Carolyn Crist

Computer-aided detection (CADe) during colonoscopy may not lead to major improvements in key measures, particularly in community-based settings, according to a new study.

In a randomized clinical trial using EndoVigilant, there wasn’t a significant difference in adenomas per colonoscopy (APC) in procedures with the CADe tool versus those without it. In addition, the adenoma detection rate (ADR) and serrated polyp detection rate were similar in the CADe and non-CADe groups.

“Although we were disappointed that AI [artificial intelligence] did not improve detection of adenomas or serrated polyps in our study, we are still optimistic that this exciting technology will eventually impact endoscopy in a very positive way,” senior author Shai Friedland, MD, a professor of medicine at Stanford (Calif.) University and gastroenterologist with the Veterans Affairs Palo Alto Health Care System, said in an interview.

“The ultimate goal should be to improve the ability of colonoscopy to prevent morbidity and mortality from colon cancer, especially for endoscopists who may not be performing as well as they could be,” he said. “AI can potentially help prevent missed lesions due to fatigue or distraction, much like a warning system that averts car accidents. It can also potentially help endoscopists recognize dangerous – but rare – subtle lesions such as small, flat, and depressed cancers.”

The study was published online in the American Journal of Gastroenterology.
 

Analyzing detection rates

Several studies have evaluated the use of different CADe devices to reduce adenoma miss rates during colonoscopy, and some have found that the technology contributed to significantly higher ADR and APC, the study authors write. However, most of these studies have been performed in academic settings.

Dr. Friedland and colleagues conducted a randomized controlled trial, called AI-SEE, to evaluate the use of CADe during colonoscopy in four community-based endoscopy centers located in California, Connecticut, Maryland, and New Jersey between September 2020 and September 2021. The trial included seven board-certified clinicians, who had ADR of 25%-37% before the study. The participants were randomly assigned to colonoscopies with or without CADe in blocks of 16 patients to ensure masking. Both groups had similar patient demographics.

The research team enrolled patients aged 45 years or older who presented for screening or low-risk surveillance colonoscopy, which was defined as a patient qualifying for a surveillance interval of 3 years or greater based on the U.S. Multi-Society Task Force 2020 Guidelines. Patients were excluded if they had a history of inflammatory bowel disease, known or suspected polyposis or hereditary colon cancer syndrome, history of colon resection, or a referral for a diagnostic colonoscopy.

Among 769 enrolled patients, 387 were randomly assigned to undergo colonoscopy with EndoVigilant, an AI-enabled CADe software for colonoscopy. It augments existing white-light colonoscopy in real time by highlighting colon polyps and displaying a graphic box around the lesion on the monitor. It can be deployed as a single- or dual-monitor device. Although the study was originally designed to use two monitors, three investigators expressed strong preference for the single-monitor mode, so the protocol allowed endoscopists to choose.

Primary outcomes included APC and adenoma per extraction (APE), which is the percentage of polyps removed that are adenomas. Secondary endpoints included procedural time, ADR, serrated polyp detection rate, serrated polyps per colonoscopy, and nonadenomatous, nonserrated polyps per colonoscopy.

Overall, the use of CADe didn’t show a significant difference in APC, at 0.73, compared with 0.67 for non-CADe.

Although the use of CADe didn’t lead to increased identification of serrated polyps per colonoscopy – both at 0.08 – CADe led to increased identification of nonadenomatous, nonserrated polyps per colonoscopy, at 0.90 versus 0.51.

There also wasn’t a significant difference in distribution regarding adenomatous polyp location, size, or morphology. However, there was a trend toward greater identification of 6-9 mm APC using CADe, at 0.13 versus 0.08.

Mean withdrawal time was longer in the CADe group, at 11.7 minutes versus 10.7 minutes. However, when no polyps were identified, the withdrawal times were similar, at 9.1 minutes versus 8.8 minutes.

In addition, there was no difference in ADR for screening colonoscopies between the non-CADe and CADe groups, at 34.6% versus 34.3%, or for surveillance procedures, at 43.9% versus 40%. CADe also didn’t improve serrated polyp detection rates for screening or surveillance.

CADe was also associated with decreased APE in all colonoscopies (44.8 vs. 56.8) as well as in screening colonoscopies (43 vs. 57.8).

A comparison of single-monitor CADe with dual-monitor CADe found no significant difference in the average number of adenomas or serrated polyps identified per colonoscopy. However, dual-monitor CADe identified significantly more non-adenomatous, nonserrated polyps per colonoscopy (1.18 vs. 0.42), more adenomas sized at least 10 mm (0.19 vs. 0.05), and more flat polyps (0.18 vs. 0).

The study was terminated early after the interim analysis point, marked by 769 valid subjects. At this point, the comparison of APC between the two groups resulted in a new sample size estimate required for final analysis of 6,557 per group. This revised large study size estimate made it impractical to continue, the study authors wrote. No adverse events were observed during the study.

“What our study shows is that current systems – and the one we used in this study performs very well when tested on a database of images or videos – don’t make a major impact on very crude outcome measures, such as the total number of adenomas detected by a group of endoscopists at typical private endoscopy centers,” Dr. Friedland said. “I’m not convinced that we have a good answer yet for where to go from here, but we need to keep working with our AI colleagues to figure out how to use this exciting technology to improve outcomes in colon cancer.”
 

Additional considerations

In a separate evaluation of EndoVigilant, the frame level sensitivity was 0.9 and the frame level specificity was 0.97. These calculations were conducted on a dataset not used in training or validation of this model, the authors noted.

In this study, it’s possible that experienced community-based endoscopists are proficient at detecting the adenomas highlighted by the CADe system, so the technology may not detect a significant number of additional adenomas, the authors wrote. It’s also possible that some endoscopists ignore lesions highlighted by CADe, including small lesions that might be difficult to identify as adenomas or are seen as clinically unimportant, which could reduce the potential benefit of CADe.

“It’s important to remember that these tools are meant to be endoscopist assistance devices, not endoscopist replacements. They provide added benefit by pointing out polyps while we do the best exam we can,” Aasma Shaukat, MD, a professor of medicine and gastroenterologist at NYU Langone Health, New York, said in an interview.

Dr. Shaukat, who wasn’t involved with this study, has researched CADe for screening and surveillance colonoscopies. She and colleagues found that CADe use improved APC without an increase in resection of nonneoplastic lesions.

“Different trials have reported different results, and at the end of the day, it’s an endoscopist assistance tool, like spellcheck in a document,” she said. “It’s nice if spellcheck points to an incorrect spelling, but you don’t have to use it. Similarly, we often don’t know in these studies what an endoscopist felt or believed about the tool when using it.”

The benefits of CADe could vary based on its software, setting, number of patients, patient characteristics, number of clinicians, provider experience and training, dual- versus single-monitor setup, and even time of day, she noted. Future studies could clarify these factors, as well as improve the technology.

“This is just the beginning of AI in this field, and while bounding boxes to indicate potential polyps is a good start, it’s not the be-all, end-all,” Dr. Shaukat said.

“We want AI software to be able to tell us more about the size of the polyp, histology, prep quality, landmarks in the colon, adequacy of resection, and more. There’s some work being geared toward developing the algorithms to do these additional aspects,” she added.

The study was sponsored by EndoVigilant. Some of the authors reported consultant roles with Neptune Medical, AgilTx, Intuitive Surgical, Capsovision, and EndoVigilant. Dr. Shaukat reported no relevant financial relationships.

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

Computer-aided detection (CADe) during colonoscopy may not lead to major improvements in key measures, particularly in community-based settings, according to a new study.

In a randomized clinical trial using EndoVigilant, there wasn’t a significant difference in adenomas per colonoscopy (APC) in procedures with the CADe tool versus those without it. In addition, the adenoma detection rate (ADR) and serrated polyp detection rate were similar in the CADe and non-CADe groups.

“Although we were disappointed that AI [artificial intelligence] did not improve detection of adenomas or serrated polyps in our study, we are still optimistic that this exciting technology will eventually impact endoscopy in a very positive way,” senior author Shai Friedland, MD, a professor of medicine at Stanford (Calif.) University and gastroenterologist with the Veterans Affairs Palo Alto Health Care System, said in an interview.

“The ultimate goal should be to improve the ability of colonoscopy to prevent morbidity and mortality from colon cancer, especially for endoscopists who may not be performing as well as they could be,” he said. “AI can potentially help prevent missed lesions due to fatigue or distraction, much like a warning system that averts car accidents. It can also potentially help endoscopists recognize dangerous – but rare – subtle lesions such as small, flat, and depressed cancers.”

The study was published online in the American Journal of Gastroenterology.
 

Analyzing detection rates

Several studies have evaluated the use of different CADe devices to reduce adenoma miss rates during colonoscopy, and some have found that the technology contributed to significantly higher ADR and APC, the study authors write. However, most of these studies have been performed in academic settings.

Dr. Friedland and colleagues conducted a randomized controlled trial, called AI-SEE, to evaluate the use of CADe during colonoscopy in four community-based endoscopy centers located in California, Connecticut, Maryland, and New Jersey between September 2020 and September 2021. The trial included seven board-certified clinicians, who had ADR of 25%-37% before the study. The participants were randomly assigned to colonoscopies with or without CADe in blocks of 16 patients to ensure masking. Both groups had similar patient demographics.

The research team enrolled patients aged 45 years or older who presented for screening or low-risk surveillance colonoscopy, which was defined as a patient qualifying for a surveillance interval of 3 years or greater based on the U.S. Multi-Society Task Force 2020 Guidelines. Patients were excluded if they had a history of inflammatory bowel disease, known or suspected polyposis or hereditary colon cancer syndrome, history of colon resection, or a referral for a diagnostic colonoscopy.

Among 769 enrolled patients, 387 were randomly assigned to undergo colonoscopy with EndoVigilant, an AI-enabled CADe software for colonoscopy. It augments existing white-light colonoscopy in real time by highlighting colon polyps and displaying a graphic box around the lesion on the monitor. It can be deployed as a single- or dual-monitor device. Although the study was originally designed to use two monitors, three investigators expressed strong preference for the single-monitor mode, so the protocol allowed endoscopists to choose.

Primary outcomes included APC and adenoma per extraction (APE), which is the percentage of polyps removed that are adenomas. Secondary endpoints included procedural time, ADR, serrated polyp detection rate, serrated polyps per colonoscopy, and nonadenomatous, nonserrated polyps per colonoscopy.

Overall, the use of CADe didn’t show a significant difference in APC, at 0.73, compared with 0.67 for non-CADe.

Although the use of CADe didn’t lead to increased identification of serrated polyps per colonoscopy – both at 0.08 – CADe led to increased identification of nonadenomatous, nonserrated polyps per colonoscopy, at 0.90 versus 0.51.

There also wasn’t a significant difference in distribution regarding adenomatous polyp location, size, or morphology. However, there was a trend toward greater identification of 6-9 mm APC using CADe, at 0.13 versus 0.08.

Mean withdrawal time was longer in the CADe group, at 11.7 minutes versus 10.7 minutes. However, when no polyps were identified, the withdrawal times were similar, at 9.1 minutes versus 8.8 minutes.

In addition, there was no difference in ADR for screening colonoscopies between the non-CADe and CADe groups, at 34.6% versus 34.3%, or for surveillance procedures, at 43.9% versus 40%. CADe also didn’t improve serrated polyp detection rates for screening or surveillance.

CADe was also associated with decreased APE in all colonoscopies (44.8 vs. 56.8) as well as in screening colonoscopies (43 vs. 57.8).

A comparison of single-monitor CADe with dual-monitor CADe found no significant difference in the average number of adenomas or serrated polyps identified per colonoscopy. However, dual-monitor CADe identified significantly more non-adenomatous, nonserrated polyps per colonoscopy (1.18 vs. 0.42), more adenomas sized at least 10 mm (0.19 vs. 0.05), and more flat polyps (0.18 vs. 0).

The study was terminated early after the interim analysis point, marked by 769 valid subjects. At this point, the comparison of APC between the two groups resulted in a new sample size estimate required for final analysis of 6,557 per group. This revised large study size estimate made it impractical to continue, the study authors wrote. No adverse events were observed during the study.

“What our study shows is that current systems – and the one we used in this study performs very well when tested on a database of images or videos – don’t make a major impact on very crude outcome measures, such as the total number of adenomas detected by a group of endoscopists at typical private endoscopy centers,” Dr. Friedland said. “I’m not convinced that we have a good answer yet for where to go from here, but we need to keep working with our AI colleagues to figure out how to use this exciting technology to improve outcomes in colon cancer.”
 

Additional considerations

In a separate evaluation of EndoVigilant, the frame level sensitivity was 0.9 and the frame level specificity was 0.97. These calculations were conducted on a dataset not used in training or validation of this model, the authors noted.

In this study, it’s possible that experienced community-based endoscopists are proficient at detecting the adenomas highlighted by the CADe system, so the technology may not detect a significant number of additional adenomas, the authors wrote. It’s also possible that some endoscopists ignore lesions highlighted by CADe, including small lesions that might be difficult to identify as adenomas or are seen as clinically unimportant, which could reduce the potential benefit of CADe.

“It’s important to remember that these tools are meant to be endoscopist assistance devices, not endoscopist replacements. They provide added benefit by pointing out polyps while we do the best exam we can,” Aasma Shaukat, MD, a professor of medicine and gastroenterologist at NYU Langone Health, New York, said in an interview.

Dr. Shaukat, who wasn’t involved with this study, has researched CADe for screening and surveillance colonoscopies. She and colleagues found that CADe use improved APC without an increase in resection of nonneoplastic lesions.

“Different trials have reported different results, and at the end of the day, it’s an endoscopist assistance tool, like spellcheck in a document,” she said. “It’s nice if spellcheck points to an incorrect spelling, but you don’t have to use it. Similarly, we often don’t know in these studies what an endoscopist felt or believed about the tool when using it.”

The benefits of CADe could vary based on its software, setting, number of patients, patient characteristics, number of clinicians, provider experience and training, dual- versus single-monitor setup, and even time of day, she noted. Future studies could clarify these factors, as well as improve the technology.

“This is just the beginning of AI in this field, and while bounding boxes to indicate potential polyps is a good start, it’s not the be-all, end-all,” Dr. Shaukat said.

“We want AI software to be able to tell us more about the size of the polyp, histology, prep quality, landmarks in the colon, adequacy of resection, and more. There’s some work being geared toward developing the algorithms to do these additional aspects,” she added.

The study was sponsored by EndoVigilant. Some of the authors reported consultant roles with Neptune Medical, AgilTx, Intuitive Surgical, Capsovision, and EndoVigilant. Dr. Shaukat reported no relevant financial relationships.

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

Computer-aided detection (CADe) during colonoscopy may not lead to major improvements in key measures, particularly in community-based settings, according to a new study.

In a randomized clinical trial using EndoVigilant, there wasn’t a significant difference in adenomas per colonoscopy (APC) in procedures with the CADe tool versus those without it. In addition, the adenoma detection rate (ADR) and serrated polyp detection rate were similar in the CADe and non-CADe groups.

“Although we were disappointed that AI [artificial intelligence] did not improve detection of adenomas or serrated polyps in our study, we are still optimistic that this exciting technology will eventually impact endoscopy in a very positive way,” senior author Shai Friedland, MD, a professor of medicine at Stanford (Calif.) University and gastroenterologist with the Veterans Affairs Palo Alto Health Care System, said in an interview.

“The ultimate goal should be to improve the ability of colonoscopy to prevent morbidity and mortality from colon cancer, especially for endoscopists who may not be performing as well as they could be,” he said. “AI can potentially help prevent missed lesions due to fatigue or distraction, much like a warning system that averts car accidents. It can also potentially help endoscopists recognize dangerous – but rare – subtle lesions such as small, flat, and depressed cancers.”

The study was published online in the American Journal of Gastroenterology.
 

Analyzing detection rates

Several studies have evaluated the use of different CADe devices to reduce adenoma miss rates during colonoscopy, and some have found that the technology contributed to significantly higher ADR and APC, the study authors write. However, most of these studies have been performed in academic settings.

Dr. Friedland and colleagues conducted a randomized controlled trial, called AI-SEE, to evaluate the use of CADe during colonoscopy in four community-based endoscopy centers located in California, Connecticut, Maryland, and New Jersey between September 2020 and September 2021. The trial included seven board-certified clinicians, who had ADR of 25%-37% before the study. The participants were randomly assigned to colonoscopies with or without CADe in blocks of 16 patients to ensure masking. Both groups had similar patient demographics.

The research team enrolled patients aged 45 years or older who presented for screening or low-risk surveillance colonoscopy, which was defined as a patient qualifying for a surveillance interval of 3 years or greater based on the U.S. Multi-Society Task Force 2020 Guidelines. Patients were excluded if they had a history of inflammatory bowel disease, known or suspected polyposis or hereditary colon cancer syndrome, history of colon resection, or a referral for a diagnostic colonoscopy.

Among 769 enrolled patients, 387 were randomly assigned to undergo colonoscopy with EndoVigilant, an AI-enabled CADe software for colonoscopy. It augments existing white-light colonoscopy in real time by highlighting colon polyps and displaying a graphic box around the lesion on the monitor. It can be deployed as a single- or dual-monitor device. Although the study was originally designed to use two monitors, three investigators expressed strong preference for the single-monitor mode, so the protocol allowed endoscopists to choose.

Primary outcomes included APC and adenoma per extraction (APE), which is the percentage of polyps removed that are adenomas. Secondary endpoints included procedural time, ADR, serrated polyp detection rate, serrated polyps per colonoscopy, and nonadenomatous, nonserrated polyps per colonoscopy.

Overall, the use of CADe didn’t show a significant difference in APC, at 0.73, compared with 0.67 for non-CADe.

Although the use of CADe didn’t lead to increased identification of serrated polyps per colonoscopy – both at 0.08 – CADe led to increased identification of nonadenomatous, nonserrated polyps per colonoscopy, at 0.90 versus 0.51.

There also wasn’t a significant difference in distribution regarding adenomatous polyp location, size, or morphology. However, there was a trend toward greater identification of 6-9 mm APC using CADe, at 0.13 versus 0.08.

Mean withdrawal time was longer in the CADe group, at 11.7 minutes versus 10.7 minutes. However, when no polyps were identified, the withdrawal times were similar, at 9.1 minutes versus 8.8 minutes.

In addition, there was no difference in ADR for screening colonoscopies between the non-CADe and CADe groups, at 34.6% versus 34.3%, or for surveillance procedures, at 43.9% versus 40%. CADe also didn’t improve serrated polyp detection rates for screening or surveillance.

CADe was also associated with decreased APE in all colonoscopies (44.8 vs. 56.8) as well as in screening colonoscopies (43 vs. 57.8).

A comparison of single-monitor CADe with dual-monitor CADe found no significant difference in the average number of adenomas or serrated polyps identified per colonoscopy. However, dual-monitor CADe identified significantly more non-adenomatous, nonserrated polyps per colonoscopy (1.18 vs. 0.42), more adenomas sized at least 10 mm (0.19 vs. 0.05), and more flat polyps (0.18 vs. 0).

The study was terminated early after the interim analysis point, marked by 769 valid subjects. At this point, the comparison of APC between the two groups resulted in a new sample size estimate required for final analysis of 6,557 per group. This revised large study size estimate made it impractical to continue, the study authors wrote. No adverse events were observed during the study.

“What our study shows is that current systems – and the one we used in this study performs very well when tested on a database of images or videos – don’t make a major impact on very crude outcome measures, such as the total number of adenomas detected by a group of endoscopists at typical private endoscopy centers,” Dr. Friedland said. “I’m not convinced that we have a good answer yet for where to go from here, but we need to keep working with our AI colleagues to figure out how to use this exciting technology to improve outcomes in colon cancer.”
 

Additional considerations

In a separate evaluation of EndoVigilant, the frame level sensitivity was 0.9 and the frame level specificity was 0.97. These calculations were conducted on a dataset not used in training or validation of this model, the authors noted.

In this study, it’s possible that experienced community-based endoscopists are proficient at detecting the adenomas highlighted by the CADe system, so the technology may not detect a significant number of additional adenomas, the authors wrote. It’s also possible that some endoscopists ignore lesions highlighted by CADe, including small lesions that might be difficult to identify as adenomas or are seen as clinically unimportant, which could reduce the potential benefit of CADe.

“It’s important to remember that these tools are meant to be endoscopist assistance devices, not endoscopist replacements. They provide added benefit by pointing out polyps while we do the best exam we can,” Aasma Shaukat, MD, a professor of medicine and gastroenterologist at NYU Langone Health, New York, said in an interview.

Dr. Shaukat, who wasn’t involved with this study, has researched CADe for screening and surveillance colonoscopies. She and colleagues found that CADe use improved APC without an increase in resection of nonneoplastic lesions.

“Different trials have reported different results, and at the end of the day, it’s an endoscopist assistance tool, like spellcheck in a document,” she said. “It’s nice if spellcheck points to an incorrect spelling, but you don’t have to use it. Similarly, we often don’t know in these studies what an endoscopist felt or believed about the tool when using it.”

The benefits of CADe could vary based on its software, setting, number of patients, patient characteristics, number of clinicians, provider experience and training, dual- versus single-monitor setup, and even time of day, she noted. Future studies could clarify these factors, as well as improve the technology.

“This is just the beginning of AI in this field, and while bounding boxes to indicate potential polyps is a good start, it’s not the be-all, end-all,” Dr. Shaukat said.

“We want AI software to be able to tell us more about the size of the polyp, histology, prep quality, landmarks in the colon, adequacy of resection, and more. There’s some work being geared toward developing the algorithms to do these additional aspects,” she added.

The study was sponsored by EndoVigilant. Some of the authors reported consultant roles with Neptune Medical, AgilTx, Intuitive Surgical, Capsovision, and EndoVigilant. Dr. Shaukat reported no relevant financial relationships.

