This transcript has been edited for clarity.

Hi. I’m Dr. Vivek Kaul, and I’m professor of medicine in the division of gastroenterology and hepatology at the University of Rochester (N.Y.) Medical Center. It gives me great pleasure to do this presentation in collaboration with Medscape. I have just returned from Digestive Disease Week 2022, which is the largest international GI conference, and it was held in person for the first time in 3 years because of the pandemic.

Whereas there are a lot of “Best of DDW” presentations for gastroenterologists, there are not that many for primary care providers, so I thought it would be a good idea to do this. What I’ve tried to do is to bring some information that is here now and almost imminently translatable into clinical practice, talk a little about the middle-future range where things will become available in the next few months to years, and then, of course, reflect upon concepts that might become more standard paradigms of care in the distant future.

My collection of papers is divided into the esophagus and the colon, and then finishes up with the liver. [Editor’s note: Some of the abstracts that Dr Kaul refers to are available here.]

The first paper in the esophagus realm is a multicenter study called “The Association of Proton Pump Inhibitor Use and Cognitive Decline and Incident Dementia in Older Adults.” The researchers looked at about 19,000 patients, 65 years and older, who were on PPI therapy and had no significant disability or prior dementia. They followed them for about 5 years and found that a total of about 566 of them developed dementia in this time frame and 235 or so had Alzheimer’s. What they concluded based on that analysis was that PPI use was not associated with dementia or changes in the overall cognitive score.

This is important information. As the American Gastroenterological Association guidelines and others have recommended, those patients who do require a PPI on clinical grounds should definitely receive it, and the side-effect profiles are quite acceptable.

The second paper, “Double-Blind Randomized Trial of the Potassium-Competitive Acid Blocker Vonoprazan vs. the Proton Pump Inhibitor Lansoprazole in U.S. and European Patients with Erosive Esophagitis,” is also related to GERD [gastroesophageal reflux disease] therapy but introduces a new paradigm known as potassium-competitive channel blockers. This is a new drug that has now become available, called vonoprazan.

This was a double-blinded, randomized trial of the potassium-competitive acid blocker vonoprazan in comparison with lansoprazole, which is a well-established medical agent available for the treatment of esophagitis. These are patients with erosive esophagitis in a multicenter U.S. and European cohort of about 1,000 patients who were prospectively treated. The crux of this study was to say that vonoprazan is quicker to provide healing and symptom relief, and that these results are maintained in both the initial phase, which is the treatment phase, and the maintenance phase.

So, there might be some advantages in terms of how quickly we can treat these patients and get them symptom free. I thought that study was worth mentioning because it reflects, after a long period of time, a new class of acid-suppression therapy, which we should all be familiar with, and certainly at the primary care level.

The next paper relates to Barrett’s esophagus and esophageal cancer. This paper came out of the OneFlorida+ Clinical Research Network and was titled “Alarming Rise Found in Esophageal Cancer and Barrett’s Esophagus in Middle-Aged Adults: Findings From a Statewide Database of Over 5 Million Patients.” This paper talks about the increasing prevalence of esophageal cancer in Barrett’s in middle-aged patients – those in the 45- to 64-years age group; the prevalence of esophageal cancer is rising in this cohort. So, as is shown in the first graph, the orange line is depicting the 45-64 age group patients whose esophageal cancer prevalence has gone up. And in the second graph, it’s actually the gray line which looks at the Barrett’s esophagus prevalence, which is also increasing. And all the other cohorts have either plateaued or are declining.

This is important information because these patients who are at risk in these age groups with these demographic profiles should be referred on for endoscopic screening to rule out Barrett’s at least once in their lifetime. And most certainly a percentage of them will be found to have dysplasia and or early esophageal cancer that might be amenable to endoscopic therapy.

The next section that we’ll talk about is the colon section. We have a few very good, high-quality papers with some provocative information in this realm. The first paper (“Multi-modal Blood-based Colorectal Cancer Screening Is a Viable Colorectal Cancer Screening Option – a Prospective Study”) in the colonoscopy section involves the concept of colorectal cancer screening. While we have multiple modalities available for colorectal cancer screening today, a third of eligible patients are not getting screened.

This study looks at a blood test for colorectal cancer screening. We have colonoscopy, we have stool DNA and other tests, but now we have a blood test looking at circulating tumor DNA. For this prospective, multicenter study, researchers from Madrid enrolled about 550 patients between 45 and 84 years of age. The blood test was completed prior to the complete colonoscopy. The prevalence of colorectal cancer screening in this study was about 2%; the sensitivity ranged from about 90% to 95%, and the specificity ranged from about 100% to 88%, depending on what confidence levels you were looking at.

In this prospective study, a blood-based colorectal cancer screening test was able to perform very similarly to stool-based options. Therefore, it may further increase the probability that patients might come in for screening.

The message from this paper is that there’s yet another modality for colorectal cancer screening, and now we have a blood test potentially, but obviously we look forward to more data on how the test itself performs. And there probably will be other candidates in the same realm.

The second paper (“Real-World Comparative Effectiveness of Fidaxomicin vs. Vancomycin Among Medicare Beneficiaries with Clostridioides difficile Infection”) in the colon section is also about a very important topic in clinical practice for all of us, and that is C. difficile infection. As you may know, current guidelines have recommended the use of fidaxomicin over vancomycin as the initial treatment for C. diff infection. This paper looked retrospectively at a cohort of patients in the real world and compared the efficacy of fidaxomicin vs. vancomycin among Medicare beneficiaries with C. diff infection.

The initial results of this multicenter study suggest that treatment with fidaxomicin had higher sustained response compared with vancomycin at both weeks 4 and 8, as well as decreased recurrence of C. difficile.  

This retrospective study further confirms that C. diff  infection remains a problem and that we might have better solutions now with fidaxomicin compared with vancomycin. That’s important information and is already endorsed by the guidelines.

The next paper in the colon realm, “A Randomized Controlled Trial on the Effectiveness of Cognitive-Behavioral and Mindfulness Intervention on Pain, Fatigue and Impairments at Work and Daily Activity in Patients With Crohn’s Disease,” is also an important paradigm that has entered our medical practice. When we are treating patients with GI symptoms, the role for cognitive-behavioral therapy and mindfulness interventions has now come of age.

This paper was a randomized controlled trial on the effectiveness of cognitive-behavioral therapy and mindfulness intervention on the aspects of pain and fatigue, as well as impairments at work and daily activity in patients with Crohn’s disease.

This is a difficult population with chronic illness, and this study comes out of Israel. About 120 patients were randomized to seven 1-hour sessions of psychological training over 12 weeks. The placebo group was the control group that did not get this treatment.

These interventions reduced both fatigue as well as pain levels, and also reduced work and home impairment, and so overall led to a better quality of life.

This paper is important because it shows us in a randomized trial design fashion that a difficult clinical population with Crohn’s disease, with a multitude of systemic symptoms and psychological, psychosomatic issues as well, can be positively impacted by these newer strategies related to cognitive-behavioral therapy and mindfulness interventions. We’ll likely be seeing more of these types of papers coming out, not just for Crohn’s and inflammatory bowel disease, but also for functional disease, which is where this started.

Our final paper in the colon section relates to an interesting concept, which is the treatment of chronic idiopathic constipation – not irritable bowel syndrome with constipation, but chronic idiopathic constipation – being managed with a novel device known as the Vibrant capsule. The Vibrant capsule is exactly that: It’s a capsule that the patient ingests, and it vibrates and therefore creates a mechanical movement.

“Efficacy and Safety of Vibrant Capsule vs. Placebo for the Treatment of Chronic Idiopathic Constipation (Vibrant)” was a U.S. multicenter study. The device is an orally ingestible, programmable vibrating capsule developed in Israel. It basically mimics the biological clock and increases the stool frequency by augmenting the circadian rhythm. This was a prospective trial of around 350 patients, and there was significant improvement in the complete spontaneous bowel movement pattern, both for one and two bowel movements per week. This significant improvement persisted at week 3, peaked at about week 6, and then remained sustained through 8 weeks.

The Vibrant capsule also was able to improve stool consistency and the overall quality of life. So this is a novel treatment intervention over and above all the medical therapies in the bowel regimens, which of course our patients find somewhat difficult, understandably. But this might be a complementary direction to go in, and we’ll probably hear more of these novel interventions for chronic constipation, which is a huge problem both at the primary care level as well as in subspecialty practice.

In the final section, which is the liver section, I found one paper very interesting, which refers to the concept of lean nonalcoholic fatty liver disease (NAFLD) (“Lean NAFLD in the United States is Characterized by Increased Central and Visceral Adiposity That Is Comparable to Overweight and Obese Persons”). NAFLD is an epidemic throughout the country, with obvious implications both for the metabolic syndrome as well as chronic liver disease. This paper from Wisconsin looks at lean NALFD in the United States, characterizes the central and visceral adiposity, and compares it with that of overweight and obese patients. Lean NAFLD occurs in about 10%-20% of patients with a normal body mass index; 1,800 patients were evaluated in this particular study, and they underwent cross-sectional analysis and the so-called gap score, which looks at the measurement of fat in the liver, DEXA measurements, and so forth.

What they found was that patients with lean NAFLD are more likely to have hypertension, diabetes, high triglycerides, and are more likely to smoke, compared with lean patients without NAFLD, despite having similar BMIs.

A couple of additional observations from the study were that central adiposity was similar in lean NAFLD compared with the obese non-NAFLD population, and the visceral abdominal fat in patients who have lean NAFLD was slightly higher, actually, than in the obese NAFLD patients, but the P values were not significant.

The overall summary from this paper was that NAFLD should be considered in lean patients with risk factors of the metabolic syndrome. This is an important paper because it highlights the fact that we don’t necessarily have to be externally obese or have a high BMI to be at risk for the metabolic syndrome. I think the importance of evaluating for the metabolic syndrome, even in those patients who have a relatively lower BMI, is underscored by this paper, which has significant implications given the larger denominator of this population in this country.

So, with that, we come to the conclusion of these top papers from Digestive Disease Week 2022. We covered the gamut of conditions, from the esophagus to the colon and to the liver. And these represent some of the best science that was presented at this very large international meeting. I hope you will find value in this information for the care of your patients, and I look forward to presenting again when the next opportunity arises.

Vivek Kaul, MD, is Segal-Watson Professor of Medicine in the gastroenterology & hepatology division at the University of Rochester Medical Center in Rochester, N.Y.

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

This transcript has been edited for clarity.

Hi. I’m Dr. Vivek Kaul, and I’m professor of medicine in the division of gastroenterology and hepatology at the University of Rochester (N.Y.) Medical Center. It gives me great pleasure to do this presentation in collaboration with Medscape. I have just returned from Digestive Disease Week 2022, which is the largest international GI conference, and it was held in person for the first time in 3 years because of the pandemic.

Whereas there are a lot of “Best of DDW” presentations for gastroenterologists, there are not that many for primary care providers, so I thought it would be a good idea to do this. What I’ve tried to do is to bring some information that is here now and almost imminently translatable into clinical practice, talk a little about the middle-future range where things will become available in the next few months to years, and then, of course, reflect upon concepts that might become more standard paradigms of care in the distant future.

My collection of papers is divided into the esophagus and the colon, and then finishes up with the liver. [Editor’s note: Some of the abstracts that Dr Kaul refers to are available here.]

The first paper in the esophagus realm is a multicenter study called “The Association of Proton Pump Inhibitor Use and Cognitive Decline and Incident Dementia in Older Adults.” The researchers looked at about 19,000 patients, 65 years and older, who were on PPI therapy and had no significant disability or prior dementia. They followed them for about 5 years and found that a total of about 566 of them developed dementia in this time frame and 235 or so had Alzheimer’s. What they concluded based on that analysis was that PPI use was not associated with dementia or changes in the overall cognitive score.

This is important information. As the American Gastroenterological Association guidelines and others have recommended, those patients who do require a PPI on clinical grounds should definitely receive it, and the side-effect profiles are quite acceptable.

The second paper, “Double-Blind Randomized Trial of the Potassium-Competitive Acid Blocker Vonoprazan vs. the Proton Pump Inhibitor Lansoprazole in U.S. and European Patients with Erosive Esophagitis,” is also related to GERD [gastroesophageal reflux disease] therapy but introduces a new paradigm known as potassium-competitive channel blockers. This is a new drug that has now become available, called vonoprazan.

This was a double-blinded, randomized trial of the potassium-competitive acid blocker vonoprazan in comparison with lansoprazole, which is a well-established medical agent available for the treatment of esophagitis. These are patients with erosive esophagitis in a multicenter U.S. and European cohort of about 1,000 patients who were prospectively treated. The crux of this study was to say that vonoprazan is quicker to provide healing and symptom relief, and that these results are maintained in both the initial phase, which is the treatment phase, and the maintenance phase.

So, there might be some advantages in terms of how quickly we can treat these patients and get them symptom free. I thought that study was worth mentioning because it reflects, after a long period of time, a new class of acid-suppression therapy, which we should all be familiar with, and certainly at the primary care level.

The next paper relates to Barrett’s esophagus and esophageal cancer. This paper came out of the OneFlorida+ Clinical Research Network and was titled “Alarming Rise Found in Esophageal Cancer and Barrett’s Esophagus in Middle-Aged Adults: Findings From a Statewide Database of Over 5 Million Patients.” This paper talks about the increasing prevalence of esophageal cancer in Barrett’s in middle-aged patients – those in the 45- to 64-years age group; the prevalence of esophageal cancer is rising in this cohort. So, as is shown in the first graph, the orange line is depicting the 45-64 age group patients whose esophageal cancer prevalence has gone up. And in the second graph, it’s actually the gray line which looks at the Barrett’s esophagus prevalence, which is also increasing. And all the other cohorts have either plateaued or are declining.

