sequential therapy that began with medication first resulted in 12% weight loss.

Different study, similar result

In a second study, also presented at DDW 2023, investigators looked at timing of liraglutide for weight loss in a randomized controlled trial. They found that administration of GLP-1RA right after transoral outlet reduction endoscopy (TORe) in people with a history of Roux-en-Y gastric bypass extended weight loss longer than a placebo injection. This strategy was also favorable versus waiting to give liraglutide 1 year later.

The researchers randomly assigned 51 people to get weekly subcutaneous liraglutide injections following TORe for 12 months, then placebo injections for 12 months. They assigned 58 patients to receive weekly placebo injections following TORe for 12 months, then liraglutide injections for 12 months.

At 12 months following the procedure, total body weight loss (TBWL) among participants receiving liraglutide was about 22%, compared with about 14% among patients receiving placebo. At 24 months following the procedure (12 months after crossover), TBWL among patients in the liraglutide-first group was almost 35%, compared with about 24% in the placebo-first/liraglutide-second group.

There was a durable effect associated with liraglutide even after switching to placebo, said Ali Lahooti, lead study author and second-year medical student at Weill Cornell Medicine, New York.

“There did seem to be a better benefit of starting on it for the first year and then stopping it,” Dr. Austin noted.

These two studies come at a time when the debate over the timing of different obesity interventions continues. Some experts believe weight loss medications can help with the rebound in weight that some people experience months after bariatric surgery, for example.
 

‘Wave of the future’

The study by Dr. Jirapinyo and colleagues is “really exciting and interesting,” said Linda S. Lee, MD, medical director of endoscopy, Brigham and Women’s Hospital, Boston, when asked to comment.

Medication begun within 6 months of the endoscopic procedure “led to superior outcomes, compared to just endoscopy alone,” Dr. Lee said. “I think that’s really the wave of the future as far as treating patients with obesity issues. We clearly know that diet and exercise alone for most people is not good enough. Of course, we have surgery, but we also realize that with surgery sometimes the weight starts to creep back up over time.”

Dr. Lee noted that the study was limited because it was retrospective. Ideally, it would be good if future, prospective research randomly assigns people to endoscopy alone or endoscopy plus medication.

Dr. Lee also noted there is a limited number of bariatric endoscopists. By the time people with obesity get to a specialist, they’ve likely tried diet and exercise and “probably have seen all the commercials for these different medications. I think the reality is that most people will ask their primary care physicians about antiobesity medication.

“From my point of view, as long as the medicine is safe and not harming them, then let’s do both of them together,” Dr. Lee added.

Dr. Lee also mentioned another study (Abstract Mo1898) presented at DDW 2023 that showed total weight loss with endoscopic sleeve gastroplasty was durable over 10 years. Follow-up was with only seven patients, however.

Larger numbers are needed to confirm the finding, but it’s “exciting,” she said.

Dr. Jirapinyo receives grant/research support from Apollo Endosurgery, Fractyl, and USGI Medical, and is a consultant for ERBE, GI Dynamics, and Spatz Medical. Dr. Lahooti, Dr. Austin, and Dr. Lee reported no relevant financial relationships.

The meeting is sponsored by the American Gastroenterological Association, the American Association for the Study of Liver Diseases, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

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

Psyllium fiber offered protection against colitis in mice models through its effect on bile acid metabolism, which in turn reduces proinflammatory signaling through activation of the farnesoid X receptor (FXR), shows a study recently published in Cellular and Molecular Gastroenterology and Hepatology

“Our results support the notion that pharmacologic FXR activation might be useful in managing IBD [inflammatory bowel disease], and thus, further investigation of its mechanisms of action are warranted,” wrote the authors, led by Andrew Gewirtz, of the Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta.

Dr. Andrew Gewirtz

Dietary fiber has long been understood to be a key component to a healthy diet by promoting intestinal and metabolic health, but it is unclear whether dietary fiber benefits IBD, specifically Crohn’s disease and ulcerative colitis, and if so, what fiber types are best for these conditions. Some studies have suggested an association between fiber-rich diets and reduced incidence of IBD, but some IBD patients experience intolerance to fiber-rich foods and associated fiber-rich foods with disease flares. In mouse models with colitis, semi-purified fibers have been associated with both the easing and exacerbation of IBD symptoms, with soluble/fermentable fibers like inulin and pectin generally worsening colitis.

The study had two goals: Identify specific fibers that might ameliorate two models of experimental colitis in mice models and to better understand the mechanism by which fiber(s) might suppress inflammation.

Mice were fed high-fiber grain-based chow or diets enriched with semi-purified fibers that included inulin, cellulose, pectin, glucomannan, and psyllium, but only psyllium, a semi-soluble derived from Plantago seeds, improved colitis, and metabolic syndrome. The other fibers often protected against obesity but worsened colitis.

Consuming diets enriched with psyllium were found to “markedly” protected against both dextran sulfate sodium– and T-cell transfer–induced colitis. The protection was independent of fermentation and occurred in animals with minimal microbiota. The animals had increased expression of genes that influence bile acid secretion, and the researchers noted increased levels of both fecal and serum BA.

The increased serum levels prompted the researchers to investigate psyllium’s role in signaling activation through BA receptors, especially FXR. An FXR agonist also reduced colitis severity, while an FXR antagonist worsened it. FXR-deficient mice gained little benefit from psyllium supplementation, further suggesting that FXR mediates psyllium’s effect.

All soluble fibers impacted gut microbiota composition, but none more than psyllium which protected mice from developing dextran sulfate sodium colitis. While other soluble fibers increased in the abundance of bacteria (that is, fecal/luminal bacterial density), psyllium decreased in this area, which may explain why some fermentable fibers, including inulin, exacerbate colitis.

“These results indicate that psyllium’s protection against colitis involves its ability to increase circulating bile acid levels, thus activating FXR signaling,” the authors wrote.

Researchers found some evidence that prolonged psyllium supplementation could lead to mild elevations in AST and ALT, suggesting that the ability of psyllium to chelate BA could lead to lipid deficiency, especially in the presence of a low-fat diet.

“We suggest that future studies of psyllium in humans measure serum BA and consider roles for FXR activation in mediating impacts of this fiber,” the authors wrote.

The study was supported by the National Institutes of Health and the Crohn’s and Colitis Foundation. The authors disclosed no conflicts.

Psyllium fiber offered protection against colitis in mice models through its effect on bile acid metabolism, which in turn reduces proinflammatory signaling through activation of the farnesoid X receptor (FXR), shows a study recently published in Cellular and Molecular Gastroenterology and Hepatology

“Our results support the notion that pharmacologic FXR activation might be useful in managing IBD [inflammatory bowel disease], and thus, further investigation of its mechanisms of action are warranted,” wrote the authors, led by Andrew Gewirtz, of the Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta.

Dr. Andrew Gewirtz

Dietary fiber has long been understood to be a key component to a healthy diet by promoting intestinal and metabolic health, but it is unclear whether dietary fiber benefits IBD, specifically Crohn’s disease and ulcerative colitis, and if so, what fiber types are best for these conditions. Some studies have suggested an association between fiber-rich diets and reduced incidence of IBD, but some IBD patients experience intolerance to fiber-rich foods and associated fiber-rich foods with disease flares. In mouse models with colitis, semi-purified fibers have been associated with both the easing and exacerbation of IBD symptoms, with soluble/fermentable fibers like inulin and pectin generally worsening colitis.

The study had two goals: Identify specific fibers that might ameliorate two models of experimental colitis in mice models and to better understand the mechanism by which fiber(s) might suppress inflammation.

Mice were fed high-fiber grain-based chow or diets enriched with semi-purified fibers that included inulin, cellulose, pectin, glucomannan, and psyllium, but only psyllium, a semi-soluble derived from Plantago seeds, improved colitis, and metabolic syndrome. The other fibers often protected against obesity but worsened colitis.

Consuming diets enriched with psyllium were found to “markedly” protected against both dextran sulfate sodium– and T-cell transfer–induced colitis. The protection was independent of fermentation and occurred in animals with minimal microbiota. The animals had increased expression of genes that influence bile acid secretion, and the researchers noted increased levels of both fecal and serum BA.

The increased serum levels prompted the researchers to investigate psyllium’s role in signaling activation through BA receptors, especially FXR. An FXR agonist also reduced colitis severity, while an FXR antagonist worsened it. FXR-deficient mice gained little benefit from psyllium supplementation, further suggesting that FXR mediates psyllium’s effect.

All soluble fibers impacted gut microbiota composition, but none more than psyllium which protected mice from developing dextran sulfate sodium colitis. While other soluble fibers increased in the abundance of bacteria (that is, fecal/luminal bacterial density), psyllium decreased in this area, which may explain why some fermentable fibers, including inulin, exacerbate colitis.

“These results indicate that psyllium’s protection against colitis involves its ability to increase circulating bile acid levels, thus activating FXR signaling,” the authors wrote.

Researchers found some evidence that prolonged psyllium supplementation could lead to mild elevations in AST and ALT, suggesting that the ability of psyllium to chelate BA could lead to lipid deficiency, especially in the presence of a low-fat diet.

“We suggest that future studies of psyllium in humans measure serum BA and consider roles for FXR activation in mediating impacts of this fiber,” the authors wrote.

The study was supported by the National Institutes of Health and the Crohn’s and Colitis Foundation. The authors disclosed no conflicts.

Psyllium fiber offered protection against colitis in mice models through its effect on bile acid metabolism, which in turn reduces proinflammatory signaling through activation of the farnesoid X receptor (FXR), shows a study recently published in Cellular and Molecular Gastroenterology and Hepatology

“Our results support the notion that pharmacologic FXR activation might be useful in managing IBD [inflammatory bowel disease], and thus, further investigation of its mechanisms of action are warranted,” wrote the authors, led by Andrew Gewirtz, of the Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta.

Dr. Andrew Gewirtz

Dietary fiber has long been understood to be a key component to a healthy diet by promoting intestinal and metabolic health, but it is unclear whether dietary fiber benefits IBD, specifically Crohn’s disease and ulcerative colitis, and if so, what fiber types are best for these conditions. Some studies have suggested an association between fiber-rich diets and reduced incidence of IBD, but some IBD patients experience intolerance to fiber-rich foods and associated fiber-rich foods with disease flares. In mouse models with colitis, semi-purified fibers have been associated with both the easing and exacerbation of IBD symptoms, with soluble/fermentable fibers like inulin and pectin generally worsening colitis.

The study had two goals: Identify specific fibers that might ameliorate two models of experimental colitis in mice models and to better understand the mechanism by which fiber(s) might suppress inflammation.

Mice were fed high-fiber grain-based chow or diets enriched with semi-purified fibers that included inulin, cellulose, pectin, glucomannan, and psyllium, but only psyllium, a semi-soluble derived from Plantago seeds, improved colitis, and metabolic syndrome. The other fibers often protected against obesity but worsened colitis.

Consuming diets enriched with psyllium were found to “markedly” protected against both dextran sulfate sodium– and T-cell transfer–induced colitis. The protection was independent of fermentation and occurred in animals with minimal microbiota. The animals had increased expression of genes that influence bile acid secretion, and the researchers noted increased levels of both fecal and serum BA.

The increased serum levels prompted the researchers to investigate psyllium’s role in signaling activation through BA receptors, especially FXR. An FXR agonist also reduced colitis severity, while an FXR antagonist worsened it. FXR-deficient mice gained little benefit from psyllium supplementation, further suggesting that FXR mediates psyllium’s effect.

All soluble fibers impacted gut microbiota composition, but none more than psyllium which protected mice from developing dextran sulfate sodium colitis. While other soluble fibers increased in the abundance of bacteria (that is, fecal/luminal bacterial density), psyllium decreased in this area, which may explain why some fermentable fibers, including inulin, exacerbate colitis.

“These results indicate that psyllium’s protection against colitis involves its ability to increase circulating bile acid levels, thus activating FXR signaling,” the authors wrote.

Researchers found some evidence that prolonged psyllium supplementation could lead to mild elevations in AST and ALT, suggesting that the ability of psyllium to chelate BA could lead to lipid deficiency, especially in the presence of a low-fat diet.

“We suggest that future studies of psyllium in humans measure serum BA and consider roles for FXR activation in mediating impacts of this fiber,” the authors wrote.

The study was supported by the National Institutes of Health and the Crohn’s and Colitis Foundation. The authors disclosed no conflicts.

Adverse neonatal outcomes occurred in 24.9% of women treated for gestational diabetes at less than 20 weeks’ gestation compared to 30.5% of controls treated later or not at all, based on data from nearly 800 women.

Screening and treatment for gestational diabetes are currently recommended at 24-28 weeks’ gestation, with earlier testing recommended for women at increased risk, but the potential benefits of earlier intervention remain debatable, wrote David Simmons, MD, of Western Sydney University, Campbelltown, Australia, and colleagues.

“Until now, there has been complete equipoise over whether to treat hyperglycemia below that of overt diabetes early in pregnancy,” Dr. Simmons said in an interview. The conflicting questions: “Would early treatment reduce the excess deposition of fat on the baby with all of its sequelae; but would early treatment reduce fuel supply to some babies at a critical time and lead to SGA [small for gestational age]?” Dr. Simmons noted.

In a study published in the New England Journal of Medicine, Dr. Simmons and colleagues randomized 406 women aged 18 years and older with singleton pregnancies to immediate treatment for gestational diabetes. Another 396 women were randomized to a control group for deferred treatment or no treatment, based on results of an oral glucose tolerance test at 24-28 weeks’ gestation. All participants had at least one risk factor for hyperglycemia, and met the World Health Organization criteria for gestational diabetes. Women with preexisting diabetes or contraindicating comorbid medical conditions were excluded.