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

The American College of Gastroenterology (ACG) issued a clinical guideline for the diagnosis and management of biliary strictures, or abnormal narrowing in the liver’s ductal drainage system.

The recommendations provide guidance on the care of patients with extrahepatic and perihilar strictures, with a focus on diagnosis and drainage. Although some of the principles may apply to intrahepatic strictures, the guideline doesn’t specifically address them. The new guideline is considered separate from the 2015 ACG guideline related to primary sclerosing cholangitis.

“The appropriate diagnosis and management of biliary strictures is still a big clinical challenge and has important implications in endoscopic, surgical, and oncological decision-making,” co-author Jennifer Maranki, MD, a professor of medicine and director of endoscopy at Penn State Hershey Medical Center, said in an interview.

“We wanted to provide the best possible guidance to gastroenterologists based on the available body of literature, with key shifts in diagnosis and management based on currently available modalities and tools,” she said.

The guideline was published in the March issue of the American Journal of Gastroenterology.

The recommendations were developed by a diverse group of authors from across the United States in recognition of the potential influence of commercial and intellectual conflicts of interest. The panel used a systematic process that involved structured literature searches by librarians and independent appraisal of the quality of evidence by dedicated methodologists, the authors write.

Overall, the team outlined 11 recommendations and 12 key concepts. A strong recommendation was made when the benefits of the test or intervention clearly outweighed the potential disadvantages. A conditional recommendation was made when some uncertainty remained about the balance of benefits and harms. Key concepts address important clinical questions that lack adequate evidence to inform recommendations. They are based on indirect evidence and expert opinion.

Epidemiology and diagnosis

The burden of biliary strictures is difficult to estimate, owing to the lack of a specific administrative code. The estimated cost of caring for biliary disease in the United States is about $16.9 billion annually, although this figure includes costs associated with gallbladder disease, choledocholithiasis, and other (nonobstructive) biliary disorders, the authors write.

Among the 57,000 new cases of pancreatic cancer each year, at least 60% will cause obstructive jaundice, resulting in about 34,000 annual cases of malignant extrahepatic biliary stricture, the team notes. In addition, about 3,000 cases of malignant perihilar stricture are expected in the United States each year. Patients may also seek care for benign strictures associated with chronic pancreatitis, primary sclerosing cholangitis, autoimmune disease, and post-cholecystectomy injury.

Under the first key concept, the authors note that biliary strictures in adults are more likely to be malignant than benign, except in certain well-defined scenarios. This underscores the importance of having a high index of clinical suspicion during evaluation, they add.

In general, a definitive tissue diagnosis is necessary to guide oncologic and endoscopic care for most strictures that aren’t surgically resectable at the time of presentation. For patients with extrahepatic biliary stricture due to an apparent or suspected pancreatic mass, endoscopic ultrasound (EUS) with fine-needle sampling (aspiration or biopsy) is recommended over endoscopic retrograde cholangiopancreatography (ERCP) as the preferred method of evaluation for malignancy.

For patients with suspected malignant perihilar stricture, multimodality sampling is recommended over brush cytology alone at the time of the index ERCP.

Guidance on drainage

For management, the principal objective is to restore the physiologic flow of bile into the duodenum. Although there is wide variability in the difficulty and risk of drainage, depending on location and complexity, perihilar strictures are generally more challenging and are riskier to drain than extrahepatic strictures. The goals should be to alleviate symptoms, reduce serum bilirubin to a level such that chemotherapy can be safely administered, and optimize surgical outcomes.

For benign extrahepatic biliary strictures, ERCP is the preferred modality for durable treatment. Fully covered self-expanding metallic stent (SEMS) placement is recommended over multiple plastic stents to reduce the number of procedures required for long-term treatment.

For extrahepatic strictures due to resectable pancreatic cancer or cholangiocarcinoma, the authors recommend against routine preoperative biliary drainage. However, drainage is warranted for some patients, including those with acute cholangitis, severe pruritus, very high serum bilirubin levels, those undergoing neoadjuvant therapy, and those for whom surgery is delayed.

For malignant extrahepatic strictures that are unresectable or borderline resectable, SEMS placement is recommended over plastic stents. The evidence is insufficient to recommend for or against uncovered SEMS versus fully covered SEMS.

For perihilar strictures due to suspected malignancy, the evidence is insufficient to recommend for or against ERCP versus percutaneous transhepatic biliary drainage. In addition, for malignant perihilar strictures, the evidence is insufficient to recommend for or against plastic stents versus uncovered SEMS.

For perihilar strictures due to cholangiocarcinoma in cases in which resection or transplantation is not possible, adjuvant endobiliary ablation plus plastic stent placement is recommended over plastic stent placement alone.

Overall, for patients with a biliary stricture for which ERCP is indicated but is unsuccessful or impossible, EUS-guided biliary access and drainage is recommended over PTBD, because it is associated with fewer adverse events. However, these interventional EUS procedures should be performed by an endoscopist with substantial experience.

“The workup of biliary strictures is challenging, invasive, and costly, requiring multiple diagnostic tools with highly variable yields,” co-author Victoria Gomez, MD, associate professor of medicine and director of bariatric endoscopy at Mayo Clinic, Jacksonville, Fla., said in an interview.

“Providers caring for these patients must be up to date with the most current evidence so that they can make the safest and most well-informed decisions for their patients,” she said. “These include considerations such as limiting the use of anesthesia, using tests that will result in the highest diagnostic yield, and providing effective therapies to decompress biliary obstruction.”

Future questions

Additional research is needed in several areas to strengthen recommendations and advance the field, the study authors write.

“Biliary strictures without an associated mass are a diagnostic challenge, and there are exciting opportunities to understand how new technologies, such as artificial intelligence, can be used to improve our assessment,” co-author Anna Tavakkoli, MD, assistant professor of internal medicine in digestive and liver diseases at the University of Texas Southwestern Medical Center, Dallas, said in an interview.

“Also, we highlighted several controversies in the drainage of perihilar strictures, including whether to use ERCP versus percutaneous drainage, whether metallic or plastic stents are better, and what the optimal stent placement should be,” she said. “Future multicenter studies are needed to address these key controversies.”

Although fully covered SEMS placement remains effective for benign biliary strictures, multiple plastic stents may be a better alternative in some cases. Such cases include those in which the stricture is close to the hilum, those in which the gallbladder is intact and in which crossing the cystic duct orifice cannot be avoided, those in which a fully covered SEMS has previously migrated or was not well tolerated, and those in which stricture has recurred after removal of a fully covered SEMS.

‘Comprehensive list’

“Overall, the authors have done a commendable job putting together a comprehensive list of recommendations that will invariably alter the practice of many therapeutic endoscopists for the diagnosis and management of biliary strictures,” Matthew Fasullo, DO, an advanced endoscopy and gastroenterology fellow at New York University Medical Center, told this news organization.

Dr. Fasullo, who wasn’t involved with the guideline, has published on advances in pathophysiology, diagnosis, and treatment for post-transplant biliary complications.

“The fact that ... cholangioscopy-directed biopsies after an initial negative evaluation via ERCP reveal malignancy in 54% of cases underscores the need for best practice guidelines and supports advancements in diagnostics to confidently rule in or out cancer,” he said.

“The movement toward multimodality sampling at the time of initial evaluation with a combination of brushing, fluoroscopy-directed biopsies, cholangioscopy-directed biopsies, and fluorescence in situ hybridization should become universally adopted in those with an ambiguous diagnosis,” he added. “As technology continues to improve, next-generation sequencing will prove to be an invaluable adjunct to the current pathological evaluation.”

The authors received no financial support for the guideline. One author has a consultant role for Takeda Pharmaceuticals and is an advisory board member role for Advarra. The other authors and Dr. Fasullo have disclosed no relevant financial relationships.

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

The American College of Gastroenterology (ACG) issued a clinical guideline for the diagnosis and management of biliary strictures, or abnormal narrowing in the liver’s ductal drainage system.

The recommendations provide guidance on the care of patients with extrahepatic and perihilar strictures, with a focus on diagnosis and drainage. Although some of the principles may apply to intrahepatic strictures, the guideline doesn’t specifically address them. The new guideline is considered separate from the 2015 ACG guideline related to primary sclerosing cholangitis.

“The appropriate diagnosis and management of biliary strictures is still a big clinical challenge and has important implications in endoscopic, surgical, and oncological decision-making,” co-author Jennifer Maranki, MD, a professor of medicine and director of endoscopy at Penn State Hershey Medical Center, said in an interview.

“We wanted to provide the best possible guidance to gastroenterologists based on the available body of literature, with key shifts in diagnosis and management based on currently available modalities and tools,” she said.

The guideline was published in the March issue of the American Journal of Gastroenterology.

The recommendations were developed by a diverse group of authors from across the United States in recognition of the potential influence of commercial and intellectual conflicts of interest. The panel used a systematic process that involved structured literature searches by librarians and independent appraisal of the quality of evidence by dedicated methodologists, the authors write.

Overall, the team outlined 11 recommendations and 12 key concepts. A strong recommendation was made when the benefits of the test or intervention clearly outweighed the potential disadvantages. A conditional recommendation was made when some uncertainty remained about the balance of benefits and harms. Key concepts address important clinical questions that lack adequate evidence to inform recommendations. They are based on indirect evidence and expert opinion.

Epidemiology and diagnosis

The burden of biliary strictures is difficult to estimate, owing to the lack of a specific administrative code. The estimated cost of caring for biliary disease in the United States is about $16.9 billion annually, although this figure includes costs associated with gallbladder disease, choledocholithiasis, and other (nonobstructive) biliary disorders, the authors write.

Among the 57,000 new cases of pancreatic cancer each year, at least 60% will cause obstructive jaundice, resulting in about 34,000 annual cases of malignant extrahepatic biliary stricture, the team notes. In addition, about 3,000 cases of malignant perihilar stricture are expected in the United States each year. Patients may also seek care for benign strictures associated with chronic pancreatitis, primary sclerosing cholangitis, autoimmune disease, and post-cholecystectomy injury.

Under the first key concept, the authors note that biliary strictures in adults are more likely to be malignant than benign, except in certain well-defined scenarios. This underscores the importance of having a high index of clinical suspicion during evaluation, they add.

In general, a definitive tissue diagnosis is necessary to guide oncologic and endoscopic care for most strictures that aren’t surgically resectable at the time of presentation. For patients with extrahepatic biliary stricture due to an apparent or suspected pancreatic mass, endoscopic ultrasound (EUS) with fine-needle sampling (aspiration or biopsy) is recommended over endoscopic retrograde cholangiopancreatography (ERCP) as the preferred method of evaluation for malignancy.

For patients with suspected malignant perihilar stricture, multimodality sampling is recommended over brush cytology alone at the time of the index ERCP.

Guidance on drainage

For management, the principal objective is to restore the physiologic flow of bile into the duodenum. Although there is wide variability in the difficulty and risk of drainage, depending on location and complexity, perihilar strictures are generally more challenging and are riskier to drain than extrahepatic strictures. The goals should be to alleviate symptoms, reduce serum bilirubin to a level such that chemotherapy can be safely administered, and optimize surgical outcomes.

For benign extrahepatic biliary strictures, ERCP is the preferred modality for durable treatment. Fully covered self-expanding metallic stent (SEMS) placement is recommended over multiple plastic stents to reduce the number of procedures required for long-term treatment.

For extrahepatic strictures due to resectable pancreatic cancer or cholangiocarcinoma, the authors recommend against routine preoperative biliary drainage. However, drainage is warranted for some patients, including those with acute cholangitis, severe pruritus, very high serum bilirubin levels, those undergoing neoadjuvant therapy, and those for whom surgery is delayed.

For malignant extrahepatic strictures that are unresectable or borderline resectable, SEMS placement is recommended over plastic stents. The evidence is insufficient to recommend for or against uncovered SEMS versus fully covered SEMS.

For perihilar strictures due to suspected malignancy, the evidence is insufficient to recommend for or against ERCP versus percutaneous transhepatic biliary drainage. In addition, for malignant perihilar strictures, the evidence is insufficient to recommend for or against plastic stents versus uncovered SEMS.

For perihilar strictures due to cholangiocarcinoma in cases in which resection or transplantation is not possible, adjuvant endobiliary ablation plus plastic stent placement is recommended over plastic stent placement alone.

Overall, for patients with a biliary stricture for which ERCP is indicated but is unsuccessful or impossible, EUS-guided biliary access and drainage is recommended over PTBD, because it is associated with fewer adverse events. However, these interventional EUS procedures should be performed by an endoscopist with substantial experience.

“The workup of biliary strictures is challenging, invasive, and costly, requiring multiple diagnostic tools with highly variable yields,” co-author Victoria Gomez, MD, associate professor of medicine and director of bariatric endoscopy at Mayo Clinic, Jacksonville, Fla., said in an interview.

“Providers caring for these patients must be up to date with the most current evidence so that they can make the safest and most well-informed decisions for their patients,” she said. “These include considerations such as limiting the use of anesthesia, using tests that will result in the highest diagnostic yield, and providing effective therapies to decompress biliary obstruction.”

Future questions

Additional research is needed in several areas to strengthen recommendations and advance the field, the study authors write.

“Biliary strictures without an associated mass are a diagnostic challenge, and there are exciting opportunities to understand how new technologies, such as artificial intelligence, can be used to improve our assessment,” co-author Anna Tavakkoli, MD, assistant professor of internal medicine in digestive and liver diseases at the University of Texas Southwestern Medical Center, Dallas, said in an interview.

“Also, we highlighted several controversies in the drainage of perihilar strictures, including whether to use ERCP versus percutaneous drainage, whether metallic or plastic stents are better, and what the optimal stent placement should be,” she said. “Future multicenter studies are needed to address these key controversies.”

Although fully covered SEMS placement remains effective for benign biliary strictures, multiple plastic stents may be a better alternative in some cases. Such cases include those in which the stricture is close to the hilum, those in which the gallbladder is intact and in which crossing the cystic duct orifice cannot be avoided, those in which a fully covered SEMS has previously migrated or was not well tolerated, and those in which stricture has recurred after removal of a fully covered SEMS.

‘Comprehensive list’

“Overall, the authors have done a commendable job putting together a comprehensive list of recommendations that will invariably alter the practice of many therapeutic endoscopists for the diagnosis and management of biliary strictures,” Matthew Fasullo, DO, an advanced endoscopy and gastroenterology fellow at New York University Medical Center, told this news organization.

Dr. Fasullo, who wasn’t involved with the guideline, has published on advances in pathophysiology, diagnosis, and treatment for post-transplant biliary complications.

“The fact that ... cholangioscopy-directed biopsies after an initial negative evaluation via ERCP reveal malignancy in 54% of cases underscores the need for best practice guidelines and supports advancements in diagnostics to confidently rule in or out cancer,” he said.

“The movement toward multimodality sampling at the time of initial evaluation with a combination of brushing, fluoroscopy-directed biopsies, cholangioscopy-directed biopsies, and fluorescence in situ hybridization should become universally adopted in those with an ambiguous diagnosis,” he added. “As technology continues to improve, next-generation sequencing will prove to be an invaluable adjunct to the current pathological evaluation.”

The authors received no financial support for the guideline. One author has a consultant role for Takeda Pharmaceuticals and is an advisory board member role for Advarra. The other authors and Dr. Fasullo have disclosed no relevant financial relationships.

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

The American College of Gastroenterology (ACG) issued a clinical guideline for the diagnosis and management of biliary strictures, or abnormal narrowing in the liver’s ductal drainage system.

The recommendations provide guidance on the care of patients with extrahepatic and perihilar strictures, with a focus on diagnosis and drainage. Although some of the principles may apply to intrahepatic strictures, the guideline doesn’t specifically address them. The new guideline is considered separate from the 2015 ACG guideline related to primary sclerosing cholangitis.

“The appropriate diagnosis and management of biliary strictures is still a big clinical challenge and has important implications in endoscopic, surgical, and oncological decision-making,” co-author Jennifer Maranki, MD, a professor of medicine and director of endoscopy at Penn State Hershey Medical Center, said in an interview.

“We wanted to provide the best possible guidance to gastroenterologists based on the available body of literature, with key shifts in diagnosis and management based on currently available modalities and tools,” she said.

The guideline was published in the March issue of the American Journal of Gastroenterology.

The recommendations were developed by a diverse group of authors from across the United States in recognition of the potential influence of commercial and intellectual conflicts of interest. The panel used a systematic process that involved structured literature searches by librarians and independent appraisal of the quality of evidence by dedicated methodologists, the authors write.

Overall, the team outlined 11 recommendations and 12 key concepts. A strong recommendation was made when the benefits of the test or intervention clearly outweighed the potential disadvantages. A conditional recommendation was made when some uncertainty remained about the balance of benefits and harms. Key concepts address important clinical questions that lack adequate evidence to inform recommendations. They are based on indirect evidence and expert opinion.

Epidemiology and diagnosis

The burden of biliary strictures is difficult to estimate, owing to the lack of a specific administrative code. The estimated cost of caring for biliary disease in the United States is about $16.9 billion annually, although this figure includes costs associated with gallbladder disease, choledocholithiasis, and other (nonobstructive) biliary disorders, the authors write.

Among the 57,000 new cases of pancreatic cancer each year, at least 60% will cause obstructive jaundice, resulting in about 34,000 annual cases of malignant extrahepatic biliary stricture, the team notes. In addition, about 3,000 cases of malignant perihilar stricture are expected in the United States each year. Patients may also seek care for benign strictures associated with chronic pancreatitis, primary sclerosing cholangitis, autoimmune disease, and post-cholecystectomy injury.

Under the first key concept, the authors note that biliary strictures in adults are more likely to be malignant than benign, except in certain well-defined scenarios. This underscores the importance of having a high index of clinical suspicion during evaluation, they add.

In general, a definitive tissue diagnosis is necessary to guide oncologic and endoscopic care for most strictures that aren’t surgically resectable at the time of presentation. For patients with extrahepatic biliary stricture due to an apparent or suspected pancreatic mass, endoscopic ultrasound (EUS) with fine-needle sampling (aspiration or biopsy) is recommended over endoscopic retrograde cholangiopancreatography (ERCP) as the preferred method of evaluation for malignancy.

For patients with suspected malignant perihilar stricture, multimodality sampling is recommended over brush cytology alone at the time of the index ERCP.

Guidance on drainage

For management, the principal objective is to restore the physiologic flow of bile into the duodenum. Although there is wide variability in the difficulty and risk of drainage, depending on location and complexity, perihilar strictures are generally more challenging and are riskier to drain than extrahepatic strictures. The goals should be to alleviate symptoms, reduce serum bilirubin to a level such that chemotherapy can be safely administered, and optimize surgical outcomes.

For benign extrahepatic biliary strictures, ERCP is the preferred modality for durable treatment. Fully covered self-expanding metallic stent (SEMS) placement is recommended over multiple plastic stents to reduce the number of procedures required for long-term treatment.

For extrahepatic strictures due to resectable pancreatic cancer or cholangiocarcinoma, the authors recommend against routine preoperative biliary drainage. However, drainage is warranted for some patients, including those with acute cholangitis, severe pruritus, very high serum bilirubin levels, those undergoing neoadjuvant therapy, and those for whom surgery is delayed.

For malignant extrahepatic strictures that are unresectable or borderline resectable, SEMS placement is recommended over plastic stents. The evidence is insufficient to recommend for or against uncovered SEMS versus fully covered SEMS.

For perihilar strictures due to suspected malignancy, the evidence is insufficient to recommend for or against ERCP versus percutaneous transhepatic biliary drainage. In addition, for malignant perihilar strictures, the evidence is insufficient to recommend for or against plastic stents versus uncovered SEMS.

For perihilar strictures due to cholangiocarcinoma in cases in which resection or transplantation is not possible, adjuvant endobiliary ablation plus plastic stent placement is recommended over plastic stent placement alone.

Overall, for patients with a biliary stricture for which ERCP is indicated but is unsuccessful or impossible, EUS-guided biliary access and drainage is recommended over PTBD, because it is associated with fewer adverse events. However, these interventional EUS procedures should be performed by an endoscopist with substantial experience.

“The workup of biliary strictures is challenging, invasive, and costly, requiring multiple diagnostic tools with highly variable yields,” co-author Victoria Gomez, MD, associate professor of medicine and director of bariatric endoscopy at Mayo Clinic, Jacksonville, Fla., said in an interview.

“Providers caring for these patients must be up to date with the most current evidence so that they can make the safest and most well-informed decisions for their patients,” she said. “These include considerations such as limiting the use of anesthesia, using tests that will result in the highest diagnostic yield, and providing effective therapies to decompress biliary obstruction.”

Future questions

Additional research is needed in several areas to strengthen recommendations and advance the field, the study authors write.

“Biliary strictures without an associated mass are a diagnostic challenge, and there are exciting opportunities to understand how new technologies, such as artificial intelligence, can be used to improve our assessment,” co-author Anna Tavakkoli, MD, assistant professor of internal medicine in digestive and liver diseases at the University of Texas Southwestern Medical Center, Dallas, said in an interview.

“Also, we highlighted several controversies in the drainage of perihilar strictures, including whether to use ERCP versus percutaneous drainage, whether metallic or plastic stents are better, and what the optimal stent placement should be,” she said. “Future multicenter studies are needed to address these key controversies.”

Although fully covered SEMS placement remains effective for benign biliary strictures, multiple plastic stents may be a better alternative in some cases. Such cases include those in which the stricture is close to the hilum, those in which the gallbladder is intact and in which crossing the cystic duct orifice cannot be avoided, those in which a fully covered SEMS has previously migrated or was not well tolerated, and those in which stricture has recurred after removal of a fully covered SEMS.