This is important information because these patients who are at risk in these age groups with these demographic profiles should be referred on for endoscopic screening to rule out Barrett’s at least once in their lifetime. And most certainly a percentage of them will be found to have dysplasia and or early esophageal cancer that might be amenable to endoscopic therapy.

The next section that we’ll talk about is the colon section. We have a few very good, high-quality papers with some provocative information in this realm. The first paper (“Multi-modal Blood-based Colorectal Cancer Screening Is a Viable Colorectal Cancer Screening Option – a Prospective Study”) in the colonoscopy section involves the concept of colorectal cancer screening. While we have multiple modalities available for colorectal cancer screening today, a third of eligible patients are not getting screened.

This study looks at a blood test for colorectal cancer screening. We have colonoscopy, we have stool DNA and other tests, but now we have a blood test looking at circulating tumor DNA. For this prospective, multicenter study, researchers from Madrid enrolled about 550 patients between 45 and 84 years of age. The blood test was completed prior to the complete colonoscopy. The prevalence of colorectal cancer screening in this study was about 2%; the sensitivity ranged from about 90% to 95%, and the specificity ranged from about 100% to 88%, depending on what confidence levels you were looking at.

In this prospective study, a blood-based colorectal cancer screening test was able to perform very similarly to stool-based options. Therefore, it may further increase the probability that patients might come in for screening.

The message from this paper is that there’s yet another modality for colorectal cancer screening, and now we have a blood test potentially, but obviously we look forward to more data on how the test itself performs. And there probably will be other candidates in the same realm.

The second paper (“Real-World Comparative Effectiveness of Fidaxomicin vs. Vancomycin Among Medicare Beneficiaries with Clostridioides difficile Infection”) in the colon section is also about a very important topic in clinical practice for all of us, and that is C. difficile infection. As you may know, current guidelines have recommended the use of fidaxomicin over vancomycin as the initial treatment for C. diff infection. This paper looked retrospectively at a cohort of patients in the real world and compared the efficacy of fidaxomicin vs. vancomycin among Medicare beneficiaries with C. diff infection.

The initial results of this multicenter study suggest that treatment with fidaxomicin had higher sustained response compared with vancomycin at both weeks 4 and 8, as well as decreased recurrence of C. difficile.  

This retrospective study further confirms that C. diff  infection remains a problem and that we might have better solutions now with fidaxomicin compared with vancomycin. That’s important information and is already endorsed by the guidelines.

The next paper in the colon realm, “A Randomized Controlled Trial on the Effectiveness of Cognitive-Behavioral and Mindfulness Intervention on Pain, Fatigue and Impairments at Work and Daily Activity in Patients With Crohn’s Disease,” is also an important paradigm that has entered our medical practice. When we are treating patients with GI symptoms, the role for cognitive-behavioral therapy and mindfulness interventions has now come of age.

This paper was a randomized controlled trial on the effectiveness of cognitive-behavioral therapy and mindfulness intervention on the aspects of pain and fatigue, as well as impairments at work and daily activity in patients with Crohn’s disease.

This is a difficult population with chronic illness, and this study comes out of Israel. About 120 patients were randomized to seven 1-hour sessions of psychological training over 12 weeks. The placebo group was the control group that did not get this treatment.

These interventions reduced both fatigue as well as pain levels, and also reduced work and home impairment, and so overall led to a better quality of life.

This paper is important because it shows us in a randomized trial design fashion that a difficult clinical population with Crohn’s disease, with a multitude of systemic symptoms and psychological, psychosomatic issues as well, can be positively impacted by these newer strategies related to cognitive-behavioral therapy and mindfulness interventions. We’ll likely be seeing more of these types of papers coming out, not just for Crohn’s and inflammatory bowel disease, but also for functional disease, which is where this started.

Our final paper in the colon section relates to an interesting concept, which is the treatment of chronic idiopathic constipation – not irritable bowel syndrome with constipation, but chronic idiopathic constipation – being managed with a novel device known as the Vibrant capsule. The Vibrant capsule is exactly that: It’s a capsule that the patient ingests, and it vibrates and therefore creates a mechanical movement.

“Efficacy and Safety of Vibrant Capsule vs. Placebo for the Treatment of Chronic Idiopathic Constipation (Vibrant)” was a U.S. multicenter study. The device is an orally ingestible, programmable vibrating capsule developed in Israel. It basically mimics the biological clock and increases the stool frequency by augmenting the circadian rhythm. This was a prospective trial of around 350 patients, and there was significant improvement in the complete spontaneous bowel movement pattern, both for one and two bowel movements per week. This significant improvement persisted at week 3, peaked at about week 6, and then remained sustained through 8 weeks.

The Vibrant capsule also was able to improve stool consistency and the overall quality of life. So this is a novel treatment intervention over and above all the medical therapies in the bowel regimens, which of course our patients find somewhat difficult, understandably. But this might be a complementary direction to go in, and we’ll probably hear more of these novel interventions for chronic constipation, which is a huge problem both at the primary care level as well as in subspecialty practice.

In the final section, which is the liver section, I found one paper very interesting, which refers to the concept of lean nonalcoholic fatty liver disease (NAFLD) (“Lean NAFLD in the United States is Characterized by Increased Central and Visceral Adiposity That Is Comparable to Overweight and Obese Persons”). NAFLD is an epidemic throughout the country, with obvious implications both for the metabolic syndrome as well as chronic liver disease. This paper from Wisconsin looks at lean NALFD in the United States, characterizes the central and visceral adiposity, and compares it with that of overweight and obese patients. Lean NAFLD occurs in about 10%-20% of patients with a normal body mass index; 1,800 patients were evaluated in this particular study, and they underwent cross-sectional analysis and the so-called gap score, which looks at the measurement of fat in the liver, DEXA measurements, and so forth.

What they found was that patients with lean NAFLD are more likely to have hypertension, diabetes, high triglycerides, and are more likely to smoke, compared with lean patients without NAFLD, despite having similar BMIs.

A couple of additional observations from the study were that central adiposity was similar in lean NAFLD compared with the obese non-NAFLD population, and the visceral abdominal fat in patients who have lean NAFLD was slightly higher, actually, than in the obese NAFLD patients, but the P values were not significant.

The overall summary from this paper was that NAFLD should be considered in lean patients with risk factors of the metabolic syndrome. This is an important paper because it highlights the fact that we don’t necessarily have to be externally obese or have a high BMI to be at risk for the metabolic syndrome. I think the importance of evaluating for the metabolic syndrome, even in those patients who have a relatively lower BMI, is underscored by this paper, which has significant implications given the larger denominator of this population in this country.

So, with that, we come to the conclusion of these top papers from Digestive Disease Week 2022. We covered the gamut of conditions, from the esophagus to the colon and to the liver. And these represent some of the best science that was presented at this very large international meeting. I hope you will find value in this information for the care of your patients, and I look forward to presenting again when the next opportunity arises.

Vivek Kaul, MD, is Segal-Watson Professor of Medicine in the gastroenterology & hepatology division at the University of Rochester Medical Center in Rochester, N.Y.

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

This transcript has been edited for clarity.

Hi. I’m Dr. Vivek Kaul, and I’m professor of medicine in the division of gastroenterology and hepatology at the University of Rochester (N.Y.) Medical Center. It gives me great pleasure to do this presentation in collaboration with Medscape. I have just returned from Digestive Disease Week 2022, which is the largest international GI conference, and it was held in person for the first time in 3 years because of the pandemic.

Whereas there are a lot of “Best of DDW” presentations for gastroenterologists, there are not that many for primary care providers, so I thought it would be a good idea to do this. What I’ve tried to do is to bring some information that is here now and almost imminently translatable into clinical practice, talk a little about the middle-future range where things will become available in the next few months to years, and then, of course, reflect upon concepts that might become more standard paradigms of care in the distant future.

My collection of papers is divided into the esophagus and the colon, and then finishes up with the liver. [Editor’s note: Some of the abstracts that Dr Kaul refers to are available here.]

The first paper in the esophagus realm is a multicenter study called “The Association of Proton Pump Inhibitor Use and Cognitive Decline and Incident Dementia in Older Adults.” The researchers looked at about 19,000 patients, 65 years and older, who were on PPI therapy and had no significant disability or prior dementia. They followed them for about 5 years and found that a total of about 566 of them developed dementia in this time frame and 235 or so had Alzheimer’s. What they concluded based on that analysis was that PPI use was not associated with dementia or changes in the overall cognitive score.

This is important information. As the American Gastroenterological Association guidelines and others have recommended, those patients who do require a PPI on clinical grounds should definitely receive it, and the side-effect profiles are quite acceptable.

The second paper, “Double-Blind Randomized Trial of the Potassium-Competitive Acid Blocker Vonoprazan vs. the Proton Pump Inhibitor Lansoprazole in U.S. and European Patients with Erosive Esophagitis,” is also related to GERD [gastroesophageal reflux disease] therapy but introduces a new paradigm known as potassium-competitive channel blockers. This is a new drug that has now become available, called vonoprazan.

This was a double-blinded, randomized trial of the potassium-competitive acid blocker vonoprazan in comparison with lansoprazole, which is a well-established medical agent available for the treatment of esophagitis. These are patients with erosive esophagitis in a multicenter U.S. and European cohort of about 1,000 patients who were prospectively treated. The crux of this study was to say that vonoprazan is quicker to provide healing and symptom relief, and that these results are maintained in both the initial phase, which is the treatment phase, and the maintenance phase.

So, there might be some advantages in terms of how quickly we can treat these patients and get them symptom free. I thought that study was worth mentioning because it reflects, after a long period of time, a new class of acid-suppression therapy, which we should all be familiar with, and certainly at the primary care level.

The next paper relates to Barrett’s esophagus and esophageal cancer. This paper came out of the OneFlorida+ Clinical Research Network and was titled “Alarming Rise Found in Esophageal Cancer and Barrett’s Esophagus in Middle-Aged Adults: Findings From a Statewide Database of Over 5 Million Patients.” This paper talks about the increasing prevalence of esophageal cancer in Barrett’s in middle-aged patients – those in the 45- to 64-years age group; the prevalence of esophageal cancer is rising in this cohort. So, as is shown in the first graph, the orange line is depicting the 45-64 age group patients whose esophageal cancer prevalence has gone up. And in the second graph, it’s actually the gray line which looks at the Barrett’s esophagus prevalence, which is also increasing. And all the other cohorts have either plateaued or are declining.

This is important information because these patients who are at risk in these age groups with these demographic profiles should be referred on for endoscopic screening to rule out Barrett’s at least once in their lifetime. And most certainly a percentage of them will be found to have dysplasia and or early esophageal cancer that might be amenable to endoscopic therapy.

The next section that we’ll talk about is the colon section. We have a few very good, high-quality papers with some provocative information in this realm. The first paper (“Multi-modal Blood-based Colorectal Cancer Screening Is a Viable Colorectal Cancer Screening Option – a Prospective Study”) in the colonoscopy section involves the concept of colorectal cancer screening. While we have multiple modalities available for colorectal cancer screening today, a third of eligible patients are not getting screened.

This study looks at a blood test for colorectal cancer screening. We have colonoscopy, we have stool DNA and other tests, but now we have a blood test looking at circulating tumor DNA. For this prospective, multicenter study, researchers from Madrid enrolled about 550 patients between 45 and 84 years of age. The blood test was completed prior to the complete colonoscopy. The prevalence of colorectal cancer screening in this study was about 2%; the sensitivity ranged from about 90% to 95%, and the specificity ranged from about 100% to 88%, depending on what confidence levels you were looking at.

In this prospective study, a blood-based colorectal cancer screening test was able to perform very similarly to stool-based options. Therefore, it may further increase the probability that patients might come in for screening.

The message from this paper is that there’s yet another modality for colorectal cancer screening, and now we have a blood test potentially, but obviously we look forward to more data on how the test itself performs. And there probably will be other candidates in the same realm.

The second paper (“Real-World Comparative Effectiveness of Fidaxomicin vs. Vancomycin Among Medicare Beneficiaries with Clostridioides difficile Infection”) in the colon section is also about a very important topic in clinical practice for all of us, and that is C. difficile infection. As you may know, current guidelines have recommended the use of fidaxomicin over vancomycin as the initial treatment for C. diff infection. This paper looked retrospectively at a cohort of patients in the real world and compared the efficacy of fidaxomicin vs. vancomycin among Medicare beneficiaries with C. diff infection.

The initial results of this multicenter study suggest that treatment with fidaxomicin had higher sustained response compared with vancomycin at both weeks 4 and 8, as well as decreased recurrence of C. difficile.  

This retrospective study further confirms that C. diff  infection remains a problem and that we might have better solutions now with fidaxomicin compared with vancomycin. That’s important information and is already endorsed by the guidelines.

The next paper in the colon realm, “A Randomized Controlled Trial on the Effectiveness of Cognitive-Behavioral and Mindfulness Intervention on Pain, Fatigue and Impairments at Work and Daily Activity in Patients With Crohn’s Disease,” is also an important paradigm that has entered our medical practice. When we are treating patients with GI symptoms, the role for cognitive-behavioral therapy and mindfulness interventions has now come of age.

This paper was a randomized controlled trial on the effectiveness of cognitive-behavioral therapy and mindfulness intervention on the aspects of pain and fatigue, as well as impairments at work and daily activity in patients with Crohn’s disease.

This is a difficult population with chronic illness, and this study comes out of Israel. About 120 patients were randomized to seven 1-hour sessions of psychological training over 12 weeks. The placebo group was the control group that did not get this treatment.

These interventions reduced both fatigue as well as pain levels, and also reduced work and home impairment, and so overall led to a better quality of life.