The study had three primary outcomes. The first was a composite of neonatal outcomes including birth before 37 weeks’ gestation, birth weight of 4,500 g or higher, birth trauma, neonatal respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia.

The final sample included 748 women for adverse neonatal outcomes, 750 for pregnancy-related hypertension, and 492 for neonatal lean body mass. The mean age of the participants was 32 years; approximately one-third were white European and another third were South Asian. Overall baseline demographics were similar between the groups, and the initial oral glucose tolerance tests were performed at a mean of 15.6 weeks’ gestation.

Overall, 24.9% of women in the early treatment group experienced an adverse neonatal event vs. 30.5% of controls, for an adjusted risk difference of –5.6% and adjusted relative risk of 0.82.

Notably, in an exploratory subgroup analysis, respiratory distress occurred in 9.8% of infants born to women in the immediate treatment group vs. 17.0% of infants in the control group. “Neonatal respiratory distress was the main driver of the between-group difference observed for the first primary outcome,” the researchers wrote. A prespecified subgroup analysis suggested that the impact of an earlier intervention on adverse neonatal outcomes might be greater among women with a higher glycemic value and those whose oral glucose tolerance tests occurred at less than 14 weeks’ gestation, they noted. Stillbirths or neonatal deaths were similar and infrequent in both groups.

Pregnancy-related hypertension occurred in 10.6% of the immediate-treatment group and 9.9% of the controls group (adjusted risk difference, 0.7%). For the third outcome, the mean neonatal lean body mass was 2.86 g in the immediate-treatment group and 2.91 g for the controls (adjusted mean difference, −0.04 g).

No differences in serious adverse events related to either screening or treatment were noted between the groups.
 

Impact on neonatal outcomes merits further study

Dr. Simmons said that he was surprised by the study findings. “We thought if there was an effect, it would be small, but it isn’t,” he told this publication.

“If you combine the severe adverse outcomes, the perineal trauma and the reduction in days in NICU/special care unit, this is a significant impact on morbidity and likely on cost,” and researchers are currently examining data for cost-effectiveness, he said.

“We did not expect the likely large impact on reducing respiratory distress and perineal trauma,” he noted. “These findings have not been previously reported, perhaps because they were not looked for.” By contrast, “we thought here might be reductions in lower gestational age and cesarean delivery, but there was not,” he added.

The findings were limited by several factors including the nonstandardized approach to gestational diabetes treatment and the use of third-trimester treatment targets that had not been tested in earlier trimesters, the researchers noted. Other limitations included the focus on women already at high risk for hyperglycemia; therefore, the results might not generalize to women not at risk, they wrote.

The current study represents a beginning of answers, with data suggesting that early treatment for gestational diabetes reduces severe adverse pregnancy outcomes, days in NICU/special care unit, and perineal trauma, likely from the first trimester, said Dr. Simmons. However, the findings must be interpreted with caution, as criteria that are too low “might lead to more small babies,” he said. “We look forward to working with others to translate these findings into practice,” he added.

Much more research is needed to answer the many questions prompted by the current study, including who did and did not have complications, Dr. Simmons told this publication. Other studies are needed to collect data on cost-effectiveness, as well as consumer views, especially “different perspectives from different parts of the globe,” he said. Although there is not enough evidence yet to draw conclusions about the role of continuous glucose monitoring (CGM) in managing gestational diabetes, many studies are underway; “we look forward to the results,” of these studies, Dr. Simmons added.
 

Findings support early screening

Gestational diabetes is one of the most common medical complications of pregnancy, and accounts for more than 80% of diabetes-related diagnoses in pregnancy, said Emily Fay, MD, a maternal-fetal medicine specialist at the University of Washington, Seattle, in an interview.

“Previous studies have found that women with gestational diabetes are at higher risk in their pregnancy, including higher chance of developing preeclampsia, higher chance of cesarean delivery, and higher risks for their baby, including risk of shoulder dystocia, birth trauma, and jaundice, and higher birth weights,” she said. “Fortunately, studies have also shown that treatment of gestational diabetes helps lower these risks,” she noted. Currently, patients undergo routine screening for gestational diabetes between 24 and 28 weeks of pregnancy, but some who have risk factors for gestational diabetes may have screening in the early part of pregnancy, said Dr. Fay.

The current findings were not surprising overall, said Dr. Fay, who was not involved in the study. “The study authors looked at a variety of outcomes including neonatal adverse outcomes, neonatal body weight, and pregnancy-related hypertension,” she said.

The researchers found that patients treated early had a lower rate of adverse neonatal outcomes, which was to be expected, Dr. Fay said. “They did not find a difference in neonatal body weight; this also was not surprising, as the women who were not in the early treatment group still received treatment at the time of diagnosis later in pregnancy, which likely helped normalize the weights,” she explained.

“My takeaway from this study is that we should continue to screen patients with risk factors for gestational diabetes early in pregnancy and treat them at the time of diagnosis,” Dr. Fay told this publication. However, barriers that may exist to early treatment involve access to care, including being able to see a provider early in pregnancy, she said. “The treatment for gestational diabetes includes dietary education with diet changes and checking blood sugars frequently. Access to nutrition education can be limited and access to healthy foods can be expensive and difficult to obtain,” she noted. “Checking blood sugars throughout the day can also be difficult for those who are busy or working and who may not have the ability to take time to do this,” she said. However, “these barriers may be overcome by health care reform that improves patient access to and coverage of pregnancy care, improved access and affordability of healthy foods, and employer flexibility to allow the time and space to check blood sugars if needed,” she added.

Looking ahead, the use of continuous glucose monitors in pregnancy is an expanding area of research, said Dr. Fay. “Patients can quickly view their blood sugar without the use of finger sticks, which may help overcome some of the barriers patients may have with using finger sticks,” she noted. “Continuous glucose monitors have been used for those with type 1 and type 2 diabetes with success, and we need to better understand if these can also be helpful in gestational diabetes,” she said. Dr. Fay and colleagues at the University of Washington are currently conducting an ongoing study to explore the use of CGM in gestational diabetes.

The study was supported by the National Health and Medical Research Council, the Region Örebro Research Committee, the Medical Scientific Fund of the Mayor of Vienna, the South Western Sydney Local Health District Academic Unit, and a Western Sydney University Ainsworth Trust Grant. The researchers had no financial conflicts to disclose. Dr. Fay had no relevant financial conflicts to disclose.

Adverse neonatal outcomes occurred in 24.9% of women treated for gestational diabetes at less than 20 weeks’ gestation compared to 30.5% of controls treated later or not at all, based on data from nearly 800 women.

Screening and treatment for gestational diabetes are currently recommended at 24-28 weeks’ gestation, with earlier testing recommended for women at increased risk, but the potential benefits of earlier intervention remain debatable, wrote David Simmons, MD, of Western Sydney University, Campbelltown, Australia, and colleagues.

“Until now, there has been complete equipoise over whether to treat hyperglycemia below that of overt diabetes early in pregnancy,” Dr. Simmons said in an interview. The conflicting questions: “Would early treatment reduce the excess deposition of fat on the baby with all of its sequelae; but would early treatment reduce fuel supply to some babies at a critical time and lead to SGA [small for gestational age]?” Dr. Simmons noted.

In a study published in the New England Journal of Medicine, Dr. Simmons and colleagues randomized 406 women aged 18 years and older with singleton pregnancies to immediate treatment for gestational diabetes. Another 396 women were randomized to a control group for deferred treatment or no treatment, based on results of an oral glucose tolerance test at 24-28 weeks’ gestation. All participants had at least one risk factor for hyperglycemia, and met the World Health Organization criteria for gestational diabetes. Women with preexisting diabetes or contraindicating comorbid medical conditions were excluded.

The study had three primary outcomes. The first was a composite of neonatal outcomes including birth before 37 weeks’ gestation, birth weight of 4,500 g or higher, birth trauma, neonatal respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia.

The final sample included 748 women for adverse neonatal outcomes, 750 for pregnancy-related hypertension, and 492 for neonatal lean body mass. The mean age of the participants was 32 years; approximately one-third were white European and another third were South Asian. Overall baseline demographics were similar between the groups, and the initial oral glucose tolerance tests were performed at a mean of 15.6 weeks’ gestation.

Overall, 24.9% of women in the early treatment group experienced an adverse neonatal event vs. 30.5% of controls, for an adjusted risk difference of –5.6% and adjusted relative risk of 0.82.

Notably, in an exploratory subgroup analysis, respiratory distress occurred in 9.8% of infants born to women in the immediate treatment group vs. 17.0% of infants in the control group. “Neonatal respiratory distress was the main driver of the between-group difference observed for the first primary outcome,” the researchers wrote. A prespecified subgroup analysis suggested that the impact of an earlier intervention on adverse neonatal outcomes might be greater among women with a higher glycemic value and those whose oral glucose tolerance tests occurred at less than 14 weeks’ gestation, they noted. Stillbirths or neonatal deaths were similar and infrequent in both groups.

Pregnancy-related hypertension occurred in 10.6% of the immediate-treatment group and 9.9% of the controls group (adjusted risk difference, 0.7%). For the third outcome, the mean neonatal lean body mass was 2.86 g in the immediate-treatment group and 2.91 g for the controls (adjusted mean difference, −0.04 g).

No differences in serious adverse events related to either screening or treatment were noted between the groups.
 

Impact on neonatal outcomes merits further study

Dr. Simmons said that he was surprised by the study findings. “We thought if there was an effect, it would be small, but it isn’t,” he told this publication.

“If you combine the severe adverse outcomes, the perineal trauma and the reduction in days in NICU/special care unit, this is a significant impact on morbidity and likely on cost,” and researchers are currently examining data for cost-effectiveness, he said.

“We did not expect the likely large impact on reducing respiratory distress and perineal trauma,” he noted. “These findings have not been previously reported, perhaps because they were not looked for.” By contrast, “we thought here might be reductions in lower gestational age and cesarean delivery, but there was not,” he added.

The findings were limited by several factors including the nonstandardized approach to gestational diabetes treatment and the use of third-trimester treatment targets that had not been tested in earlier trimesters, the researchers noted. Other limitations included the focus on women already at high risk for hyperglycemia; therefore, the results might not generalize to women not at risk, they wrote.

The current study represents a beginning of answers, with data suggesting that early treatment for gestational diabetes reduces severe adverse pregnancy outcomes, days in NICU/special care unit, and perineal trauma, likely from the first trimester, said Dr. Simmons. However, the findings must be interpreted with caution, as criteria that are too low “might lead to more small babies,” he said. “We look forward to working with others to translate these findings into practice,” he added.

Much more research is needed to answer the many questions prompted by the current study, including who did and did not have complications, Dr. Simmons told this publication. Other studies are needed to collect data on cost-effectiveness, as well as consumer views, especially “different perspectives from different parts of the globe,” he said. Although there is not enough evidence yet to draw conclusions about the role of continuous glucose monitoring (CGM) in managing gestational diabetes, many studies are underway; “we look forward to the results,” of these studies, Dr. Simmons added.
 

Findings support early screening

Gestational diabetes is one of the most common medical complications of pregnancy, and accounts for more than 80% of diabetes-related diagnoses in pregnancy, said Emily Fay, MD, a maternal-fetal medicine specialist at the University of Washington, Seattle, in an interview.

“Previous studies have found that women with gestational diabetes are at higher risk in their pregnancy, including higher chance of developing preeclampsia, higher chance of cesarean delivery, and higher risks for their baby, including risk of shoulder dystocia, birth trauma, and jaundice, and higher birth weights,” she said. “Fortunately, studies have also shown that treatment of gestational diabetes helps lower these risks,” she noted. Currently, patients undergo routine screening for gestational diabetes between 24 and 28 weeks of pregnancy, but some who have risk factors for gestational diabetes may have screening in the early part of pregnancy, said Dr. Fay.

The current findings were not surprising overall, said Dr. Fay, who was not involved in the study. “The study authors looked at a variety of outcomes including neonatal adverse outcomes, neonatal body weight, and pregnancy-related hypertension,” she said.

The researchers found that patients treated early had a lower rate of adverse neonatal outcomes, which was to be expected, Dr. Fay said. “They did not find a difference in neonatal body weight; this also was not surprising, as the women who were not in the early treatment group still received treatment at the time of diagnosis later in pregnancy, which likely helped normalize the weights,” she explained.

“My takeaway from this study is that we should continue to screen patients with risk factors for gestational diabetes early in pregnancy and treat them at the time of diagnosis,” Dr. Fay told this publication. However, barriers that may exist to early treatment involve access to care, including being able to see a provider early in pregnancy, she said. “The treatment for gestational diabetes includes dietary education with diet changes and checking blood sugars frequently. Access to nutrition education can be limited and access to healthy foods can be expensive and difficult to obtain,” she noted. “Checking blood sugars throughout the day can also be difficult for those who are busy or working and who may not have the ability to take time to do this,” she said. However, “these barriers may be overcome by health care reform that improves patient access to and coverage of pregnancy care, improved access and affordability of healthy foods, and employer flexibility to allow the time and space to check blood sugars if needed,” she added.