‘Comprehensive list’

“Overall, the authors have done a commendable job putting together a comprehensive list of recommendations that will invariably alter the practice of many therapeutic endoscopists for the diagnosis and management of biliary strictures,” Matthew Fasullo, DO, an advanced endoscopy and gastroenterology fellow at New York University Medical Center, told this news organization.

Dr. Fasullo, who wasn’t involved with the guideline, has published on advances in pathophysiology, diagnosis, and treatment for post-transplant biliary complications.

“The fact that ... cholangioscopy-directed biopsies after an initial negative evaluation via ERCP reveal malignancy in 54% of cases underscores the need for best practice guidelines and supports advancements in diagnostics to confidently rule in or out cancer,” he said.

“The movement toward multimodality sampling at the time of initial evaluation with a combination of brushing, fluoroscopy-directed biopsies, cholangioscopy-directed biopsies, and fluorescence in situ hybridization should become universally adopted in those with an ambiguous diagnosis,” he added. “As technology continues to improve, next-generation sequencing will prove to be an invaluable adjunct to the current pathological evaluation.”

The authors received no financial support for the guideline. One author has a consultant role for Takeda Pharmaceuticals and is an advisory board member role for Advarra. The other authors and Dr. Fasullo have disclosed no relevant financial relationships.

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

To defend the gut from microbes and pathogens, Paneth cells rely on TMEM16A, a calcium-activated chloride channel, and TMEM16F, a phospholipid scramblase, according to a new study published in Gastro Hep Advances.

The Paneth cells in mice missing TMEM16A or TMEM16F showed defects in signaling and release of secretary factors, researchers reported.

Inhibiting or activating TMEM16A and TMEM16F is likely to affect microbial content and immune functions in the small intestine, concluded Rainer Schreiber, Dr. rer. nat., of the Institute of Physiology at Universität Regensburg, Germany, and colleagues.

“Many small molecules and numerous natural or herbal compounds have been identified that either inhibit or activate TMEM16A or TMEM16F,” they wrote. “Some of these compounds may turn out to be useful therapeutics in inflammatory bowel disease, intestinal allergies, or abnormal colonization of the gut.”

Paneth cells play a central role in intestinal innate immune response, the authors wrote. Located at the base of small intestinal crypts and occasionally found in the proximal colon, these cells have defensive functions, such as protecting stem cells in response to invading microbes and eradicating ingested pathogens from intestinal crypts. Through secretion, they also regulate the composition and number of commensal intestinal bacteria. In inflammatory bowel disease, the Paneth cell zone expands due to an increase in cell size and cell number.

In previous studies, cholinergic stimulation provided enhanced protection in animals orally infected with virulent Salmonella enterica. However, the mechanisms of luminal stimulation of Paneth cell secretion in response to bacteria or lipopolysaccharide are unclear. Recent reports show that TMEM16A (also known as anoctamin 1, or ANO1) and TMEM16F (anoctamin 6, or ANO6) control intracellular calcium (Ca2+) signaling and that high local Ca2+ levels support exocytosis in intestinal cells.

The researchers analyzed the roles of the two molecules in Paneth cell secretion using mice with intestinal epithelial-specific knockout of TMEM16A or TMEM16F. They examined tissue structures and Paneth cells in the mice, as well as Paneth cell exocytosis in small intestinal organoids in vitro. They also compared Ca2+ signals between wild-type and knockout mice and analyzed bacterial colonization and intestinal apoptosis.

In wild-type mice, TMEM16A was detected at the apical pole of crypt epithelial cells, while TMEM16F was located predominantly at the basolateral side. Notably, TMEM16A was also located in intestinal smooth muscle cells.

Compared with wild-type mice, the TMEM16 knockout mice had pronounced accumulation of lysozyme in jejunal Paneth cells. This suggests a defect in Paneth cell secretion in the absence of TMEM16A and TMEM16F, the authors wrote.

Previous studies had found an accumulation of mucus in intestinal goblet cells in mice with tissue-specific knockout of TMEM16A and TMEM16F. In this study, a more detailed analysis of mucus using periodic acid-Schiff staining of duodenum, jejunum, and ileum confirmed those results and demonstrated enhanced mucus in the small intestine of knockout mice. This suggests that a lack of TMEM16A or TMEM16F causes a broad secretion defect in secretory cells, including Paneth cells, the authors wrote.

Because granules of Paneth cells contain antimicrobial peptides, cytokines, and other factors that control proliferation or epithelial cell death, the researchers analyzed the presence of Gram-positive and Gram-negative bacteria in the jejunum and ileum. Compared to wild-type mice, the number of bacteria was higher in the ileum of both TMEM16A and TMEM16F knockout mice and in the jejunum of TMEM16F knockout mice, suggesting reduced antimicrobial activity in the absence of TMEM16 proteins.

The researchers also compared regulated cell death of intestinal epithelial cells in jejuna of wild-type and knockout mice. They found largely reduced cell death in both TMEM16A and TMEM16F knockout mice.

“Intestinal inflammatory diseases such as Crohn’s disease, necrotizing enterocolitis, and intestinal microbiota dysbiosis have been related to abnormal Paneth cell physiology,” the authors wrote. “The present findings may therefore provide the basis for a novel anti-inflammatory therapy for intestinal diseases and may improve our understanding of the molecular mechanism of some of the currently available drugs.”

The study was supported by the Deutsche Forschungsgemeinschaft funding program. The authors disclosed no conflicts of interest.

To defend the gut from microbes and pathogens, Paneth cells rely on TMEM16A, a calcium-activated chloride channel, and TMEM16F, a phospholipid scramblase, according to a new study published in Gastro Hep Advances.

The Paneth cells in mice missing TMEM16A or TMEM16F showed defects in signaling and release of secretary factors, researchers reported.

Inhibiting or activating TMEM16A and TMEM16F is likely to affect microbial content and immune functions in the small intestine, concluded Rainer Schreiber, Dr. rer. nat., of the Institute of Physiology at Universität Regensburg, Germany, and colleagues.

“Many small molecules and numerous natural or herbal compounds have been identified that either inhibit or activate TMEM16A or TMEM16F,” they wrote. “Some of these compounds may turn out to be useful therapeutics in inflammatory bowel disease, intestinal allergies, or abnormal colonization of the gut.”

Paneth cells play a central role in intestinal innate immune response, the authors wrote. Located at the base of small intestinal crypts and occasionally found in the proximal colon, these cells have defensive functions, such as protecting stem cells in response to invading microbes and eradicating ingested pathogens from intestinal crypts. Through secretion, they also regulate the composition and number of commensal intestinal bacteria. In inflammatory bowel disease, the Paneth cell zone expands due to an increase in cell size and cell number.

In previous studies, cholinergic stimulation provided enhanced protection in animals orally infected with virulent Salmonella enterica. However, the mechanisms of luminal stimulation of Paneth cell secretion in response to bacteria or lipopolysaccharide are unclear. Recent reports show that TMEM16A (also known as anoctamin 1, or ANO1) and TMEM16F (anoctamin 6, or ANO6) control intracellular calcium (Ca2+) signaling and that high local Ca2+ levels support exocytosis in intestinal cells.

The researchers analyzed the roles of the two molecules in Paneth cell secretion using mice with intestinal epithelial-specific knockout of TMEM16A or TMEM16F. They examined tissue structures and Paneth cells in the mice, as well as Paneth cell exocytosis in small intestinal organoids in vitro. They also compared Ca2+ signals between wild-type and knockout mice and analyzed bacterial colonization and intestinal apoptosis.

In wild-type mice, TMEM16A was detected at the apical pole of crypt epithelial cells, while TMEM16F was located predominantly at the basolateral side. Notably, TMEM16A was also located in intestinal smooth muscle cells.

Compared with wild-type mice, the TMEM16 knockout mice had pronounced accumulation of lysozyme in jejunal Paneth cells. This suggests a defect in Paneth cell secretion in the absence of TMEM16A and TMEM16F, the authors wrote.

Previous studies had found an accumulation of mucus in intestinal goblet cells in mice with tissue-specific knockout of TMEM16A and TMEM16F. In this study, a more detailed analysis of mucus using periodic acid-Schiff staining of duodenum, jejunum, and ileum confirmed those results and demonstrated enhanced mucus in the small intestine of knockout mice. This suggests that a lack of TMEM16A or TMEM16F causes a broad secretion defect in secretory cells, including Paneth cells, the authors wrote.

Because granules of Paneth cells contain antimicrobial peptides, cytokines, and other factors that control proliferation or epithelial cell death, the researchers analyzed the presence of Gram-positive and Gram-negative bacteria in the jejunum and ileum. Compared to wild-type mice, the number of bacteria was higher in the ileum of both TMEM16A and TMEM16F knockout mice and in the jejunum of TMEM16F knockout mice, suggesting reduced antimicrobial activity in the absence of TMEM16 proteins.

The researchers also compared regulated cell death of intestinal epithelial cells in jejuna of wild-type and knockout mice. They found largely reduced cell death in both TMEM16A and TMEM16F knockout mice.

“Intestinal inflammatory diseases such as Crohn’s disease, necrotizing enterocolitis, and intestinal microbiota dysbiosis have been related to abnormal Paneth cell physiology,” the authors wrote. “The present findings may therefore provide the basis for a novel anti-inflammatory therapy for intestinal diseases and may improve our understanding of the molecular mechanism of some of the currently available drugs.”

The study was supported by the Deutsche Forschungsgemeinschaft funding program. The authors disclosed no conflicts of interest.

To defend the gut from microbes and pathogens, Paneth cells rely on TMEM16A, a calcium-activated chloride channel, and TMEM16F, a phospholipid scramblase, according to a new study published in Gastro Hep Advances.

The Paneth cells in mice missing TMEM16A or TMEM16F showed defects in signaling and release of secretary factors, researchers reported.

Inhibiting or activating TMEM16A and TMEM16F is likely to affect microbial content and immune functions in the small intestine, concluded Rainer Schreiber, Dr. rer. nat., of the Institute of Physiology at Universität Regensburg, Germany, and colleagues.

“Many small molecules and numerous natural or herbal compounds have been identified that either inhibit or activate TMEM16A or TMEM16F,” they wrote. “Some of these compounds may turn out to be useful therapeutics in inflammatory bowel disease, intestinal allergies, or abnormal colonization of the gut.”

Paneth cells play a central role in intestinal innate immune response, the authors wrote. Located at the base of small intestinal crypts and occasionally found in the proximal colon, these cells have defensive functions, such as protecting stem cells in response to invading microbes and eradicating ingested pathogens from intestinal crypts. Through secretion, they also regulate the composition and number of commensal intestinal bacteria. In inflammatory bowel disease, the Paneth cell zone expands due to an increase in cell size and cell number.

In previous studies, cholinergic stimulation provided enhanced protection in animals orally infected with virulent Salmonella enterica. However, the mechanisms of luminal stimulation of Paneth cell secretion in response to bacteria or lipopolysaccharide are unclear. Recent reports show that TMEM16A (also known as anoctamin 1, or ANO1) and TMEM16F (anoctamin 6, or ANO6) control intracellular calcium (Ca2+) signaling and that high local Ca2+ levels support exocytosis in intestinal cells.

The researchers analyzed the roles of the two molecules in Paneth cell secretion using mice with intestinal epithelial-specific knockout of TMEM16A or TMEM16F. They examined tissue structures and Paneth cells in the mice, as well as Paneth cell exocytosis in small intestinal organoids in vitro. They also compared Ca2+ signals between wild-type and knockout mice and analyzed bacterial colonization and intestinal apoptosis.

In wild-type mice, TMEM16A was detected at the apical pole of crypt epithelial cells, while TMEM16F was located predominantly at the basolateral side. Notably, TMEM16A was also located in intestinal smooth muscle cells.

Compared with wild-type mice, the TMEM16 knockout mice had pronounced accumulation of lysozyme in jejunal Paneth cells. This suggests a defect in Paneth cell secretion in the absence of TMEM16A and TMEM16F, the authors wrote.

Previous studies had found an accumulation of mucus in intestinal goblet cells in mice with tissue-specific knockout of TMEM16A and TMEM16F. In this study, a more detailed analysis of mucus using periodic acid-Schiff staining of duodenum, jejunum, and ileum confirmed those results and demonstrated enhanced mucus in the small intestine of knockout mice. This suggests that a lack of TMEM16A or TMEM16F causes a broad secretion defect in secretory cells, including Paneth cells, the authors wrote.

Because granules of Paneth cells contain antimicrobial peptides, cytokines, and other factors that control proliferation or epithelial cell death, the researchers analyzed the presence of Gram-positive and Gram-negative bacteria in the jejunum and ileum. Compared to wild-type mice, the number of bacteria was higher in the ileum of both TMEM16A and TMEM16F knockout mice and in the jejunum of TMEM16F knockout mice, suggesting reduced antimicrobial activity in the absence of TMEM16 proteins.

The researchers also compared regulated cell death of intestinal epithelial cells in jejuna of wild-type and knockout mice. They found largely reduced cell death in both TMEM16A and TMEM16F knockout mice.

“Intestinal inflammatory diseases such as Crohn’s disease, necrotizing enterocolitis, and intestinal microbiota dysbiosis have been related to abnormal Paneth cell physiology,” the authors wrote. “The present findings may therefore provide the basis for a novel anti-inflammatory therapy for intestinal diseases and may improve our understanding of the molecular mechanism of some of the currently available drugs.”

The study was supported by the Deutsche Forschungsgemeinschaft funding program. The authors disclosed no conflicts of interest.

Metformin appears to play a role in preventing long COVID when taken early during a COVID-19 infection, according to preprints with The Lancet on SSRN. The preprint hasn’t yet been peer-reviewed or published in a journal.

In particular, metformin led to a 42% drop in long COVID among people who had a mild to moderate COVID-19 infection. 

“Long COVID affects millions of people, and preventing long COVID through a treatment like metformin could prevent significant disruptions in people’s lives,” said lead author Carolyn Bramante, MD, assistant professor of internal medicine and pediatrics at the University of Minnesota, Minneapolis.

Between January 2021 and February 2022, Dr. Bramante and colleagues tested three oral medications – metformin (typically used to treat type 2 diabetes), ivermectin (an antiparasitic), and fluvoxamine (an antidepressant) – in a clinical trial across the United States called COVID-OUT. The people being studied, investigators, care providers, and others involved in the study were blinded to the randomized treatments. The trial was decentralized, with no in-person contact with participants.

The researchers included patients who were aged 30-85 with overweight or obesity, had documentation of a confirmed COVID-19 infection, had fewer than 7 days of symptoms, had no known prior infection, and joined the study within 3 days of their positive test. The study included monthly follow-up for 300 days, and participants indicated whether they received a long COVID diagnosis from a medical doctor, which the researchers confirmed in medical records after participants gave consent.

The medications were prepackaged into pill boxes for fast delivery to participants and to ensure they took the correct number of each type of pill. The packages were sent via same-day courier or overnight shipping.

The metformin doses were doled out over 14 days, with 500 milligrams on the first day, 500 milligrams twice a day for the next 4 days, and then 500 milligrams in the morning and 1,000 milligrams in the evening for the remaining 9 days.

Among the 1,323 people studied, 1,125 agreed to do long-term follow-up for long COVID: 564 in the metformin group and 561 in the blinded placebo group. The average age was 45, and 56% were women, including 7% who were pregnant. 

The average time from the start of symptoms to starting medication was 5 days, and 47% began taking the drug within 4 days or less. About 55% had received the primary COVID-19 vaccination series, including 5.1% who received an initial booster, before enrolling in the study.

Overall, 8.4% of participants reported that a medical provider diagnosed them with long COVID. Of those who took metformin, 6.3% developed long COVID, compared to 10.6% among those who took the identical-matched placebo.

The risk reduction for metformin was 42% versus the placebo, which was consistent across subgroups, including vaccination status and different COVID-19 variants.

When metformin was started less than 4 days after COVID-19 symptoms started, the effect was potentially even greater, with a 64% reduction, as compared with a 36% reduction among those who started metformin after 4 or more days after symptoms.

Neither ivermectin nor fluvoxamine showed any benefits for preventing long COVID.

At the same time, the study authors caution that more research is needed. 

“The COVID-OUT trial does not indicate whether or not metformin would be effective at preventing long COVID if started at the time of emergency department visit or hospitalization for COVID-19, nor whether metformin would be effective as treatment in persons who already have long COVID,” they wrote. “With the burden of long COVID on society, confirmation is urgently needed in a trial that addresses our study’s limitations in order to translate these results into practice and policy.”

Several risk factors for long COVID emerged in the analysis. About 11.1% of the women had a long COVID diagnosis, compared with 4.9% of the men. Also, those who had received at least the primary vaccine series had a lower risk of developing long COVID, at 6.6%, as compared with 10.5% among the unvaccinated. Only 1 of the 57 people who received a booster shot developed long COVID.

Notably, pregnant and lactating people were included in this study, which is important given that pregnant people face higher risks for poor COVID-19 outcomes and are excluded from most nonobstetric clinical trials, the study authors wrote. In this study, they were randomized to metformin or placebo but not ivermectin or fluvoxamine due to limited research about the safety of those drugs during pregnancy and lactation.

The results are now under journal review but show findings consistent with those from other recent studies. Also, in August 2022, the authors published results from COVID-OUT that showed metformin led to a 42% reduction in hospital visits, emergency department visits, and deaths related to severe COVID-19.

“Given the lack of side effects and cost for a 2-week course, I think these data support use of metformin now,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief of Medscape, WebMD’s sister site for health care professionals. 

Dr. Topol, who wasn’t involved with this study, has been a leading voice on COVID-19 research throughout the pandemic. He noted the need for more studies, including a factorial design trial to test metformin and Paxlovid, which has shown promise in preventing long COVID. Dr. Topol also wrote about the preprint in Ground Truths, his online newsletter.

“As I’ve written in the past, I don’t use the term ‘breakthrough’ lightly,” he wrote. “But to see such a pronounced benefit in the current randomized trial of metformin, in the context of its being so safe and low cost, I’d give it a breakthrough categorization.”

Another way to put it, Dr. Topol wrote, is that based on this study, he would take metformin if he became infected with COVID-19. 

Jeremy Faust, MD, an emergency medicine doctor at Brigham and Women’s Hospital in Boston, also wrote about the study in his newsletter, Inside Medicine. He noted that the 42% reduction in long COVID means that 23 COVID-19 patients need to be treated with metformin to prevent one long COVID diagnosis, which is an “important reduction.”

“Bottom line: If a person who meets criteria for obesity or overweight status were to ask me if they should take metformin (for 2 weeks) starting as soon as they learn they have COVID-19, I would say yes in many if not most cases, based on this new data,” he wrote. “This is starting to look like a real win.”

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

Metformin appears to play a role in preventing long COVID when taken early during a COVID-19 infection, according to preprints with The Lancet on SSRN. The preprint hasn’t yet been peer-reviewed or published in a journal.

In particular, metformin led to a 42% drop in long COVID among people who had a mild to moderate COVID-19 infection. 

“Long COVID affects millions of people, and preventing long COVID through a treatment like metformin could prevent significant disruptions in people’s lives,” said lead author Carolyn Bramante, MD, assistant professor of internal medicine and pediatrics at the University of Minnesota, Minneapolis.

Between January 2021 and February 2022, Dr. Bramante and colleagues tested three oral medications – metformin (typically used to treat type 2 diabetes), ivermectin (an antiparasitic), and fluvoxamine (an antidepressant) – in a clinical trial across the United States called COVID-OUT. The people being studied, investigators, care providers, and others involved in the study were blinded to the randomized treatments. The trial was decentralized, with no in-person contact with participants.

The researchers included patients who were aged 30-85 with overweight or obesity, had documentation of a confirmed COVID-19 infection, had fewer than 7 days of symptoms, had no known prior infection, and joined the study within 3 days of their positive test. The study included monthly follow-up for 300 days, and participants indicated whether they received a long COVID diagnosis from a medical doctor, which the researchers confirmed in medical records after participants gave consent.

The medications were prepackaged into pill boxes for fast delivery to participants and to ensure they took the correct number of each type of pill. The packages were sent via same-day courier or overnight shipping.

The metformin doses were doled out over 14 days, with 500 milligrams on the first day, 500 milligrams twice a day for the next 4 days, and then 500 milligrams in the morning and 1,000 milligrams in the evening for the remaining 9 days.

Among the 1,323 people studied, 1,125 agreed to do long-term follow-up for long COVID: 564 in the metformin group and 561 in the blinded placebo group. The average age was 45, and 56% were women, including 7% who were pregnant. 

The average time from the start of symptoms to starting medication was 5 days, and 47% began taking the drug within 4 days or less. About 55% had received the primary COVID-19 vaccination series, including 5.1% who received an initial booster, before enrolling in the study.

Overall, 8.4% of participants reported that a medical provider diagnosed them with long COVID. Of those who took metformin, 6.3% developed long COVID, compared to 10.6% among those who took the identical-matched placebo.

The risk reduction for metformin was 42% versus the placebo, which was consistent across subgroups, including vaccination status and different COVID-19 variants.

When metformin was started less than 4 days after COVID-19 symptoms started, the effect was potentially even greater, with a 64% reduction, as compared with a 36% reduction among those who started metformin after 4 or more days after symptoms.

Neither ivermectin nor fluvoxamine showed any benefits for preventing long COVID.

At the same time, the study authors caution that more research is needed. 

“The COVID-OUT trial does not indicate whether or not metformin would be effective at preventing long COVID if started at the time of emergency department visit or hospitalization for COVID-19, nor whether metformin would be effective as treatment in persons who already have long COVID,” they wrote. “With the burden of long COVID on society, confirmation is urgently needed in a trial that addresses our study’s limitations in order to translate these results into practice and policy.”

Several risk factors for long COVID emerged in the analysis. About 11.1% of the women had a long COVID diagnosis, compared with 4.9% of the men. Also, those who had received at least the primary vaccine series had a lower risk of developing long COVID, at 6.6%, as compared with 10.5% among the unvaccinated. Only 1 of the 57 people who received a booster shot developed long COVID.