This paper is important because it shows us in a randomized trial design fashion that a difficult clinical population with Crohn’s disease, with a multitude of systemic symptoms and psychological, psychosomatic issues as well, can be positively impacted by these newer strategies related to cognitive-behavioral therapy and mindfulness interventions. We’ll likely be seeing more of these types of papers coming out, not just for Crohn’s and inflammatory bowel disease, but also for functional disease, which is where this started.

Our final paper in the colon section relates to an interesting concept, which is the treatment of chronic idiopathic constipation – not irritable bowel syndrome with constipation, but chronic idiopathic constipation – being managed with a novel device known as the Vibrant capsule. The Vibrant capsule is exactly that: It’s a capsule that the patient ingests, and it vibrates and therefore creates a mechanical movement.

“Efficacy and Safety of Vibrant Capsule vs. Placebo for the Treatment of Chronic Idiopathic Constipation (Vibrant)” was a U.S. multicenter study. The device is an orally ingestible, programmable vibrating capsule developed in Israel. It basically mimics the biological clock and increases the stool frequency by augmenting the circadian rhythm. This was a prospective trial of around 350 patients, and there was significant improvement in the complete spontaneous bowel movement pattern, both for one and two bowel movements per week. This significant improvement persisted at week 3, peaked at about week 6, and then remained sustained through 8 weeks.

The Vibrant capsule also was able to improve stool consistency and the overall quality of life. So this is a novel treatment intervention over and above all the medical therapies in the bowel regimens, which of course our patients find somewhat difficult, understandably. But this might be a complementary direction to go in, and we’ll probably hear more of these novel interventions for chronic constipation, which is a huge problem both at the primary care level as well as in subspecialty practice.

In the final section, which is the liver section, I found one paper very interesting, which refers to the concept of lean nonalcoholic fatty liver disease (NAFLD) (“Lean NAFLD in the United States is Characterized by Increased Central and Visceral Adiposity That Is Comparable to Overweight and Obese Persons”). NAFLD is an epidemic throughout the country, with obvious implications both for the metabolic syndrome as well as chronic liver disease. This paper from Wisconsin looks at lean NALFD in the United States, characterizes the central and visceral adiposity, and compares it with that of overweight and obese patients. Lean NAFLD occurs in about 10%-20% of patients with a normal body mass index; 1,800 patients were evaluated in this particular study, and they underwent cross-sectional analysis and the so-called gap score, which looks at the measurement of fat in the liver, DEXA measurements, and so forth.

What they found was that patients with lean NAFLD are more likely to have hypertension, diabetes, high triglycerides, and are more likely to smoke, compared with lean patients without NAFLD, despite having similar BMIs.

A couple of additional observations from the study were that central adiposity was similar in lean NAFLD compared with the obese non-NAFLD population, and the visceral abdominal fat in patients who have lean NAFLD was slightly higher, actually, than in the obese NAFLD patients, but the P values were not significant.

The overall summary from this paper was that NAFLD should be considered in lean patients with risk factors of the metabolic syndrome. This is an important paper because it highlights the fact that we don’t necessarily have to be externally obese or have a high BMI to be at risk for the metabolic syndrome. I think the importance of evaluating for the metabolic syndrome, even in those patients who have a relatively lower BMI, is underscored by this paper, which has significant implications given the larger denominator of this population in this country.

So, with that, we come to the conclusion of these top papers from Digestive Disease Week 2022. We covered the gamut of conditions, from the esophagus to the colon and to the liver. And these represent some of the best science that was presented at this very large international meeting. I hope you will find value in this information for the care of your patients, and I look forward to presenting again when the next opportunity arises.

Vivek Kaul, MD, is Segal-Watson Professor of Medicine in the gastroenterology & hepatology division at the University of Rochester Medical Center in Rochester, N.Y.

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

Gastroenterology 

May 2022 
Predicting Pancreatic Cancer in the UK Biobank Cohort Using Polygenic Risk Scores and Diabetes Mellitus
Sharma S et al. Gastroenterology. 2022 May;162(6):1665-1674.e2. doi: 10.1053/j.gastro.2022.01.016.

Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study
Shoda T et al. Gastroenterology. 2022 May;162(6):1635-1649. doi: 10.1053/j.gastro.2022.01.022.

June 2022
How to Incorporate Advanced Tissue Resection Techniques in Your Institution
Repici A et al. Gastroenterology. 2022 Jun; 162(7):1825-1830. doi: 10.1053/j.gastro.2022.03.034.

July 2022 
Pregnancy-Associated Liver Diseases
Terrault NA, Williamson C. Gastroenterology. 2022 Jul;163(1):97-117.e1. doi: 10.1053/j.gastro.2022.01.060.

Databases for Gastrointestinal Clinical and Public Health Research: Have Database, Will Research
Rustgi SD et al. Gastroenterology. 2022 Jul;163(1):31-34. doi: 10.1053/j.gastro.2022.04.024. 

Impact of Artificial Intelligence on Miss Rate of Colorectal Neoplasia
Wallace MB et al. Gastroenterology. 2022 Jul;163(1):295-304.e5. doi: 10.1053/j.gastro.2022.03.007.

The Association Between Proton Pump Inhibitor Exposure and Key Liver-Related Outcomes in Patients With Cirrhosis: A Veterans Affairs Cohort Study
Mahmud N et al. Gastroenterology. 2022 Jul;163(1):257-269.e6. doi: 10.1053/j.gastro.2022.03.052.

Clinical Gastroenterology and Hepatology

May 2022

Practice Patterns and Predictors of Stopping Colonoscopy in Older Adults With Colorectal Polyps
Rege S et al. Clin Gastroenterol Hepatol. 2022 May;20(5):e1050-e1060. doi: 10.1016/j.cgh.2021.06.041.

Duodenal Mucosal Barrier in Functional Dyspepsia
Narayanan SP et al. Clin Gastroenterol Hepatol. 2022 May;20(5):1019-1028.e3. doi: 10.1016/j.cgh.2021.09.029.

June 2022
Ultra-processed Foods and Risk of Crohn’s Disease and Ulcerative Colitis: A Prospective Cohort Study
Lo CH et al. Clin Gastroenterol Hepatol. 2022 Jun;20(6):e1323-e1337. doi: 10.1016/j.cgh.2021.08.031.

Changes in Lifestyle Factors After Endoscopic Screening: A Prospective Study in the United States
Knudsen MD et al. Clin Gastroenterol Hepatol. 2022 Jun;20(6):e1240-e1249. doi: 10.1016/j.cgh.2021.07.014.

Trends in Early-onset vs Late-onset Colorectal Cancer Incidence by Race/Ethnicity in the United States Cancer Statistics Database
Chang SH et al. Clin Gastroenterol Hepatol. 2022 Jun;20(6):e1365-e1377. doi: 10.1016/j.cgh.2021.07.035.

July 2022
Updates in Telemedicine for Gastroenterology Practices in the United States
Serper M, Volk ML. Clin Gastroenterol Hepatol. 2022 Jul;20(7):1432-1435. doi: 10.1016/j.cgh.2022.03.024.

Prevalence and Financial Burden of Digestive Diseases in a Commercially Insured Population
Mathews SC et al. Clin Gastroenterol Hepatol. 2022 Jul;20(7):1480-1487.e7. doi: 10.1016/j.cgh.2021.06.047.

Prevalence of Forceps Polypectomy of Nondiminutive Polyps Is Substantial But Modifiable
Fudman DI et al. Clin Gastroenterol Hepatol. 2022 Jul;20(7):1508-1515. doi: 10.1016/j.cgh.2021.11.031.

Long-Term Treatment of Eosinophilic Esophagitis With Budesonide Oral Suspension
Dellon ES et al. Clin Gastroenterol Hepatol. 2022 Jul;20(7):1488-1498.e11. doi: 10.1016/j.cgh.2021.06.020.

Techniques and Innovations in Gastrointestinal Endoscopy

Intervention Versus Observation in Patients Presenting With Lower Gastrointestinal Bleeding
Lipcsey MS et al. Tech Innov Gastrointest Endosc. 2022 Jan 01;24(2):145-152. doi: 10.1016/j.tige.2021.12.001.

Physician Reimbursement for Endoscopic Submucosal Dissection: A Single Center Analysis
Gajula P et al. Tech Innov Gastrointest Endosc. 2022 Jan 01;24(2):153-158. doi: 10.1016/j.tige.2021.12.003.

Gastroenterology 

May 2022 
Predicting Pancreatic Cancer in the UK Biobank Cohort Using Polygenic Risk Scores and Diabetes Mellitus
Sharma S et al. Gastroenterology. 2022 May;162(6):1665-1674.e2. doi: 10.1053/j.gastro.2022.01.016.

Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study
Shoda T et al. Gastroenterology. 2022 May;162(6):1635-1649. doi: 10.1053/j.gastro.2022.01.022.

June 2022
How to Incorporate Advanced Tissue Resection Techniques in Your Institution
Repici A et al. Gastroenterology. 2022 Jun; 162(7):1825-1830. doi: 10.1053/j.gastro.2022.03.034.

July 2022 
Pregnancy-Associated Liver Diseases
Terrault NA, Williamson C. Gastroenterology. 2022 Jul;163(1):97-117.e1. doi: 10.1053/j.gastro.2022.01.060.

Databases for Gastrointestinal Clinical and Public Health Research: Have Database, Will Research
Rustgi SD et al. Gastroenterology. 2022 Jul;163(1):31-34. doi: 10.1053/j.gastro.2022.04.024. 

Impact of Artificial Intelligence on Miss Rate of Colorectal Neoplasia
Wallace MB et al. Gastroenterology. 2022 Jul;163(1):295-304.e5. doi: 10.1053/j.gastro.2022.03.007.

The Association Between Proton Pump Inhibitor Exposure and Key Liver-Related Outcomes in Patients With Cirrhosis: A Veterans Affairs Cohort Study
Mahmud N et al. Gastroenterology. 2022 Jul;163(1):257-269.e6. doi: 10.1053/j.gastro.2022.03.052.

Clinical Gastroenterology and Hepatology

May 2022

Practice Patterns and Predictors of Stopping Colonoscopy in Older Adults With Colorectal Polyps
Rege S et al. Clin Gastroenterol Hepatol. 2022 May;20(5):e1050-e1060. doi: 10.1016/j.cgh.2021.06.041.

Duodenal Mucosal Barrier in Functional Dyspepsia
Narayanan SP et al. Clin Gastroenterol Hepatol. 2022 May;20(5):1019-1028.e3. doi: 10.1016/j.cgh.2021.09.029.

June 2022
Ultra-processed Foods and Risk of Crohn’s Disease and Ulcerative Colitis: A Prospective Cohort Study
Lo CH et al. Clin Gastroenterol Hepatol. 2022 Jun;20(6):e1323-e1337. doi: 10.1016/j.cgh.2021.08.031.

Changes in Lifestyle Factors After Endoscopic Screening: A Prospective Study in the United States
Knudsen MD et al. Clin Gastroenterol Hepatol. 2022 Jun;20(6):e1240-e1249. doi: 10.1016/j.cgh.2021.07.014.

Trends in Early-onset vs Late-onset Colorectal Cancer Incidence by Race/Ethnicity in the United States Cancer Statistics Database
Chang SH et al. Clin Gastroenterol Hepatol. 2022 Jun;20(6):e1365-e1377. doi: 10.1016/j.cgh.2021.07.035.

July 2022
Updates in Telemedicine for Gastroenterology Practices in the United States
Serper M, Volk ML. Clin Gastroenterol Hepatol. 2022 Jul;20(7):1432-1435. doi: 10.1016/j.cgh.2022.03.024.

Prevalence and Financial Burden of Digestive Diseases in a Commercially Insured Population
Mathews SC et al. Clin Gastroenterol Hepatol. 2022 Jul;20(7):1480-1487.e7. doi: 10.1016/j.cgh.2021.06.047.

Prevalence of Forceps Polypectomy of Nondiminutive Polyps Is Substantial But Modifiable
Fudman DI et al. Clin Gastroenterol Hepatol. 2022 Jul;20(7):1508-1515. doi: 10.1016/j.cgh.2021.11.031.

Long-Term Treatment of Eosinophilic Esophagitis With Budesonide Oral Suspension
Dellon ES et al. Clin Gastroenterol Hepatol. 2022 Jul;20(7):1488-1498.e11. doi: 10.1016/j.cgh.2021.06.020.

Techniques and Innovations in Gastrointestinal Endoscopy

Intervention Versus Observation in Patients Presenting With Lower Gastrointestinal Bleeding
Lipcsey MS et al. Tech Innov Gastrointest Endosc. 2022 Jan 01;24(2):145-152. doi: 10.1016/j.tige.2021.12.001.

Physician Reimbursement for Endoscopic Submucosal Dissection: A Single Center Analysis
Gajula P et al. Tech Innov Gastrointest Endosc. 2022 Jan 01;24(2):153-158. doi: 10.1016/j.tige.2021.12.003.

Gastroenterology 

May 2022 
Predicting Pancreatic Cancer in the UK Biobank Cohort Using Polygenic Risk Scores and Diabetes Mellitus
Sharma S et al. Gastroenterology. 2022 May;162(6):1665-1674.e2. doi: 10.1053/j.gastro.2022.01.016.

Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study
Shoda T et al. Gastroenterology. 2022 May;162(6):1635-1649. doi: 10.1053/j.gastro.2022.01.022.

June 2022
How to Incorporate Advanced Tissue Resection Techniques in Your Institution
Repici A et al. Gastroenterology. 2022 Jun; 162(7):1825-1830. doi: 10.1053/j.gastro.2022.03.034.

July 2022 
Pregnancy-Associated Liver Diseases
Terrault NA, Williamson C. Gastroenterology. 2022 Jul;163(1):97-117.e1. doi: 10.1053/j.gastro.2022.01.060.