Looking ahead, the use of continuous glucose monitors in pregnancy is an expanding area of research, said Dr. Fay. “Patients can quickly view their blood sugar without the use of finger sticks, which may help overcome some of the barriers patients may have with using finger sticks,” she noted. “Continuous glucose monitors have been used for those with type 1 and type 2 diabetes with success, and we need to better understand if these can also be helpful in gestational diabetes,” she said. Dr. Fay and colleagues at the University of Washington are currently conducting an ongoing study to explore the use of CGM in gestational diabetes.

The study was supported by the National Health and Medical Research Council, the Region Örebro Research Committee, the Medical Scientific Fund of the Mayor of Vienna, the South Western Sydney Local Health District Academic Unit, and a Western Sydney University Ainsworth Trust Grant. The researchers had no financial conflicts to disclose. Dr. Fay had no relevant financial conflicts to disclose.

Adverse neonatal outcomes occurred in 24.9% of women treated for gestational diabetes at less than 20 weeks’ gestation compared to 30.5% of controls treated later or not at all, based on data from nearly 800 women.

Screening and treatment for gestational diabetes are currently recommended at 24-28 weeks’ gestation, with earlier testing recommended for women at increased risk, but the potential benefits of earlier intervention remain debatable, wrote David Simmons, MD, of Western Sydney University, Campbelltown, Australia, and colleagues.

“Until now, there has been complete equipoise over whether to treat hyperglycemia below that of overt diabetes early in pregnancy,” Dr. Simmons said in an interview. The conflicting questions: “Would early treatment reduce the excess deposition of fat on the baby with all of its sequelae; but would early treatment reduce fuel supply to some babies at a critical time and lead to SGA [small for gestational age]?” Dr. Simmons noted.

In a study published in the New England Journal of Medicine, Dr. Simmons and colleagues randomized 406 women aged 18 years and older with singleton pregnancies to immediate treatment for gestational diabetes. Another 396 women were randomized to a control group for deferred treatment or no treatment, based on results of an oral glucose tolerance test at 24-28 weeks’ gestation. All participants had at least one risk factor for hyperglycemia, and met the World Health Organization criteria for gestational diabetes. Women with preexisting diabetes or contraindicating comorbid medical conditions were excluded.

The study had three primary outcomes. The first was a composite of neonatal outcomes including birth before 37 weeks’ gestation, birth weight of 4,500 g or higher, birth trauma, neonatal respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia.

The final sample included 748 women for adverse neonatal outcomes, 750 for pregnancy-related hypertension, and 492 for neonatal lean body mass. The mean age of the participants was 32 years; approximately one-third were white European and another third were South Asian. Overall baseline demographics were similar between the groups, and the initial oral glucose tolerance tests were performed at a mean of 15.6 weeks’ gestation.

Overall, 24.9% of women in the early treatment group experienced an adverse neonatal event vs. 30.5% of controls, for an adjusted risk difference of –5.6% and adjusted relative risk of 0.82.

Notably, in an exploratory subgroup analysis, respiratory distress occurred in 9.8% of infants born to women in the immediate treatment group vs. 17.0% of infants in the control group. “Neonatal respiratory distress was the main driver of the between-group difference observed for the first primary outcome,” the researchers wrote. A prespecified subgroup analysis suggested that the impact of an earlier intervention on adverse neonatal outcomes might be greater among women with a higher glycemic value and those whose oral glucose tolerance tests occurred at less than 14 weeks’ gestation, they noted. Stillbirths or neonatal deaths were similar and infrequent in both groups.

Pregnancy-related hypertension occurred in 10.6% of the immediate-treatment group and 9.9% of the controls group (adjusted risk difference, 0.7%). For the third outcome, the mean neonatal lean body mass was 2.86 g in the immediate-treatment group and 2.91 g for the controls (adjusted mean difference, −0.04 g).

No differences in serious adverse events related to either screening or treatment were noted between the groups.
 

Impact on neonatal outcomes merits further study

Dr. Simmons said that he was surprised by the study findings. “We thought if there was an effect, it would be small, but it isn’t,” he told this publication.

“If you combine the severe adverse outcomes, the perineal trauma and the reduction in days in NICU/special care unit, this is a significant impact on morbidity and likely on cost,” and researchers are currently examining data for cost-effectiveness, he said.

“We did not expect the likely large impact on reducing respiratory distress and perineal trauma,” he noted. “These findings have not been previously reported, perhaps because they were not looked for.” By contrast, “we thought here might be reductions in lower gestational age and cesarean delivery, but there was not,” he added.

The findings were limited by several factors including the nonstandardized approach to gestational diabetes treatment and the use of third-trimester treatment targets that had not been tested in earlier trimesters, the researchers noted. Other limitations included the focus on women already at high risk for hyperglycemia; therefore, the results might not generalize to women not at risk, they wrote.

The current study represents a beginning of answers, with data suggesting that early treatment for gestational diabetes reduces severe adverse pregnancy outcomes, days in NICU/special care unit, and perineal trauma, likely from the first trimester, said Dr. Simmons. However, the findings must be interpreted with caution, as criteria that are too low “might lead to more small babies,” he said. “We look forward to working with others to translate these findings into practice,” he added.

Much more research is needed to answer the many questions prompted by the current study, including who did and did not have complications, Dr. Simmons told this publication. Other studies are needed to collect data on cost-effectiveness, as well as consumer views, especially “different perspectives from different parts of the globe,” he said. Although there is not enough evidence yet to draw conclusions about the role of continuous glucose monitoring (CGM) in managing gestational diabetes, many studies are underway; “we look forward to the results,” of these studies, Dr. Simmons added.
 

Findings support early screening

Gestational diabetes is one of the most common medical complications of pregnancy, and accounts for more than 80% of diabetes-related diagnoses in pregnancy, said Emily Fay, MD, a maternal-fetal medicine specialist at the University of Washington, Seattle, in an interview.

“Previous studies have found that women with gestational diabetes are at higher risk in their pregnancy, including higher chance of developing preeclampsia, higher chance of cesarean delivery, and higher risks for their baby, including risk of shoulder dystocia, birth trauma, and jaundice, and higher birth weights,” she said. “Fortunately, studies have also shown that treatment of gestational diabetes helps lower these risks,” she noted. Currently, patients undergo routine screening for gestational diabetes between 24 and 28 weeks of pregnancy, but some who have risk factors for gestational diabetes may have screening in the early part of pregnancy, said Dr. Fay.

The current findings were not surprising overall, said Dr. Fay, who was not involved in the study. “The study authors looked at a variety of outcomes including neonatal adverse outcomes, neonatal body weight, and pregnancy-related hypertension,” she said.

The researchers found that patients treated early had a lower rate of adverse neonatal outcomes, which was to be expected, Dr. Fay said. “They did not find a difference in neonatal body weight; this also was not surprising, as the women who were not in the early treatment group still received treatment at the time of diagnosis later in pregnancy, which likely helped normalize the weights,” she explained.

“My takeaway from this study is that we should continue to screen patients with risk factors for gestational diabetes early in pregnancy and treat them at the time of diagnosis,” Dr. Fay told this publication. However, barriers that may exist to early treatment involve access to care, including being able to see a provider early in pregnancy, she said. “The treatment for gestational diabetes includes dietary education with diet changes and checking blood sugars frequently. Access to nutrition education can be limited and access to healthy foods can be expensive and difficult to obtain,” she noted. “Checking blood sugars throughout the day can also be difficult for those who are busy or working and who may not have the ability to take time to do this,” she said. However, “these barriers may be overcome by health care reform that improves patient access to and coverage of pregnancy care, improved access and affordability of healthy foods, and employer flexibility to allow the time and space to check blood sugars if needed,” she added.

Looking ahead, the use of continuous glucose monitors in pregnancy is an expanding area of research, said Dr. Fay. “Patients can quickly view their blood sugar without the use of finger sticks, which may help overcome some of the barriers patients may have with using finger sticks,” she noted. “Continuous glucose monitors have been used for those with type 1 and type 2 diabetes with success, and we need to better understand if these can also be helpful in gestational diabetes,” she said. Dr. Fay and colleagues at the University of Washington are currently conducting an ongoing study to explore the use of CGM in gestational diabetes.

The study was supported by the National Health and Medical Research Council, the Region Örebro Research Committee, the Medical Scientific Fund of the Mayor of Vienna, the South Western Sydney Local Health District Academic Unit, and a Western Sydney University Ainsworth Trust Grant. The researchers had no financial conflicts to disclose. Dr. Fay had no relevant financial conflicts to disclose.

The number of cancer survivors who report functional limitation has more than doubled in 20 years, according to a research letter published in JAMA Oncology.

Vishal Patel, BS, a student at the Dell Medical School at The University of Texas at Austin, and colleagues identified 51,258 cancer survivors from the National Health Interview Survey, representing a weighted population of approximately 178.8 million from 1999 to 2018.

Most survivors were women (60.2%) and were at least 65 years old (55.4%). In 1999, 3.6 million weighted survivors reported functional limitation. In 2018, the number increased to 8.2 million, a 2.25-fold increase.

The number of survivors who reported no limitations also increased, but not by as much. That group grew 1.34-fold during the study period.

For context, “the 70% prevalence of functional limitation among survivors in 2018 is nearly twice that of the general population,” the authors wrote.
 

Patients surveyed on function

Functional limitation was defined as “self-reported difficulty performing any of 12 routine physical or social activities without assistance.” Examples of the activities included difficulty sitting for more than 2 hours, difficulty participating in social activities or difficulty pushing or pulling an object the size of a living room chair.

Over the 2 decades analyzed, the adjusted prevalence of functional limitation was highest among survivors of pancreatic cancer (80.3%) and lung cancer (76.5%). Prevalence was lowest for survivors of melanoma (62.2%), breast (61.8%) and prostate (59.5%) cancers.
 

Not just a result of living longer

Mr. Patel told this publication that one assumption people might make when they read these results is that people are just living longer with cancer and losing functional ability accordingly.

“But, in fact, we found that the youngest [– those less than 65 years–] actually contributed to this trend more than the oldest people, which means it’s not just [happening], because people are getting older,” he said.

Hispanic and Black individuals had disproportionately higher increases in functional limitation; percentage point increases over the 2 decades were 19.5 for Black people, 25.1 for Hispanic people and 12.5 for White people. There may be a couple of reasons for that, Mr. Patel noted.

Those who are Black or Hispanic tend to have less access to cancer survivorship care for reasons including insurance status and historic health care inequities, he noted.

“The other potential reason is that they have had less access to cancer care historically. And if, 20 years ago Black and Hispanic individuals didn’t have access to some chemotherapies, and now they do, maybe it’s the increased access to care that’s causing these functional limitations. Because chemotherapy can sometimes be very toxic. It may be sort of a catch-up toxicity,” he said.
 

Quality of life beyond survivorship

Mr. Patel said the results seem to call for building on improved survival rates by tracking and improving function.

“It’s good to celebrate that there are more survivors. But now that we can keep people alive longer, maybe we can shift gears to improving their quality of life,” he said.

The more-than-doubling of functional limitations over 2 decades “is a very sobering trend,” he noted, while pointing out that the functional limitations applied to 8 million people in the United States – people whose needs are not being met.

There’s no sign of the trend stopping, he continued. “We saw no downward trend, only an upward trend.”

Increasingly, including functionality as an endpoint in cancer trials, in addition to improvements in mortality, is one place to start, he added.

“Our findings suggest an urgent need for care teams to understand and address function, for researchers to evaluate function as a core outcome in trials, and for health systems and policy makers to reimagine survivorship care, recognizing the burden of cancer and its treatment on physical, psychosocial, and cognitive function,” the authors wrote in their paper. Limitations of the study include the potential for recall bias, lack of cancer staging or treatment information, and the subjective perception of function.

A coauthor reported personal fees from Astellas, AstraZeneca, AAA, Blue Earth, Janssen, Lantheus, Myovant, Myriad Genetics, Novartis, Telix, and Sanofi, as well as grants from Pfizer and Bayer during the conduct of the study. No other disclosures were reported.

The number of cancer survivors who report functional limitation has more than doubled in 20 years, according to a research letter published in JAMA Oncology.

Vishal Patel, BS, a student at the Dell Medical School at The University of Texas at Austin, and colleagues identified 51,258 cancer survivors from the National Health Interview Survey, representing a weighted population of approximately 178.8 million from 1999 to 2018.

Most survivors were women (60.2%) and were at least 65 years old (55.4%). In 1999, 3.6 million weighted survivors reported functional limitation. In 2018, the number increased to 8.2 million, a 2.25-fold increase.

The number of survivors who reported no limitations also increased, but not by as much. That group grew 1.34-fold during the study period.

For context, “the 70% prevalence of functional limitation among survivors in 2018 is nearly twice that of the general population,” the authors wrote.
 

Patients surveyed on function

Functional limitation was defined as “self-reported difficulty performing any of 12 routine physical or social activities without assistance.” Examples of the activities included difficulty sitting for more than 2 hours, difficulty participating in social activities or difficulty pushing or pulling an object the size of a living room chair.

Over the 2 decades analyzed, the adjusted prevalence of functional limitation was highest among survivors of pancreatic cancer (80.3%) and lung cancer (76.5%). Prevalence was lowest for survivors of melanoma (62.2%), breast (61.8%) and prostate (59.5%) cancers.
 

Not just a result of living longer

Mr. Patel told this publication that one assumption people might make when they read these results is that people are just living longer with cancer and losing functional ability accordingly.

“But, in fact, we found that the youngest [– those less than 65 years–] actually contributed to this trend more than the oldest people, which means it’s not just [happening], because people are getting older,” he said.