Notably, pregnant and lactating people were included in this study, which is important given that pregnant people face higher risks for poor COVID-19 outcomes and are excluded from most nonobstetric clinical trials, the study authors wrote. In this study, they were randomized to metformin or placebo but not ivermectin or fluvoxamine due to limited research about the safety of those drugs during pregnancy and lactation.

The results are now under journal review but show findings consistent with those from other recent studies. Also, in August 2022, the authors published results from COVID-OUT that showed metformin led to a 42% reduction in hospital visits, emergency department visits, and deaths related to severe COVID-19.

“Given the lack of side effects and cost for a 2-week course, I think these data support use of metformin now,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief of Medscape, WebMD’s sister site for health care professionals. 

Dr. Topol, who wasn’t involved with this study, has been a leading voice on COVID-19 research throughout the pandemic. He noted the need for more studies, including a factorial design trial to test metformin and Paxlovid, which has shown promise in preventing long COVID. Dr. Topol also wrote about the preprint in Ground Truths, his online newsletter.

“As I’ve written in the past, I don’t use the term ‘breakthrough’ lightly,” he wrote. “But to see such a pronounced benefit in the current randomized trial of metformin, in the context of its being so safe and low cost, I’d give it a breakthrough categorization.”

Another way to put it, Dr. Topol wrote, is that based on this study, he would take metformin if he became infected with COVID-19. 

Jeremy Faust, MD, an emergency medicine doctor at Brigham and Women’s Hospital in Boston, also wrote about the study in his newsletter, Inside Medicine. He noted that the 42% reduction in long COVID means that 23 COVID-19 patients need to be treated with metformin to prevent one long COVID diagnosis, which is an “important reduction.”

“Bottom line: If a person who meets criteria for obesity or overweight status were to ask me if they should take metformin (for 2 weeks) starting as soon as they learn they have COVID-19, I would say yes in many if not most cases, based on this new data,” he wrote. “This is starting to look like a real win.”

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

Metformin appears to play a role in preventing long COVID when taken early during a COVID-19 infection, according to preprints with The Lancet on SSRN. The preprint hasn’t yet been peer-reviewed or published in a journal.

In particular, metformin led to a 42% drop in long COVID among people who had a mild to moderate COVID-19 infection. 

“Long COVID affects millions of people, and preventing long COVID through a treatment like metformin could prevent significant disruptions in people’s lives,” said lead author Carolyn Bramante, MD, assistant professor of internal medicine and pediatrics at the University of Minnesota, Minneapolis.

Between January 2021 and February 2022, Dr. Bramante and colleagues tested three oral medications – metformin (typically used to treat type 2 diabetes), ivermectin (an antiparasitic), and fluvoxamine (an antidepressant) – in a clinical trial across the United States called COVID-OUT. The people being studied, investigators, care providers, and others involved in the study were blinded to the randomized treatments. The trial was decentralized, with no in-person contact with participants.

The researchers included patients who were aged 30-85 with overweight or obesity, had documentation of a confirmed COVID-19 infection, had fewer than 7 days of symptoms, had no known prior infection, and joined the study within 3 days of their positive test. The study included monthly follow-up for 300 days, and participants indicated whether they received a long COVID diagnosis from a medical doctor, which the researchers confirmed in medical records after participants gave consent.

The medications were prepackaged into pill boxes for fast delivery to participants and to ensure they took the correct number of each type of pill. The packages were sent via same-day courier or overnight shipping.

The metformin doses were doled out over 14 days, with 500 milligrams on the first day, 500 milligrams twice a day for the next 4 days, and then 500 milligrams in the morning and 1,000 milligrams in the evening for the remaining 9 days.

Among the 1,323 people studied, 1,125 agreed to do long-term follow-up for long COVID: 564 in the metformin group and 561 in the blinded placebo group. The average age was 45, and 56% were women, including 7% who were pregnant. 

The average time from the start of symptoms to starting medication was 5 days, and 47% began taking the drug within 4 days or less. About 55% had received the primary COVID-19 vaccination series, including 5.1% who received an initial booster, before enrolling in the study.

Overall, 8.4% of participants reported that a medical provider diagnosed them with long COVID. Of those who took metformin, 6.3% developed long COVID, compared to 10.6% among those who took the identical-matched placebo.

The risk reduction for metformin was 42% versus the placebo, which was consistent across subgroups, including vaccination status and different COVID-19 variants.

When metformin was started less than 4 days after COVID-19 symptoms started, the effect was potentially even greater, with a 64% reduction, as compared with a 36% reduction among those who started metformin after 4 or more days after symptoms.

Neither ivermectin nor fluvoxamine showed any benefits for preventing long COVID.

At the same time, the study authors caution that more research is needed. 

“The COVID-OUT trial does not indicate whether or not metformin would be effective at preventing long COVID if started at the time of emergency department visit or hospitalization for COVID-19, nor whether metformin would be effective as treatment in persons who already have long COVID,” they wrote. “With the burden of long COVID on society, confirmation is urgently needed in a trial that addresses our study’s limitations in order to translate these results into practice and policy.”

Several risk factors for long COVID emerged in the analysis. About 11.1% of the women had a long COVID diagnosis, compared with 4.9% of the men. Also, those who had received at least the primary vaccine series had a lower risk of developing long COVID, at 6.6%, as compared with 10.5% among the unvaccinated. Only 1 of the 57 people who received a booster shot developed long COVID.

Notably, pregnant and lactating people were included in this study, which is important given that pregnant people face higher risks for poor COVID-19 outcomes and are excluded from most nonobstetric clinical trials, the study authors wrote. In this study, they were randomized to metformin or placebo but not ivermectin or fluvoxamine due to limited research about the safety of those drugs during pregnancy and lactation.

The results are now under journal review but show findings consistent with those from other recent studies. Also, in August 2022, the authors published results from COVID-OUT that showed metformin led to a 42% reduction in hospital visits, emergency department visits, and deaths related to severe COVID-19.

“Given the lack of side effects and cost for a 2-week course, I think these data support use of metformin now,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief of Medscape, WebMD’s sister site for health care professionals. 

Dr. Topol, who wasn’t involved with this study, has been a leading voice on COVID-19 research throughout the pandemic. He noted the need for more studies, including a factorial design trial to test metformin and Paxlovid, which has shown promise in preventing long COVID. Dr. Topol also wrote about the preprint in Ground Truths, his online newsletter.

“As I’ve written in the past, I don’t use the term ‘breakthrough’ lightly,” he wrote. “But to see such a pronounced benefit in the current randomized trial of metformin, in the context of its being so safe and low cost, I’d give it a breakthrough categorization.”

Another way to put it, Dr. Topol wrote, is that based on this study, he would take metformin if he became infected with COVID-19. 

Jeremy Faust, MD, an emergency medicine doctor at Brigham and Women’s Hospital in Boston, also wrote about the study in his newsletter, Inside Medicine. He noted that the 42% reduction in long COVID means that 23 COVID-19 patients need to be treated with metformin to prevent one long COVID diagnosis, which is an “important reduction.”

“Bottom line: If a person who meets criteria for obesity or overweight status were to ask me if they should take metformin (for 2 weeks) starting as soon as they learn they have COVID-19, I would say yes in many if not most cases, based on this new data,” he wrote. “This is starting to look like a real win.”

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

Midwives provide safe primary care for pregnant women who are at various levels of medical risk in British Columbia, Canada, new data suggest.

In most cases, for midwifery clients, birth outcomes were similar to or were better than birth outcomes of patients who had physician-led or obstetrician-led care.

In addition, midwifery clients were less likely to experience preterm births or have low-birth-weight babies and to experience cesarean deliveries or births involving instruments.

“Based on previous research, we know that midwives provide safe care for healthy childbearing people or those with no or few risk factors that might complicate the pregnancy or birth,” lead author Kathrin Stoll, PhD, a research associate in the University of British Columbia’s department of family practice, told this news organization.

“What we didn’t know until now is whether midwives provide safe care to people with moderate and high medical risks and what proportion of B.C. [British Columbia] midwifery clients are low, moderate, and high risk,” she said. “This is important to know because of the misperception that midwives only look after low-risk people. This misperception is sometimes used against midwives to justify giving them fewer resources and supports.”

The study was published  in the Canadian Medical Association Journal.
 

Increasing demand

Registered midwives have been part of the health care system in British Columbia since 1998, according to the study authors. The number of pregnant people who are attended by midwives during birth has steadily increased from 4.8% in 2004-2005 to 15.6% in 2019-2020.

The investigators analyzed 2008-2018 data from the British Columbia Perinatal Data Registry, which contains data for 99% of births, including home births. Their analysis included 425,056 births for which a family physician, an obstetrician, or a midwife was listed as the most responsible provider (MRP). The investigators assessed pregnancy risk status (low, moderate, or high), which was determined on the basis of an adapted perinatal risk scoring system used by the Alberta Perinatal Health Program. They estimated the differences in neonatal and maternal outcomes between MRP groups by calculating adjusted absolute and relative risks.

Among the 425,056 births, 63,151 (14.9%) had a midwife as the MRP, 189,679 (44.6%) had a family physician, and 172,226 (40.5%) had an obstetrician. The antenatal risk score ranged from 0 to 23 (median score, 2).

The proportion of births with midwife-led care increased from 9.2% to 19.8% from 2008-2018. In 2018, midwives were listed as the MRP for 24.3% of low-risk, 14.3% of moderate-risk, and 7.9% of high-risk births in the province. This represented an absolute increase of 9.1% for low-risk, 7.7% for moderate-risk, and 5.7% for high-risk births during the study period.

Among the 12,169 at-home births that took place during the study period, 9,776 (80.3%) were low-risk, 2,329 (19.1%) were moderate-risk, and 64 (0.5%) were high-risk births. As the risk score increased, so did the proportion of midwifery and family physician clients who were delivered by obstetricians. Across all risk strata, more family physician clients than midwifery clients underwent deliveries by obstetricians.

Overall, the risk of perinatal death for midwifery clients was similar to the risk for those under the care of family physicians across all risk levels. Low- and moderate-risk clients with midwife-led care were significantly less likely to experience a perinatal death, compared with those with obstetrician-led care, although the adjusted absolute risk differences were small. In the high-risk group, there was no significant difference in the rate of perinatal deaths between midwife-led and physician-led care.

In addition, clients with midwife-led care were significantly less likely to experience preterm birth and have a low-birth-weight baby regardless of medical risk level. The adjusted relative risk of an Apgar score of less than 7 at 5 minutes was significantly lower for midwife-led care than for physician-led care for nearly all comparisons.

The cesarean delivery rate among midwifery clients in the low-risk group was 7.2%, compared with 12.2% for family physicians and 42.3% for obstetrician clients. Cesarean delivery rates increased for midwifery clients as medical risk increased but were significantly lower than the physician rates across all medical risk levels.

Among low-risk clients, the absolute risk reduction for cesarean delivery was 34.4% with midwife-led care, compared with obstetrician-led care. The absolute risk difference increased to 55.3% for moderate-risk clients and to 42.2% for high-risk clients.
 

Labor induction varied

Although low-risk midwifery clients were significantly less likely to experience labor induction with oxytocin, high-risk midwifery clients were more than twice as likely to undergo induction with oxytocin than obstetrician clients (adjusted absolute difference, 11.3%).

For most risk levels, midwifery clients were less likely to have an assisted vaginal birth than physician clients, and they were significantly more likely to have a spontaneous vaginal birth. Low-risk clients who had a midwife as the MRP were nearly twice as likely to have a spontaneous vaginal birth than obstetricians’ clients, and moderate-risk clients were nearly four times as likely to have a spontaneous vaginal birth.

The rates of vaginal birth after cesarean delivery (VBAC) were significantly higher when a midwife was the MRP. In comparing midwifery clients with family physician clients, the relative and absolute differences were small, but they were larger when comparing midwifery clients with obstetrician clients. Among low-risk clients, the VBAC rate was 85.3% among midwifery clients, compared with 78.6% among family physician clients and 51.5% among obstetrician clients.

In general, the prevalence rates of adverse maternal outcomes (including blood transfusion, intensive care admissions, uterine rupture, and postpartum wound infection) were low for midwifery clients across all risk levels.

Breast- or chest-feeding at birth was significantly more common among midwifery clients across all risk levels as well.

Today, nearly 1 in 4 childbearing people in British Columbia receive care from a midwife at some point during pregnancy, birth, or the postpartum period, the study authors write. During the past 20 years, the profile of clients has evolved to include more moderate- and high-risk patients.

“Clients with more complex medical needs take more time and need more support,” said Dr. Stoll. “This means that midwives continue to stay on call, responding to pages and urgent medical concerns for their clients with no pay for being on call, no days off even for sick days, and unsafe working hours, often working more than 24 hours at a time. If we want to expand midwifery to communities where they are needed most, we need to provide an enabling environment.”

Additional studies are needed as to how different practice and remuneration models affect clinical outcomes, health care costs, and client and provider experiences, the study authors write. At the same time, there are several barriers to obtaining funding, conducting studies, and publishing research by and about midwives in Canada, Dr. Stoll said – barriers that she and her co-authors faced.
 

Seeking broader access

Alixandra Bacon, a registered midwife and president of the Canadian Association of Midwives, said, “These findings demonstrate that pregnant people at any level of medical risk can benefit from midwifery care. This is a testament both to the benefits of the Canadian midwifery model of care and to the seamless integration of midwifery into collaborative teams and the health system.” Ms. Bacon wasn’t involved with this study.

“If we can realize our goal of equitable access to midwifery care for all families in Canada, we can help to decrease rates of unnecessary medical intervention, preterm labor, and stillbirth,” she added.

“Midwifery is well established across most of Canada. This is yet one more piece of evidence that shows the clinical benefits of midwifery care,” Jasmin Tecson, a registered midwife and president of the Association of Ontario Midwives, said in an interview.

Ms. Tecson, who wasn’t involved with this study, noted the increasing number of clients with more complex health and social needs in Ontario. “It is time to think about how the skills and knowledge of midwives can be used with clients of different risk profiles and how the current scope of practice of midwives can be optimized and expanded,” she said. “For example, Ontario midwives are still required to prescribe medications from a limited list, despite the potential additional clinical risks and health system costs that this creates.”

The study received financial support from the University of British Columbia Stollery Fund and the University of British Columbia Work Learn Program. Dr. Stoll has an unpaid role with the Midwives Association Contract Negotiation Advisory Council. Ms. Bacon and Ms. Tecson disclosed no relevant financial relationships.

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

Midwives provide safe primary care for pregnant women who are at various levels of medical risk in British Columbia, Canada, new data suggest.

In most cases, for midwifery clients, birth outcomes were similar to or were better than birth outcomes of patients who had physician-led or obstetrician-led care.

In addition, midwifery clients were less likely to experience preterm births or have low-birth-weight babies and to experience cesarean deliveries or births involving instruments.

“Based on previous research, we know that midwives provide safe care for healthy childbearing people or those with no or few risk factors that might complicate the pregnancy or birth,” lead author Kathrin Stoll, PhD, a research associate in the University of British Columbia’s department of family practice, told this news organization.

“What we didn’t know until now is whether midwives provide safe care to people with moderate and high medical risks and what proportion of B.C. [British Columbia] midwifery clients are low, moderate, and high risk,” she said. “This is important to know because of the misperception that midwives only look after low-risk people. This misperception is sometimes used against midwives to justify giving them fewer resources and supports.”

The study was published  in the Canadian Medical Association Journal.
 

Increasing demand

Registered midwives have been part of the health care system in British Columbia since 1998, according to the study authors. The number of pregnant people who are attended by midwives during birth has steadily increased from 4.8% in 2004-2005 to 15.6% in 2019-2020.

The investigators analyzed 2008-2018 data from the British Columbia Perinatal Data Registry, which contains data for 99% of births, including home births. Their analysis included 425,056 births for which a family physician, an obstetrician, or a midwife was listed as the most responsible provider (MRP). The investigators assessed pregnancy risk status (low, moderate, or high), which was determined on the basis of an adapted perinatal risk scoring system used by the Alberta Perinatal Health Program. They estimated the differences in neonatal and maternal outcomes between MRP groups by calculating adjusted absolute and relative risks.

Among the 425,056 births, 63,151 (14.9%) had a midwife as the MRP, 189,679 (44.6%) had a family physician, and 172,226 (40.5%) had an obstetrician. The antenatal risk score ranged from 0 to 23 (median score, 2).

The proportion of births with midwife-led care increased from 9.2% to 19.8% from 2008-2018. In 2018, midwives were listed as the MRP for 24.3% of low-risk, 14.3% of moderate-risk, and 7.9% of high-risk births in the province. This represented an absolute increase of 9.1% for low-risk, 7.7% for moderate-risk, and 5.7% for high-risk births during the study period.

Among the 12,169 at-home births that took place during the study period, 9,776 (80.3%) were low-risk, 2,329 (19.1%) were moderate-risk, and 64 (0.5%) were high-risk births. As the risk score increased, so did the proportion of midwifery and family physician clients who were delivered by obstetricians. Across all risk strata, more family physician clients than midwifery clients underwent deliveries by obstetricians.

Overall, the risk of perinatal death for midwifery clients was similar to the risk for those under the care of family physicians across all risk levels. Low- and moderate-risk clients with midwife-led care were significantly less likely to experience a perinatal death, compared with those with obstetrician-led care, although the adjusted absolute risk differences were small. In the high-risk group, there was no significant difference in the rate of perinatal deaths between midwife-led and physician-led care.

In addition, clients with midwife-led care were significantly less likely to experience preterm birth and have a low-birth-weight baby regardless of medical risk level. The adjusted relative risk of an Apgar score of less than 7 at 5 minutes was significantly lower for midwife-led care than for physician-led care for nearly all comparisons.

The cesarean delivery rate among midwifery clients in the low-risk group was 7.2%, compared with 12.2% for family physicians and 42.3% for obstetrician clients. Cesarean delivery rates increased for midwifery clients as medical risk increased but were significantly lower than the physician rates across all medical risk levels.

Among low-risk clients, the absolute risk reduction for cesarean delivery was 34.4% with midwife-led care, compared with obstetrician-led care. The absolute risk difference increased to 55.3% for moderate-risk clients and to 42.2% for high-risk clients.
 

Labor induction varied

Although low-risk midwifery clients were significantly less likely to experience labor induction with oxytocin, high-risk midwifery clients were more than twice as likely to undergo induction with oxytocin than obstetrician clients (adjusted absolute difference, 11.3%).

For most risk levels, midwifery clients were less likely to have an assisted vaginal birth than physician clients, and they were significantly more likely to have a spontaneous vaginal birth. Low-risk clients who had a midwife as the MRP were nearly twice as likely to have a spontaneous vaginal birth than obstetricians’ clients, and moderate-risk clients were nearly four times as likely to have a spontaneous vaginal birth.

The rates of vaginal birth after cesarean delivery (VBAC) were significantly higher when a midwife was the MRP. In comparing midwifery clients with family physician clients, the relative and absolute differences were small, but they were larger when comparing midwifery clients with obstetrician clients. Among low-risk clients, the VBAC rate was 85.3% among midwifery clients, compared with 78.6% among family physician clients and 51.5% among obstetrician clients.

In general, the prevalence rates of adverse maternal outcomes (including blood transfusion, intensive care admissions, uterine rupture, and postpartum wound infection) were low for midwifery clients across all risk levels.

Breast- or chest-feeding at birth was significantly more common among midwifery clients across all risk levels as well.

Today, nearly 1 in 4 childbearing people in British Columbia receive care from a midwife at some point during pregnancy, birth, or the postpartum period, the study authors write. During the past 20 years, the profile of clients has evolved to include more moderate- and high-risk patients.

“Clients with more complex medical needs take more time and need more support,” said Dr. Stoll. “This means that midwives continue to stay on call, responding to pages and urgent medical concerns for their clients with no pay for being on call, no days off even for sick days, and unsafe working hours, often working more than 24 hours at a time. If we want to expand midwifery to communities where they are needed most, we need to provide an enabling environment.”

Additional studies are needed as to how different practice and remuneration models affect clinical outcomes, health care costs, and client and provider experiences, the study authors write. At the same time, there are several barriers to obtaining funding, conducting studies, and publishing research by and about midwives in Canada, Dr. Stoll said – barriers that she and her co-authors faced.
 

Seeking broader access

Alixandra Bacon, a registered midwife and president of the Canadian Association of Midwives, said, “These findings demonstrate that pregnant people at any level of medical risk can benefit from midwifery care. This is a testament both to the benefits of the Canadian midwifery model of care and to the seamless integration of midwifery into collaborative teams and the health system.” Ms. Bacon wasn’t involved with this study.

“If we can realize our goal of equitable access to midwifery care for all families in Canada, we can help to decrease rates of unnecessary medical intervention, preterm labor, and stillbirth,” she added.

“Midwifery is well established across most of Canada. This is yet one more piece of evidence that shows the clinical benefits of midwifery care,” Jasmin Tecson, a registered midwife and president of the Association of Ontario Midwives, said in an interview.

Ms. Tecson, who wasn’t involved with this study, noted the increasing number of clients with more complex health and social needs in Ontario. “It is time to think about how the skills and knowledge of midwives can be used with clients of different risk profiles and how the current scope of practice of midwives can be optimized and expanded,” she said. “For example, Ontario midwives are still required to prescribe medications from a limited list, despite the potential additional clinical risks and health system costs that this creates.”

The study received financial support from the University of British Columbia Stollery Fund and the University of British Columbia Work Learn Program. Dr. Stoll has an unpaid role with the Midwives Association Contract Negotiation Advisory Council. Ms. Bacon and Ms. Tecson disclosed no relevant financial relationships.