Databases for Gastrointestinal Clinical and Public Health Research: Have Database, Will Research
Rustgi SD et al. Gastroenterology. 2022 Jul;163(1):31-34. doi: 10.1053/j.gastro.2022.04.024. 

Impact of Artificial Intelligence on Miss Rate of Colorectal Neoplasia
Wallace MB et al. Gastroenterology. 2022 Jul;163(1):295-304.e5. doi: 10.1053/j.gastro.2022.03.007.

The Association Between Proton Pump Inhibitor Exposure and Key Liver-Related Outcomes in Patients With Cirrhosis: A Veterans Affairs Cohort Study
Mahmud N et al. Gastroenterology. 2022 Jul;163(1):257-269.e6. doi: 10.1053/j.gastro.2022.03.052.

Clinical Gastroenterology and Hepatology

May 2022

Practice Patterns and Predictors of Stopping Colonoscopy in Older Adults With Colorectal Polyps
Rege S et al. Clin Gastroenterol Hepatol. 2022 May;20(5):e1050-e1060. doi: 10.1016/j.cgh.2021.06.041.

Duodenal Mucosal Barrier in Functional Dyspepsia
Narayanan SP et al. Clin Gastroenterol Hepatol. 2022 May;20(5):1019-1028.e3. doi: 10.1016/j.cgh.2021.09.029.

June 2022
Ultra-processed Foods and Risk of Crohn’s Disease and Ulcerative Colitis: A Prospective Cohort Study
Lo CH et al. Clin Gastroenterol Hepatol. 2022 Jun;20(6):e1323-e1337. doi: 10.1016/j.cgh.2021.08.031.

Changes in Lifestyle Factors After Endoscopic Screening: A Prospective Study in the United States
Knudsen MD et al. Clin Gastroenterol Hepatol. 2022 Jun;20(6):e1240-e1249. doi: 10.1016/j.cgh.2021.07.014.

Trends in Early-onset vs Late-onset Colorectal Cancer Incidence by Race/Ethnicity in the United States Cancer Statistics Database
Chang SH et al. Clin Gastroenterol Hepatol. 2022 Jun;20(6):e1365-e1377. doi: 10.1016/j.cgh.2021.07.035.

July 2022
Updates in Telemedicine for Gastroenterology Practices in the United States
Serper M, Volk ML. Clin Gastroenterol Hepatol. 2022 Jul;20(7):1432-1435. doi: 10.1016/j.cgh.2022.03.024.

Prevalence and Financial Burden of Digestive Diseases in a Commercially Insured Population
Mathews SC et al. Clin Gastroenterol Hepatol. 2022 Jul;20(7):1480-1487.e7. doi: 10.1016/j.cgh.2021.06.047.

Prevalence of Forceps Polypectomy of Nondiminutive Polyps Is Substantial But Modifiable
Fudman DI et al. Clin Gastroenterol Hepatol. 2022 Jul;20(7):1508-1515. doi: 10.1016/j.cgh.2021.11.031.

Long-Term Treatment of Eosinophilic Esophagitis With Budesonide Oral Suspension
Dellon ES et al. Clin Gastroenterol Hepatol. 2022 Jul;20(7):1488-1498.e11. doi: 10.1016/j.cgh.2021.06.020.

Techniques and Innovations in Gastrointestinal Endoscopy

Intervention Versus Observation in Patients Presenting With Lower Gastrointestinal Bleeding
Lipcsey MS et al. Tech Innov Gastrointest Endosc. 2022 Jan 01;24(2):145-152. doi: 10.1016/j.tige.2021.12.001.

Physician Reimbursement for Endoscopic Submucosal Dissection: A Single Center Analysis
Gajula P et al. Tech Innov Gastrointest Endosc. 2022 Jan 01;24(2):153-158. doi: 10.1016/j.tige.2021.12.003.

Patients with a history of depression who are also being treated with opioid analgesics have a lower risk for overdose and self-harm after taking antidepressants, new research suggests.

Investigators analyzed insurance claims for more than 200,000 adults with a history of depression. Of these, 8,200 experienced adverse events (AEs) during the year after initiation of opioid therapy.

However, the risk for an AE such as overdose and other forms of self-harm was reduced among patients who had been treated with antidepressants for at least 6 weeks.

The take-home message is that clinicians and health systems need to be more aware that individuals in pain are more likely to be depressed and at higher risk for AEs – so the depression should be treated “more liberally,” corresponding author Bradley Stein, MD, PhD, a practicing psychiatrist in Pittsburgh and director of the Rand Corporation Opioid Policy Center, told this news organization.

“If you are treating someone with pain, particularly chronic pain, it’s critically important to better assess their depression and not to attribute depressive symptoms only to pain,” Dr. Stein said.

The findings were published online  in Psychiatric Services.
 

Promising approach?

Opioid treatment for pain “complicates the interactions among pain, depression, and self-harm,” the investigators write. Individuals with depression receiving long-term opioid therapy are two to three times more likely to misuse opioids, compared with individuals who do not have depression.

Although comorbid depression “substantially increases overdose and suicide risk, it remains underdiagnosed and undertreated among individuals with chronic pain,” the researchers note. They add that increasing access to depression treatment may be a “potentially promising approach to preventing overdoses and suicide” in these patients.

“We know that individuals using opioids who have a history of depression are more likely to have negative outcomes, such as overdoses and self-harm events,” Dr. Stein said. “We wanted to see whether antidepressants, which would treat depression in these individuals, would help with that.”

The researchers assessed a database of commercial insurance claims of adults with a history of depression who received opioids between 2007 and 2017 (n = 283,374). The data included 336,599 opioid treatment episodes.

To be included in the study, patients had to have been diagnosed with depression before they filled their first opioid prescription.

The “outcome of interest” was time from the beginning of an opioid episode until an adverse event, such as opioid poisoning, overdose of nonopioid controlled or illicit substances, or self-harm unrelated to overdose.

Participants were followed from the onset of the opioid episode until an AE occurred, loss to follow-up, or week 52, whichever came first.

The “key independent variable” was filling an antidepressant prescription. The patient’s sex and age were considered to be independent variables as well.
 

Teasing out antidepressant effect

Of participants with a history of depression treatment, 8,203 experienced at least one AE during the 12 months after treatment initiation (n = 47,486 AEs). Approximately half (50.8%) filled an antidepressant prescription at least once during the 12 months after the opioid episode began.

AEs were more likely among men than among women. The highest risk was in patients aged 18-24 years.

After adjusting for age and sex, participants who had received antidepressants had a greater risk for all adverse outcomes during the first 6 weeks of antidepressant treatment. However, those who had received antidepressants for 6 weeks or longer were at reduced risk for all adverse outcomes.

Consider CBT?

Andrew Saxon, MD, professor, department of psychiatry and behavioral sciences, University of Washington School of Medicine, Seattle, said clinicians “tend to think categorically and give people diagnoses that are clear-cut.” But neurobiologically, “it may be hard to distinguish where chronic pain ends and depression begins, or whether there’s some commonality.”

For patients with chronic pain and those taking opioids, “we need to be very attuned to the possibility or likelihood that they have major depression and other psychiatric diagnoses, like PTSD and anxiety disorders, which are very common,” said Dr. Saxon, who is also the director of the Center of Excellence in Substance Abuse Treatment and Education at the VA Puget Sound Health Care System. He was not involved with the current research.

He noted that treating those disorders “is a very important component of managing chronic pain.” However, “patients just starting antidepressants need to be carefully monitored when they’re getting stabilized on their antidepressants because they can have side effects, particularly early on, that can destabilize them.”

Dr. Saxon added that beyond pharmacotherapy, cognitive-behavioral therapy (CBT) for pain might be an even better intervention for addressing both pain and depression.

Also commenting for this article, Brian Hurley, MD, an addiction medicine specialist and the medical director of the Division of Substance Abuse Prevention and Control for the Los Angeles County Department of Public Health, said: “In the context of the largest wave of overdose mortality in U.S. history, we know comparatively little about the impact of mental health interventions that mitigate overdose risks.”

This study “contributes important new information that treating depression with antidepressant medications reduces overdose and self-harm risks for people who are prescribed opioids,” said Dr. Hurley, who is also the president-elect of the American Society of Addiction Medicine.

It also “underscores the general importance of integrated mental health and substance use disorder treatment in both primary care and in mental health settings,” added Dr. Hurley, who was not involved with the study.

The study was funded by the National Institute on Drug Abuse. The investigators and commenters reported no relevant financial relationships.

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

Patients with a history of depression who are also being treated with opioid analgesics have a lower risk for overdose and self-harm after taking antidepressants, new research suggests.

Investigators analyzed insurance claims for more than 200,000 adults with a history of depression. Of these, 8,200 experienced adverse events (AEs) during the year after initiation of opioid therapy.

However, the risk for an AE such as overdose and other forms of self-harm was reduced among patients who had been treated with antidepressants for at least 6 weeks.

The take-home message is that clinicians and health systems need to be more aware that individuals in pain are more likely to be depressed and at higher risk for AEs – so the depression should be treated “more liberally,” corresponding author Bradley Stein, MD, PhD, a practicing psychiatrist in Pittsburgh and director of the Rand Corporation Opioid Policy Center, told this news organization.

“If you are treating someone with pain, particularly chronic pain, it’s critically important to better assess their depression and not to attribute depressive symptoms only to pain,” Dr. Stein said.

The findings were published online  in Psychiatric Services.
 

Promising approach?

Opioid treatment for pain “complicates the interactions among pain, depression, and self-harm,” the investigators write. Individuals with depression receiving long-term opioid therapy are two to three times more likely to misuse opioids, compared with individuals who do not have depression.

Although comorbid depression “substantially increases overdose and suicide risk, it remains underdiagnosed and undertreated among individuals with chronic pain,” the researchers note. They add that increasing access to depression treatment may be a “potentially promising approach to preventing overdoses and suicide” in these patients.

“We know that individuals using opioids who have a history of depression are more likely to have negative outcomes, such as overdoses and self-harm events,” Dr. Stein said. “We wanted to see whether antidepressants, which would treat depression in these individuals, would help with that.”

The researchers assessed a database of commercial insurance claims of adults with a history of depression who received opioids between 2007 and 2017 (n = 283,374). The data included 336,599 opioid treatment episodes.

To be included in the study, patients had to have been diagnosed with depression before they filled their first opioid prescription.

The “outcome of interest” was time from the beginning of an opioid episode until an adverse event, such as opioid poisoning, overdose of nonopioid controlled or illicit substances, or self-harm unrelated to overdose.

Participants were followed from the onset of the opioid episode until an AE occurred, loss to follow-up, or week 52, whichever came first.

The “key independent variable” was filling an antidepressant prescription. The patient’s sex and age were considered to be independent variables as well.
 

Teasing out antidepressant effect

Of participants with a history of depression treatment, 8,203 experienced at least one AE during the 12 months after treatment initiation (n = 47,486 AEs). Approximately half (50.8%) filled an antidepressant prescription at least once during the 12 months after the opioid episode began.

AEs were more likely among men than among women. The highest risk was in patients aged 18-24 years.

After adjusting for age and sex, participants who had received antidepressants had a greater risk for all adverse outcomes during the first 6 weeks of antidepressant treatment. However, those who had received antidepressants for 6 weeks or longer were at reduced risk for all adverse outcomes.

Consider CBT?

Andrew Saxon, MD, professor, department of psychiatry and behavioral sciences, University of Washington School of Medicine, Seattle, said clinicians “tend to think categorically and give people diagnoses that are clear-cut.” But neurobiologically, “it may be hard to distinguish where chronic pain ends and depression begins, or whether there’s some commonality.”

For patients with chronic pain and those taking opioids, “we need to be very attuned to the possibility or likelihood that they have major depression and other psychiatric diagnoses, like PTSD and anxiety disorders, which are very common,” said Dr. Saxon, who is also the director of the Center of Excellence in Substance Abuse Treatment and Education at the VA Puget Sound Health Care System. He was not involved with the current research.

He noted that treating those disorders “is a very important component of managing chronic pain.” However, “patients just starting antidepressants need to be carefully monitored when they’re getting stabilized on their antidepressants because they can have side effects, particularly early on, that can destabilize them.”

Dr. Saxon added that beyond pharmacotherapy, cognitive-behavioral therapy (CBT) for pain might be an even better intervention for addressing both pain and depression.

Also commenting for this article, Brian Hurley, MD, an addiction medicine specialist and the medical director of the Division of Substance Abuse Prevention and Control for the Los Angeles County Department of Public Health, said: “In the context of the largest wave of overdose mortality in U.S. history, we know comparatively little about the impact of mental health interventions that mitigate overdose risks.”

This study “contributes important new information that treating depression with antidepressant medications reduces overdose and self-harm risks for people who are prescribed opioids,” said Dr. Hurley, who is also the president-elect of the American Society of Addiction Medicine.

It also “underscores the general importance of integrated mental health and substance use disorder treatment in both primary care and in mental health settings,” added Dr. Hurley, who was not involved with the study.

The study was funded by the National Institute on Drug Abuse. The investigators and commenters reported no relevant financial relationships.

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

Patients with a history of depression who are also being treated with opioid analgesics have a lower risk for overdose and self-harm after taking antidepressants, new research suggests.

Investigators analyzed insurance claims for more than 200,000 adults with a history of depression. Of these, 8,200 experienced adverse events (AEs) during the year after initiation of opioid therapy.

However, the risk for an AE such as overdose and other forms of self-harm was reduced among patients who had been treated with antidepressants for at least 6 weeks.

The take-home message is that clinicians and health systems need to be more aware that individuals in pain are more likely to be depressed and at higher risk for AEs – so the depression should be treated “more liberally,” corresponding author Bradley Stein, MD, PhD, a practicing psychiatrist in Pittsburgh and director of the Rand Corporation Opioid Policy Center, told this news organization.