Hispanic and Black individuals had disproportionately higher increases in functional limitation; percentage point increases over the 2 decades were 19.5 for Black people, 25.1 for Hispanic people and 12.5 for White people. There may be a couple of reasons for that, Mr. Patel noted.

Those who are Black or Hispanic tend to have less access to cancer survivorship care for reasons including insurance status and historic health care inequities, he noted.

“The other potential reason is that they have had less access to cancer care historically. And if, 20 years ago Black and Hispanic individuals didn’t have access to some chemotherapies, and now they do, maybe it’s the increased access to care that’s causing these functional limitations. Because chemotherapy can sometimes be very toxic. It may be sort of a catch-up toxicity,” he said.
 

Quality of life beyond survivorship

Mr. Patel said the results seem to call for building on improved survival rates by tracking and improving function.

“It’s good to celebrate that there are more survivors. But now that we can keep people alive longer, maybe we can shift gears to improving their quality of life,” he said.

The more-than-doubling of functional limitations over 2 decades “is a very sobering trend,” he noted, while pointing out that the functional limitations applied to 8 million people in the United States – people whose needs are not being met.

There’s no sign of the trend stopping, he continued. “We saw no downward trend, only an upward trend.”

Increasingly, including functionality as an endpoint in cancer trials, in addition to improvements in mortality, is one place to start, he added.

“Our findings suggest an urgent need for care teams to understand and address function, for researchers to evaluate function as a core outcome in trials, and for health systems and policy makers to reimagine survivorship care, recognizing the burden of cancer and its treatment on physical, psychosocial, and cognitive function,” the authors wrote in their paper. Limitations of the study include the potential for recall bias, lack of cancer staging or treatment information, and the subjective perception of function.

A coauthor reported personal fees from Astellas, AstraZeneca, AAA, Blue Earth, Janssen, Lantheus, Myovant, Myriad Genetics, Novartis, Telix, and Sanofi, as well as grants from Pfizer and Bayer during the conduct of the study. No other disclosures were reported.

The number of cancer survivors who report functional limitation has more than doubled in 20 years, according to a research letter published in JAMA Oncology.

Vishal Patel, BS, a student at the Dell Medical School at The University of Texas at Austin, and colleagues identified 51,258 cancer survivors from the National Health Interview Survey, representing a weighted population of approximately 178.8 million from 1999 to 2018.

Most survivors were women (60.2%) and were at least 65 years old (55.4%). In 1999, 3.6 million weighted survivors reported functional limitation. In 2018, the number increased to 8.2 million, a 2.25-fold increase.

The number of survivors who reported no limitations also increased, but not by as much. That group grew 1.34-fold during the study period.

For context, “the 70% prevalence of functional limitation among survivors in 2018 is nearly twice that of the general population,” the authors wrote.
 

Patients surveyed on function

Functional limitation was defined as “self-reported difficulty performing any of 12 routine physical or social activities without assistance.” Examples of the activities included difficulty sitting for more than 2 hours, difficulty participating in social activities or difficulty pushing or pulling an object the size of a living room chair.

Over the 2 decades analyzed, the adjusted prevalence of functional limitation was highest among survivors of pancreatic cancer (80.3%) and lung cancer (76.5%). Prevalence was lowest for survivors of melanoma (62.2%), breast (61.8%) and prostate (59.5%) cancers.
 

Not just a result of living longer

Mr. Patel told this publication that one assumption people might make when they read these results is that people are just living longer with cancer and losing functional ability accordingly.

“But, in fact, we found that the youngest [– those less than 65 years–] actually contributed to this trend more than the oldest people, which means it’s not just [happening], because people are getting older,” he said.

Hispanic and Black individuals had disproportionately higher increases in functional limitation; percentage point increases over the 2 decades were 19.5 for Black people, 25.1 for Hispanic people and 12.5 for White people. There may be a couple of reasons for that, Mr. Patel noted.

Those who are Black or Hispanic tend to have less access to cancer survivorship care for reasons including insurance status and historic health care inequities, he noted.

“The other potential reason is that they have had less access to cancer care historically. And if, 20 years ago Black and Hispanic individuals didn’t have access to some chemotherapies, and now they do, maybe it’s the increased access to care that’s causing these functional limitations. Because chemotherapy can sometimes be very toxic. It may be sort of a catch-up toxicity,” he said.
 

Quality of life beyond survivorship

Mr. Patel said the results seem to call for building on improved survival rates by tracking and improving function.

“It’s good to celebrate that there are more survivors. But now that we can keep people alive longer, maybe we can shift gears to improving their quality of life,” he said.

The more-than-doubling of functional limitations over 2 decades “is a very sobering trend,” he noted, while pointing out that the functional limitations applied to 8 million people in the United States – people whose needs are not being met.

There’s no sign of the trend stopping, he continued. “We saw no downward trend, only an upward trend.”

Increasingly, including functionality as an endpoint in cancer trials, in addition to improvements in mortality, is one place to start, he added.

“Our findings suggest an urgent need for care teams to understand and address function, for researchers to evaluate function as a core outcome in trials, and for health systems and policy makers to reimagine survivorship care, recognizing the burden of cancer and its treatment on physical, psychosocial, and cognitive function,” the authors wrote in their paper. Limitations of the study include the potential for recall bias, lack of cancer staging or treatment information, and the subjective perception of function.

A coauthor reported personal fees from Astellas, AstraZeneca, AAA, Blue Earth, Janssen, Lantheus, Myovant, Myriad Genetics, Novartis, Telix, and Sanofi, as well as grants from Pfizer and Bayer during the conduct of the study. No other disclosures were reported.

Rheumatoid arthritis (RA) is linked to almost a twofold increased risk for Parkinson’s disease (PD), new research shows.

Claims data in 55,000 patients with RA and 273,000 age- and sex-matched controls show that those with RA were 1.74 times more likely than controls to be diagnosed with PD.

“If patients with rheumatoid arthritis begin exhibiting motor symptoms such as muscle rigidity, tremors, or slowed movement, it is imperative that they be evaluated by a qualified neurologist to rule out the possibility of developing Parkinson’s disease,” study investigator Hyungjin Kim, MD, PhD, told this news organization.

Dr. Kim is an associate professor in the department of medical humanities at Sungkyunkwan University School of Medicine in Seoul, South Korea.

The findings were published online in JAMA Neurology.
 

Conflicting findings

The investigators note that a number of studies have examined the link between RA and PD, with conflicting results – one even showing a 35% reduced risk for PD for individuals with RA. A more recent population-based study in Taiwan showed a 37% higher rate of PD in patients with rheumatic disease.

However, previous studies did not control for important variables such as body mass index or diabetes.

For the current study, the investigators analyzed claims on about 55,000 patients diagnosed with RA between 2010 and 2017, with follow-up until 2019, and compared the outcomes of this group vs. those of 273,000 controls.

The mean age of claimants was 58 years, and 75% were female.

Results showed that those diagnosed with seropositive RA were about twice as likely as controls to be diagnosed with PD. Those with seronegative RA were 1.2 times as likely as controls to be diagnosed with PD.

Dr. Kim noted that although the pathogenic link between RA and PD remains elusive, inflammation probably plays an important role. “Inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, which are increased in RA patients, can induce microglial activation, leading to neuroinflammation,” he stated.

“These inflammatory cytokines are known to be associated with the dysfunction and degeneration of nigral dopaminergic neurons, which are important in the pathogenesis of PD,” he added.

The investigators noted that patients with RA may have been subject to more frequent health care services than controls and so were more likely to obtain a PD diagnosis.

Another possibility was that because patients with health check-ups were included in the analysis, the findings may have been biased toward those who were older and who had a higher income.

Dr. Kim noted that additional research is required to clarify the pathogenic connection between RA and PD.

“Moreover, additional studies are necessary to explore the potential influence of novel therapeutic treatments for RA on Parkinson’s disease susceptibility in patients with RA,” he said.

Commenting on the findings for this news organization, David Sulzer, PhD, professor of psychiatry, neurology, and pharmacology at Columbia University in New York, said that the study adds to the growing body of evidence showing there is an autoimmune component to PD.

Dr. Sulzer pointed to data in several papers he published with others to this effect, including one showing higher rates of PD in people with inflammatory bowel disease.

The study had no specific funding. The study investigators and Dr. Sulzer report no relevant disclosures.

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

Rheumatoid arthritis (RA) is linked to almost a twofold increased risk for Parkinson’s disease (PD), new research shows.

Claims data in 55,000 patients with RA and 273,000 age- and sex-matched controls show that those with RA were 1.74 times more likely than controls to be diagnosed with PD.

“If patients with rheumatoid arthritis begin exhibiting motor symptoms such as muscle rigidity, tremors, or slowed movement, it is imperative that they be evaluated by a qualified neurologist to rule out the possibility of developing Parkinson’s disease,” study investigator Hyungjin Kim, MD, PhD, told this news organization.

Dr. Kim is an associate professor in the department of medical humanities at Sungkyunkwan University School of Medicine in Seoul, South Korea.

The findings were published online in JAMA Neurology.
 

Conflicting findings

The investigators note that a number of studies have examined the link between RA and PD, with conflicting results – one even showing a 35% reduced risk for PD for individuals with RA. A more recent population-based study in Taiwan showed a 37% higher rate of PD in patients with rheumatic disease.

However, previous studies did not control for important variables such as body mass index or diabetes.

For the current study, the investigators analyzed claims on about 55,000 patients diagnosed with RA between 2010 and 2017, with follow-up until 2019, and compared the outcomes of this group vs. those of 273,000 controls.

The mean age of claimants was 58 years, and 75% were female.

Results showed that those diagnosed with seropositive RA were about twice as likely as controls to be diagnosed with PD. Those with seronegative RA were 1.2 times as likely as controls to be diagnosed with PD.

Dr. Kim noted that although the pathogenic link between RA and PD remains elusive, inflammation probably plays an important role. “Inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, which are increased in RA patients, can induce microglial activation, leading to neuroinflammation,” he stated.

“These inflammatory cytokines are known to be associated with the dysfunction and degeneration of nigral dopaminergic neurons, which are important in the pathogenesis of PD,” he added.

The investigators noted that patients with RA may have been subject to more frequent health care services than controls and so were more likely to obtain a PD diagnosis.

Another possibility was that because patients with health check-ups were included in the analysis, the findings may have been biased toward those who were older and who had a higher income.

Dr. Kim noted that additional research is required to clarify the pathogenic connection between RA and PD.

“Moreover, additional studies are necessary to explore the potential influence of novel therapeutic treatments for RA on Parkinson’s disease susceptibility in patients with RA,” he said.

Commenting on the findings for this news organization, David Sulzer, PhD, professor of psychiatry, neurology, and pharmacology at Columbia University in New York, said that the study adds to the growing body of evidence showing there is an autoimmune component to PD.

Dr. Sulzer pointed to data in several papers he published with others to this effect, including one showing higher rates of PD in people with inflammatory bowel disease.

The study had no specific funding. The study investigators and Dr. Sulzer report no relevant disclosures.

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

Rheumatoid arthritis (RA) is linked to almost a twofold increased risk for Parkinson’s disease (PD), new research shows.

Claims data in 55,000 patients with RA and 273,000 age- and sex-matched controls show that those with RA were 1.74 times more likely than controls to be diagnosed with PD.

“If patients with rheumatoid arthritis begin exhibiting motor symptoms such as muscle rigidity, tremors, or slowed movement, it is imperative that they be evaluated by a qualified neurologist to rule out the possibility of developing Parkinson’s disease,” study investigator Hyungjin Kim, MD, PhD, told this news organization.

Dr. Kim is an associate professor in the department of medical humanities at Sungkyunkwan University School of Medicine in Seoul, South Korea.

The findings were published online in JAMA Neurology.
 

Conflicting findings

The investigators note that a number of studies have examined the link between RA and PD, with conflicting results – one even showing a 35% reduced risk for PD for individuals with RA. A more recent population-based study in Taiwan showed a 37% higher rate of PD in patients with rheumatic disease.

However, previous studies did not control for important variables such as body mass index or diabetes.

For the current study, the investigators analyzed claims on about 55,000 patients diagnosed with RA between 2010 and 2017, with follow-up until 2019, and compared the outcomes of this group vs. those of 273,000 controls.

The mean age of claimants was 58 years, and 75% were female.

Results showed that those diagnosed with seropositive RA were about twice as likely as controls to be diagnosed with PD. Those with seronegative RA were 1.2 times as likely as controls to be diagnosed with PD.

Dr. Kim noted that although the pathogenic link between RA and PD remains elusive, inflammation probably plays an important role. “Inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, which are increased in RA patients, can induce microglial activation, leading to neuroinflammation,” he stated.

“These inflammatory cytokines are known to be associated with the dysfunction and degeneration of nigral dopaminergic neurons, which are important in the pathogenesis of PD,” he added.

The investigators noted that patients with RA may have been subject to more frequent health care services than controls and so were more likely to obtain a PD diagnosis.

Another possibility was that because patients with health check-ups were included in the analysis, the findings may have been biased toward those who were older and who had a higher income.

Dr. Kim noted that additional research is required to clarify the pathogenic connection between RA and PD.

“Moreover, additional studies are necessary to explore the potential influence of novel therapeutic treatments for RA on Parkinson’s disease susceptibility in patients with RA,” he said.

Commenting on the findings for this news organization, David Sulzer, PhD, professor of psychiatry, neurology, and pharmacology at Columbia University in New York, said that the study adds to the growing body of evidence showing there is an autoimmune component to PD.