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

Midwives provide safe primary care for pregnant women who are at various levels of medical risk in British Columbia, Canada, new data suggest.

In most cases, for midwifery clients, birth outcomes were similar to or were better than birth outcomes of patients who had physician-led or obstetrician-led care.

In addition, midwifery clients were less likely to experience preterm births or have low-birth-weight babies and to experience cesarean deliveries or births involving instruments.

“Based on previous research, we know that midwives provide safe care for healthy childbearing people or those with no or few risk factors that might complicate the pregnancy or birth,” lead author Kathrin Stoll, PhD, a research associate in the University of British Columbia’s department of family practice, told this news organization.

“What we didn’t know until now is whether midwives provide safe care to people with moderate and high medical risks and what proportion of B.C. [British Columbia] midwifery clients are low, moderate, and high risk,” she said. “This is important to know because of the misperception that midwives only look after low-risk people. This misperception is sometimes used against midwives to justify giving them fewer resources and supports.”

The study was published  in the Canadian Medical Association Journal.
 

Increasing demand

Registered midwives have been part of the health care system in British Columbia since 1998, according to the study authors. The number of pregnant people who are attended by midwives during birth has steadily increased from 4.8% in 2004-2005 to 15.6% in 2019-2020.

The investigators analyzed 2008-2018 data from the British Columbia Perinatal Data Registry, which contains data for 99% of births, including home births. Their analysis included 425,056 births for which a family physician, an obstetrician, or a midwife was listed as the most responsible provider (MRP). The investigators assessed pregnancy risk status (low, moderate, or high), which was determined on the basis of an adapted perinatal risk scoring system used by the Alberta Perinatal Health Program. They estimated the differences in neonatal and maternal outcomes between MRP groups by calculating adjusted absolute and relative risks.

Among the 425,056 births, 63,151 (14.9%) had a midwife as the MRP, 189,679 (44.6%) had a family physician, and 172,226 (40.5%) had an obstetrician. The antenatal risk score ranged from 0 to 23 (median score, 2).

The proportion of births with midwife-led care increased from 9.2% to 19.8% from 2008-2018. In 2018, midwives were listed as the MRP for 24.3% of low-risk, 14.3% of moderate-risk, and 7.9% of high-risk births in the province. This represented an absolute increase of 9.1% for low-risk, 7.7% for moderate-risk, and 5.7% for high-risk births during the study period.

Among the 12,169 at-home births that took place during the study period, 9,776 (80.3%) were low-risk, 2,329 (19.1%) were moderate-risk, and 64 (0.5%) were high-risk births. As the risk score increased, so did the proportion of midwifery and family physician clients who were delivered by obstetricians. Across all risk strata, more family physician clients than midwifery clients underwent deliveries by obstetricians.

Overall, the risk of perinatal death for midwifery clients was similar to the risk for those under the care of family physicians across all risk levels. Low- and moderate-risk clients with midwife-led care were significantly less likely to experience a perinatal death, compared with those with obstetrician-led care, although the adjusted absolute risk differences were small. In the high-risk group, there was no significant difference in the rate of perinatal deaths between midwife-led and physician-led care.

In addition, clients with midwife-led care were significantly less likely to experience preterm birth and have a low-birth-weight baby regardless of medical risk level. The adjusted relative risk of an Apgar score of less than 7 at 5 minutes was significantly lower for midwife-led care than for physician-led care for nearly all comparisons.

The cesarean delivery rate among midwifery clients in the low-risk group was 7.2%, compared with 12.2% for family physicians and 42.3% for obstetrician clients. Cesarean delivery rates increased for midwifery clients as medical risk increased but were significantly lower than the physician rates across all medical risk levels.

Among low-risk clients, the absolute risk reduction for cesarean delivery was 34.4% with midwife-led care, compared with obstetrician-led care. The absolute risk difference increased to 55.3% for moderate-risk clients and to 42.2% for high-risk clients.
 

Labor induction varied

Although low-risk midwifery clients were significantly less likely to experience labor induction with oxytocin, high-risk midwifery clients were more than twice as likely to undergo induction with oxytocin than obstetrician clients (adjusted absolute difference, 11.3%).

For most risk levels, midwifery clients were less likely to have an assisted vaginal birth than physician clients, and they were significantly more likely to have a spontaneous vaginal birth. Low-risk clients who had a midwife as the MRP were nearly twice as likely to have a spontaneous vaginal birth than obstetricians’ clients, and moderate-risk clients were nearly four times as likely to have a spontaneous vaginal birth.

The rates of vaginal birth after cesarean delivery (VBAC) were significantly higher when a midwife was the MRP. In comparing midwifery clients with family physician clients, the relative and absolute differences were small, but they were larger when comparing midwifery clients with obstetrician clients. Among low-risk clients, the VBAC rate was 85.3% among midwifery clients, compared with 78.6% among family physician clients and 51.5% among obstetrician clients.

In general, the prevalence rates of adverse maternal outcomes (including blood transfusion, intensive care admissions, uterine rupture, and postpartum wound infection) were low for midwifery clients across all risk levels.

Breast- or chest-feeding at birth was significantly more common among midwifery clients across all risk levels as well.

Today, nearly 1 in 4 childbearing people in British Columbia receive care from a midwife at some point during pregnancy, birth, or the postpartum period, the study authors write. During the past 20 years, the profile of clients has evolved to include more moderate- and high-risk patients.

“Clients with more complex medical needs take more time and need more support,” said Dr. Stoll. “This means that midwives continue to stay on call, responding to pages and urgent medical concerns for their clients with no pay for being on call, no days off even for sick days, and unsafe working hours, often working more than 24 hours at a time. If we want to expand midwifery to communities where they are needed most, we need to provide an enabling environment.”

Additional studies are needed as to how different practice and remuneration models affect clinical outcomes, health care costs, and client and provider experiences, the study authors write. At the same time, there are several barriers to obtaining funding, conducting studies, and publishing research by and about midwives in Canada, Dr. Stoll said – barriers that she and her co-authors faced.
 

Seeking broader access

Alixandra Bacon, a registered midwife and president of the Canadian Association of Midwives, said, “These findings demonstrate that pregnant people at any level of medical risk can benefit from midwifery care. This is a testament both to the benefits of the Canadian midwifery model of care and to the seamless integration of midwifery into collaborative teams and the health system.” Ms. Bacon wasn’t involved with this study.

“If we can realize our goal of equitable access to midwifery care for all families in Canada, we can help to decrease rates of unnecessary medical intervention, preterm labor, and stillbirth,” she added.

“Midwifery is well established across most of Canada. This is yet one more piece of evidence that shows the clinical benefits of midwifery care,” Jasmin Tecson, a registered midwife and president of the Association of Ontario Midwives, said in an interview.

Ms. Tecson, who wasn’t involved with this study, noted the increasing number of clients with more complex health and social needs in Ontario. “It is time to think about how the skills and knowledge of midwives can be used with clients of different risk profiles and how the current scope of practice of midwives can be optimized and expanded,” she said. “For example, Ontario midwives are still required to prescribe medications from a limited list, despite the potential additional clinical risks and health system costs that this creates.”

The study received financial support from the University of British Columbia Stollery Fund and the University of British Columbia Work Learn Program. Dr. Stoll has an unpaid role with the Midwives Association Contract Negotiation Advisory Council. Ms. Bacon and Ms. Tecson disclosed no relevant financial relationships.

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

For adults with eosinophilic esophagitis (EoE), eliminating animal milk alone appears to be as effective for treating the disease as forgoing milk and five other foods, according to a new report.

A one-food elimination diet (1FED) led to histologic remission in 34% of patients, as determined on the basis of eosinophil count at 6 weeks, and in 40% of patients who followed a six-food elimination diet (6FED) – a nonstatistical difference, the research team wrote.

“The takeaway message is that one-food (milk) elimination is an effective treatment and a reasonable first-line treatment for EoE,” senior study author Marc Rothenberg, MD, PhD, a professor of pediatrics and director of the allergy and immunology division at the Cincinnati Center for Eosinophilic Disorders at Cincinnati Children’s Hospital Medical Center, said in an interview.

“The study was designed by the Consortium of Eosinophilic Disease Researchers (CEGIR), which includes the nation’s top institutions working with patient advocacy groups, together with the National Institutes of Health,” he said. “The group, under advice from patients, determined that it was an important question to research if one-food elimination would be effective – and how effective – compared with six-food elimination.”

The study was published in The Lancet Gastroenterology and Hepatology.
 

Studying EOE and food elimination

Previous studies have found that eliminating six common foods that trigger esophageal injury – milk, eggs, wheat, soy, fish, and nuts – can substantially reduce EoE symptoms. The 6FED has become a common approach to managing the disease.

In recent years, however, researchers have conducted small, nonrandomized studies of the less restrictive 1FED and have found some success.

In a multisite, randomized trial, Dr. Rothenberg and colleagues compared the 6FED with the 1FED among 129 adults aged 18-60 years with a confirmed EoE diagnosis, active EoE symptoms, and a high number of eosinophils in esophageal tissue. The participants enrolled at 1 of 10 U.S. medical centers that participate in CEGIR, which is part of the NIH-funded Rare Diseases Clinical Research Network.

Between 2016 and 2019, 67 participants were assigned to the 1FED group, which eliminated only animal milk from the diet, and 62 participants were assigned to the 6FED group, which eliminated milk, eggs, wheat, soy, fish/shellfish, and peanuts/tree nuts. After following the diet for 6 weeks, participants underwent an upper endoscopy exam and esophageal tissue biopsy. The primary endpoint was the proportion of patients with histologic remission, or a peak count of less than 15 eosinophils per high-power field (eos/hpf).

If the number of eosinophils indicated that EoE was in remission, the participant exited the study. If EoE wasn’t in remission, those who were on 1FED could proceed to 6FED, and those who were on 6FED could take fluticasone propionate 880 mcg two times per day with an unrestricted diet. Both groups followed the protocols for 6 weeks and underwent another exam with tissue biopsy.

At 6 weeks, 25 patients (40%) on 6FED and 23 patients (34%) on 1FED achieved histologic remission. The difference was not statistically significant.

There were also no significant differences between the groups at stricter thresholds for partial remission, defined as peak counts of 10 eos/hpf or less and 6 eos/hpf or less. The rate of complete remission (at a peak count of ≤ 1 eos/hpf) favored 6FED, at 19% versus 6% among 1FED.

The two diets had a similar impact across several other measures, including reduction in peak eosinophil counts, reduction in EoE symptoms, and improvement in quality of life. For 6FED versus 1FED, the mean changes from baseline in the Eosinophilic Esophagitis Histology Scoring System were –0.23 versus –0.15. In addition, the mean changes in the Eosinophilic Esophagitis Endoscopic Reference Score were 1 versus –0.6, and in the Eosinophilic Esophagitis Activity Index, they were –8.2 versus –3. None of the differences were significant.

Among the patients who didn’t respond to 1FED, 21 opted to follow 6FED in the study’s second phase. Of those patients, nine (43%) attained remission after following the more restrictive diet. Among the 11 patients who didn’t initially respond to 6FED and who opted to receive fluticasone propionate, nine patients (82%) achieved remission.

“We examined a series of validated endpoints that have not previously been examined in diet trials,” Dr. Rothenberg said. “We are surprised to see that one food was equally effective as six foods.”
 

Incorporating food elimination therapy

Dr. Rothenberg and colleagues are continuing their research into EoE and food-elimination diets, with a strong focus on furthering diet therapy. In particular, the research team wants to understand how to potentially add milk – and other foods – back to the diet.

Wael Sayej, MD, associate professor of pediatrics at the University of Massachusetts Baystate Regional Campus, Springfield, has found success with the one-food elimination diet among children with EoE, he said in an interview.

In a retrospective study, Dr. Sayej and colleagues found that a one-food elimination diet was an effective first-line treatment option for pediatric patients.

“Once we get past the one-food or two-food elimination, it becomes much more difficult and cumbersome for patients to follow,” said Dr. Sayej, who is also a pediatric gastroenterologist with Baystate Health in Springfield and who wasn’t involved with the CEGIR study. “Obviously, I prefer my patients to follow a strict dairy-free diet as long-term therapy, rather than have them on a medication for the rest of their life.”

Dr. Sayej advises patients to follow the one-food elimination diet in his practice. If patients aren’t responsive, he offers options for additional dietary elimination or initiation of steroid therapy.

“The most important thing about initiating dietary elimination therapy is to take the time to educate the patient and family about the disease, the risks or complications associated with untreated disease, and the pros and cons of the treatment options,” he said.

The study was cofunded by the National Institute of Allergy and Infectious Diseases, the National Center for Advancing Translational Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have research, consultant, and leadership relationships with several pharmaceutical companies and organizations not related to this study. Dr. Sayej disclosed no relevant financial relationships.
 

For adults with eosinophilic esophagitis (EoE), eliminating animal milk alone appears to be as effective for treating the disease as forgoing milk and five other foods, according to a new report.

A one-food elimination diet (1FED) led to histologic remission in 34% of patients, as determined on the basis of eosinophil count at 6 weeks, and in 40% of patients who followed a six-food elimination diet (6FED) – a nonstatistical difference, the research team wrote.

“The takeaway message is that one-food (milk) elimination is an effective treatment and a reasonable first-line treatment for EoE,” senior study author Marc Rothenberg, MD, PhD, a professor of pediatrics and director of the allergy and immunology division at the Cincinnati Center for Eosinophilic Disorders at Cincinnati Children’s Hospital Medical Center, said in an interview.

“The study was designed by the Consortium of Eosinophilic Disease Researchers (CEGIR), which includes the nation’s top institutions working with patient advocacy groups, together with the National Institutes of Health,” he said. “The group, under advice from patients, determined that it was an important question to research if one-food elimination would be effective – and how effective – compared with six-food elimination.”

The study was published in The Lancet Gastroenterology and Hepatology.
 

Studying EOE and food elimination

Previous studies have found that eliminating six common foods that trigger esophageal injury – milk, eggs, wheat, soy, fish, and nuts – can substantially reduce EoE symptoms. The 6FED has become a common approach to managing the disease.

In recent years, however, researchers have conducted small, nonrandomized studies of the less restrictive 1FED and have found some success.

In a multisite, randomized trial, Dr. Rothenberg and colleagues compared the 6FED with the 1FED among 129 adults aged 18-60 years with a confirmed EoE diagnosis, active EoE symptoms, and a high number of eosinophils in esophageal tissue. The participants enrolled at 1 of 10 U.S. medical centers that participate in CEGIR, which is part of the NIH-funded Rare Diseases Clinical Research Network.

Between 2016 and 2019, 67 participants were assigned to the 1FED group, which eliminated only animal milk from the diet, and 62 participants were assigned to the 6FED group, which eliminated milk, eggs, wheat, soy, fish/shellfish, and peanuts/tree nuts. After following the diet for 6 weeks, participants underwent an upper endoscopy exam and esophageal tissue biopsy. The primary endpoint was the proportion of patients with histologic remission, or a peak count of less than 15 eosinophils per high-power field (eos/hpf).

If the number of eosinophils indicated that EoE was in remission, the participant exited the study. If EoE wasn’t in remission, those who were on 1FED could proceed to 6FED, and those who were on 6FED could take fluticasone propionate 880 mcg two times per day with an unrestricted diet. Both groups followed the protocols for 6 weeks and underwent another exam with tissue biopsy.

At 6 weeks, 25 patients (40%) on 6FED and 23 patients (34%) on 1FED achieved histologic remission. The difference was not statistically significant.

There were also no significant differences between the groups at stricter thresholds for partial remission, defined as peak counts of 10 eos/hpf or less and 6 eos/hpf or less. The rate of complete remission (at a peak count of ≤ 1 eos/hpf) favored 6FED, at 19% versus 6% among 1FED.

The two diets had a similar impact across several other measures, including reduction in peak eosinophil counts, reduction in EoE symptoms, and improvement in quality of life. For 6FED versus 1FED, the mean changes from baseline in the Eosinophilic Esophagitis Histology Scoring System were –0.23 versus –0.15. In addition, the mean changes in the Eosinophilic Esophagitis Endoscopic Reference Score were 1 versus –0.6, and in the Eosinophilic Esophagitis Activity Index, they were –8.2 versus –3. None of the differences were significant.

Among the patients who didn’t respond to 1FED, 21 opted to follow 6FED in the study’s second phase. Of those patients, nine (43%) attained remission after following the more restrictive diet. Among the 11 patients who didn’t initially respond to 6FED and who opted to receive fluticasone propionate, nine patients (82%) achieved remission.

“We examined a series of validated endpoints that have not previously been examined in diet trials,” Dr. Rothenberg said. “We are surprised to see that one food was equally effective as six foods.”
 

Incorporating food elimination therapy

Dr. Rothenberg and colleagues are continuing their research into EoE and food-elimination diets, with a strong focus on furthering diet therapy. In particular, the research team wants to understand how to potentially add milk – and other foods – back to the diet.

Wael Sayej, MD, associate professor of pediatrics at the University of Massachusetts Baystate Regional Campus, Springfield, has found success with the one-food elimination diet among children with EoE, he said in an interview.

In a retrospective study, Dr. Sayej and colleagues found that a one-food elimination diet was an effective first-line treatment option for pediatric patients.

“Once we get past the one-food or two-food elimination, it becomes much more difficult and cumbersome for patients to follow,” said Dr. Sayej, who is also a pediatric gastroenterologist with Baystate Health in Springfield and who wasn’t involved with the CEGIR study. “Obviously, I prefer my patients to follow a strict dairy-free diet as long-term therapy, rather than have them on a medication for the rest of their life.”

Dr. Sayej advises patients to follow the one-food elimination diet in his practice. If patients aren’t responsive, he offers options for additional dietary elimination or initiation of steroid therapy.

“The most important thing about initiating dietary elimination therapy is to take the time to educate the patient and family about the disease, the risks or complications associated with untreated disease, and the pros and cons of the treatment options,” he said.

The study was cofunded by the National Institute of Allergy and Infectious Diseases, the National Center for Advancing Translational Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have research, consultant, and leadership relationships with several pharmaceutical companies and organizations not related to this study. Dr. Sayej disclosed no relevant financial relationships.
 

For adults with eosinophilic esophagitis (EoE), eliminating animal milk alone appears to be as effective for treating the disease as forgoing milk and five other foods, according to a new report.

A one-food elimination diet (1FED) led to histologic remission in 34% of patients, as determined on the basis of eosinophil count at 6 weeks, and in 40% of patients who followed a six-food elimination diet (6FED) – a nonstatistical difference, the research team wrote.

“The takeaway message is that one-food (milk) elimination is an effective treatment and a reasonable first-line treatment for EoE,” senior study author Marc Rothenberg, MD, PhD, a professor of pediatrics and director of the allergy and immunology division at the Cincinnati Center for Eosinophilic Disorders at Cincinnati Children’s Hospital Medical Center, said in an interview.

“The study was designed by the Consortium of Eosinophilic Disease Researchers (CEGIR), which includes the nation’s top institutions working with patient advocacy groups, together with the National Institutes of Health,” he said. “The group, under advice from patients, determined that it was an important question to research if one-food elimination would be effective – and how effective – compared with six-food elimination.”

The study was published in The Lancet Gastroenterology and Hepatology.
 

Studying EOE and food elimination

Previous studies have found that eliminating six common foods that trigger esophageal injury – milk, eggs, wheat, soy, fish, and nuts – can substantially reduce EoE symptoms. The 6FED has become a common approach to managing the disease.

In recent years, however, researchers have conducted small, nonrandomized studies of the less restrictive 1FED and have found some success.

In a multisite, randomized trial, Dr. Rothenberg and colleagues compared the 6FED with the 1FED among 129 adults aged 18-60 years with a confirmed EoE diagnosis, active EoE symptoms, and a high number of eosinophils in esophageal tissue. The participants enrolled at 1 of 10 U.S. medical centers that participate in CEGIR, which is part of the NIH-funded Rare Diseases Clinical Research Network.

Between 2016 and 2019, 67 participants were assigned to the 1FED group, which eliminated only animal milk from the diet, and 62 participants were assigned to the 6FED group, which eliminated milk, eggs, wheat, soy, fish/shellfish, and peanuts/tree nuts. After following the diet for 6 weeks, participants underwent an upper endoscopy exam and esophageal tissue biopsy. The primary endpoint was the proportion of patients with histologic remission, or a peak count of less than 15 eosinophils per high-power field (eos/hpf).

If the number of eosinophils indicated that EoE was in remission, the participant exited the study. If EoE wasn’t in remission, those who were on 1FED could proceed to 6FED, and those who were on 6FED could take fluticasone propionate 880 mcg two times per day with an unrestricted diet. Both groups followed the protocols for 6 weeks and underwent another exam with tissue biopsy.

At 6 weeks, 25 patients (40%) on 6FED and 23 patients (34%) on 1FED achieved histologic remission. The difference was not statistically significant.

There were also no significant differences between the groups at stricter thresholds for partial remission, defined as peak counts of 10 eos/hpf or less and 6 eos/hpf or less. The rate of complete remission (at a peak count of ≤ 1 eos/hpf) favored 6FED, at 19% versus 6% among 1FED.

The two diets had a similar impact across several other measures, including reduction in peak eosinophil counts, reduction in EoE symptoms, and improvement in quality of life. For 6FED versus 1FED, the mean changes from baseline in the Eosinophilic Esophagitis Histology Scoring System were –0.23 versus –0.15. In addition, the mean changes in the Eosinophilic Esophagitis Endoscopic Reference Score were 1 versus –0.6, and in the Eosinophilic Esophagitis Activity Index, they were –8.2 versus –3. None of the differences were significant.

Among the patients who didn’t respond to 1FED, 21 opted to follow 6FED in the study’s second phase. Of those patients, nine (43%) attained remission after following the more restrictive diet. Among the 11 patients who didn’t initially respond to 6FED and who opted to receive fluticasone propionate, nine patients (82%) achieved remission.