“If you are treating someone with pain, particularly chronic pain, it’s critically important to better assess their depression and not to attribute depressive symptoms only to pain,” Dr. Stein said.

The findings were published online  in Psychiatric Services.
 

Promising approach?

Opioid treatment for pain “complicates the interactions among pain, depression, and self-harm,” the investigators write. Individuals with depression receiving long-term opioid therapy are two to three times more likely to misuse opioids, compared with individuals who do not have depression.

Although comorbid depression “substantially increases overdose and suicide risk, it remains underdiagnosed and undertreated among individuals with chronic pain,” the researchers note. They add that increasing access to depression treatment may be a “potentially promising approach to preventing overdoses and suicide” in these patients.

“We know that individuals using opioids who have a history of depression are more likely to have negative outcomes, such as overdoses and self-harm events,” Dr. Stein said. “We wanted to see whether antidepressants, which would treat depression in these individuals, would help with that.”

The researchers assessed a database of commercial insurance claims of adults with a history of depression who received opioids between 2007 and 2017 (n = 283,374). The data included 336,599 opioid treatment episodes.

To be included in the study, patients had to have been diagnosed with depression before they filled their first opioid prescription.

The “outcome of interest” was time from the beginning of an opioid episode until an adverse event, such as opioid poisoning, overdose of nonopioid controlled or illicit substances, or self-harm unrelated to overdose.

Participants were followed from the onset of the opioid episode until an AE occurred, loss to follow-up, or week 52, whichever came first.

The “key independent variable” was filling an antidepressant prescription. The patient’s sex and age were considered to be independent variables as well.
 

Teasing out antidepressant effect

Of participants with a history of depression treatment, 8,203 experienced at least one AE during the 12 months after treatment initiation (n = 47,486 AEs). Approximately half (50.8%) filled an antidepressant prescription at least once during the 12 months after the opioid episode began.

AEs were more likely among men than among women. The highest risk was in patients aged 18-24 years.

After adjusting for age and sex, participants who had received antidepressants had a greater risk for all adverse outcomes during the first 6 weeks of antidepressant treatment. However, those who had received antidepressants for 6 weeks or longer were at reduced risk for all adverse outcomes.

Consider CBT?

Andrew Saxon, MD, professor, department of psychiatry and behavioral sciences, University of Washington School of Medicine, Seattle, said clinicians “tend to think categorically and give people diagnoses that are clear-cut.” But neurobiologically, “it may be hard to distinguish where chronic pain ends and depression begins, or whether there’s some commonality.”

For patients with chronic pain and those taking opioids, “we need to be very attuned to the possibility or likelihood that they have major depression and other psychiatric diagnoses, like PTSD and anxiety disorders, which are very common,” said Dr. Saxon, who is also the director of the Center of Excellence in Substance Abuse Treatment and Education at the VA Puget Sound Health Care System. He was not involved with the current research.

He noted that treating those disorders “is a very important component of managing chronic pain.” However, “patients just starting antidepressants need to be carefully monitored when they’re getting stabilized on their antidepressants because they can have side effects, particularly early on, that can destabilize them.”

Dr. Saxon added that beyond pharmacotherapy, cognitive-behavioral therapy (CBT) for pain might be an even better intervention for addressing both pain and depression.

Also commenting for this article, Brian Hurley, MD, an addiction medicine specialist and the medical director of the Division of Substance Abuse Prevention and Control for the Los Angeles County Department of Public Health, said: “In the context of the largest wave of overdose mortality in U.S. history, we know comparatively little about the impact of mental health interventions that mitigate overdose risks.”

This study “contributes important new information that treating depression with antidepressant medications reduces overdose and self-harm risks for people who are prescribed opioids,” said Dr. Hurley, who is also the president-elect of the American Society of Addiction Medicine.

It also “underscores the general importance of integrated mental health and substance use disorder treatment in both primary care and in mental health settings,” added Dr. Hurley, who was not involved with the study.

The study was funded by the National Institute on Drug Abuse. The investigators and commenters reported no relevant financial relationships.

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

Only about 6% of cancer drugs tested in a phase 1 study in 2015 were ultimately approved by the U.S. Food and Drug Administration by 2021, a new analysis suggests.

The researchers also found that about 8% of approved agents were subsequently taken off the market.

“The 6% is not a big surprise to us, since a few other studies using different methodologies and foci have estimated similar percentages,” Alyson Haslam, PhD, University of California, San Francisco, told this news organization. “When you look at drug development, it makes sense that you have to test a lot of drugs to get one that works, but sometimes it is nice to quantify the actual percentage in order to fully appreciate the process.”

The fact that 8% were withdrawn, however, “elicits the question of how the approval process can be improved to avoid ineffective or harmful drugs from coming onto the market,” Dr. Haslam added.

The study was published online  in the International Journal of Cancer.
 

More desirable features?

Monitoring trends over time helps oncologists assess whether more drugs are making it to market and if certain factors make some drugs more likely to get approved.

Prior published estimates put the likelihood of approval between 6.7% and 13.4%, but these estimates were for drugs tested more than a decade ago.

To provide updated estimates, the researchers searched the literature for all oncology drugs tested in phase 1 studies during 2015 and evaluated their fate in subsequent phase 2/3 studies through FDA clearance.

Overall, the team found 803 phase 1 studies that met initial inclusion criteria; 48 trials that included only Japanese participants were excluded because these studies often evaluated drugs already approved in the United States, leaving 755 studies for the analysis.

The most common tumor types were solid/multiple tumors (24.2%), leukemias (12.8%), and lung cancer (8.5%). Just under half (47%) of the trials tested a drug as monotherapy; 43% were combination trials with one dose-escalated drug; and about 10% were combination trials with both drugs dose-escalated.

The FDA approved 51 drugs during the study period. Four (7.8%) were subsequently withdrawn: nivolumab (Opdivo) and pembrolizumab (Keytruda) for small cell lung cancer, olaratumab (Lartruvo) for soft tissue sarcoma, and melflufen (Pepaxto) for multiple myeloma. These four were not counted in the overall number of approvals.

“We really wanted to look at the end fate of drugs (within a reasonable time frame), which is why we did not include the four drugs that were initially approved but later withdrawn, although this had little impact on the main finding,” Dr. Haslam explained.

The estimated probability of any drug or drug combination tested in a phase 1 trial published in 2015 and approved that year was 1.7% and reached 6.2% by the end of 2021, the researchers found.

Monoclonal antibodies had a higher probability of being approved (15.3%), compared with inhibitors (5.1%) and chemotherapy drugs (4.2%).

The FDA was also more apt to green-light drugs tested as monotherapy, compared with drug combinations (odds ratio, 0.22). Drugs tested in monotherapy had a 9.4% probability of approval versus those tested in combination, which had a 5.6% probability of being approved when pairing a novel drug with one or more established agents, as well as when combining two novel drugs. The probability of approval was less than 1% for trials testing two established drug combinations.

Other factors that boosted the odds of FDA approval include having a response rate over 40% in phase 1 testing, demonstrating an overall survival benefit in phase 3 testing, and having the trial sponsored by a top-20 drug company, compared with a non–top-20 drug company.

Dr. Haslam found the last finding rather surprising, given the recent trend for bigger companies to invest in smaller companies who are developing promising drugs, rather than doing all of the development themselves. “In fact, a recent analysis found that only 25% of new drugs are sponsored by larger companies,” she noted.

Reached for comment, Jeff Allen, PhD, who wasn’t involved in the study, noted that “these types of landscape analyses are quite helpful in understanding the current state of oncology science and drug development.”

When looking at a 6.2% success rate for phase 1–tested oncology drugs, “it can be difficult holistically to determine all factors for which development didn’t continue,” said Dr. Allen, president and CEO of the nonprofit Friends of Cancer Research.

For instance, lack of approval may not signal the drug was a failure “but rather an artifact of circumstances such as resource limitations or reprioritization,” Dr. Allen said.

Plus, he commented, “I don’t think that we should expect all these early studies to lead to eventual approvals, but it’s clear from the authors’ findings that continued efforts to improve the overall success rate in developing new cancer medicines are greatly needed.”

The study was funded by Arnold Ventures. Dr. Haslam and Dr. Allen have no relevant disclosures. Study author Vinay Prasad, MD, MPH, receives royalties from Arnold Ventures.

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

Only about 6% of cancer drugs tested in a phase 1 study in 2015 were ultimately approved by the U.S. Food and Drug Administration by 2021, a new analysis suggests.

The researchers also found that about 8% of approved agents were subsequently taken off the market.

“The 6% is not a big surprise to us, since a few other studies using different methodologies and foci have estimated similar percentages,” Alyson Haslam, PhD, University of California, San Francisco, told this news organization. “When you look at drug development, it makes sense that you have to test a lot of drugs to get one that works, but sometimes it is nice to quantify the actual percentage in order to fully appreciate the process.”

The fact that 8% were withdrawn, however, “elicits the question of how the approval process can be improved to avoid ineffective or harmful drugs from coming onto the market,” Dr. Haslam added.

The study was published online  in the International Journal of Cancer.
 

More desirable features?

Monitoring trends over time helps oncologists assess whether more drugs are making it to market and if certain factors make some drugs more likely to get approved.

Prior published estimates put the likelihood of approval between 6.7% and 13.4%, but these estimates were for drugs tested more than a decade ago.

To provide updated estimates, the researchers searched the literature for all oncology drugs tested in phase 1 studies during 2015 and evaluated their fate in subsequent phase 2/3 studies through FDA clearance.

Overall, the team found 803 phase 1 studies that met initial inclusion criteria; 48 trials that included only Japanese participants were excluded because these studies often evaluated drugs already approved in the United States, leaving 755 studies for the analysis.

The most common tumor types were solid/multiple tumors (24.2%), leukemias (12.8%), and lung cancer (8.5%). Just under half (47%) of the trials tested a drug as monotherapy; 43% were combination trials with one dose-escalated drug; and about 10% were combination trials with both drugs dose-escalated.

The FDA approved 51 drugs during the study period. Four (7.8%) were subsequently withdrawn: nivolumab (Opdivo) and pembrolizumab (Keytruda) for small cell lung cancer, olaratumab (Lartruvo) for soft tissue sarcoma, and melflufen (Pepaxto) for multiple myeloma. These four were not counted in the overall number of approvals.

“We really wanted to look at the end fate of drugs (within a reasonable time frame), which is why we did not include the four drugs that were initially approved but later withdrawn, although this had little impact on the main finding,” Dr. Haslam explained.

The estimated probability of any drug or drug combination tested in a phase 1 trial published in 2015 and approved that year was 1.7% and reached 6.2% by the end of 2021, the researchers found.

Monoclonal antibodies had a higher probability of being approved (15.3%), compared with inhibitors (5.1%) and chemotherapy drugs (4.2%).

The FDA was also more apt to green-light drugs tested as monotherapy, compared with drug combinations (odds ratio, 0.22). Drugs tested in monotherapy had a 9.4% probability of approval versus those tested in combination, which had a 5.6% probability of being approved when pairing a novel drug with one or more established agents, as well as when combining two novel drugs. The probability of approval was less than 1% for trials testing two established drug combinations.

Other factors that boosted the odds of FDA approval include having a response rate over 40% in phase 1 testing, demonstrating an overall survival benefit in phase 3 testing, and having the trial sponsored by a top-20 drug company, compared with a non–top-20 drug company.

Dr. Haslam found the last finding rather surprising, given the recent trend for bigger companies to invest in smaller companies who are developing promising drugs, rather than doing all of the development themselves. “In fact, a recent analysis found that only 25% of new drugs are sponsored by larger companies,” she noted.

Reached for comment, Jeff Allen, PhD, who wasn’t involved in the study, noted that “these types of landscape analyses are quite helpful in understanding the current state of oncology science and drug development.”

When looking at a 6.2% success rate for phase 1–tested oncology drugs, “it can be difficult holistically to determine all factors for which development didn’t continue,” said Dr. Allen, president and CEO of the nonprofit Friends of Cancer Research.

For instance, lack of approval may not signal the drug was a failure “but rather an artifact of circumstances such as resource limitations or reprioritization,” Dr. Allen said.

Plus, he commented, “I don’t think that we should expect all these early studies to lead to eventual approvals, but it’s clear from the authors’ findings that continued efforts to improve the overall success rate in developing new cancer medicines are greatly needed.”

The study was funded by Arnold Ventures. Dr. Haslam and Dr. Allen have no relevant disclosures. Study author Vinay Prasad, MD, MPH, receives royalties from Arnold Ventures.

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

Only about 6% of cancer drugs tested in a phase 1 study in 2015 were ultimately approved by the U.S. Food and Drug Administration by 2021, a new analysis suggests.

The researchers also found that about 8% of approved agents were subsequently taken off the market.

“The 6% is not a big surprise to us, since a few other studies using different methodologies and foci have estimated similar percentages,” Alyson Haslam, PhD, University of California, San Francisco, told this news organization. “When you look at drug development, it makes sense that you have to test a lot of drugs to get one that works, but sometimes it is nice to quantify the actual percentage in order to fully appreciate the process.”

The fact that 8% were withdrawn, however, “elicits the question of how the approval process can be improved to avoid ineffective or harmful drugs from coming onto the market,” Dr. Haslam added.

The study was published online  in the International Journal of Cancer.
 

More desirable features?

Monitoring trends over time helps oncologists assess whether more drugs are making it to market and if certain factors make some drugs more likely to get approved.

Prior published estimates put the likelihood of approval between 6.7% and 13.4%, but these estimates were for drugs tested more than a decade ago.