Dr. Sulzer pointed to data in several papers he published with others to this effect, including one showing higher rates of PD in people with inflammatory bowel disease.

The study had no specific funding. The study investigators and Dr. Sulzer report no relevant disclosures.

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

The U.S. Food and Drug Administration has approved pegunigalsidase alfa (Elfabrio, Chiesi Global Rare Diseases/Protalix BioTherapeutics), an enzyme replacement therapy (ERT) to treat adults with confirmed Fabry disease.

Fabry disease is a rare inherited X-linked lysosomal disorder caused by a deficiency of the enzyme alpha-galactosidase A (GLA), which leads to the buildup of globotriaosylceramide (GL-3) in blood vessels, kidneys, the heart, nerves, and other organs, increasing the risk for kidney failure, myocardial infarction, stroke, and other problems.

Elfabrio delivers a functional version of GLA. It’s given by intravenous infusion every 2 weeks.

Evidence for safety, tolerability, and efficacy of Elfabrio stems from a comprehensive clinical program in more than 140 patients with up to 7.5 years of follow up treatment.

It has been studied in both ERT-naïve and ERT-experienced patients. In one head-to-head trial, Elfabrio was non-inferior in safety and efficacy to agalsidase beta (Fabrazyme, Sanofi Genzyme), the companies said in a press statement announcing approval.

“The totality of clinical data suggests that Elfabrio has the potential to be a long-lasting therapy,” Dror Bashan, president and CEO of Protalix, said in the statement.

Patients treated with Elfabrio have experienced hypersensitivity reactions, including anaphylaxis. In clinical trials, 20 (14%) patients treated with Elfabrio experienced hypersensitivity reactions; 4 patients (3%) experienced anaphylaxis reactions that occurred within 5-40 minutes of the start of the initial infusion.

Before administering Elfabrio, pretreatment with antihistamines, antipyretics, and/or corticosteroids should be considered, the label advises.

Patients and caregivers should be informed of the signs and symptoms of hypersensitivity reactions and infusion-associated reactions and instructed to seek medical care immediately if such symptoms occur.

A case of membranoproliferative glomerulonephritis with immune depositions in the kidney was reported during clinical trials. Monitoring serum creatinine and urinary protein-to-creatinine ratio is advised. If glomerulonephritis is suspected, treatment should be stopped until a diagnostic evaluation can be conducted.

Full prescribing information is available online.

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

The U.S. Food and Drug Administration has approved pegunigalsidase alfa (Elfabrio, Chiesi Global Rare Diseases/Protalix BioTherapeutics), an enzyme replacement therapy (ERT) to treat adults with confirmed Fabry disease.

Fabry disease is a rare inherited X-linked lysosomal disorder caused by a deficiency of the enzyme alpha-galactosidase A (GLA), which leads to the buildup of globotriaosylceramide (GL-3) in blood vessels, kidneys, the heart, nerves, and other organs, increasing the risk for kidney failure, myocardial infarction, stroke, and other problems.

Elfabrio delivers a functional version of GLA. It’s given by intravenous infusion every 2 weeks.

Evidence for safety, tolerability, and efficacy of Elfabrio stems from a comprehensive clinical program in more than 140 patients with up to 7.5 years of follow up treatment.

It has been studied in both ERT-naïve and ERT-experienced patients. In one head-to-head trial, Elfabrio was non-inferior in safety and efficacy to agalsidase beta (Fabrazyme, Sanofi Genzyme), the companies said in a press statement announcing approval.

“The totality of clinical data suggests that Elfabrio has the potential to be a long-lasting therapy,” Dror Bashan, president and CEO of Protalix, said in the statement.

Patients treated with Elfabrio have experienced hypersensitivity reactions, including anaphylaxis. In clinical trials, 20 (14%) patients treated with Elfabrio experienced hypersensitivity reactions; 4 patients (3%) experienced anaphylaxis reactions that occurred within 5-40 minutes of the start of the initial infusion.

Before administering Elfabrio, pretreatment with antihistamines, antipyretics, and/or corticosteroids should be considered, the label advises.

Patients and caregivers should be informed of the signs and symptoms of hypersensitivity reactions and infusion-associated reactions and instructed to seek medical care immediately if such symptoms occur.

A case of membranoproliferative glomerulonephritis with immune depositions in the kidney was reported during clinical trials. Monitoring serum creatinine and urinary protein-to-creatinine ratio is advised. If glomerulonephritis is suspected, treatment should be stopped until a diagnostic evaluation can be conducted.

Full prescribing information is available online.

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

The U.S. Food and Drug Administration has approved pegunigalsidase alfa (Elfabrio, Chiesi Global Rare Diseases/Protalix BioTherapeutics), an enzyme replacement therapy (ERT) to treat adults with confirmed Fabry disease.

Fabry disease is a rare inherited X-linked lysosomal disorder caused by a deficiency of the enzyme alpha-galactosidase A (GLA), which leads to the buildup of globotriaosylceramide (GL-3) in blood vessels, kidneys, the heart, nerves, and other organs, increasing the risk for kidney failure, myocardial infarction, stroke, and other problems.

Elfabrio delivers a functional version of GLA. It’s given by intravenous infusion every 2 weeks.

Evidence for safety, tolerability, and efficacy of Elfabrio stems from a comprehensive clinical program in more than 140 patients with up to 7.5 years of follow up treatment.

It has been studied in both ERT-naïve and ERT-experienced patients. In one head-to-head trial, Elfabrio was non-inferior in safety and efficacy to agalsidase beta (Fabrazyme, Sanofi Genzyme), the companies said in a press statement announcing approval.

“The totality of clinical data suggests that Elfabrio has the potential to be a long-lasting therapy,” Dror Bashan, president and CEO of Protalix, said in the statement.

Patients treated with Elfabrio have experienced hypersensitivity reactions, including anaphylaxis. In clinical trials, 20 (14%) patients treated with Elfabrio experienced hypersensitivity reactions; 4 patients (3%) experienced anaphylaxis reactions that occurred within 5-40 minutes of the start of the initial infusion.

Before administering Elfabrio, pretreatment with antihistamines, antipyretics, and/or corticosteroids should be considered, the label advises.

Patients and caregivers should be informed of the signs and symptoms of hypersensitivity reactions and infusion-associated reactions and instructed to seek medical care immediately if such symptoms occur.

A case of membranoproliferative glomerulonephritis with immune depositions in the kidney was reported during clinical trials. Monitoring serum creatinine and urinary protein-to-creatinine ratio is advised. If glomerulonephritis is suspected, treatment should be stopped until a diagnostic evaluation can be conducted.

Full prescribing information is available online.

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

When people ask Paul Offit, MD, what worries him the most about the COVID-19 pandemic, he names two concerns. “One is the lack of socialization and education that came from keeping kids out of school for so long,” Dr. Offit said in a recent interview. “And I think vaccines have suffered.”

Dr. Offit is director of the Vaccine Education Center and a professor of pediatrics at Children’s Hospital of Philadelphia. He has watched with alarm as the American public appears to be losing faith in the lifesaving vaccines the public health community has worked hard to promote. The Centers for Disease Control and Prevention estimates that the proportion of kids entering kindergarten who have received state-required vaccines dipped to 94% in the 2020-2021 school year – a full point less than the year before the pandemic – then dropped by another percentage point, to 93%, the following year.

Although a couple of percentage points may sound trivial, were only 93% of kindergarteners to receive the vaccine against measles, mumps, and rubella (MMR), approximately 250,000 vulnerable 5-year-olds could spark the next big outbreak, such as the recent measles outbreaks in Ohio and Minnesota.

Dr. Offit is one of many public health officials and clinicians who are working to reverse the concerning trends in pediatric vaccinations. Their efforts combine conventional approaches, such as community outreach, with newer strategies, including using social media and even lending a sympathetic ear to parents voicing anti-science imaginings.

“I just don’t want to see an outbreak of something that we could have avoided because we were not protected enough,” Judith Shlay, MD, associate director of the Public Health Institute at Denver Health, said.
 

Official stumbles in part to blame

Disruptions in health care from the COVID-19 pandemic certainly played a role in the decline. Parents were afraid to expose their children to other sick kids, providers shifted to a telehealth model, and routine preventive care was difficult to access.

But Dr. Offit also blamed erosion of trust on mistakes made by government and public health institutions for the alarming trend. “I think that health care professionals have lost some level of trust in the Food and Drug Administration and CDC.”

He cited as an example poor messaging during a large outbreak in Massachusetts in summer 2021, when the CDC published a report that highlighted the high proportion of COVID-19 cases among vaccinated people. Health officials called those cases “breakthrough” infections, although most were mild or asymptomatic.

Dr. Offit said the CDC should have focused the message instead on the low rate (1%) of hospitalizations and the low number of deaths from the infections. Instead, they had to walk back their promise that vaccinated people didn’t need to wear masks. At other times, the Biden administration pressured public health officials by promising to make booster shots available to the American public when the FDA and CDC felt they lacked evidence to recommend the injections.

Rupali Limaye, PhD, an associate professor of international health at the Bloomberg School of Public Health at Johns Hopkins University, Baltimore, studies vaccine behavior and decision-making. She would go a step further in characterizing the roots of worsening vaccine hesitancy.

“In the last 20 years, we’ve seen there’s less and less trust in health care providers in general,” Dr. Limaye said. “More people are turning to their social networks or social contacts for that kind of information.” In the maelstrom of the COVID-19 pandemic, digital social networks facilitated the spread of misinformation about COVID-19 faster than scientists could unravel the mysteries of the disease.

“There’s always been this underlying hesitancy for some people about vaccines,” Dr. Shlay said. But she has noticed more resistance to the COVID-19 vaccine from parents nervous about the new mRNA technology. “There was a lot of politicization of the vaccine, even though the mRNA vaccine technology has been around for a long time,” she said.
 

Multipronged approaches

Dr. Shlay is committed to restoring childhood vaccination uptake to prepandemic levels now that clinics are open again. To do so, she is relying on a combination of quality improvement strategies and outreach to undervaccinated populations.

Denver Health, for instance, offers vaccinations at any inpatient or outpatient visit – not just well-child visits – with the help of alerts built into their electronic health records that notify clinicians if a patient is due for a vaccine.

COVID-19 revealed marked health inequities in underserved communities as Black, Hispanic, and people from other minority communities experienced higher rates of COVID-19 cases and deaths, compared with White people. The Public Health Institute, which is part of Denver Health, has responded with vaccine outreach teams that go to schools, shelters, churches, and community-based organizations to vaccinate children. They focus their efforts on areas where immunization rates are low. Health centers in schools throughout Colorado vaccinate students, and the Public Health Institute partners with Denver-area public schools to provide vaccines to students in schools that don’t have such centers. (They also provide dental care and behavioral health services.)

But it is unlikely that restoring clinic operations and making vaccines more accessible will fill the gap. After 3 years of fear and mistrust, parents are still nervous about routine shots. To help clinicians facilitate conversations about vaccination, Denver Health trains providers in communication techniques using motivational interviewing (MI), a collaborative goal-oriented approach that encourages changes in health behaviors.

Dr. Shlay, who stressed the value of persistence, advised, “Through motivational interviewing, discussing things, talking about it, you can actually address most of the concerns.”
 

Giving parents a boost in the right direction

That spirit drives the work of Boost Oregon, a parent-led nonprofit organization founded in 2015 that helps parents make science-based decisions for themselves and their families. Even before the pandemic, primary care providers needed better strategies for addressing parents who had concerns about vaccines and found themselves failing in the effort while trying to see 20 patients a day.

For families that have questions about vaccines, Boost Oregon holds community meetings in which parents meet with clinicians, share their concerns with other parents, and get answers to their questions in a nonjudgmental way. The 1- to 2-hour sessions enable deeper discussions of the issues than many clinicians can manage in a 20-minute patient visit.

Boost Oregon also trains providers in communication techniques using MI. Ryan Hassan, MD, a pediatrician in private practice who serves as the medical director for the organization, has made the approach an integral part of his day. A key realization for him about the use of MI is that if providers want to build trust with parents, they need to accept that their role is not simply to educate but also to listen.

“Even if it’s the wildest conspiracy theory I’ve ever heard, that is my opportunity to show them that I’m listening and to empathize,” Dr. Hassan said.

His next step, a central tenet of MI, is to make reflective statements that summarize the parent’s concerns, demonstrate empathy, and help him get to the heart of their concerns. He then tailors his message to their issues.

Dr. Hassan tells people who are learning the technique to acknowledge that patients have the autonomy to make their own decisions. Coercing them into a decision is unhelpful and potentially counterproductive. “You can’t change anyone else’s mind,” he said. “You have to help them change their own mind.”

Dr. Limaye reinforced that message. Overwhelmed by conflicting messages on the internet, people are just trying to find answers. She trains providers not to dismiss patients’ concerns, because dismissal erodes trust.

“When you’re dealing with misinformation and conspiracy, to me, one thing to keep in mind is that it’s the long game,” Dr. Limaye said, “You’re not going to be able to sway them in one conversation.”

Can the powers of social media be harnessed for pro-vaccine messaging? Dr. Limaye has studied social media strategies to promote vaccine acceptance and has identified several elements that can be useful for swaying opinions about vaccine.

One is the messenger – as people trust their physicians less, “it’s important to find influencers that people might trust to actually spread a message,” she said. Another factor is that as society has become more polarized, interaction with the leadership of groups that hold influence has become key. To promote vaccine acceptance, for example, leaders of moms’ groups on Facebook could be equipped with evidence-based information.