“We examined a series of validated endpoints that have not previously been examined in diet trials,” Dr. Rothenberg said. “We are surprised to see that one food was equally effective as six foods.”
 

Incorporating food elimination therapy

Dr. Rothenberg and colleagues are continuing their research into EoE and food-elimination diets, with a strong focus on furthering diet therapy. In particular, the research team wants to understand how to potentially add milk – and other foods – back to the diet.

Wael Sayej, MD, associate professor of pediatrics at the University of Massachusetts Baystate Regional Campus, Springfield, has found success with the one-food elimination diet among children with EoE, he said in an interview.

In a retrospective study, Dr. Sayej and colleagues found that a one-food elimination diet was an effective first-line treatment option for pediatric patients.

“Once we get past the one-food or two-food elimination, it becomes much more difficult and cumbersome for patients to follow,” said Dr. Sayej, who is also a pediatric gastroenterologist with Baystate Health in Springfield and who wasn’t involved with the CEGIR study. “Obviously, I prefer my patients to follow a strict dairy-free diet as long-term therapy, rather than have them on a medication for the rest of their life.”

Dr. Sayej advises patients to follow the one-food elimination diet in his practice. If patients aren’t responsive, he offers options for additional dietary elimination or initiation of steroid therapy.

“The most important thing about initiating dietary elimination therapy is to take the time to educate the patient and family about the disease, the risks or complications associated with untreated disease, and the pros and cons of the treatment options,” he said.

The study was cofunded by the National Institute of Allergy and Infectious Diseases, the National Center for Advancing Translational Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have research, consultant, and leadership relationships with several pharmaceutical companies and organizations not related to this study. Dr. Sayej disclosed no relevant financial relationships.
 

Although virtual visits have decreased and in-person visits have risen since the initial COVID-19 wave in 2020, telemedicine remains an important option in gastroenterology and requires clear guidance for best practices moving forward, according to a new clinical practice update from the American Gastroenterological Association.

The postpandemic era must balance patient and provider preferences, medical needs, quality of care, regulatory requirements, and reimbursement rules, Ziad Gellad, MD, associate professor of medicine in the gastroenterology division at Duke University, Durham, N.C., and colleagues wrote.

Duke University

“Spurred by the COVID-19 pandemic, telehealth, and specifically telemedicine, has become an integral part of outpatient gastrointestinal care in the United States,” the authors wrote.

Dr. Gellad and colleagues penned a clinical practice update based on recently published studies and the experiences of the authors, who are active gastroenterologists and hepatologists with extensive experience using telemedicine in clinical practice.

First, the group addressed patient preferences for telemedicine in gastroenterology based on emerging data. During the past 2 years, studies in both the United States and Australia found that most patients voiced ongoing interest and willingness to use video visits, as well as satisfaction with their medical concerns being addressed via telemedicine. They also reported significantly decreased absenteeism, as compared with face-to-face visits.

At the same time, patient preferences may vary based on age, race, and other factors. For instance, younger adults, those with higher incomes, and Hispanic and Latino patients appear to be more likely to prefer video visits than older adults, those with lower incomes, and White or Black patients. In gastroenterology, specific telemedicine studies, especially among patients with inflammatory bowel disease (IBD) or chronic liver disease, older patients, Black patients, and those with Medicaid or Medicare insurance were more likely to complete a phone-based visit rather than a video visit.

Even still, barriers exist for some patients, which should be recognized, the authors wrote. Studies have found racial and socioeconomic disparities in accessing telemedicine, including video visits. When possible, ambulatory practices, institutions, and health systems should provide technical solutions and individual support to help patients overcome these barriers.

So far, telemedicine appears to be better suited for stable chronic conditions rather than acute illnesses, which are more likely to require a follow-up in-person visit or ED care. At the gastrointestinal level, patients being evaluated for liver transplantation via telemedicine had a reduced time from referral to evaluation by a hepatologist and to transplant listing, and liver transplant recipients had lower readmission rates, improved physical function, and better general health. Among studies of IBD patients, telemedicine led to similar quality of care metrics and higher IBD-specific quality of life.

At this time, decisions about using telemedicine for patients with digestive diseases remain nuanced, the authors wrote. In general, those with stable conditions, such as gastroesophageal reflux, irritable bowel syndrome, IBD, chronic constipation, chronic liver disease, and chronic pancreatitis, appear to be good candidates for telemedicine. Patients who are considering a change in therapy and wish to schedule a visit for additional information may also use telemedicine.

In addition, those who live in remote areas could be appropriate candidates for telemedicine as long as they have access, particularly for video visits. Among these patients, studies have shown that telemedicine can be appropriate for patients with IBD and the transition of care from pediatric to adult gastroenterologists. Ultimately, the decision depends on several factors, including the practice setting, geography, and complexity of care.

Many times, the main barrier to virtual care is the regulatory requirement to be licensed in the state where the patient lives. Although these requirements were eased during the COVID-19 pandemic, many restrictions have now returned in most states. Some practices may now support their clinicians in obtaining licenses for surrounding states, but ultimately, some regulatory compromise will be needed to continue multistate telemedicine without additional licensure, the authors wrote.

Reimbursement rules have also remained a barrier. Despite some changes during the pandemic, reimbursement will likely shift in the future, and additional documentation requirements are suggested. For instance, it’s important to document patient consent to telemedicine, the method of telemedicine (whether a secure two-way interactive video or phone call), patient location, provider location, a listing of all clinical participants’ roles and actions, and other individuals (such as trainees) present at the visit.

Finally, the clinical workflow for telemedicine should include a few additional steps, the authors wrote. Office staff should connect with patients before the visit to address any technical issues and ensure a proper connection, set up any assistive services such as an interpreter, complete previsit questionnaires via secure messaging, and conduct standard practices such as medication review. Postvisit instructions should then be sent through a secure portal or mail.

Moving forward, additional studies are needed to verify long-term outcomes associated with telemedicine, as well as the optimal ratio of in-person versus telemedicine visits for various disease states, the authors wrote.

“Telemedicine is accepted by both patients and providers, and is associated with certain key advantages, including reducing patient travel time and cost and work absenteeism,” they wrote. However, “gastroenterology providers need to be cognizant of certain patient and illness barriers to telemedicine and adhere to best practices to ensure high-quality gastrointestinal virtual care.”

The clinical practice update received no funding support. Dr. Gellad disclosed financial relationships with Higgs Boson, Inc.; Merck & Co; and Novo Nordisk. Author Seth Crockett is a consultant for IngenioRx and has received research funding from Freenome, Guardant, and Exact Sciences. Raymond Cross disclosed financial relationships with AbbvVie, BMS, Fzata, Janssen, Magellan Health, Pfizer, and Takeda and has received support from the Crohn's and Colitis Foundation, IBD Education Group, and CorEvitas.

Although virtual visits have decreased and in-person visits have risen since the initial COVID-19 wave in 2020, telemedicine remains an important option in gastroenterology and requires clear guidance for best practices moving forward, according to a new clinical practice update from the American Gastroenterological Association.

The postpandemic era must balance patient and provider preferences, medical needs, quality of care, regulatory requirements, and reimbursement rules, Ziad Gellad, MD, associate professor of medicine in the gastroenterology division at Duke University, Durham, N.C., and colleagues wrote.

Duke University

“Spurred by the COVID-19 pandemic, telehealth, and specifically telemedicine, has become an integral part of outpatient gastrointestinal care in the United States,” the authors wrote.

Dr. Gellad and colleagues penned a clinical practice update based on recently published studies and the experiences of the authors, who are active gastroenterologists and hepatologists with extensive experience using telemedicine in clinical practice.

First, the group addressed patient preferences for telemedicine in gastroenterology based on emerging data. During the past 2 years, studies in both the United States and Australia found that most patients voiced ongoing interest and willingness to use video visits, as well as satisfaction with their medical concerns being addressed via telemedicine. They also reported significantly decreased absenteeism, as compared with face-to-face visits.

At the same time, patient preferences may vary based on age, race, and other factors. For instance, younger adults, those with higher incomes, and Hispanic and Latino patients appear to be more likely to prefer video visits than older adults, those with lower incomes, and White or Black patients. In gastroenterology, specific telemedicine studies, especially among patients with inflammatory bowel disease (IBD) or chronic liver disease, older patients, Black patients, and those with Medicaid or Medicare insurance were more likely to complete a phone-based visit rather than a video visit.

Even still, barriers exist for some patients, which should be recognized, the authors wrote. Studies have found racial and socioeconomic disparities in accessing telemedicine, including video visits. When possible, ambulatory practices, institutions, and health systems should provide technical solutions and individual support to help patients overcome these barriers.

So far, telemedicine appears to be better suited for stable chronic conditions rather than acute illnesses, which are more likely to require a follow-up in-person visit or ED care. At the gastrointestinal level, patients being evaluated for liver transplantation via telemedicine had a reduced time from referral to evaluation by a hepatologist and to transplant listing, and liver transplant recipients had lower readmission rates, improved physical function, and better general health. Among studies of IBD patients, telemedicine led to similar quality of care metrics and higher IBD-specific quality of life.

At this time, decisions about using telemedicine for patients with digestive diseases remain nuanced, the authors wrote. In general, those with stable conditions, such as gastroesophageal reflux, irritable bowel syndrome, IBD, chronic constipation, chronic liver disease, and chronic pancreatitis, appear to be good candidates for telemedicine. Patients who are considering a change in therapy and wish to schedule a visit for additional information may also use telemedicine.

In addition, those who live in remote areas could be appropriate candidates for telemedicine as long as they have access, particularly for video visits. Among these patients, studies have shown that telemedicine can be appropriate for patients with IBD and the transition of care from pediatric to adult gastroenterologists. Ultimately, the decision depends on several factors, including the practice setting, geography, and complexity of care.

Many times, the main barrier to virtual care is the regulatory requirement to be licensed in the state where the patient lives. Although these requirements were eased during the COVID-19 pandemic, many restrictions have now returned in most states. Some practices may now support their clinicians in obtaining licenses for surrounding states, but ultimately, some regulatory compromise will be needed to continue multistate telemedicine without additional licensure, the authors wrote.

Reimbursement rules have also remained a barrier. Despite some changes during the pandemic, reimbursement will likely shift in the future, and additional documentation requirements are suggested. For instance, it’s important to document patient consent to telemedicine, the method of telemedicine (whether a secure two-way interactive video or phone call), patient location, provider location, a listing of all clinical participants’ roles and actions, and other individuals (such as trainees) present at the visit.

Finally, the clinical workflow for telemedicine should include a few additional steps, the authors wrote. Office staff should connect with patients before the visit to address any technical issues and ensure a proper connection, set up any assistive services such as an interpreter, complete previsit questionnaires via secure messaging, and conduct standard practices such as medication review. Postvisit instructions should then be sent through a secure portal or mail.

Moving forward, additional studies are needed to verify long-term outcomes associated with telemedicine, as well as the optimal ratio of in-person versus telemedicine visits for various disease states, the authors wrote.

“Telemedicine is accepted by both patients and providers, and is associated with certain key advantages, including reducing patient travel time and cost and work absenteeism,” they wrote. However, “gastroenterology providers need to be cognizant of certain patient and illness barriers to telemedicine and adhere to best practices to ensure high-quality gastrointestinal virtual care.”

The clinical practice update received no funding support. Dr. Gellad disclosed financial relationships with Higgs Boson, Inc.; Merck & Co; and Novo Nordisk. Author Seth Crockett is a consultant for IngenioRx and has received research funding from Freenome, Guardant, and Exact Sciences. Raymond Cross disclosed financial relationships with AbbvVie, BMS, Fzata, Janssen, Magellan Health, Pfizer, and Takeda and has received support from the Crohn's and Colitis Foundation, IBD Education Group, and CorEvitas.

Although virtual visits have decreased and in-person visits have risen since the initial COVID-19 wave in 2020, telemedicine remains an important option in gastroenterology and requires clear guidance for best practices moving forward, according to a new clinical practice update from the American Gastroenterological Association.

The postpandemic era must balance patient and provider preferences, medical needs, quality of care, regulatory requirements, and reimbursement rules, Ziad Gellad, MD, associate professor of medicine in the gastroenterology division at Duke University, Durham, N.C., and colleagues wrote.

Duke University

“Spurred by the COVID-19 pandemic, telehealth, and specifically telemedicine, has become an integral part of outpatient gastrointestinal care in the United States,” the authors wrote.

Dr. Gellad and colleagues penned a clinical practice update based on recently published studies and the experiences of the authors, who are active gastroenterologists and hepatologists with extensive experience using telemedicine in clinical practice.

First, the group addressed patient preferences for telemedicine in gastroenterology based on emerging data. During the past 2 years, studies in both the United States and Australia found that most patients voiced ongoing interest and willingness to use video visits, as well as satisfaction with their medical concerns being addressed via telemedicine. They also reported significantly decreased absenteeism, as compared with face-to-face visits.

At the same time, patient preferences may vary based on age, race, and other factors. For instance, younger adults, those with higher incomes, and Hispanic and Latino patients appear to be more likely to prefer video visits than older adults, those with lower incomes, and White or Black patients. In gastroenterology, specific telemedicine studies, especially among patients with inflammatory bowel disease (IBD) or chronic liver disease, older patients, Black patients, and those with Medicaid or Medicare insurance were more likely to complete a phone-based visit rather than a video visit.

Even still, barriers exist for some patients, which should be recognized, the authors wrote. Studies have found racial and socioeconomic disparities in accessing telemedicine, including video visits. When possible, ambulatory practices, institutions, and health systems should provide technical solutions and individual support to help patients overcome these barriers.

So far, telemedicine appears to be better suited for stable chronic conditions rather than acute illnesses, which are more likely to require a follow-up in-person visit or ED care. At the gastrointestinal level, patients being evaluated for liver transplantation via telemedicine had a reduced time from referral to evaluation by a hepatologist and to transplant listing, and liver transplant recipients had lower readmission rates, improved physical function, and better general health. Among studies of IBD patients, telemedicine led to similar quality of care metrics and higher IBD-specific quality of life.

At this time, decisions about using telemedicine for patients with digestive diseases remain nuanced, the authors wrote. In general, those with stable conditions, such as gastroesophageal reflux, irritable bowel syndrome, IBD, chronic constipation, chronic liver disease, and chronic pancreatitis, appear to be good candidates for telemedicine. Patients who are considering a change in therapy and wish to schedule a visit for additional information may also use telemedicine.

In addition, those who live in remote areas could be appropriate candidates for telemedicine as long as they have access, particularly for video visits. Among these patients, studies have shown that telemedicine can be appropriate for patients with IBD and the transition of care from pediatric to adult gastroenterologists. Ultimately, the decision depends on several factors, including the practice setting, geography, and complexity of care.

Many times, the main barrier to virtual care is the regulatory requirement to be licensed in the state where the patient lives. Although these requirements were eased during the COVID-19 pandemic, many restrictions have now returned in most states. Some practices may now support their clinicians in obtaining licenses for surrounding states, but ultimately, some regulatory compromise will be needed to continue multistate telemedicine without additional licensure, the authors wrote.

Reimbursement rules have also remained a barrier. Despite some changes during the pandemic, reimbursement will likely shift in the future, and additional documentation requirements are suggested. For instance, it’s important to document patient consent to telemedicine, the method of telemedicine (whether a secure two-way interactive video or phone call), patient location, provider location, a listing of all clinical participants’ roles and actions, and other individuals (such as trainees) present at the visit.

Finally, the clinical workflow for telemedicine should include a few additional steps, the authors wrote. Office staff should connect with patients before the visit to address any technical issues and ensure a proper connection, set up any assistive services such as an interpreter, complete previsit questionnaires via secure messaging, and conduct standard practices such as medication review. Postvisit instructions should then be sent through a secure portal or mail.

Moving forward, additional studies are needed to verify long-term outcomes associated with telemedicine, as well as the optimal ratio of in-person versus telemedicine visits for various disease states, the authors wrote.

“Telemedicine is accepted by both patients and providers, and is associated with certain key advantages, including reducing patient travel time and cost and work absenteeism,” they wrote. However, “gastroenterology providers need to be cognizant of certain patient and illness barriers to telemedicine and adhere to best practices to ensure high-quality gastrointestinal virtual care.”

The clinical practice update received no funding support. Dr. Gellad disclosed financial relationships with Higgs Boson, Inc.; Merck & Co; and Novo Nordisk. Author Seth Crockett is a consultant for IngenioRx and has received research funding from Freenome, Guardant, and Exact Sciences. Raymond Cross disclosed financial relationships with AbbvVie, BMS, Fzata, Janssen, Magellan Health, Pfizer, and Takeda and has received support from the Crohn's and Colitis Foundation, IBD Education Group, and CorEvitas.

The risks of all-cause and liver-related mortality increase substantially based on fibrosis stage in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD), according to a study published in Clinical Gastroenterology and Hepatology.

In particular, patients with NAFLD and advanced fibrosis have a threefold higher risk of all-cause mortality and 10-fold higher risk of liver-related mortality, as compared with patients with NAFLD but not advanced fibrosis, Cheng Han Ng, with the National University of Singapore, and colleagues wrote.

“These data provide high-level evidence that provides prognostication for each stage of fibrosis to inform care providers and patients,” they wrote. “In addition, these findings have important implications for clinical trial design and highlight the importance of developing therapeutics.”

Although previous studies have found higher risks of all-cause and liver-related mortality in patients with NAFLD with increasing fibrosis stages, they examined the risk of mortality in reference to stage 0 fibrosis and didn’t include comparisons across different stages of fibrosis. In addition, the studies typically used pooled risk ratios, didn’t account for time-to-event analysis, or incorporate the most recent data.

The study investigators conducted an updated time-to-event meta-analysis to understand the impact of fibrosis stage on all-cause and liver-related mortality in biopsy-confirmed NAFLD. In addition, they pooled the survival estimates of individual fibrosis stages based on reconstructed individual patient data and compared mortality between fibrosis stages.

In 14 included studies, 17,301 patients had biopsy-proven NAFLD, including 6,069 assessed for overall mortality and 3,421 for liver-related mortality. The studies were conducted in the United States, Canada, Sweden, Israel, Japan, and Hong Kong, with four multicenter studies across multiple regions. The median follow-up duration was 7.7 years, and the average age of patients was 50.5.

For nonadvanced fibrosis (F0-F2), the 1-, 3-, 5-, 8-, and 10-year all-cause mortality were 0.1%, 1.9%, 3.3%, 6%, and 7.7%, respectively. For clinically significant fibrosis (F2-F4), the rates were 0.3%, 8.4%, 14%, 23.7%, and 29.3%, respectively. For advanced fibrosis (F3-F4), the rates were 0.3%, 8.8%, 14.9%, 25.5%, and 32.2%, respectively. For cirrhosis (F4), the rates were 0.3%, 13%, 20.6%, 33.3%, and 41.5%, respectively.

Compared with F0 as a reference, there were no statistically significant differences in all-cause mortality for F1. However, the risk significantly increased for F2 (HR, 1.46; 95% confidence interval, 1.08-1.98; P 1⁄4 .01), F3 (HR, 1.96; 95% CI, 1.41-2.72; P < .01), and F4 (HR, 3.66; 95% CI, 2.65-5.05; P < .01). In addition, early fibrosis (F1-F2) resulted in a statistically significant increase in all-cause mortality, as did the presence of clinically significant fibrosis or advanced fibrosis.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in a statistically significant increase in mortality (HR, 2.06; 95% CI, 1.52-2.81; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a significantly increased risk of mortality (HR, 3.32; 95% CI, 2.38-4.65; P < .01).

In a comparison between F3 and F4, F4 resulted in a statistically significant increase in mortality (HR, 2.67; 95% CI, 1.47-4.83; P < .01). In a sensitivity analysis with three studies including nonalcoholic steatohepatitis, patients with NASH had a significantly increased risk of mortality in F4 (HR, 5.08; 95% CI, 2.70-9.55; P < .01).

For liver-related mortality, F1 didn’t result in a statistically significant increase, as compared with F0. However, increased risks were found for F2 (HR, 4.07; 95% CI, 1.44-11.5; P < .01), F3 (HR, 7.59; 95% CI, 2.80-20.5; P < .01), and F4 (HR, 15.1; 95% CI, 5.27-43.4; P < .01). In addition, any fibrosis (F1-F4) resulted in an increased risk of mortality, early fibrosis resulted in a borderline nonsignificant increase, and clinically significant or advanced fibrosis led to an increased risk.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in an increase in liver-related mortality (HR, 6.49; 95% CI, 3.30-12.8; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a statistically significant increase in liver-related mortality (HR, 10.4; 95% CI, 6.18-17.5; P < .01).

In a comparison between F3 and F4, F4 resulted in a significant increase in liver-related mortality (HR, 2.57; 95% CI, 1.22-5.42; P < .01).

Although the presence of F4 leads to the greatest risk of mortality, selection criteria in NASH clinical trials have predominately targeted patients with F0-F3, the authors wrote.

“NASH is currently the fastest growing cause for liver transplant and [transplant] remains the only known curative treatment for cirrhosis,” they wrote. “However, with the global shortage of suitable grafts for transplant and lack of viable treatment, our results highlight that there is an urgent need for an efficacious treatment for patients with NASH and F4.”

The researchers outlined several limitations of their study. The development of hepatocellular carcinoma and its effects on survival were outside the scope of the study, they wrote. Analysis of liver-related mortality by proportion was not conducted because of insufficient studies. Data were insufficient to perform subgroup analyses by gender, age, study design, medication use, and diagnostic modality for fibrosis stage.

The authors reported funding support from several national U.S. grants and disclosed consultant and advisory rules for numerous pharmaceutical companies.