To provide updated estimates, the researchers searched the literature for all oncology drugs tested in phase 1 studies during 2015 and evaluated their fate in subsequent phase 2/3 studies through FDA clearance.

Overall, the team found 803 phase 1 studies that met initial inclusion criteria; 48 trials that included only Japanese participants were excluded because these studies often evaluated drugs already approved in the United States, leaving 755 studies for the analysis.

The most common tumor types were solid/multiple tumors (24.2%), leukemias (12.8%), and lung cancer (8.5%). Just under half (47%) of the trials tested a drug as monotherapy; 43% were combination trials with one dose-escalated drug; and about 10% were combination trials with both drugs dose-escalated.

The FDA approved 51 drugs during the study period. Four (7.8%) were subsequently withdrawn: nivolumab (Opdivo) and pembrolizumab (Keytruda) for small cell lung cancer, olaratumab (Lartruvo) for soft tissue sarcoma, and melflufen (Pepaxto) for multiple myeloma. These four were not counted in the overall number of approvals.

“We really wanted to look at the end fate of drugs (within a reasonable time frame), which is why we did not include the four drugs that were initially approved but later withdrawn, although this had little impact on the main finding,” Dr. Haslam explained.

The estimated probability of any drug or drug combination tested in a phase 1 trial published in 2015 and approved that year was 1.7% and reached 6.2% by the end of 2021, the researchers found.

Monoclonal antibodies had a higher probability of being approved (15.3%), compared with inhibitors (5.1%) and chemotherapy drugs (4.2%).

The FDA was also more apt to green-light drugs tested as monotherapy, compared with drug combinations (odds ratio, 0.22). Drugs tested in monotherapy had a 9.4% probability of approval versus those tested in combination, which had a 5.6% probability of being approved when pairing a novel drug with one or more established agents, as well as when combining two novel drugs. The probability of approval was less than 1% for trials testing two established drug combinations.

Other factors that boosted the odds of FDA approval include having a response rate over 40% in phase 1 testing, demonstrating an overall survival benefit in phase 3 testing, and having the trial sponsored by a top-20 drug company, compared with a non–top-20 drug company.

Dr. Haslam found the last finding rather surprising, given the recent trend for bigger companies to invest in smaller companies who are developing promising drugs, rather than doing all of the development themselves. “In fact, a recent analysis found that only 25% of new drugs are sponsored by larger companies,” she noted.

Reached for comment, Jeff Allen, PhD, who wasn’t involved in the study, noted that “these types of landscape analyses are quite helpful in understanding the current state of oncology science and drug development.”

When looking at a 6.2% success rate for phase 1–tested oncology drugs, “it can be difficult holistically to determine all factors for which development didn’t continue,” said Dr. Allen, president and CEO of the nonprofit Friends of Cancer Research.

For instance, lack of approval may not signal the drug was a failure “but rather an artifact of circumstances such as resource limitations or reprioritization,” Dr. Allen said.

Plus, he commented, “I don’t think that we should expect all these early studies to lead to eventual approvals, but it’s clear from the authors’ findings that continued efforts to improve the overall success rate in developing new cancer medicines are greatly needed.”

The study was funded by Arnold Ventures. Dr. Haslam and Dr. Allen have no relevant disclosures. Study author Vinay Prasad, MD, MPH, receives royalties from Arnold Ventures.

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

A new geographic analysis of U.S. death rates from young-onset colorectal cancer found distinctive regional patterns that varied by age.

The so-called hot and cold spots of mortality from young-onset CRC differed slightly for people younger than 50 and those younger than 35, report the researchers, who say such studies may lead to better understanding of the underlying factors as well as to targeted interventions.

The authors suggest that deaths in the youngest young-onset CRC individuals “may be driven by a distinct set of factors, compared with deaths among older young-onset CRC and average-onset CRC patients.”

They add that “unmeasured factors ... may drive anomalous young-onset CRC mortality rates, either independently or in conjunction with demographic [and] modifiable variables accounted for here.”

The research was published online in Gastroenterology.
 

Incidence, mortality rates on the rise

The incidence and mortality rates of young-onset CRC have been increasing for decades, the authors write, but it has only recently begun to attract public health attention.

Risk factors and prognostic indicators, such as smoking, obesity, alcohol consumption, diabetes, sex, race, and socioeconomic factors, have been implicated in the development of the condition.

Geospatial distribution of young-onset CRC adds an “important [layer] for understanding the underlying drivers of mortality and allocating public health resources,” the authors write.

It is “too soon” to draw conclusions about the cause of the hot and cold spots, cautioned senior author Stephanie L. Schmit, PhD, vice chair of the Genomic Medicine Institute at the Lerner Research Institute, Cleveland Clinic.

Speaking to this news organization, she said, “Additional factors like proximity to primary care, gastroenterology, and cancer care facilities or novel environmental exposures may contribute to hot spots.”

On the other hand, “lifestyle factors like diet and exercise might contribute to some extent to cold spots,” she added.

While Dr. Schmit said it would be “challenging” to replicate the findings nationally, “further analyses at more granular geographic levels would be incredibly helpful.”
 

Exploring the geographical distribution

To explore the geographical distribution of young-onset CRC mortality, the researchers gathered 20 years of data on more than 1 million CRC deaths from 3,036 U.S. counties. With aggregated county-level information from 1999 to 2019, they derived mortality rates from CDC WONDER underlying cause of death data.

Over the study period, there were 69,976 deaths from CRC among individuals diagnosed before age 50, including 7,325 persons diagnosed younger than 35. Most CRC deaths (1,033,541) occurred in people diagnosed at age 50 and older.

The researchers calculated an average county-level young-onset CRC mortality rate of 1.78 deaths per 100,000 population, compared with a CRC mortality rate of 56.82 per 100,000 population among individuals 50 and older.

Overall, for individuals younger than 50 at diagnosis, the researchers found two hot spots – in the Southeast (relative risk, 1.24) and in the Great Lakes region (RR, 1.10). They identified cold spots in lower Wisconsin (RR, 0.87), the Northeast (RR, 0.92), southwest Texas (RR, 0.90), and Western counties more broadly, including Alaska (RR, 0.82).

Further analysis of those diagnosed when younger than 35 revealed two significant young-onset CRC mortality hot spots – in the Northeast (RR, 1.25) and the upper Midwest (RR, 1.11). In this youngest group, the team also found three significant cold spots – in the Southwest (RR, 0.74), in California (RR, 0.78), and in the Mountain West (RR, 0.82).

Among those aged 35-49 years at diagnosis, researchers found three hot spots – two in the Southeast (RR,1.20 and 1.16) and in the Great Lakes region (RR, 1.12). Several cold spots emerged from the mortality data on young-onset CRC in this age group – in the Pacific/Mountain West (RR, 0.90), in California (RR, 0.82), southern Texas (RR, 0.89), and the Southwest more broadly (RR, 0.86).

“Though cold spots were similar across strata, young-onset CRC hot spots shifted southward in the 35-49 age stratum in comparison to the less than 35 group,” the team notes.

They acknowledge several limitations to the study, including its “ecological nature” and the lack of adjustment for stage at diagnosis.

In comments to this news organization, Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, Boston, said the approach used by the researchers was “very interesting.”

Dr. Chan said that this is “one of the first studies that has given us insight into whether there is potential geographic variation in the incidence of young-onset colorectal cancer.”

This, he continued, is “very helpful in terms of thinking about potential risk factors for early-onset cancer and giving us more information about where we might want to focus our efforts in terms of prevention.”

Dr. Chan added that another interesting aspect of the study was that “the patterns might be different, depending on how you define early-onset cancer,” whether as “very-early onset,” defined as onset in those younger than 35, or the “less stringent definition” of 35-49 years.

He said that, “within the group that we’re calling very-early onset, there may be enriched factors,” compared with people who are “a little bit older.”

The research was supported by a National Cancer Institute of the National Institutes of Health grant to Case Comprehensive Cancer Center. Dr. Schmit reports no relevant financial relationships. Other authors have relationships with Exelixis, Tempus, Olympus, Anthos, Bayer, BMS, Janssen, Nektar Therapeutics, Pfizer, Sanofi, and WebMD/Medscape. Dr. Chan reports no relevant financial relationships.

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

A new geographic analysis of U.S. death rates from young-onset colorectal cancer found distinctive regional patterns that varied by age.

The so-called hot and cold spots of mortality from young-onset CRC differed slightly for people younger than 50 and those younger than 35, report the researchers, who say such studies may lead to better understanding of the underlying factors as well as to targeted interventions.

The authors suggest that deaths in the youngest young-onset CRC individuals “may be driven by a distinct set of factors, compared with deaths among older young-onset CRC and average-onset CRC patients.”

They add that “unmeasured factors ... may drive anomalous young-onset CRC mortality rates, either independently or in conjunction with demographic [and] modifiable variables accounted for here.”

The research was published online in Gastroenterology.
 

Incidence, mortality rates on the rise

The incidence and mortality rates of young-onset CRC have been increasing for decades, the authors write, but it has only recently begun to attract public health attention.

Risk factors and prognostic indicators, such as smoking, obesity, alcohol consumption, diabetes, sex, race, and socioeconomic factors, have been implicated in the development of the condition.

Geospatial distribution of young-onset CRC adds an “important [layer] for understanding the underlying drivers of mortality and allocating public health resources,” the authors write.

It is “too soon” to draw conclusions about the cause of the hot and cold spots, cautioned senior author Stephanie L. Schmit, PhD, vice chair of the Genomic Medicine Institute at the Lerner Research Institute, Cleveland Clinic.

Speaking to this news organization, she said, “Additional factors like proximity to primary care, gastroenterology, and cancer care facilities or novel environmental exposures may contribute to hot spots.”

On the other hand, “lifestyle factors like diet and exercise might contribute to some extent to cold spots,” she added.

While Dr. Schmit said it would be “challenging” to replicate the findings nationally, “further analyses at more granular geographic levels would be incredibly helpful.”
 

Exploring the geographical distribution

To explore the geographical distribution of young-onset CRC mortality, the researchers gathered 20 years of data on more than 1 million CRC deaths from 3,036 U.S. counties. With aggregated county-level information from 1999 to 2019, they derived mortality rates from CDC WONDER underlying cause of death data.

Over the study period, there were 69,976 deaths from CRC among individuals diagnosed before age 50, including 7,325 persons diagnosed younger than 35. Most CRC deaths (1,033,541) occurred in people diagnosed at age 50 and older.

The researchers calculated an average county-level young-onset CRC mortality rate of 1.78 deaths per 100,000 population, compared with a CRC mortality rate of 56.82 per 100,000 population among individuals 50 and older.

Overall, for individuals younger than 50 at diagnosis, the researchers found two hot spots – in the Southeast (relative risk, 1.24) and in the Great Lakes region (RR, 1.10). They identified cold spots in lower Wisconsin (RR, 0.87), the Northeast (RR, 0.92), southwest Texas (RR, 0.90), and Western counties more broadly, including Alaska (RR, 0.82).

Further analysis of those diagnosed when younger than 35 revealed two significant young-onset CRC mortality hot spots – in the Northeast (RR, 1.25) and the upper Midwest (RR, 1.11). In this youngest group, the team also found three significant cold spots – in the Southwest (RR, 0.74), in California (RR, 0.78), and in the Mountain West (RR, 0.82).

Among those aged 35-49 years at diagnosis, researchers found three hot spots – two in the Southeast (RR,1.20 and 1.16) and in the Great Lakes region (RR, 1.12). Several cold spots emerged from the mortality data on young-onset CRC in this age group – in the Pacific/Mountain West (RR, 0.90), in California (RR, 0.82), southern Texas (RR, 0.89), and the Southwest more broadly (RR, 0.86).

“Though cold spots were similar across strata, young-onset CRC hot spots shifted southward in the 35-49 age stratum in comparison to the less than 35 group,” the team notes.

They acknowledge several limitations to the study, including its “ecological nature” and the lack of adjustment for stage at diagnosis.

In comments to this news organization, Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, Boston, said the approach used by the researchers was “very interesting.”

Dr. Chan said that this is “one of the first studies that has given us insight into whether there is potential geographic variation in the incidence of young-onset colorectal cancer.”

This, he continued, is “very helpful in terms of thinking about potential risk factors for early-onset cancer and giving us more information about where we might want to focus our efforts in terms of prevention.”

Dr. Chan added that another interesting aspect of the study was that “the patterns might be different, depending on how you define early-onset cancer,” whether as “very-early onset,” defined as onset in those younger than 35, or the “less stringent definition” of 35-49 years.

He said that, “within the group that we’re calling very-early onset, there may be enriched factors,” compared with people who are “a little bit older.”

The research was supported by a National Cancer Institute of the National Institutes of Health grant to Case Comprehensive Cancer Center. Dr. Schmit reports no relevant financial relationships. Other authors have relationships with Exelixis, Tempus, Olympus, Anthos, Bayer, BMS, Janssen, Nektar Therapeutics, Pfizer, Sanofi, and WebMD/Medscape. Dr. Chan reports no relevant financial relationships.

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

A new geographic analysis of U.S. death rates from young-onset colorectal cancer found distinctive regional patterns that varied by age.

The so-called hot and cold spots of mortality from young-onset CRC differed slightly for people younger than 50 and those younger than 35, report the researchers, who say such studies may lead to better understanding of the underlying factors as well as to targeted interventions.

The authors suggest that deaths in the youngest young-onset CRC individuals “may be driven by a distinct set of factors, compared with deaths among older young-onset CRC and average-onset CRC patients.”

They add that “unmeasured factors ... may drive anomalous young-onset CRC mortality rates, either independently or in conjunction with demographic [and] modifiable variables accounted for here.”

The research was published online in Gastroenterology.
 