“It’s important for us to reach out and engage with those that are leaders in those groups, because they kind of hold the power,” Dr. Limaye said.

Framing the message is critical. Dr. Limaye has found that personal narratives can be persuasive and that to influence vaccine behavior, it is necessary to tailor the approach to the specific audience. Danish researchers, for example, in 2017 launched a campaign to increase uptake of HPV vaccinations among teenagers. The researchers provided facts about the safety and effectiveness of the vaccine, cited posts by clinicians about the importance of immunization against the virus, and relayed personal stories, such as one about a father who chose to vaccinate his daughter and another about a blogger’s encounter with a woman with cervical cancer. The researchers found that the highest engagement rates were achieved through personal content and that such content generated the highest proportion of positive comments.

According to Dr. Limaye, to change behavior, social media messaging must address the issues of risk perception and self-efficacy. For risk perception regarding vaccines, a successful message needs to address the parents’ questions about whether their child is at risk for catching a disease, such as measles or pertussis, and if they are, whether the child will wind up in the hospital.

Self-efficacy is the belief that one can accomplish a task. An effective message would provide information on where to find free or low-cost vaccines and would identify locations that are easy to reach and that have expanded hours for working parents, Dr. Limaye said.

What’s the best approach for boosting vaccination rates in the post-pandemic era? In the 1850s, Massachusetts enacted the first vaccine mandate in the United States to prevent smallpox, and by the 1900s, similar laws had been passed in almost half of states. But recent polls suggest that support for vaccine mandates is dwindling. In a poll by the Kaiser Family Foundation last fall, 71% of adults said that healthy children should be required to be vaccinated against measles before entering school, which was down from 82% in a similar poll in 2019.

So perhaps a better approach for promoting vaccine confidence in the 21st century would involve wider use of MI by clinicians and more focus by public health agencies taking advantage of the potential power of social media. As Dr. Offit put it, “I think trust is the key thing.”

Dr. Offit, Dr. Limaye, Dr. Shlay, and Dr. Hassan report no relevant financial relationships.

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

When people ask Paul Offit, MD, what worries him the most about the COVID-19 pandemic, he names two concerns. “One is the lack of socialization and education that came from keeping kids out of school for so long,” Dr. Offit said in a recent interview. “And I think vaccines have suffered.”

Dr. Offit is director of the Vaccine Education Center and a professor of pediatrics at Children’s Hospital of Philadelphia. He has watched with alarm as the American public appears to be losing faith in the lifesaving vaccines the public health community has worked hard to promote. The Centers for Disease Control and Prevention estimates that the proportion of kids entering kindergarten who have received state-required vaccines dipped to 94% in the 2020-2021 school year – a full point less than the year before the pandemic – then dropped by another percentage point, to 93%, the following year.

Although a couple of percentage points may sound trivial, were only 93% of kindergarteners to receive the vaccine against measles, mumps, and rubella (MMR), approximately 250,000 vulnerable 5-year-olds could spark the next big outbreak, such as the recent measles outbreaks in Ohio and Minnesota.

Dr. Offit is one of many public health officials and clinicians who are working to reverse the concerning trends in pediatric vaccinations. Their efforts combine conventional approaches, such as community outreach, with newer strategies, including using social media and even lending a sympathetic ear to parents voicing anti-science imaginings.

“I just don’t want to see an outbreak of something that we could have avoided because we were not protected enough,” Judith Shlay, MD, associate director of the Public Health Institute at Denver Health, said.
 

Official stumbles in part to blame

Disruptions in health care from the COVID-19 pandemic certainly played a role in the decline. Parents were afraid to expose their children to other sick kids, providers shifted to a telehealth model, and routine preventive care was difficult to access.

But Dr. Offit also blamed erosion of trust on mistakes made by government and public health institutions for the alarming trend. “I think that health care professionals have lost some level of trust in the Food and Drug Administration and CDC.”

He cited as an example poor messaging during a large outbreak in Massachusetts in summer 2021, when the CDC published a report that highlighted the high proportion of COVID-19 cases among vaccinated people. Health officials called those cases “breakthrough” infections, although most were mild or asymptomatic.

Dr. Offit said the CDC should have focused the message instead on the low rate (1%) of hospitalizations and the low number of deaths from the infections. Instead, they had to walk back their promise that vaccinated people didn’t need to wear masks. At other times, the Biden administration pressured public health officials by promising to make booster shots available to the American public when the FDA and CDC felt they lacked evidence to recommend the injections.

Rupali Limaye, PhD, an associate professor of international health at the Bloomberg School of Public Health at Johns Hopkins University, Baltimore, studies vaccine behavior and decision-making. She would go a step further in characterizing the roots of worsening vaccine hesitancy.

“In the last 20 years, we’ve seen there’s less and less trust in health care providers in general,” Dr. Limaye said. “More people are turning to their social networks or social contacts for that kind of information.” In the maelstrom of the COVID-19 pandemic, digital social networks facilitated the spread of misinformation about COVID-19 faster than scientists could unravel the mysteries of the disease.

“There’s always been this underlying hesitancy for some people about vaccines,” Dr. Shlay said. But she has noticed more resistance to the COVID-19 vaccine from parents nervous about the new mRNA technology. “There was a lot of politicization of the vaccine, even though the mRNA vaccine technology has been around for a long time,” she said.
 

Multipronged approaches

Dr. Shlay is committed to restoring childhood vaccination uptake to prepandemic levels now that clinics are open again. To do so, she is relying on a combination of quality improvement strategies and outreach to undervaccinated populations.

Denver Health, for instance, offers vaccinations at any inpatient or outpatient visit – not just well-child visits – with the help of alerts built into their electronic health records that notify clinicians if a patient is due for a vaccine.

COVID-19 revealed marked health inequities in underserved communities as Black, Hispanic, and people from other minority communities experienced higher rates of COVID-19 cases and deaths, compared with White people. The Public Health Institute, which is part of Denver Health, has responded with vaccine outreach teams that go to schools, shelters, churches, and community-based organizations to vaccinate children. They focus their efforts on areas where immunization rates are low. Health centers in schools throughout Colorado vaccinate students, and the Public Health Institute partners with Denver-area public schools to provide vaccines to students in schools that don’t have such centers. (They also provide dental care and behavioral health services.)

But it is unlikely that restoring clinic operations and making vaccines more accessible will fill the gap. After 3 years of fear and mistrust, parents are still nervous about routine shots. To help clinicians facilitate conversations about vaccination, Denver Health trains providers in communication techniques using motivational interviewing (MI), a collaborative goal-oriented approach that encourages changes in health behaviors.

Dr. Shlay, who stressed the value of persistence, advised, “Through motivational interviewing, discussing things, talking about it, you can actually address most of the concerns.”
 

Giving parents a boost in the right direction

That spirit drives the work of Boost Oregon, a parent-led nonprofit organization founded in 2015 that helps parents make science-based decisions for themselves and their families. Even before the pandemic, primary care providers needed better strategies for addressing parents who had concerns about vaccines and found themselves failing in the effort while trying to see 20 patients a day.

For families that have questions about vaccines, Boost Oregon holds community meetings in which parents meet with clinicians, share their concerns with other parents, and get answers to their questions in a nonjudgmental way. The 1- to 2-hour sessions enable deeper discussions of the issues than many clinicians can manage in a 20-minute patient visit.

Boost Oregon also trains providers in communication techniques using MI. Ryan Hassan, MD, a pediatrician in private practice who serves as the medical director for the organization, has made the approach an integral part of his day. A key realization for him about the use of MI is that if providers want to build trust with parents, they need to accept that their role is not simply to educate but also to listen.

“Even if it’s the wildest conspiracy theory I’ve ever heard, that is my opportunity to show them that I’m listening and to empathize,” Dr. Hassan said.

His next step, a central tenet of MI, is to make reflective statements that summarize the parent’s concerns, demonstrate empathy, and help him get to the heart of their concerns. He then tailors his message to their issues.

Dr. Hassan tells people who are learning the technique to acknowledge that patients have the autonomy to make their own decisions. Coercing them into a decision is unhelpful and potentially counterproductive. “You can’t change anyone else’s mind,” he said. “You have to help them change their own mind.”

Dr. Limaye reinforced that message. Overwhelmed by conflicting messages on the internet, people are just trying to find answers. She trains providers not to dismiss patients’ concerns, because dismissal erodes trust.

“When you’re dealing with misinformation and conspiracy, to me, one thing to keep in mind is that it’s the long game,” Dr. Limaye said, “You’re not going to be able to sway them in one conversation.”

Can the powers of social media be harnessed for pro-vaccine messaging? Dr. Limaye has studied social media strategies to promote vaccine acceptance and has identified several elements that can be useful for swaying opinions about vaccine.

One is the messenger – as people trust their physicians less, “it’s important to find influencers that people might trust to actually spread a message,” she said. Another factor is that as society has become more polarized, interaction with the leadership of groups that hold influence has become key. To promote vaccine acceptance, for example, leaders of moms’ groups on Facebook could be equipped with evidence-based information.

“It’s important for us to reach out and engage with those that are leaders in those groups, because they kind of hold the power,” Dr. Limaye said.

Framing the message is critical. Dr. Limaye has found that personal narratives can be persuasive and that to influence vaccine behavior, it is necessary to tailor the approach to the specific audience. Danish researchers, for example, in 2017 launched a campaign to increase uptake of HPV vaccinations among teenagers. The researchers provided facts about the safety and effectiveness of the vaccine, cited posts by clinicians about the importance of immunization against the virus, and relayed personal stories, such as one about a father who chose to vaccinate his daughter and another about a blogger’s encounter with a woman with cervical cancer. The researchers found that the highest engagement rates were achieved through personal content and that such content generated the highest proportion of positive comments.

According to Dr. Limaye, to change behavior, social media messaging must address the issues of risk perception and self-efficacy. For risk perception regarding vaccines, a successful message needs to address the parents’ questions about whether their child is at risk for catching a disease, such as measles or pertussis, and if they are, whether the child will wind up in the hospital.

Self-efficacy is the belief that one can accomplish a task. An effective message would provide information on where to find free or low-cost vaccines and would identify locations that are easy to reach and that have expanded hours for working parents, Dr. Limaye said.

What’s the best approach for boosting vaccination rates in the post-pandemic era? In the 1850s, Massachusetts enacted the first vaccine mandate in the United States to prevent smallpox, and by the 1900s, similar laws had been passed in almost half of states. But recent polls suggest that support for vaccine mandates is dwindling. In a poll by the Kaiser Family Foundation last fall, 71% of adults said that healthy children should be required to be vaccinated against measles before entering school, which was down from 82% in a similar poll in 2019.

So perhaps a better approach for promoting vaccine confidence in the 21st century would involve wider use of MI by clinicians and more focus by public health agencies taking advantage of the potential power of social media. As Dr. Offit put it, “I think trust is the key thing.”

Dr. Offit, Dr. Limaye, Dr. Shlay, and Dr. Hassan report no relevant financial relationships.

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

When people ask Paul Offit, MD, what worries him the most about the COVID-19 pandemic, he names two concerns. “One is the lack of socialization and education that came from keeping kids out of school for so long,” Dr. Offit said in a recent interview. “And I think vaccines have suffered.”

Dr. Offit is director of the Vaccine Education Center and a professor of pediatrics at Children’s Hospital of Philadelphia. He has watched with alarm as the American public appears to be losing faith in the lifesaving vaccines the public health community has worked hard to promote. The Centers for Disease Control and Prevention estimates that the proportion of kids entering kindergarten who have received state-required vaccines dipped to 94% in the 2020-2021 school year – a full point less than the year before the pandemic – then dropped by another percentage point, to 93%, the following year.

Although a couple of percentage points may sound trivial, were only 93% of kindergarteners to receive the vaccine against measles, mumps, and rubella (MMR), approximately 250,000 vulnerable 5-year-olds could spark the next big outbreak, such as the recent measles outbreaks in Ohio and Minnesota.

Dr. Offit is one of many public health officials and clinicians who are working to reverse the concerning trends in pediatric vaccinations. Their efforts combine conventional approaches, such as community outreach, with newer strategies, including using social media and even lending a sympathetic ear to parents voicing anti-science imaginings.

“I just don’t want to see an outbreak of something that we could have avoided because we were not protected enough,” Judith Shlay, MD, associate director of the Public Health Institute at Denver Health, said.
 

Official stumbles in part to blame

Disruptions in health care from the COVID-19 pandemic certainly played a role in the decline. Parents were afraid to expose their children to other sick kids, providers shifted to a telehealth model, and routine preventive care was difficult to access.

But Dr. Offit also blamed erosion of trust on mistakes made by government and public health institutions for the alarming trend. “I think that health care professionals have lost some level of trust in the Food and Drug Administration and CDC.”

He cited as an example poor messaging during a large outbreak in Massachusetts in summer 2021, when the CDC published a report that highlighted the high proportion of COVID-19 cases among vaccinated people. Health officials called those cases “breakthrough” infections, although most were mild or asymptomatic.

Dr. Offit said the CDC should have focused the message instead on the low rate (1%) of hospitalizations and the low number of deaths from the infections. Instead, they had to walk back their promise that vaccinated people didn’t need to wear masks. At other times, the Biden administration pressured public health officials by promising to make booster shots available to the American public when the FDA and CDC felt they lacked evidence to recommend the injections.

Rupali Limaye, PhD, an associate professor of international health at the Bloomberg School of Public Health at Johns Hopkins University, Baltimore, studies vaccine behavior and decision-making. She would go a step further in characterizing the roots of worsening vaccine hesitancy.