The risks of all-cause and liver-related mortality increase substantially based on fibrosis stage in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD), according to a study published in Clinical Gastroenterology and Hepatology.

In particular, patients with NAFLD and advanced fibrosis have a threefold higher risk of all-cause mortality and 10-fold higher risk of liver-related mortality, as compared with patients with NAFLD but not advanced fibrosis, Cheng Han Ng, with the National University of Singapore, and colleagues wrote.

“These data provide high-level evidence that provides prognostication for each stage of fibrosis to inform care providers and patients,” they wrote. “In addition, these findings have important implications for clinical trial design and highlight the importance of developing therapeutics.”

Although previous studies have found higher risks of all-cause and liver-related mortality in patients with NAFLD with increasing fibrosis stages, they examined the risk of mortality in reference to stage 0 fibrosis and didn’t include comparisons across different stages of fibrosis. In addition, the studies typically used pooled risk ratios, didn’t account for time-to-event analysis, or incorporate the most recent data.

The study investigators conducted an updated time-to-event meta-analysis to understand the impact of fibrosis stage on all-cause and liver-related mortality in biopsy-confirmed NAFLD. In addition, they pooled the survival estimates of individual fibrosis stages based on reconstructed individual patient data and compared mortality between fibrosis stages.

In 14 included studies, 17,301 patients had biopsy-proven NAFLD, including 6,069 assessed for overall mortality and 3,421 for liver-related mortality. The studies were conducted in the United States, Canada, Sweden, Israel, Japan, and Hong Kong, with four multicenter studies across multiple regions. The median follow-up duration was 7.7 years, and the average age of patients was 50.5.

For nonadvanced fibrosis (F0-F2), the 1-, 3-, 5-, 8-, and 10-year all-cause mortality were 0.1%, 1.9%, 3.3%, 6%, and 7.7%, respectively. For clinically significant fibrosis (F2-F4), the rates were 0.3%, 8.4%, 14%, 23.7%, and 29.3%, respectively. For advanced fibrosis (F3-F4), the rates were 0.3%, 8.8%, 14.9%, 25.5%, and 32.2%, respectively. For cirrhosis (F4), the rates were 0.3%, 13%, 20.6%, 33.3%, and 41.5%, respectively.

Compared with F0 as a reference, there were no statistically significant differences in all-cause mortality for F1. However, the risk significantly increased for F2 (HR, 1.46; 95% confidence interval, 1.08-1.98; P 1⁄4 .01), F3 (HR, 1.96; 95% CI, 1.41-2.72; P < .01), and F4 (HR, 3.66; 95% CI, 2.65-5.05; P < .01). In addition, early fibrosis (F1-F2) resulted in a statistically significant increase in all-cause mortality, as did the presence of clinically significant fibrosis or advanced fibrosis.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in a statistically significant increase in mortality (HR, 2.06; 95% CI, 1.52-2.81; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a significantly increased risk of mortality (HR, 3.32; 95% CI, 2.38-4.65; P < .01).

In a comparison between F3 and F4, F4 resulted in a statistically significant increase in mortality (HR, 2.67; 95% CI, 1.47-4.83; P < .01). In a sensitivity analysis with three studies including nonalcoholic steatohepatitis, patients with NASH had a significantly increased risk of mortality in F4 (HR, 5.08; 95% CI, 2.70-9.55; P < .01).

For liver-related mortality, F1 didn’t result in a statistically significant increase, as compared with F0. However, increased risks were found for F2 (HR, 4.07; 95% CI, 1.44-11.5; P < .01), F3 (HR, 7.59; 95% CI, 2.80-20.5; P < .01), and F4 (HR, 15.1; 95% CI, 5.27-43.4; P < .01). In addition, any fibrosis (F1-F4) resulted in an increased risk of mortality, early fibrosis resulted in a borderline nonsignificant increase, and clinically significant or advanced fibrosis led to an increased risk.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in an increase in liver-related mortality (HR, 6.49; 95% CI, 3.30-12.8; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a statistically significant increase in liver-related mortality (HR, 10.4; 95% CI, 6.18-17.5; P < .01).

In a comparison between F3 and F4, F4 resulted in a significant increase in liver-related mortality (HR, 2.57; 95% CI, 1.22-5.42; P < .01).

Although the presence of F4 leads to the greatest risk of mortality, selection criteria in NASH clinical trials have predominately targeted patients with F0-F3, the authors wrote.

“NASH is currently the fastest growing cause for liver transplant and [transplant] remains the only known curative treatment for cirrhosis,” they wrote. “However, with the global shortage of suitable grafts for transplant and lack of viable treatment, our results highlight that there is an urgent need for an efficacious treatment for patients with NASH and F4.”

The researchers outlined several limitations of their study. The development of hepatocellular carcinoma and its effects on survival were outside the scope of the study, they wrote. Analysis of liver-related mortality by proportion was not conducted because of insufficient studies. Data were insufficient to perform subgroup analyses by gender, age, study design, medication use, and diagnostic modality for fibrosis stage.

The authors reported funding support from several national U.S. grants and disclosed consultant and advisory rules for numerous pharmaceutical companies.

The risks of all-cause and liver-related mortality increase substantially based on fibrosis stage in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD), according to a study published in Clinical Gastroenterology and Hepatology.

In particular, patients with NAFLD and advanced fibrosis have a threefold higher risk of all-cause mortality and 10-fold higher risk of liver-related mortality, as compared with patients with NAFLD but not advanced fibrosis, Cheng Han Ng, with the National University of Singapore, and colleagues wrote.

“These data provide high-level evidence that provides prognostication for each stage of fibrosis to inform care providers and patients,” they wrote. “In addition, these findings have important implications for clinical trial design and highlight the importance of developing therapeutics.”

Although previous studies have found higher risks of all-cause and liver-related mortality in patients with NAFLD with increasing fibrosis stages, they examined the risk of mortality in reference to stage 0 fibrosis and didn’t include comparisons across different stages of fibrosis. In addition, the studies typically used pooled risk ratios, didn’t account for time-to-event analysis, or incorporate the most recent data.

The study investigators conducted an updated time-to-event meta-analysis to understand the impact of fibrosis stage on all-cause and liver-related mortality in biopsy-confirmed NAFLD. In addition, they pooled the survival estimates of individual fibrosis stages based on reconstructed individual patient data and compared mortality between fibrosis stages.

In 14 included studies, 17,301 patients had biopsy-proven NAFLD, including 6,069 assessed for overall mortality and 3,421 for liver-related mortality. The studies were conducted in the United States, Canada, Sweden, Israel, Japan, and Hong Kong, with four multicenter studies across multiple regions. The median follow-up duration was 7.7 years, and the average age of patients was 50.5.

For nonadvanced fibrosis (F0-F2), the 1-, 3-, 5-, 8-, and 10-year all-cause mortality were 0.1%, 1.9%, 3.3%, 6%, and 7.7%, respectively. For clinically significant fibrosis (F2-F4), the rates were 0.3%, 8.4%, 14%, 23.7%, and 29.3%, respectively. For advanced fibrosis (F3-F4), the rates were 0.3%, 8.8%, 14.9%, 25.5%, and 32.2%, respectively. For cirrhosis (F4), the rates were 0.3%, 13%, 20.6%, 33.3%, and 41.5%, respectively.

Compared with F0 as a reference, there were no statistically significant differences in all-cause mortality for F1. However, the risk significantly increased for F2 (HR, 1.46; 95% confidence interval, 1.08-1.98; P 1⁄4 .01), F3 (HR, 1.96; 95% CI, 1.41-2.72; P < .01), and F4 (HR, 3.66; 95% CI, 2.65-5.05; P < .01). In addition, early fibrosis (F1-F2) resulted in a statistically significant increase in all-cause mortality, as did the presence of clinically significant fibrosis or advanced fibrosis.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in a statistically significant increase in mortality (HR, 2.06; 95% CI, 1.52-2.81; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a significantly increased risk of mortality (HR, 3.32; 95% CI, 2.38-4.65; P < .01).

In a comparison between F3 and F4, F4 resulted in a statistically significant increase in mortality (HR, 2.67; 95% CI, 1.47-4.83; P < .01). In a sensitivity analysis with three studies including nonalcoholic steatohepatitis, patients with NASH had a significantly increased risk of mortality in F4 (HR, 5.08; 95% CI, 2.70-9.55; P < .01).

For liver-related mortality, F1 didn’t result in a statistically significant increase, as compared with F0. However, increased risks were found for F2 (HR, 4.07; 95% CI, 1.44-11.5; P < .01), F3 (HR, 7.59; 95% CI, 2.80-20.5; P < .01), and F4 (HR, 15.1; 95% CI, 5.27-43.4; P < .01). In addition, any fibrosis (F1-F4) resulted in an increased risk of mortality, early fibrosis resulted in a borderline nonsignificant increase, and clinically significant or advanced fibrosis led to an increased risk.

Compared with non–clinically significant fibrosis (F0-F1), clinically significant fibrosis (F2-F4) resulted in an increase in liver-related mortality (HR, 6.49; 95% CI, 3.30-12.8; P < .01).

Compared with nonadvanced fibrosis (F0-F2), advanced fibrosis (F3-F4) resulted in a statistically significant increase in liver-related mortality (HR, 10.4; 95% CI, 6.18-17.5; P < .01).

In a comparison between F3 and F4, F4 resulted in a significant increase in liver-related mortality (HR, 2.57; 95% CI, 1.22-5.42; P < .01).

Although the presence of F4 leads to the greatest risk of mortality, selection criteria in NASH clinical trials have predominately targeted patients with F0-F3, the authors wrote.

“NASH is currently the fastest growing cause for liver transplant and [transplant] remains the only known curative treatment for cirrhosis,” they wrote. “However, with the global shortage of suitable grafts for transplant and lack of viable treatment, our results highlight that there is an urgent need for an efficacious treatment for patients with NASH and F4.”

The researchers outlined several limitations of their study. The development of hepatocellular carcinoma and its effects on survival were outside the scope of the study, they wrote. Analysis of liver-related mortality by proportion was not conducted because of insufficient studies. Data were insufficient to perform subgroup analyses by gender, age, study design, medication use, and diagnostic modality for fibrosis stage.

The authors reported funding support from several national U.S. grants and disclosed consultant and advisory rules for numerous pharmaceutical companies.

Several digital therapeutics (DTx) – evidence-based interventions delivered via mobile app or Web-based platforms – could help patients with irritable bowel syndrome (IBS), according to a new review of available products.

These tools aren’t widely used by gastroenterologists yet, but the market is expected to grow broadly during the next decade.

“Digital therapeutics make so much sense and solve so many access issues,” coauthor William Chey, MD, chief of gastroenterology at the University of Michigan, Ann Arbor, said in an interview. “Because of this, their promise could easily outstrip their substance. We need to hold digital therapeutics companies accountable for proper evidence of benefit, so patients and doctors don’t end up chasing the latest shiny object.”

The review was published online in The American Journal of Gastroenterology.
 

Understanding the apps

IBS is most effectively treated with a combination of medications, diet changes, and behavioral interventions that are specific to the patient, the authors write. Cognitive behavioral therapy (CBT) and gut-directed hypnotherapy (GDH) have been effective at modifying behaviors and thought patterns, they add.

However, many gastroenterologists and their patients with IBS don’t have easy access to the mental health services component of integrated gastrointestinal (GI) care. DTx may offer a solution.

The review by Dr. Chey and colleagues is intended to serve as a primer for gastroenterologists about the current generation of DTx that provide virtual behavioral health interventions. For each product, they include a description of its services, evidence supporting its use, and other key information.

Mahana IBS, made by Mahana Therapeutics, is an FDA-approved, prescription-only CBT program for adults with IBS. The maximum out-of-pocket cost is $90. The product includes 10 sessions over 12 weeks.

Available as a mobile app or Web-based platform, Mahana IBS was validated in a randomized comparative effectiveness trial in a group of 558 patients, divided into three groups who received Web-based CBT, phone-based CBT, or treatment as usual. Before treatment, the mean IBS Symptom Severity Score for the entire group was 265.

At 12 weeks, the control group had an average reduction of 52.9 points, while the phone-based therapy group had a reduction of 133.3 points, and the Web-based therapy group had a reduction of 101.2 points. The average Work and Social Adjustment Scale (WSAS) decreased by an additional 3.5 points in the phone-based group and 3 points in the Web-based group, compared with the control group.

Zemedy, made by Bold Health, is a mobile app that provides virtual CBT through a chat bot for patients with IBS. It costs $19.49 per month or $154.99 per year. The app isn’t FDA-approved and doesn’t require a prescription.

The program includes six weekly psychoeducational modules with information about IBS and CBT, followed by CBT training modules. Users can chat with an automated system that provides computer-generated responses for support. A “flare module” supports patients when symptoms worsen.

Zemedy was evaluated in a crossover randomized controlled trial with 62 people in an active treatment group and 59 people in a wait-list control group. The app improved several measures, including self-reported IBS-quality of life, GI symptoms on the IBS rating scale, the Fear of Food Questionnaire, the Visceral Sensitivity Index, and the Depression Anxiety Stress Scale.

A larger clinical trial to validate the results is ongoing.

Regulora, made by metaMe Health, is an FDA-approved, prescription-only GDH program aimed at addressing abdominal pain related to IBS. The maximum out-of-pocket cost is $75. The protocols were developed by GI behavioral health researchers at the University of North Carolina at Chapel Hill. Available on a Web-based platform or as a mobile app, the program includes seven sessions of 30 minutes each over 12 weeks.

Regulora was evaluated in a randomized comparative effectiveness trial of 362 patients who used either this program or an app focused on muscle relaxation. The primary endpoint was the proportion of patients with a 30% or more reduction in abdominal pain intensity, and although the researchers found no significant difference between them, there was some relief. In the GDH group, 31% of participants reported a 30% or greater reduction in abdominal pain intensity, and 45% experienced a 30% or greater improvement in the proportion of stools with normal consistency.

The complete results of the trial still need to receive formal peer review and publication in a scientific journal.

Nerva, made by Mindset Health, is a GDH program delivered by mobile app or Web browser that costs $79.99 for 3 months. It isn’t FDA-approved and doesn’t require a prescription. The protocols were developed in collaboration with researchers from Monash University in Melbourne. The program features 6 weeks of daily sessions, psychoeducation readings, and breathing techniques.

Nerva was evaluated in an observational cohort study of 190 patients who completed all 42 sessions, typically within 2 months. About 64% responded to the program, with a 20 mm or greater symptom reduction on the Visual Analog Scale and median improvement of 33 mm. Participants also reported improvements in abdominal pain, bloating, dissatisfaction with stool consistency, flatulence, and nausea.

Results were reported as an abstract, and full findings from a formal randomized controlled trial aren’t yet available.
 

Patient and provider benefits

Although DTx tools are still in the early stages of development and validation, they can improve patient care and add value to a gastroenterologist’s practice, the authors write.

The products should undergo the same level of scientific rigor as pharmaceutical therapies, including randomized controlled trials in diverse patient groups, and patient data handling must be secure and transparent, the authors write. Cost analyses will be an important factor in clinical integration and adoption, they add.

“Change is inevitable, and the right change will bring benefits to providers and their patients,” Dr. Chey said. “Don’t be afraid of it, but do your due diligence before you embrace it. Our primer is intended to help providers conduct that due diligence.”

While behavioral health care is essential for many patients with IBS, there aren’t enough therapists with GI knowledge to meet the demand, Melissa Hunt, PhD, associate director of clinical training in psychology at the University of Pennsylvania, Philadelphia, said in an interview. The population prevalence of IBS is 6%, which means about 18 million people in the United States need guidance, she said.

Dr. Hunt, who wasn’t involved with this paper, has evaluated DTx options for patients with IBS, including the randomized controlled trial of Zemedy. Her research suggests that about 50% of IBS patients could benefit from self-help DTx.

“I get two to three new patient referrals a week and have a 6-month wait-list for my private practice,” Dr. Hunt said. “DTx is a cutting edge, evidence-based way to address the gaps in service and meet the needs of this population.”

The study didn’t receive any funding. The authors disclosed research, consultant, and leadership relationships with several companies not related to this report. Dr. Hunt declared no relevant financial relationships.

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

Several digital therapeutics (DTx) – evidence-based interventions delivered via mobile app or Web-based platforms – could help patients with irritable bowel syndrome (IBS), according to a new review of available products.

These tools aren’t widely used by gastroenterologists yet, but the market is expected to grow broadly during the next decade.

“Digital therapeutics make so much sense and solve so many access issues,” coauthor William Chey, MD, chief of gastroenterology at the University of Michigan, Ann Arbor, said in an interview. “Because of this, their promise could easily outstrip their substance. We need to hold digital therapeutics companies accountable for proper evidence of benefit, so patients and doctors don’t end up chasing the latest shiny object.”

The review was published online in The American Journal of Gastroenterology.
 

Understanding the apps

IBS is most effectively treated with a combination of medications, diet changes, and behavioral interventions that are specific to the patient, the authors write. Cognitive behavioral therapy (CBT) and gut-directed hypnotherapy (GDH) have been effective at modifying behaviors and thought patterns, they add.

However, many gastroenterologists and their patients with IBS don’t have easy access to the mental health services component of integrated gastrointestinal (GI) care. DTx may offer a solution.

The review by Dr. Chey and colleagues is intended to serve as a primer for gastroenterologists about the current generation of DTx that provide virtual behavioral health interventions. For each product, they include a description of its services, evidence supporting its use, and other key information.

Mahana IBS, made by Mahana Therapeutics, is an FDA-approved, prescription-only CBT program for adults with IBS. The maximum out-of-pocket cost is $90. The product includes 10 sessions over 12 weeks.

Available as a mobile app or Web-based platform, Mahana IBS was validated in a randomized comparative effectiveness trial in a group of 558 patients, divided into three groups who received Web-based CBT, phone-based CBT, or treatment as usual. Before treatment, the mean IBS Symptom Severity Score for the entire group was 265.

At 12 weeks, the control group had an average reduction of 52.9 points, while the phone-based therapy group had a reduction of 133.3 points, and the Web-based therapy group had a reduction of 101.2 points. The average Work and Social Adjustment Scale (WSAS) decreased by an additional 3.5 points in the phone-based group and 3 points in the Web-based group, compared with the control group.

Zemedy, made by Bold Health, is a mobile app that provides virtual CBT through a chat bot for patients with IBS. It costs $19.49 per month or $154.99 per year. The app isn’t FDA-approved and doesn’t require a prescription.

The program includes six weekly psychoeducational modules with information about IBS and CBT, followed by CBT training modules. Users can chat with an automated system that provides computer-generated responses for support. A “flare module” supports patients when symptoms worsen.

Zemedy was evaluated in a crossover randomized controlled trial with 62 people in an active treatment group and 59 people in a wait-list control group. The app improved several measures, including self-reported IBS-quality of life, GI symptoms on the IBS rating scale, the Fear of Food Questionnaire, the Visceral Sensitivity Index, and the Depression Anxiety Stress Scale.

A larger clinical trial to validate the results is ongoing.

Regulora, made by metaMe Health, is an FDA-approved, prescription-only GDH program aimed at addressing abdominal pain related to IBS. The maximum out-of-pocket cost is $75. The protocols were developed by GI behavioral health researchers at the University of North Carolina at Chapel Hill. Available on a Web-based platform or as a mobile app, the program includes seven sessions of 30 minutes each over 12 weeks.

Regulora was evaluated in a randomized comparative effectiveness trial of 362 patients who used either this program or an app focused on muscle relaxation. The primary endpoint was the proportion of patients with a 30% or more reduction in abdominal pain intensity, and although the researchers found no significant difference between them, there was some relief. In the GDH group, 31% of participants reported a 30% or greater reduction in abdominal pain intensity, and 45% experienced a 30% or greater improvement in the proportion of stools with normal consistency.

The complete results of the trial still need to receive formal peer review and publication in a scientific journal.

Nerva, made by Mindset Health, is a GDH program delivered by mobile app or Web browser that costs $79.99 for 3 months. It isn’t FDA-approved and doesn’t require a prescription. The protocols were developed in collaboration with researchers from Monash University in Melbourne. The program features 6 weeks of daily sessions, psychoeducation readings, and breathing techniques.

Nerva was evaluated in an observational cohort study of 190 patients who completed all 42 sessions, typically within 2 months. About 64% responded to the program, with a 20 mm or greater symptom reduction on the Visual Analog Scale and median improvement of 33 mm. Participants also reported improvements in abdominal pain, bloating, dissatisfaction with stool consistency, flatulence, and nausea.

Results were reported as an abstract, and full findings from a formal randomized controlled trial aren’t yet available.
 

Patient and provider benefits

Although DTx tools are still in the early stages of development and validation, they can improve patient care and add value to a gastroenterologist’s practice, the authors write.

The products should undergo the same level of scientific rigor as pharmaceutical therapies, including randomized controlled trials in diverse patient groups, and patient data handling must be secure and transparent, the authors write. Cost analyses will be an important factor in clinical integration and adoption, they add.

“Change is inevitable, and the right change will bring benefits to providers and their patients,” Dr. Chey said. “Don’t be afraid of it, but do your due diligence before you embrace it. Our primer is intended to help providers conduct that due diligence.”

While behavioral health care is essential for many patients with IBS, there aren’t enough therapists with GI knowledge to meet the demand, Melissa Hunt, PhD, associate director of clinical training in psychology at the University of Pennsylvania, Philadelphia, said in an interview. The population prevalence of IBS is 6%, which means about 18 million people in the United States need guidance, she said.

Dr. Hunt, who wasn’t involved with this paper, has evaluated DTx options for patients with IBS, including the randomized controlled trial of Zemedy. Her research suggests that about 50% of IBS patients could benefit from self-help DTx.

“I get two to three new patient referrals a week and have a 6-month wait-list for my private practice,” Dr. Hunt said. “DTx is a cutting edge, evidence-based way to address the gaps in service and meet the needs of this population.”