Incidence, mortality rates on the rise

The incidence and mortality rates of young-onset CRC have been increasing for decades, the authors write, but it has only recently begun to attract public health attention.

Risk factors and prognostic indicators, such as smoking, obesity, alcohol consumption, diabetes, sex, race, and socioeconomic factors, have been implicated in the development of the condition.

Geospatial distribution of young-onset CRC adds an “important [layer] for understanding the underlying drivers of mortality and allocating public health resources,” the authors write.

It is “too soon” to draw conclusions about the cause of the hot and cold spots, cautioned senior author Stephanie L. Schmit, PhD, vice chair of the Genomic Medicine Institute at the Lerner Research Institute, Cleveland Clinic.

Speaking to this news organization, she said, “Additional factors like proximity to primary care, gastroenterology, and cancer care facilities or novel environmental exposures may contribute to hot spots.”

On the other hand, “lifestyle factors like diet and exercise might contribute to some extent to cold spots,” she added.

While Dr. Schmit said it would be “challenging” to replicate the findings nationally, “further analyses at more granular geographic levels would be incredibly helpful.”
 

Exploring the geographical distribution

To explore the geographical distribution of young-onset CRC mortality, the researchers gathered 20 years of data on more than 1 million CRC deaths from 3,036 U.S. counties. With aggregated county-level information from 1999 to 2019, they derived mortality rates from CDC WONDER underlying cause of death data.

Over the study period, there were 69,976 deaths from CRC among individuals diagnosed before age 50, including 7,325 persons diagnosed younger than 35. Most CRC deaths (1,033,541) occurred in people diagnosed at age 50 and older.

The researchers calculated an average county-level young-onset CRC mortality rate of 1.78 deaths per 100,000 population, compared with a CRC mortality rate of 56.82 per 100,000 population among individuals 50 and older.

Overall, for individuals younger than 50 at diagnosis, the researchers found two hot spots – in the Southeast (relative risk, 1.24) and in the Great Lakes region (RR, 1.10). They identified cold spots in lower Wisconsin (RR, 0.87), the Northeast (RR, 0.92), southwest Texas (RR, 0.90), and Western counties more broadly, including Alaska (RR, 0.82).

Further analysis of those diagnosed when younger than 35 revealed two significant young-onset CRC mortality hot spots – in the Northeast (RR, 1.25) and the upper Midwest (RR, 1.11). In this youngest group, the team also found three significant cold spots – in the Southwest (RR, 0.74), in California (RR, 0.78), and in the Mountain West (RR, 0.82).

Among those aged 35-49 years at diagnosis, researchers found three hot spots – two in the Southeast (RR,1.20 and 1.16) and in the Great Lakes region (RR, 1.12). Several cold spots emerged from the mortality data on young-onset CRC in this age group – in the Pacific/Mountain West (RR, 0.90), in California (RR, 0.82), southern Texas (RR, 0.89), and the Southwest more broadly (RR, 0.86).

“Though cold spots were similar across strata, young-onset CRC hot spots shifted southward in the 35-49 age stratum in comparison to the less than 35 group,” the team notes.

They acknowledge several limitations to the study, including its “ecological nature” and the lack of adjustment for stage at diagnosis.

In comments to this news organization, Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, Boston, said the approach used by the researchers was “very interesting.”

Dr. Chan said that this is “one of the first studies that has given us insight into whether there is potential geographic variation in the incidence of young-onset colorectal cancer.”

This, he continued, is “very helpful in terms of thinking about potential risk factors for early-onset cancer and giving us more information about where we might want to focus our efforts in terms of prevention.”

Dr. Chan added that another interesting aspect of the study was that “the patterns might be different, depending on how you define early-onset cancer,” whether as “very-early onset,” defined as onset in those younger than 35, or the “less stringent definition” of 35-49 years.

He said that, “within the group that we’re calling very-early onset, there may be enriched factors,” compared with people who are “a little bit older.”

The research was supported by a National Cancer Institute of the National Institutes of Health grant to Case Comprehensive Cancer Center. Dr. Schmit reports no relevant financial relationships. Other authors have relationships with Exelixis, Tempus, Olympus, Anthos, Bayer, BMS, Janssen, Nektar Therapeutics, Pfizer, Sanofi, and WebMD/Medscape. Dr. Chan reports no relevant financial relationships.

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

Hepatocellular carcinoma risk declines after direct-acting antiviral treatment but remains high enough to justify screening for at least 7 years after hepatitis C cure, according to a new report.

Among patients with cirrhosis and fibrosis-4 (FIB-4) scores of 3.25 or higher, the incidence of hepatocellular carcinoma appeared to decline progressively each year up to 7 years after a sustained virologic response, although the rate remained above the 1% per year threshold that warrants screening.

“The majority of patients with hepatitis C have been treated and cured in the United States,” George Ioannou, MD, the senior study author and professor of medicine at the University of Washington, Seattle, said in an interview. “After hepatitis C eradication, these patients generally do very well from the liver standpoint, but the one thing they have to continue worrying about is development of liver cancer.”

Dr. Ioannou, who is also director of hepatology at the Veterans Affairs Puget Sound Health Care System, Seattle, noted that patients may be screened “indefinitely,” which places a burden on the patients and the health care system.

“We are still not sure to what extent the risk of liver cancer declines after hepatitis C eradication as more and more time accrues,” he said. “In those who had cirrhosis of the liver prior to hepatitis C cure, we are still not certain if there is a time point after hepatitis C cure when we can tell a patient that their risk of liver cancer is now very low and we no longer need to keep screening for liver cancer.”

The study was published online in Gastroenterology.
 

Risk calculations

In a previous study, Dr. Ioannou and colleagues found that hepatocellular carcinoma risk declined during the first 4 years of follow-up after a sustained virologic response from direct-acting antiviral medications. But the follow-up time wasn’t long enough to determine whether the cancer risk continues to decline to levels low enough to forgo screening.

In this study, Dr. Ioannou and colleagues extended the follow-up to 7 years. They were curious to see whether the cancer risk declines enough to drop the screening requirement, particularly as related to pretreatment cirrhosis and fibrosis-4 scores.

The research team analyzed electronic health records from the Veterans Affairs Corporate Data Warehouse, a national repository of Veterans Health Administration records developed specifically for research purposes.

The researchers included 29,033 patients in the Veterans Affairs health care system who had been infected with hepatitis C virus and were treated with direct-acting antivirals between January 2013 and December 2015. The patients had a sustained virologic response, which is defined as a viral load below the lower limit of detection at least 12 weeks after therapy completion.

The patients were followed for incident hepatocellular carcinoma until December 2021. The researchers then calculated the annual incidence during each year of follow-up after treatment.

About 96.6% of patients were men, and 52.2% were non-Hispanic White persons. The average age was 61 years. The most common conditions were alcohol use disorder (43.7%), substance use disorder (37.7%), and diabetes (28.9%).

Among the 7,533 patients with pretreatment cirrhosis, 948 (12.6%) developed hepatocellular carcinoma during a mean follow-up period of 4.9 years. Among patients with FIB-4 scores of 3.25 or higher, the annual incidence decreased from 3.8% in the first year to 1.4% in the seventh year but remained substantial up to 7 years after sustained virologic response. Among patients with both cirrhosis and a high FIB-4 score, the annual rate ranged from 0.7% to 1.3% and didn’t change significantly over time.

Among the 21,500 patients without pretreatment cirrhosis, 541 (or 2.5%) developed hepatocellular carcinoma during a mean follow-up period of 5.4 years. The incidence rate was significantly higher for patients with high FIB-4 scores. Among patients without cirrhosis but who had a high FIB-4 score, the annual rate remained stable but substantial (from 0.8% to 1.3%) for up to 7 years.

In a subgroup analysis that examined incidence according to changes in FIB-4 scores before and after treatment, the rate remained high among those with cirrhosis regardless of a score change. Among those without cirrhosis but who had a persistently high FIB-4 score, the incidence was high. In those without cirrhosis whose FIB-4 score dropped, the incidence was lower.

“The study demonstrates a clear decline in the risk of liver cancer over time after hepatitis C cure in the highest-risk group. This is very positive news for patients,” Dr. Ioannou said. “However, even with that decline in risk up to 7 years after eradication of hepatitis C with direct-acting antivirals, the risk is still high enough to warrant liver cancer screening.”
 

Future concerns

For a follow-up study, Dr. Ioannou and colleagues plan to adjust their analyses for other factors that influence the risk of liver cancer, such as age and nonalcoholic fatty liver disease. Other studies could increase the follow-up time beyond 7 years and assess how changes in diabetes, weight management, and alcohol use might affect liver cancer risk.

“With the availability of safe and effective direct-acting antiviral treatments, a growing number of patients have been or will be treated and cured of their hepatitis C infection,” Nicole Kim, MD, one of the lead authors and a transplant hepatology fellow at the University of Washington, Seattle, told this news organization.

“It is therefore important for us to develop a better understanding of how liver cancer risk might change after treatment, so we can improve the care we provide to this patient population,” she said.

The results require validation in nonveteran cohorts, the study authors write, as well as follow-up after the COVID-19 pandemic, when screening and diagnostic practices were restricted.

“Several studies have demonstrated that HCC [hepatocellular carcinoma] surveillance is underused in clinical practice, including in patients after [sustained virologic response],” Amit Singal, MD, clinical chief of hepatology and medical director of the liver tumor program at the University of Texas Southwestern Medical Center, told this news organization.

Dr. Singal, who wasn’t involved with this study, is evaluating several intervention strategies to increase surveillance utilization. His research group is conducting a multicenter randomized trial using mailed outreach invitations and is also evaluating a biomarker, PLSec-AFP, to identify patients with the highest risks who may warrant more intensive surveillance strategies.

“We have recently validated the performance of this biomarker in a large cohort of patients with cirrhosis, including some with cured hepatitis C virus infection,” he said.

The study was funded by an NIH/NCI grant and a VA CSR under Dr. Ioannou. The manuscript writing was supported by the NIH under Dr. Kim and co-author Philip Vutien. Dr. Singal has disclosed no relevant financial relationships.

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

Hepatocellular carcinoma risk declines after direct-acting antiviral treatment but remains high enough to justify screening for at least 7 years after hepatitis C cure, according to a new report.

Among patients with cirrhosis and fibrosis-4 (FIB-4) scores of 3.25 or higher, the incidence of hepatocellular carcinoma appeared to decline progressively each year up to 7 years after a sustained virologic response, although the rate remained above the 1% per year threshold that warrants screening.

“The majority of patients with hepatitis C have been treated and cured in the United States,” George Ioannou, MD, the senior study author and professor of medicine at the University of Washington, Seattle, said in an interview. “After hepatitis C eradication, these patients generally do very well from the liver standpoint, but the one thing they have to continue worrying about is development of liver cancer.”

Dr. Ioannou, who is also director of hepatology at the Veterans Affairs Puget Sound Health Care System, Seattle, noted that patients may be screened “indefinitely,” which places a burden on the patients and the health care system.

“We are still not sure to what extent the risk of liver cancer declines after hepatitis C eradication as more and more time accrues,” he said. “In those who had cirrhosis of the liver prior to hepatitis C cure, we are still not certain if there is a time point after hepatitis C cure when we can tell a patient that their risk of liver cancer is now very low and we no longer need to keep screening for liver cancer.”

The study was published online in Gastroenterology.
 

Risk calculations

In a previous study, Dr. Ioannou and colleagues found that hepatocellular carcinoma risk declined during the first 4 years of follow-up after a sustained virologic response from direct-acting antiviral medications. But the follow-up time wasn’t long enough to determine whether the cancer risk continues to decline to levels low enough to forgo screening.

In this study, Dr. Ioannou and colleagues extended the follow-up to 7 years. They were curious to see whether the cancer risk declines enough to drop the screening requirement, particularly as related to pretreatment cirrhosis and fibrosis-4 scores.

The research team analyzed electronic health records from the Veterans Affairs Corporate Data Warehouse, a national repository of Veterans Health Administration records developed specifically for research purposes.

The researchers included 29,033 patients in the Veterans Affairs health care system who had been infected with hepatitis C virus and were treated with direct-acting antivirals between January 2013 and December 2015. The patients had a sustained virologic response, which is defined as a viral load below the lower limit of detection at least 12 weeks after therapy completion.

The patients were followed for incident hepatocellular carcinoma until December 2021. The researchers then calculated the annual incidence during each year of follow-up after treatment.

About 96.6% of patients were men, and 52.2% were non-Hispanic White persons. The average age was 61 years. The most common conditions were alcohol use disorder (43.7%), substance use disorder (37.7%), and diabetes (28.9%).

Among the 7,533 patients with pretreatment cirrhosis, 948 (12.6%) developed hepatocellular carcinoma during a mean follow-up period of 4.9 years. Among patients with FIB-4 scores of 3.25 or higher, the annual incidence decreased from 3.8% in the first year to 1.4% in the seventh year but remained substantial up to 7 years after sustained virologic response. Among patients with both cirrhosis and a high FIB-4 score, the annual rate ranged from 0.7% to 1.3% and didn’t change significantly over time.

Among the 21,500 patients without pretreatment cirrhosis, 541 (or 2.5%) developed hepatocellular carcinoma during a mean follow-up period of 5.4 years. The incidence rate was significantly higher for patients with high FIB-4 scores. Among patients without cirrhosis but who had a high FIB-4 score, the annual rate remained stable but substantial (from 0.8% to 1.3%) for up to 7 years.

In a subgroup analysis that examined incidence according to changes in FIB-4 scores before and after treatment, the rate remained high among those with cirrhosis regardless of a score change. Among those without cirrhosis but who had a persistently high FIB-4 score, the incidence was high. In those without cirrhosis whose FIB-4 score dropped, the incidence was lower.