“In the last 20 years, we’ve seen there’s less and less trust in health care providers in general,” Dr. Limaye said. “More people are turning to their social networks or social contacts for that kind of information.” In the maelstrom of the COVID-19 pandemic, digital social networks facilitated the spread of misinformation about COVID-19 faster than scientists could unravel the mysteries of the disease.

“There’s always been this underlying hesitancy for some people about vaccines,” Dr. Shlay said. But she has noticed more resistance to the COVID-19 vaccine from parents nervous about the new mRNA technology. “There was a lot of politicization of the vaccine, even though the mRNA vaccine technology has been around for a long time,” she said.
 

Multipronged approaches

Dr. Shlay is committed to restoring childhood vaccination uptake to prepandemic levels now that clinics are open again. To do so, she is relying on a combination of quality improvement strategies and outreach to undervaccinated populations.

Denver Health, for instance, offers vaccinations at any inpatient or outpatient visit – not just well-child visits – with the help of alerts built into their electronic health records that notify clinicians if a patient is due for a vaccine.

COVID-19 revealed marked health inequities in underserved communities as Black, Hispanic, and people from other minority communities experienced higher rates of COVID-19 cases and deaths, compared with White people. The Public Health Institute, which is part of Denver Health, has responded with vaccine outreach teams that go to schools, shelters, churches, and community-based organizations to vaccinate children. They focus their efforts on areas where immunization rates are low. Health centers in schools throughout Colorado vaccinate students, and the Public Health Institute partners with Denver-area public schools to provide vaccines to students in schools that don’t have such centers. (They also provide dental care and behavioral health services.)

But it is unlikely that restoring clinic operations and making vaccines more accessible will fill the gap. After 3 years of fear and mistrust, parents are still nervous about routine shots. To help clinicians facilitate conversations about vaccination, Denver Health trains providers in communication techniques using motivational interviewing (MI), a collaborative goal-oriented approach that encourages changes in health behaviors.

Dr. Shlay, who stressed the value of persistence, advised, “Through motivational interviewing, discussing things, talking about it, you can actually address most of the concerns.”
 

Giving parents a boost in the right direction

That spirit drives the work of Boost Oregon, a parent-led nonprofit organization founded in 2015 that helps parents make science-based decisions for themselves and their families. Even before the pandemic, primary care providers needed better strategies for addressing parents who had concerns about vaccines and found themselves failing in the effort while trying to see 20 patients a day.

For families that have questions about vaccines, Boost Oregon holds community meetings in which parents meet with clinicians, share their concerns with other parents, and get answers to their questions in a nonjudgmental way. The 1- to 2-hour sessions enable deeper discussions of the issues than many clinicians can manage in a 20-minute patient visit.

Boost Oregon also trains providers in communication techniques using MI. Ryan Hassan, MD, a pediatrician in private practice who serves as the medical director for the organization, has made the approach an integral part of his day. A key realization for him about the use of MI is that if providers want to build trust with parents, they need to accept that their role is not simply to educate but also to listen.

“Even if it’s the wildest conspiracy theory I’ve ever heard, that is my opportunity to show them that I’m listening and to empathize,” Dr. Hassan said.

His next step, a central tenet of MI, is to make reflective statements that summarize the parent’s concerns, demonstrate empathy, and help him get to the heart of their concerns. He then tailors his message to their issues.

Dr. Hassan tells people who are learning the technique to acknowledge that patients have the autonomy to make their own decisions. Coercing them into a decision is unhelpful and potentially counterproductive. “You can’t change anyone else’s mind,” he said. “You have to help them change their own mind.”

Dr. Limaye reinforced that message. Overwhelmed by conflicting messages on the internet, people are just trying to find answers. She trains providers not to dismiss patients’ concerns, because dismissal erodes trust.

“When you’re dealing with misinformation and conspiracy, to me, one thing to keep in mind is that it’s the long game,” Dr. Limaye said, “You’re not going to be able to sway them in one conversation.”

Can the powers of social media be harnessed for pro-vaccine messaging? Dr. Limaye has studied social media strategies to promote vaccine acceptance and has identified several elements that can be useful for swaying opinions about vaccine.

One is the messenger – as people trust their physicians less, “it’s important to find influencers that people might trust to actually spread a message,” she said. Another factor is that as society has become more polarized, interaction with the leadership of groups that hold influence has become key. To promote vaccine acceptance, for example, leaders of moms’ groups on Facebook could be equipped with evidence-based information.

“It’s important for us to reach out and engage with those that are leaders in those groups, because they kind of hold the power,” Dr. Limaye said.

Framing the message is critical. Dr. Limaye has found that personal narratives can be persuasive and that to influence vaccine behavior, it is necessary to tailor the approach to the specific audience. Danish researchers, for example, in 2017 launched a campaign to increase uptake of HPV vaccinations among teenagers. The researchers provided facts about the safety and effectiveness of the vaccine, cited posts by clinicians about the importance of immunization against the virus, and relayed personal stories, such as one about a father who chose to vaccinate his daughter and another about a blogger’s encounter with a woman with cervical cancer. The researchers found that the highest engagement rates were achieved through personal content and that such content generated the highest proportion of positive comments.

According to Dr. Limaye, to change behavior, social media messaging must address the issues of risk perception and self-efficacy. For risk perception regarding vaccines, a successful message needs to address the parents’ questions about whether their child is at risk for catching a disease, such as measles or pertussis, and if they are, whether the child will wind up in the hospital.

Self-efficacy is the belief that one can accomplish a task. An effective message would provide information on where to find free or low-cost vaccines and would identify locations that are easy to reach and that have expanded hours for working parents, Dr. Limaye said.

What’s the best approach for boosting vaccination rates in the post-pandemic era? In the 1850s, Massachusetts enacted the first vaccine mandate in the United States to prevent smallpox, and by the 1900s, similar laws had been passed in almost half of states. But recent polls suggest that support for vaccine mandates is dwindling. In a poll by the Kaiser Family Foundation last fall, 71% of adults said that healthy children should be required to be vaccinated against measles before entering school, which was down from 82% in a similar poll in 2019.

So perhaps a better approach for promoting vaccine confidence in the 21st century would involve wider use of MI by clinicians and more focus by public health agencies taking advantage of the potential power of social media. As Dr. Offit put it, “I think trust is the key thing.”

Dr. Offit, Dr. Limaye, Dr. Shlay, and Dr. Hassan report no relevant financial relationships.

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

Researchers have developed an artificial intelligence (AI) machine-learning platform that can predict the prognosis and likely treatment response of patients with colorectal cancer (CRC) using histopathology images, according to a new study published in Nature Communications.
 

Specifically, the tool can aid doctors in identifying a “molecular diagnosis” based on a patient’s tumor and cancer characteristics, Kun-Hsing Yu, MD, PhD, the study’s senior author and an assistant professor of biomedical informatics at Harvard Medical School, Boston, said in an interview.

The Multi-omics Multi-cohort Assessment (MOMA) “successfully identified indicators of how aggressive a tumor was and how likely it was to behave in response to a particular treatment,” as well as patients’ overall and disease-free survival, noted Harvard Medical School in a press release. “Based on an image alone, the model also pinpointed characteristics associated with the presence or absence of specific genetic mutations – something that typically requires genomic sequencing of the tumor.”

The researchers designed the tool to offer “transparent reasoning,” so that if a clinician asks it why it made a certain prediction, it would be able to explain its reasoning and the variables it used, the press release noted.

“We first allow AI to explore any correlation, and then we try to explain those correlations using existing pathology terms that experts will be able to understand,” Dr. Yu said in an interview.

Although the tool is freely available to clinicians and researchers, it’s not yet ready for clinical use. When it is, the tool has the potential to provide timely, accurate decision support based on tumor imaging.

Colorectal cancer is the second most common cause of death from cancer in the United States, with more than 53,000 deaths each year, and the patient population has been gradually skewing younger over the past 2 decades.

Although clinicians already use histopathology and genetic analysis to guide treatment, the process can take several days or weeks in some areas, and these services may not be available in all parts of the world.

“Currently, a clinician has to send a [tissue] sample from the tumor specimen to genomic sequencing labs and wait for a week, sometimes up to 3 or more weeks, to get genomic sequencing results,” Dr. Yu said. That means a patient’s anxiety grows as they wait to find out which treatments might benefit them or how they might respond to a particular treatment.

Additionally, current knowledge for predicting patient survival, beyond considering the patient’s cancer stage, age, and general health status, is limited, Dr. Yu said.
 

Predictive ability

The MOMA platform was trained on information from 1,888 patients with colorectal cancer from three national cohorts: 628 patients from The Cancer Genome Atlas (TCGA) program, 927 patients from the Nurses’ Health Study with Health Professionals Follow-Up Study (NHS-HPFS), and 333 patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

During the training, they fed the model information about the patients’ age, sex, cancer stage, and outcomes, as well as their tumors’ “multi-omic” information: the cancers’ genomic, epigenetic, protein, and metabolic profiles. Researchers showed the AI model digital, whole-slide histopathology images of tumor samples and asked it to look for visual markers related to tumor types, genetic mutations, epigenetic alterations, disease progression, and patient survival with the goal of enabling the platform to detect patterns that are indiscernible to the human eye.

They then tested the MOMA platform’s ability to interpret images by feeding it new tumor sample images from different patients and asking it to predict their survival and progression-free survival.

The researchers found that the tool successfully identified overall survival outcomes in patients with stage I or II cancer in the TCGA cohort, which they further validated with the NHS-HPFS and PLCO cohorts. The platform revealed that “dense clusters of adenocarcinoma cells are highly indicative of worse overall survival outcomes” and that the interaction of cancer cells with smooth muscle cells in cancerous areas predicted poorer overall survival.

MOMA was slightly more effective in predicting progression-free survival for stage I and stage II colorectal cancer across all three cohorts.

“Compared with the overall survival prediction, our progression-free survival model puts more emphasis on infiltrating lymphocytes and regions associated with extracellular mucin in its prediction,” the authors noted.

Prediction of overall survival and progression-free survival for stage III colorectal cancer showed similar levels of accuracy, they noted.

The tool also successfully assessed patients’ likely response to immunotherapy using predictions of microsatellite instability, since high MSI indicates a better response to immune checkpoint inhibitors.

MOMA outperformed a different machine-learning algorithm in predicting the copy number alterations and other features related to cancer development, and it predicted the likelihood of a BRAF mutation, which is linked to poorer prognosis.
 

Pushing the envelope?

MOMA presents an “intriguing new avenue of adding to how we think about and assess someone who has cancer,” Stacey Cohen, MD, an associate professor in the clinical research division of Fred Hutchinson Cancer Center at the University of Washington Medicine, Seattle, said in an interview.

However, the tool as it’s currently described appears primarily to duplicate what clinicians already are doing, which is considering a wide range of factors – including pathologic features, patient features and demographics, and the patient’s other medical illnesses – to develop a treatment plan within the context of current guidelines, noted Dr. Cohen, who was not involved in the project.

“I’m looking for these types of models to not just prognosticate an outcome but to really predict how someone should be treated, and to do that better than [using] standard clinical features,” Dr. Cohen said. “To some degree, they’re taking this AI model and trying to catch up to what we’re currently doing. Clearly, if they could do that, they can then push the envelope.”

Dr. Cohen acknowledged that a strength of using an AI platform is the speed at which it can provide its predictions in areas with few medical resources and few health care professionals – as long as the necessary imaging is available and physicians have a way to use the platform.

“On the one hand, I do see this as an opportunity to share the wealth of knowledge in a more rapid fashion, but I don’t think anybody is going to let a computer program dictate their treatment without a human medical oncologist being able to interpret that information,” Dr. Cohen said. “It still will require a lot of education by the users and not just by the people who are designing the study.”

Although the MOMA platform looked at multiple pathologic features in multiple cohorts, the results remain limited by the fact that the patients in those cohorts were treated decades ago, before many current treatments may have been available, Dr. Cohen said.

She also added that the cohorts did not have much ethnic diversity. In the NHS-HPFS, the largest cohort, 57% of the patients were White, and researchers lacked data on race for 42% of patients, so only about 1% of participants were of a known non-White race. Similarly, 47% of the TCGA patients were White and 41% had no data on race, leaving only 12% of patients from known, non-White racial backgrounds, including 10% Black or African American.

Additional studies that focus on specific patient populations are needed to evaluate the model’s applicability in clinical settings, the investigators note. More research is required to “identify the optimal prognostic prediction methods and enable personalized treatments and advance care planning,” they added.

These are the early days for this type of technology, Dr. Cohen noted.

“I’m very excited to see how this technology develops and how it could be potentially additive or improve upon our current treatment planning for patients,” she said.

Dr. Yu developed the invention “Quantitative Pathology Analysis and Diagnosis using Neural Networks,” whose patent is held by Harvard University, and has consulted for Curatio. One coauthor is a stakeholder and employee of Vertex Pharmaceuticals. The study’s funding sources included the National Institute of General Medical Sciences, the Google Research Scholar Award, the Blavatnik Center for Computational Biomedicine Award, the National Science and Technology Council Taiwan, and the National Center for High-performance Computing Taiwan. Dr. Cohen has advised or consulted for Natera.

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

Researchers have developed an artificial intelligence (AI) machine-learning platform that can predict the prognosis and likely treatment response of patients with colorectal cancer (CRC) using histopathology images, according to a new study published in Nature Communications.
 