The study didn’t receive any funding. The authors disclosed research, consultant, and leadership relationships with several companies not related to this report. Dr. Hunt declared no relevant financial relationships.

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

Several digital therapeutics (DTx) – evidence-based interventions delivered via mobile app or Web-based platforms – could help patients with irritable bowel syndrome (IBS), according to a new review of available products.

These tools aren’t widely used by gastroenterologists yet, but the market is expected to grow broadly during the next decade.

“Digital therapeutics make so much sense and solve so many access issues,” coauthor William Chey, MD, chief of gastroenterology at the University of Michigan, Ann Arbor, said in an interview. “Because of this, their promise could easily outstrip their substance. We need to hold digital therapeutics companies accountable for proper evidence of benefit, so patients and doctors don’t end up chasing the latest shiny object.”

The review was published online in The American Journal of Gastroenterology.
 

Understanding the apps

IBS is most effectively treated with a combination of medications, diet changes, and behavioral interventions that are specific to the patient, the authors write. Cognitive behavioral therapy (CBT) and gut-directed hypnotherapy (GDH) have been effective at modifying behaviors and thought patterns, they add.

However, many gastroenterologists and their patients with IBS don’t have easy access to the mental health services component of integrated gastrointestinal (GI) care. DTx may offer a solution.

The review by Dr. Chey and colleagues is intended to serve as a primer for gastroenterologists about the current generation of DTx that provide virtual behavioral health interventions. For each product, they include a description of its services, evidence supporting its use, and other key information.

Mahana IBS, made by Mahana Therapeutics, is an FDA-approved, prescription-only CBT program for adults with IBS. The maximum out-of-pocket cost is $90. The product includes 10 sessions over 12 weeks.

Available as a mobile app or Web-based platform, Mahana IBS was validated in a randomized comparative effectiveness trial in a group of 558 patients, divided into three groups who received Web-based CBT, phone-based CBT, or treatment as usual. Before treatment, the mean IBS Symptom Severity Score for the entire group was 265.

At 12 weeks, the control group had an average reduction of 52.9 points, while the phone-based therapy group had a reduction of 133.3 points, and the Web-based therapy group had a reduction of 101.2 points. The average Work and Social Adjustment Scale (WSAS) decreased by an additional 3.5 points in the phone-based group and 3 points in the Web-based group, compared with the control group.

Zemedy, made by Bold Health, is a mobile app that provides virtual CBT through a chat bot for patients with IBS. It costs $19.49 per month or $154.99 per year. The app isn’t FDA-approved and doesn’t require a prescription.

The program includes six weekly psychoeducational modules with information about IBS and CBT, followed by CBT training modules. Users can chat with an automated system that provides computer-generated responses for support. A “flare module” supports patients when symptoms worsen.

Zemedy was evaluated in a crossover randomized controlled trial with 62 people in an active treatment group and 59 people in a wait-list control group. The app improved several measures, including self-reported IBS-quality of life, GI symptoms on the IBS rating scale, the Fear of Food Questionnaire, the Visceral Sensitivity Index, and the Depression Anxiety Stress Scale.

A larger clinical trial to validate the results is ongoing.

Regulora, made by metaMe Health, is an FDA-approved, prescription-only GDH program aimed at addressing abdominal pain related to IBS. The maximum out-of-pocket cost is $75. The protocols were developed by GI behavioral health researchers at the University of North Carolina at Chapel Hill. Available on a Web-based platform or as a mobile app, the program includes seven sessions of 30 minutes each over 12 weeks.

Regulora was evaluated in a randomized comparative effectiveness trial of 362 patients who used either this program or an app focused on muscle relaxation. The primary endpoint was the proportion of patients with a 30% or more reduction in abdominal pain intensity, and although the researchers found no significant difference between them, there was some relief. In the GDH group, 31% of participants reported a 30% or greater reduction in abdominal pain intensity, and 45% experienced a 30% or greater improvement in the proportion of stools with normal consistency.

The complete results of the trial still need to receive formal peer review and publication in a scientific journal.

Nerva, made by Mindset Health, is a GDH program delivered by mobile app or Web browser that costs $79.99 for 3 months. It isn’t FDA-approved and doesn’t require a prescription. The protocols were developed in collaboration with researchers from Monash University in Melbourne. The program features 6 weeks of daily sessions, psychoeducation readings, and breathing techniques.

Nerva was evaluated in an observational cohort study of 190 patients who completed all 42 sessions, typically within 2 months. About 64% responded to the program, with a 20 mm or greater symptom reduction on the Visual Analog Scale and median improvement of 33 mm. Participants also reported improvements in abdominal pain, bloating, dissatisfaction with stool consistency, flatulence, and nausea.

Results were reported as an abstract, and full findings from a formal randomized controlled trial aren’t yet available.
 

Patient and provider benefits

Although DTx tools are still in the early stages of development and validation, they can improve patient care and add value to a gastroenterologist’s practice, the authors write.

The products should undergo the same level of scientific rigor as pharmaceutical therapies, including randomized controlled trials in diverse patient groups, and patient data handling must be secure and transparent, the authors write. Cost analyses will be an important factor in clinical integration and adoption, they add.

“Change is inevitable, and the right change will bring benefits to providers and their patients,” Dr. Chey said. “Don’t be afraid of it, but do your due diligence before you embrace it. Our primer is intended to help providers conduct that due diligence.”

While behavioral health care is essential for many patients with IBS, there aren’t enough therapists with GI knowledge to meet the demand, Melissa Hunt, PhD, associate director of clinical training in psychology at the University of Pennsylvania, Philadelphia, said in an interview. The population prevalence of IBS is 6%, which means about 18 million people in the United States need guidance, she said.

Dr. Hunt, who wasn’t involved with this paper, has evaluated DTx options for patients with IBS, including the randomized controlled trial of Zemedy. Her research suggests that about 50% of IBS patients could benefit from self-help DTx.

“I get two to three new patient referrals a week and have a 6-month wait-list for my private practice,” Dr. Hunt said. “DTx is a cutting edge, evidence-based way to address the gaps in service and meet the needs of this population.”

The study didn’t receive any funding. The authors disclosed research, consultant, and leadership relationships with several companies not related to this report. Dr. Hunt declared no relevant financial relationships.

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

The age-adjusted incidence rate of pancreatic cancer is increasing in young women in the United States, and it doesn’t show signs of slowing down, according to a new study published in Gastroenterology.

Cedars-Sinai Medical Center

Between 2001 and 2018, there was a greater than 200% difference in the incidence trend between men and women for ages 15-34, wrote Yazan Abboud, MD, a postdoctoral research fellow in the pancreaticobiliary department of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai Medical Center, Los Angeles, and colleagues.

“The exact cause of the trend among younger women is unclear and may be driven by sex-based disproportional exposure or response to known or yet-to-be-explored risk factors,” they wrote. “Future efforts should aim to elucidate the causes of such a trend with the goal to formulate possible preventive measures.”

Although previous studies have found increasing pancreatic cancer incidence rates, especially in younger women, the data haven’t been externally validated outside of the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) data, they wrote. In addition, there are limited data about the contributing factors, such as race, histopathological subtype, tumor location, and stage at diagnosis.

Using SEER-excluded data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR), Dr. Abboud and colleagues conducted a population-based time-trend analysis of pancreatic cancer incidence rates from 2001 to 2018 in younger adults under age 55, including the role of demographics and tumor characteristics. They analyzed age-adjusted incidence rates (aIR), mortality rates, annual percentage change (APC), and average annual percentage change (AAPC) for ages 55 and older and ages 55 and younger. In addition, the research team evaluated the impact of incidence trends on sex-specific mortality trends in younger adults using the CDC’s National Center of Health Statistics database.

Between 2001 and 2018, 748,132 patients were diagnosed with pancreatic cancer. After excluding SEER data, 454,611 patients met the inclusion criteria. About 48.9% were women.

The overall aIR of pancreatic cancer during that time was 12.18 per 100,000 people. Women had a significantly lower aIR, at 10.69 per 100,000, compared with men at 13.95 per 100,000.

In general, pancreatic cancer aIR significantly increased during that time (AAPC = 1.17%). Sex-specific trends increased among both women (AAPC = 1.27%) and men (AAPC = 1.14%), though they showed no significant difference and were parallel.

In ages 55 and older, 401,419 patients (49.7% women) were diagnosed with pancreatic cancer. The aIR significantly increased during the study period (AAPC = 1.11%), with sex-specific aIR increasing in both women (AAPC = 1.11%) and men (AAPC = 1.17%), without a significant difference.

However, a difference appeared in the 53,051 patients (42.9% women) who were ages 55 and younger. The aIR relatively increased (AAPC = 1.29%), with faster jumps in women (AAPC = 2.36%), compared with men (AAPC = .62%). There was an absolute significant difference of 1.74%.

The trends continued in breakdowns by age. For 50,599 patients (42.2% women) between ages 35 and 54, the aIR relatively increased (AAPC = 1.10%). Sex-specific aIR increased among women (AAPC = 2.09%) but remained stable among men (AAPC = 0.54%), with an absolute significant difference of 1.55%.

In the youngest cohort of 2,452 patients (57.3% women) between ages 15 and 34, aIR relatively increased (AAPC = 4.93). Sex-specific aIR also increased in both women (AAPC = 6.45%) and men (AAPC = 2.97%), with an absolute significant difference of 3.48%.

By race, although White women under age 55 experienced increasing aIR at a greater rate than men (AAPC difference = 1.59%), an even more dramatic increase was seen in Black women, as compared to counterpart men (AAPC difference = 2.23%). Sex-specific trends in people of other races were parallel.

Based on tumor characteristics in ages 55 and younger, the pancreatic ductal adenocarcinoma histopathological subtype had an AAPC difference of 0.89%, and a tumor location in the head-of-pancreas had an AAPC difference of 1.64%.

When evaluating tumors based on stage-at-diagnosis, the AAPC difference was nonsignificant in all subgroups. However, sex-specific trends differed in tumors diagnosed at localized stages, suggesting that aIR in women may be increasing at a greater rate than in men (AAPC difference = 1.64%).

Among 64,239 patients (39.3% women) who died from pancreatic cancer under age 55, the mortality rates were unchanged in women (AAPC = –0.09%) but declined in men (AAPC = –0.64%), with an absolute significant AAPC difference of 0.54%.

UCLA

“Pancreatic cancer has a very poor overall survival, accounting for 7% of cancer-related deaths. The incidence of cancers, in general, is expected to rise as life expectancy increases in the United States,” said Danny Issa, MD, a gastroenterologist at the University of California, Los Angeles, who wasn’t involved with this study.

“Recently, noncomparative studies showed a possible increase in the incidence of pancreatic cancer in younger White women and in older White men and women. These reports had limitations,” he said. “The findings of this study are monumental as they confirmed that age-adjusted incidence rates have been increasing at a higher rate in younger women compared to younger men.”

In addition, Dr. Issa said, the significant increases among Black women for adenocarcinoma and for cancers located in the head of the pancreas are notable and should be studied further.

“Over the past few decades, research studies have helped improve cancer treatment by uncovering risk factors and identifying the most affected (or protected) population,” he said. “Therefore, epidemiologic studies are crucial, especially for hard-to-treat cancers such as pancreatic cancer.”

The study was supported in part by a philanthropic grant from The Widjaja Family Fund for Pancreatic Cancer Research. The authors disclosed no conflicts of interest. Dr. Issa reported no relevant disclosures.

The age-adjusted incidence rate of pancreatic cancer is increasing in young women in the United States, and it doesn’t show signs of slowing down, according to a new study published in Gastroenterology.

Cedars-Sinai Medical Center

Between 2001 and 2018, there was a greater than 200% difference in the incidence trend between men and women for ages 15-34, wrote Yazan Abboud, MD, a postdoctoral research fellow in the pancreaticobiliary department of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai Medical Center, Los Angeles, and colleagues.

“The exact cause of the trend among younger women is unclear and may be driven by sex-based disproportional exposure or response to known or yet-to-be-explored risk factors,” they wrote. “Future efforts should aim to elucidate the causes of such a trend with the goal to formulate possible preventive measures.”

Although previous studies have found increasing pancreatic cancer incidence rates, especially in younger women, the data haven’t been externally validated outside of the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) data, they wrote. In addition, there are limited data about the contributing factors, such as race, histopathological subtype, tumor location, and stage at diagnosis.

Using SEER-excluded data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR), Dr. Abboud and colleagues conducted a population-based time-trend analysis of pancreatic cancer incidence rates from 2001 to 2018 in younger adults under age 55, including the role of demographics and tumor characteristics. They analyzed age-adjusted incidence rates (aIR), mortality rates, annual percentage change (APC), and average annual percentage change (AAPC) for ages 55 and older and ages 55 and younger. In addition, the research team evaluated the impact of incidence trends on sex-specific mortality trends in younger adults using the CDC’s National Center of Health Statistics database.

Between 2001 and 2018, 748,132 patients were diagnosed with pancreatic cancer. After excluding SEER data, 454,611 patients met the inclusion criteria. About 48.9% were women.

The overall aIR of pancreatic cancer during that time was 12.18 per 100,000 people. Women had a significantly lower aIR, at 10.69 per 100,000, compared with men at 13.95 per 100,000.

In general, pancreatic cancer aIR significantly increased during that time (AAPC = 1.17%). Sex-specific trends increased among both women (AAPC = 1.27%) and men (AAPC = 1.14%), though they showed no significant difference and were parallel.

In ages 55 and older, 401,419 patients (49.7% women) were diagnosed with pancreatic cancer. The aIR significantly increased during the study period (AAPC = 1.11%), with sex-specific aIR increasing in both women (AAPC = 1.11%) and men (AAPC = 1.17%), without a significant difference.

However, a difference appeared in the 53,051 patients (42.9% women) who were ages 55 and younger. The aIR relatively increased (AAPC = 1.29%), with faster jumps in women (AAPC = 2.36%), compared with men (AAPC = .62%). There was an absolute significant difference of 1.74%.

The trends continued in breakdowns by age. For 50,599 patients (42.2% women) between ages 35 and 54, the aIR relatively increased (AAPC = 1.10%). Sex-specific aIR increased among women (AAPC = 2.09%) but remained stable among men (AAPC = 0.54%), with an absolute significant difference of 1.55%.

In the youngest cohort of 2,452 patients (57.3% women) between ages 15 and 34, aIR relatively increased (AAPC = 4.93). Sex-specific aIR also increased in both women (AAPC = 6.45%) and men (AAPC = 2.97%), with an absolute significant difference of 3.48%.

By race, although White women under age 55 experienced increasing aIR at a greater rate than men (AAPC difference = 1.59%), an even more dramatic increase was seen in Black women, as compared to counterpart men (AAPC difference = 2.23%). Sex-specific trends in people of other races were parallel.

Based on tumor characteristics in ages 55 and younger, the pancreatic ductal adenocarcinoma histopathological subtype had an AAPC difference of 0.89%, and a tumor location in the head-of-pancreas had an AAPC difference of 1.64%.

When evaluating tumors based on stage-at-diagnosis, the AAPC difference was nonsignificant in all subgroups. However, sex-specific trends differed in tumors diagnosed at localized stages, suggesting that aIR in women may be increasing at a greater rate than in men (AAPC difference = 1.64%).

Among 64,239 patients (39.3% women) who died from pancreatic cancer under age 55, the mortality rates were unchanged in women (AAPC = –0.09%) but declined in men (AAPC = –0.64%), with an absolute significant AAPC difference of 0.54%.

UCLA

“Pancreatic cancer has a very poor overall survival, accounting for 7% of cancer-related deaths. The incidence of cancers, in general, is expected to rise as life expectancy increases in the United States,” said Danny Issa, MD, a gastroenterologist at the University of California, Los Angeles, who wasn’t involved with this study.

“Recently, noncomparative studies showed a possible increase in the incidence of pancreatic cancer in younger White women and in older White men and women. These reports had limitations,” he said. “The findings of this study are monumental as they confirmed that age-adjusted incidence rates have been increasing at a higher rate in younger women compared to younger men.”

In addition, Dr. Issa said, the significant increases among Black women for adenocarcinoma and for cancers located in the head of the pancreas are notable and should be studied further.

“Over the past few decades, research studies have helped improve cancer treatment by uncovering risk factors and identifying the most affected (or protected) population,” he said. “Therefore, epidemiologic studies are crucial, especially for hard-to-treat cancers such as pancreatic cancer.”

The study was supported in part by a philanthropic grant from The Widjaja Family Fund for Pancreatic Cancer Research. The authors disclosed no conflicts of interest. Dr. Issa reported no relevant disclosures.

The age-adjusted incidence rate of pancreatic cancer is increasing in young women in the United States, and it doesn’t show signs of slowing down, according to a new study published in Gastroenterology.

Cedars-Sinai Medical Center

Between 2001 and 2018, there was a greater than 200% difference in the incidence trend between men and women for ages 15-34, wrote Yazan Abboud, MD, a postdoctoral research fellow in the pancreaticobiliary department of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai Medical Center, Los Angeles, and colleagues.

“The exact cause of the trend among younger women is unclear and may be driven by sex-based disproportional exposure or response to known or yet-to-be-explored risk factors,” they wrote. “Future efforts should aim to elucidate the causes of such a trend with the goal to formulate possible preventive measures.”

Although previous studies have found increasing pancreatic cancer incidence rates, especially in younger women, the data haven’t been externally validated outside of the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) data, they wrote. In addition, there are limited data about the contributing factors, such as race, histopathological subtype, tumor location, and stage at diagnosis.

Using SEER-excluded data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR), Dr. Abboud and colleagues conducted a population-based time-trend analysis of pancreatic cancer incidence rates from 2001 to 2018 in younger adults under age 55, including the role of demographics and tumor characteristics. They analyzed age-adjusted incidence rates (aIR), mortality rates, annual percentage change (APC), and average annual percentage change (AAPC) for ages 55 and older and ages 55 and younger. In addition, the research team evaluated the impact of incidence trends on sex-specific mortality trends in younger adults using the CDC’s National Center of Health Statistics database.

Between 2001 and 2018, 748,132 patients were diagnosed with pancreatic cancer. After excluding SEER data, 454,611 patients met the inclusion criteria. About 48.9% were women.

The overall aIR of pancreatic cancer during that time was 12.18 per 100,000 people. Women had a significantly lower aIR, at 10.69 per 100,000, compared with men at 13.95 per 100,000.

In general, pancreatic cancer aIR significantly increased during that time (AAPC = 1.17%). Sex-specific trends increased among both women (AAPC = 1.27%) and men (AAPC = 1.14%), though they showed no significant difference and were parallel.

In ages 55 and older, 401,419 patients (49.7% women) were diagnosed with pancreatic cancer. The aIR significantly increased during the study period (AAPC = 1.11%), with sex-specific aIR increasing in both women (AAPC = 1.11%) and men (AAPC = 1.17%), without a significant difference.

However, a difference appeared in the 53,051 patients (42.9% women) who were ages 55 and younger. The aIR relatively increased (AAPC = 1.29%), with faster jumps in women (AAPC = 2.36%), compared with men (AAPC = .62%). There was an absolute significant difference of 1.74%.

The trends continued in breakdowns by age. For 50,599 patients (42.2% women) between ages 35 and 54, the aIR relatively increased (AAPC = 1.10%). Sex-specific aIR increased among women (AAPC = 2.09%) but remained stable among men (AAPC = 0.54%), with an absolute significant difference of 1.55%.

In the youngest cohort of 2,452 patients (57.3% women) between ages 15 and 34, aIR relatively increased (AAPC = 4.93). Sex-specific aIR also increased in both women (AAPC = 6.45%) and men (AAPC = 2.97%), with an absolute significant difference of 3.48%.

By race, although White women under age 55 experienced increasing aIR at a greater rate than men (AAPC difference = 1.59%), an even more dramatic increase was seen in Black women, as compared to counterpart men (AAPC difference = 2.23%). Sex-specific trends in people of other races were parallel.

Based on tumor characteristics in ages 55 and younger, the pancreatic ductal adenocarcinoma histopathological subtype had an AAPC difference of 0.89%, and a tumor location in the head-of-pancreas had an AAPC difference of 1.64%.

When evaluating tumors based on stage-at-diagnosis, the AAPC difference was nonsignificant in all subgroups. However, sex-specific trends differed in tumors diagnosed at localized stages, suggesting that aIR in women may be increasing at a greater rate than in men (AAPC difference = 1.64%).

Among 64,239 patients (39.3% women) who died from pancreatic cancer under age 55, the mortality rates were unchanged in women (AAPC = –0.09%) but declined in men (AAPC = –0.64%), with an absolute significant AAPC difference of 0.54%.

UCLA

“Pancreatic cancer has a very poor overall survival, accounting for 7% of cancer-related deaths. The incidence of cancers, in general, is expected to rise as life expectancy increases in the United States,” said Danny Issa, MD, a gastroenterologist at the University of California, Los Angeles, who wasn’t involved with this study.

“Recently, noncomparative studies showed a possible increase in the incidence of pancreatic cancer in younger White women and in older White men and women. These reports had limitations,” he said. “The findings of this study are monumental as they confirmed that age-adjusted incidence rates have been increasing at a higher rate in younger women compared to younger men.”

In addition, Dr. Issa said, the significant increases among Black women for adenocarcinoma and for cancers located in the head of the pancreas are notable and should be studied further.

“Over the past few decades, research studies have helped improve cancer treatment by uncovering risk factors and identifying the most affected (or protected) population,” he said. “Therefore, epidemiologic studies are crucial, especially for hard-to-treat cancers such as pancreatic cancer.”

The study was supported in part by a philanthropic grant from The Widjaja Family Fund for Pancreatic Cancer Research. The authors disclosed no conflicts of interest. Dr. Issa reported no relevant disclosures.