Specifically, the tool can aid doctors in identifying a “molecular diagnosis” based on a patient’s tumor and cancer characteristics, Kun-Hsing Yu, MD, PhD, the study’s senior author and an assistant professor of biomedical informatics at Harvard Medical School, Boston, said in an interview.

The Multi-omics Multi-cohort Assessment (MOMA) “successfully identified indicators of how aggressive a tumor was and how likely it was to behave in response to a particular treatment,” as well as patients’ overall and disease-free survival, noted Harvard Medical School in a press release. “Based on an image alone, the model also pinpointed characteristics associated with the presence or absence of specific genetic mutations – something that typically requires genomic sequencing of the tumor.”

The researchers designed the tool to offer “transparent reasoning,” so that if a clinician asks it why it made a certain prediction, it would be able to explain its reasoning and the variables it used, the press release noted.

“We first allow AI to explore any correlation, and then we try to explain those correlations using existing pathology terms that experts will be able to understand,” Dr. Yu said in an interview.

Although the tool is freely available to clinicians and researchers, it’s not yet ready for clinical use. When it is, the tool has the potential to provide timely, accurate decision support based on tumor imaging.

Colorectal cancer is the second most common cause of death from cancer in the United States, with more than 53,000 deaths each year, and the patient population has been gradually skewing younger over the past 2 decades.

Although clinicians already use histopathology and genetic analysis to guide treatment, the process can take several days or weeks in some areas, and these services may not be available in all parts of the world.

“Currently, a clinician has to send a [tissue] sample from the tumor specimen to genomic sequencing labs and wait for a week, sometimes up to 3 or more weeks, to get genomic sequencing results,” Dr. Yu said. That means a patient’s anxiety grows as they wait to find out which treatments might benefit them or how they might respond to a particular treatment.

Additionally, current knowledge for predicting patient survival, beyond considering the patient’s cancer stage, age, and general health status, is limited, Dr. Yu said.
 

Predictive ability

The MOMA platform was trained on information from 1,888 patients with colorectal cancer from three national cohorts: 628 patients from The Cancer Genome Atlas (TCGA) program, 927 patients from the Nurses’ Health Study with Health Professionals Follow-Up Study (NHS-HPFS), and 333 patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

During the training, they fed the model information about the patients’ age, sex, cancer stage, and outcomes, as well as their tumors’ “multi-omic” information: the cancers’ genomic, epigenetic, protein, and metabolic profiles. Researchers showed the AI model digital, whole-slide histopathology images of tumor samples and asked it to look for visual markers related to tumor types, genetic mutations, epigenetic alterations, disease progression, and patient survival with the goal of enabling the platform to detect patterns that are indiscernible to the human eye.

They then tested the MOMA platform’s ability to interpret images by feeding it new tumor sample images from different patients and asking it to predict their survival and progression-free survival.

The researchers found that the tool successfully identified overall survival outcomes in patients with stage I or II cancer in the TCGA cohort, which they further validated with the NHS-HPFS and PLCO cohorts. The platform revealed that “dense clusters of adenocarcinoma cells are highly indicative of worse overall survival outcomes” and that the interaction of cancer cells with smooth muscle cells in cancerous areas predicted poorer overall survival.

MOMA was slightly more effective in predicting progression-free survival for stage I and stage II colorectal cancer across all three cohorts.

“Compared with the overall survival prediction, our progression-free survival model puts more emphasis on infiltrating lymphocytes and regions associated with extracellular mucin in its prediction,” the authors noted.

Prediction of overall survival and progression-free survival for stage III colorectal cancer showed similar levels of accuracy, they noted.

The tool also successfully assessed patients’ likely response to immunotherapy using predictions of microsatellite instability, since high MSI indicates a better response to immune checkpoint inhibitors.

MOMA outperformed a different machine-learning algorithm in predicting the copy number alterations and other features related to cancer development, and it predicted the likelihood of a BRAF mutation, which is linked to poorer prognosis.
 

Pushing the envelope?

MOMA presents an “intriguing new avenue of adding to how we think about and assess someone who has cancer,” Stacey Cohen, MD, an associate professor in the clinical research division of Fred Hutchinson Cancer Center at the University of Washington Medicine, Seattle, said in an interview.

However, the tool as it’s currently described appears primarily to duplicate what clinicians already are doing, which is considering a wide range of factors – including pathologic features, patient features and demographics, and the patient’s other medical illnesses – to develop a treatment plan within the context of current guidelines, noted Dr. Cohen, who was not involved in the project.

“I’m looking for these types of models to not just prognosticate an outcome but to really predict how someone should be treated, and to do that better than [using] standard clinical features,” Dr. Cohen said. “To some degree, they’re taking this AI model and trying to catch up to what we’re currently doing. Clearly, if they could do that, they can then push the envelope.”

Dr. Cohen acknowledged that a strength of using an AI platform is the speed at which it can provide its predictions in areas with few medical resources and few health care professionals – as long as the necessary imaging is available and physicians have a way to use the platform.

“On the one hand, I do see this as an opportunity to share the wealth of knowledge in a more rapid fashion, but I don’t think anybody is going to let a computer program dictate their treatment without a human medical oncologist being able to interpret that information,” Dr. Cohen said. “It still will require a lot of education by the users and not just by the people who are designing the study.”

Although the MOMA platform looked at multiple pathologic features in multiple cohorts, the results remain limited by the fact that the patients in those cohorts were treated decades ago, before many current treatments may have been available, Dr. Cohen said.

She also added that the cohorts did not have much ethnic diversity. In the NHS-HPFS, the largest cohort, 57% of the patients were White, and researchers lacked data on race for 42% of patients, so only about 1% of participants were of a known non-White race. Similarly, 47% of the TCGA patients were White and 41% had no data on race, leaving only 12% of patients from known, non-White racial backgrounds, including 10% Black or African American.

Additional studies that focus on specific patient populations are needed to evaluate the model’s applicability in clinical settings, the investigators note. More research is required to “identify the optimal prognostic prediction methods and enable personalized treatments and advance care planning,” they added.

These are the early days for this type of technology, Dr. Cohen noted.

“I’m very excited to see how this technology develops and how it could be potentially additive or improve upon our current treatment planning for patients,” she said.

Dr. Yu developed the invention “Quantitative Pathology Analysis and Diagnosis using Neural Networks,” whose patent is held by Harvard University, and has consulted for Curatio. One coauthor is a stakeholder and employee of Vertex Pharmaceuticals. The study’s funding sources included the National Institute of General Medical Sciences, the Google Research Scholar Award, the Blavatnik Center for Computational Biomedicine Award, the National Science and Technology Council Taiwan, and the National Center for High-performance Computing Taiwan. Dr. Cohen has advised or consulted for Natera.

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

Researchers have developed an artificial intelligence (AI) machine-learning platform that can predict the prognosis and likely treatment response of patients with colorectal cancer (CRC) using histopathology images, according to a new study published in Nature Communications.
 

Specifically, the tool can aid doctors in identifying a “molecular diagnosis” based on a patient’s tumor and cancer characteristics, Kun-Hsing Yu, MD, PhD, the study’s senior author and an assistant professor of biomedical informatics at Harvard Medical School, Boston, said in an interview.

The Multi-omics Multi-cohort Assessment (MOMA) “successfully identified indicators of how aggressive a tumor was and how likely it was to behave in response to a particular treatment,” as well as patients’ overall and disease-free survival, noted Harvard Medical School in a press release. “Based on an image alone, the model also pinpointed characteristics associated with the presence or absence of specific genetic mutations – something that typically requires genomic sequencing of the tumor.”

The researchers designed the tool to offer “transparent reasoning,” so that if a clinician asks it why it made a certain prediction, it would be able to explain its reasoning and the variables it used, the press release noted.

“We first allow AI to explore any correlation, and then we try to explain those correlations using existing pathology terms that experts will be able to understand,” Dr. Yu said in an interview.

Although the tool is freely available to clinicians and researchers, it’s not yet ready for clinical use. When it is, the tool has the potential to provide timely, accurate decision support based on tumor imaging.

Colorectal cancer is the second most common cause of death from cancer in the United States, with more than 53,000 deaths each year, and the patient population has been gradually skewing younger over the past 2 decades.

Although clinicians already use histopathology and genetic analysis to guide treatment, the process can take several days or weeks in some areas, and these services may not be available in all parts of the world.

“Currently, a clinician has to send a [tissue] sample from the tumor specimen to genomic sequencing labs and wait for a week, sometimes up to 3 or more weeks, to get genomic sequencing results,” Dr. Yu said. That means a patient’s anxiety grows as they wait to find out which treatments might benefit them or how they might respond to a particular treatment.

Additionally, current knowledge for predicting patient survival, beyond considering the patient’s cancer stage, age, and general health status, is limited, Dr. Yu said.
 

Predictive ability

The MOMA platform was trained on information from 1,888 patients with colorectal cancer from three national cohorts: 628 patients from The Cancer Genome Atlas (TCGA) program, 927 patients from the Nurses’ Health Study with Health Professionals Follow-Up Study (NHS-HPFS), and 333 patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

During the training, they fed the model information about the patients’ age, sex, cancer stage, and outcomes, as well as their tumors’ “multi-omic” information: the cancers’ genomic, epigenetic, protein, and metabolic profiles. Researchers showed the AI model digital, whole-slide histopathology images of tumor samples and asked it to look for visual markers related to tumor types, genetic mutations, epigenetic alterations, disease progression, and patient survival with the goal of enabling the platform to detect patterns that are indiscernible to the human eye.

They then tested the MOMA platform’s ability to interpret images by feeding it new tumor sample images from different patients and asking it to predict their survival and progression-free survival.

The researchers found that the tool successfully identified overall survival outcomes in patients with stage I or II cancer in the TCGA cohort, which they further validated with the NHS-HPFS and PLCO cohorts. The platform revealed that “dense clusters of adenocarcinoma cells are highly indicative of worse overall survival outcomes” and that the interaction of cancer cells with smooth muscle cells in cancerous areas predicted poorer overall survival.

MOMA was slightly more effective in predicting progression-free survival for stage I and stage II colorectal cancer across all three cohorts.

“Compared with the overall survival prediction, our progression-free survival model puts more emphasis on infiltrating lymphocytes and regions associated with extracellular mucin in its prediction,” the authors noted.

Prediction of overall survival and progression-free survival for stage III colorectal cancer showed similar levels of accuracy, they noted.

The tool also successfully assessed patients’ likely response to immunotherapy using predictions of microsatellite instability, since high MSI indicates a better response to immune checkpoint inhibitors.

MOMA outperformed a different machine-learning algorithm in predicting the copy number alterations and other features related to cancer development, and it predicted the likelihood of a BRAF mutation, which is linked to poorer prognosis.
 

Pushing the envelope?

MOMA presents an “intriguing new avenue of adding to how we think about and assess someone who has cancer,” Stacey Cohen, MD, an associate professor in the clinical research division of Fred Hutchinson Cancer Center at the University of Washington Medicine, Seattle, said in an interview.

However, the tool as it’s currently described appears primarily to duplicate what clinicians already are doing, which is considering a wide range of factors – including pathologic features, patient features and demographics, and the patient’s other medical illnesses – to develop a treatment plan within the context of current guidelines, noted Dr. Cohen, who was not involved in the project.

“I’m looking for these types of models to not just prognosticate an outcome but to really predict how someone should be treated, and to do that better than [using] standard clinical features,” Dr. Cohen said. “To some degree, they’re taking this AI model and trying to catch up to what we’re currently doing. Clearly, if they could do that, they can then push the envelope.”

Dr. Cohen acknowledged that a strength of using an AI platform is the speed at which it can provide its predictions in areas with few medical resources and few health care professionals – as long as the necessary imaging is available and physicians have a way to use the platform.

“On the one hand, I do see this as an opportunity to share the wealth of knowledge in a more rapid fashion, but I don’t think anybody is going to let a computer program dictate their treatment without a human medical oncologist being able to interpret that information,” Dr. Cohen said. “It still will require a lot of education by the users and not just by the people who are designing the study.”

Although the MOMA platform looked at multiple pathologic features in multiple cohorts, the results remain limited by the fact that the patients in those cohorts were treated decades ago, before many current treatments may have been available, Dr. Cohen said.

She also added that the cohorts did not have much ethnic diversity. In the NHS-HPFS, the largest cohort, 57% of the patients were White, and researchers lacked data on race for 42% of patients, so only about 1% of participants were of a known non-White race. Similarly, 47% of the TCGA patients were White and 41% had no data on race, leaving only 12% of patients from known, non-White racial backgrounds, including 10% Black or African American.

Additional studies that focus on specific patient populations are needed to evaluate the model’s applicability in clinical settings, the investigators note. More research is required to “identify the optimal prognostic prediction methods and enable personalized treatments and advance care planning,” they added.

These are the early days for this type of technology, Dr. Cohen noted.

“I’m very excited to see how this technology develops and how it could be potentially additive or improve upon our current treatment planning for patients,” she said.

Dr. Yu developed the invention “Quantitative Pathology Analysis and Diagnosis using Neural Networks,” whose patent is held by Harvard University, and has consulted for Curatio. One coauthor is a stakeholder and employee of Vertex Pharmaceuticals. The study’s funding sources included the National Institute of General Medical Sciences, the Google Research Scholar Award, the Blavatnik Center for Computational Biomedicine Award, the National Science and Technology Council Taiwan, and the National Center for High-performance Computing Taiwan. Dr. Cohen has advised or consulted for Natera.

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