“The study demonstrates a clear decline in the risk of liver cancer over time after hepatitis C cure in the highest-risk group. This is very positive news for patients,” Dr. Ioannou said. “However, even with that decline in risk up to 7 years after eradication of hepatitis C with direct-acting antivirals, the risk is still high enough to warrant liver cancer screening.”
 

Future concerns

For a follow-up study, Dr. Ioannou and colleagues plan to adjust their analyses for other factors that influence the risk of liver cancer, such as age and nonalcoholic fatty liver disease. Other studies could increase the follow-up time beyond 7 years and assess how changes in diabetes, weight management, and alcohol use might affect liver cancer risk.

“With the availability of safe and effective direct-acting antiviral treatments, a growing number of patients have been or will be treated and cured of their hepatitis C infection,” Nicole Kim, MD, one of the lead authors and a transplant hepatology fellow at the University of Washington, Seattle, told this news organization.

“It is therefore important for us to develop a better understanding of how liver cancer risk might change after treatment, so we can improve the care we provide to this patient population,” she said.

The results require validation in nonveteran cohorts, the study authors write, as well as follow-up after the COVID-19 pandemic, when screening and diagnostic practices were restricted.

“Several studies have demonstrated that HCC [hepatocellular carcinoma] surveillance is underused in clinical practice, including in patients after [sustained virologic response],” Amit Singal, MD, clinical chief of hepatology and medical director of the liver tumor program at the University of Texas Southwestern Medical Center, told this news organization.

Dr. Singal, who wasn’t involved with this study, is evaluating several intervention strategies to increase surveillance utilization. His research group is conducting a multicenter randomized trial using mailed outreach invitations and is also evaluating a biomarker, PLSec-AFP, to identify patients with the highest risks who may warrant more intensive surveillance strategies.

“We have recently validated the performance of this biomarker in a large cohort of patients with cirrhosis, including some with cured hepatitis C virus infection,” he said.

The study was funded by an NIH/NCI grant and a VA CSR under Dr. Ioannou. The manuscript writing was supported by the NIH under Dr. Kim and co-author Philip Vutien. Dr. Singal has disclosed no relevant financial relationships.

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

Hepatocellular carcinoma risk declines after direct-acting antiviral treatment but remains high enough to justify screening for at least 7 years after hepatitis C cure, according to a new report.

Among patients with cirrhosis and fibrosis-4 (FIB-4) scores of 3.25 or higher, the incidence of hepatocellular carcinoma appeared to decline progressively each year up to 7 years after a sustained virologic response, although the rate remained above the 1% per year threshold that warrants screening.

“The majority of patients with hepatitis C have been treated and cured in the United States,” George Ioannou, MD, the senior study author and professor of medicine at the University of Washington, Seattle, said in an interview. “After hepatitis C eradication, these patients generally do very well from the liver standpoint, but the one thing they have to continue worrying about is development of liver cancer.”

Dr. Ioannou, who is also director of hepatology at the Veterans Affairs Puget Sound Health Care System, Seattle, noted that patients may be screened “indefinitely,” which places a burden on the patients and the health care system.

“We are still not sure to what extent the risk of liver cancer declines after hepatitis C eradication as more and more time accrues,” he said. “In those who had cirrhosis of the liver prior to hepatitis C cure, we are still not certain if there is a time point after hepatitis C cure when we can tell a patient that their risk of liver cancer is now very low and we no longer need to keep screening for liver cancer.”

The study was published online in Gastroenterology.
 

Risk calculations

In a previous study, Dr. Ioannou and colleagues found that hepatocellular carcinoma risk declined during the first 4 years of follow-up after a sustained virologic response from direct-acting antiviral medications. But the follow-up time wasn’t long enough to determine whether the cancer risk continues to decline to levels low enough to forgo screening.

In this study, Dr. Ioannou and colleagues extended the follow-up to 7 years. They were curious to see whether the cancer risk declines enough to drop the screening requirement, particularly as related to pretreatment cirrhosis and fibrosis-4 scores.

The research team analyzed electronic health records from the Veterans Affairs Corporate Data Warehouse, a national repository of Veterans Health Administration records developed specifically for research purposes.

The researchers included 29,033 patients in the Veterans Affairs health care system who had been infected with hepatitis C virus and were treated with direct-acting antivirals between January 2013 and December 2015. The patients had a sustained virologic response, which is defined as a viral load below the lower limit of detection at least 12 weeks after therapy completion.

The patients were followed for incident hepatocellular carcinoma until December 2021. The researchers then calculated the annual incidence during each year of follow-up after treatment.

About 96.6% of patients were men, and 52.2% were non-Hispanic White persons. The average age was 61 years. The most common conditions were alcohol use disorder (43.7%), substance use disorder (37.7%), and diabetes (28.9%).

Among the 7,533 patients with pretreatment cirrhosis, 948 (12.6%) developed hepatocellular carcinoma during a mean follow-up period of 4.9 years. Among patients with FIB-4 scores of 3.25 or higher, the annual incidence decreased from 3.8% in the first year to 1.4% in the seventh year but remained substantial up to 7 years after sustained virologic response. Among patients with both cirrhosis and a high FIB-4 score, the annual rate ranged from 0.7% to 1.3% and didn’t change significantly over time.

Among the 21,500 patients without pretreatment cirrhosis, 541 (or 2.5%) developed hepatocellular carcinoma during a mean follow-up period of 5.4 years. The incidence rate was significantly higher for patients with high FIB-4 scores. Among patients without cirrhosis but who had a high FIB-4 score, the annual rate remained stable but substantial (from 0.8% to 1.3%) for up to 7 years.

In a subgroup analysis that examined incidence according to changes in FIB-4 scores before and after treatment, the rate remained high among those with cirrhosis regardless of a score change. Among those without cirrhosis but who had a persistently high FIB-4 score, the incidence was high. In those without cirrhosis whose FIB-4 score dropped, the incidence was lower.

“The study demonstrates a clear decline in the risk of liver cancer over time after hepatitis C cure in the highest-risk group. This is very positive news for patients,” Dr. Ioannou said. “However, even with that decline in risk up to 7 years after eradication of hepatitis C with direct-acting antivirals, the risk is still high enough to warrant liver cancer screening.”
 

Future concerns

For a follow-up study, Dr. Ioannou and colleagues plan to adjust their analyses for other factors that influence the risk of liver cancer, such as age and nonalcoholic fatty liver disease. Other studies could increase the follow-up time beyond 7 years and assess how changes in diabetes, weight management, and alcohol use might affect liver cancer risk.

“With the availability of safe and effective direct-acting antiviral treatments, a growing number of patients have been or will be treated and cured of their hepatitis C infection,” Nicole Kim, MD, one of the lead authors and a transplant hepatology fellow at the University of Washington, Seattle, told this news organization.

“It is therefore important for us to develop a better understanding of how liver cancer risk might change after treatment, so we can improve the care we provide to this patient population,” she said.

The results require validation in nonveteran cohorts, the study authors write, as well as follow-up after the COVID-19 pandemic, when screening and diagnostic practices were restricted.

“Several studies have demonstrated that HCC [hepatocellular carcinoma] surveillance is underused in clinical practice, including in patients after [sustained virologic response],” Amit Singal, MD, clinical chief of hepatology and medical director of the liver tumor program at the University of Texas Southwestern Medical Center, told this news organization.

Dr. Singal, who wasn’t involved with this study, is evaluating several intervention strategies to increase surveillance utilization. His research group is conducting a multicenter randomized trial using mailed outreach invitations and is also evaluating a biomarker, PLSec-AFP, to identify patients with the highest risks who may warrant more intensive surveillance strategies.

“We have recently validated the performance of this biomarker in a large cohort of patients with cirrhosis, including some with cured hepatitis C virus infection,” he said.

The study was funded by an NIH/NCI grant and a VA CSR under Dr. Ioannou. The manuscript writing was supported by the NIH under Dr. Kim and co-author Philip Vutien. Dr. Singal has disclosed no relevant financial relationships.

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

Summer heat is notorious for making the strain of pregnancy worse. But for many pregnant people, sweltering temperatures are much worse than a sweaty annoyance.

New research shows that the risk of miscarriage rises sharply as the mercury climbs. In late August, for example, the risk of losing a pregnancy is 44% higher than in February, according to the findings.

“One of our hypotheses is that heat may trigger miscarriage, which is something that we are now exploring further,” says Amelia Wesselink, PhD, an assistant professor of epidemiology at Boston University School of Public Health, who led the study team. “Our next step is to dig into drivers of this seasonal pattern.”

She and her colleagues analyzed seasonal differences and pregnancy outcomes for over 12,000 women. Spontaneous abortion rates peaked in late August, especially for those living in the southern and midwestern United States.

Spontaneous abortion was defined as miscarriage, chemical pregnancy (a very early miscarriage where the embryo stops growing), or blighted ovum (the embryo stops developing or never develops).

From 2013 to 2020, 12,197 women living in the United States and Canada were followed for up to 1 year using Pregnancy Study Online (PRESTO), an internet-based fertility study from the Boston University School of Public Health. Those in the study answered questions about their income, education, race/ethnicity, and lifestyle, as well as follow-up questions about their pregnancy and/or loss of pregnancy.

Most of the people studied were non-Hispanic White (86%) and had at least a college degree (79%). Almost half earned more than $100,000 annually (47%). Those seeking fertility treatments were excluded from the study.

Half of the women (6,104) said they conceived in the first 12 months of trying to get pregnant, and almost one in five (19.5%) of those who conceived miscarried.

The risk of miscarriage was 44% higher in late August than it was in late February, the month with the lowest rate of lost pregnancies. This trend was almost exclusively seen for pregnancies in their first 8 weeks. The risk of miscarriage increased 31% in late August for pregnancies at any stage.

The link between miscarriage and extreme heat was strongest in the South and Midwest, with peaks in late August and early September, respectively.

“We know so little about the causes of miscarriage that it’s difficult to tie seasonal variation in risk to any particular cause,” says David Savitz, PhD, a professor of epidemiology and obstetrics, gynecology & pediatrics at Brown University, Providence, R.I., who helped conduct the study. “Exposures vary by summer, including a lower risk of respiratory infection in the warm season, changes in diet and physical activity, and physical factors such as temperature and sunlight.”

But another expert warned that extreme heat may not be the only culprit in summer’s observed miscarriage rates.

“You need to be careful when linking summer months to miscarriage, as women may pursue more outdoor activities during summer,” says Saifuddin Ahmed PhD, a researcher at Johns Hopkins Bloomberg School of Public Health, Baltimore.

Although the paper suggested physical activity may play a role in miscarriage frequency, no analysis supported this claim, Dr. Ahmed says.

Also, participants in the study were mostly White and tended to be wealthier than the general population, so the findings may not apply to everyone, Dr. Wesselink says. Although the researchers saw some similarities between participants with income above $100,000 a year and those who earned less, socioeconomic status plays an important role in environmental exposures – including heat – so the results may not hold among lower-income populations, Dr. Wesselink says.

Dr. Wesselink and her colleagues published their findings in the journal Epidemiology.

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

Summer heat is notorious for making the strain of pregnancy worse. But for many pregnant people, sweltering temperatures are much worse than a sweaty annoyance.

New research shows that the risk of miscarriage rises sharply as the mercury climbs. In late August, for example, the risk of losing a pregnancy is 44% higher than in February, according to the findings.

“One of our hypotheses is that heat may trigger miscarriage, which is something that we are now exploring further,” says Amelia Wesselink, PhD, an assistant professor of epidemiology at Boston University School of Public Health, who led the study team. “Our next step is to dig into drivers of this seasonal pattern.”

She and her colleagues analyzed seasonal differences and pregnancy outcomes for over 12,000 women. Spontaneous abortion rates peaked in late August, especially for those living in the southern and midwestern United States.

Spontaneous abortion was defined as miscarriage, chemical pregnancy (a very early miscarriage where the embryo stops growing), or blighted ovum (the embryo stops developing or never develops).

From 2013 to 2020, 12,197 women living in the United States and Canada were followed for up to 1 year using Pregnancy Study Online (PRESTO), an internet-based fertility study from the Boston University School of Public Health. Those in the study answered questions about their income, education, race/ethnicity, and lifestyle, as well as follow-up questions about their pregnancy and/or loss of pregnancy.

Most of the people studied were non-Hispanic White (86%) and had at least a college degree (79%). Almost half earned more than $100,000 annually (47%). Those seeking fertility treatments were excluded from the study.

Half of the women (6,104) said they conceived in the first 12 months of trying to get pregnant, and almost one in five (19.5%) of those who conceived miscarried.

The risk of miscarriage was 44% higher in late August than it was in late February, the month with the lowest rate of lost pregnancies. This trend was almost exclusively seen for pregnancies in their first 8 weeks. The risk of miscarriage increased 31% in late August for pregnancies at any stage.

The link between miscarriage and extreme heat was strongest in the South and Midwest, with peaks in late August and early September, respectively.

“We know so little about the causes of miscarriage that it’s difficult to tie seasonal variation in risk to any particular cause,” says David Savitz, PhD, a professor of epidemiology and obstetrics, gynecology & pediatrics at Brown University, Providence, R.I., who helped conduct the study. “Exposures vary by summer, including a lower risk of respiratory infection in the warm season, changes in diet and physical activity, and physical factors such as temperature and sunlight.”

But another expert warned that extreme heat may not be the only culprit in summer’s observed miscarriage rates.

“You need to be careful when linking summer months to miscarriage, as women may pursue more outdoor activities during summer,” says Saifuddin Ahmed PhD, a researcher at Johns Hopkins Bloomberg School of Public Health, Baltimore.

Although the paper suggested physical activity may play a role in miscarriage frequency, no analysis supported this claim, Dr. Ahmed says.

Also, participants in the study were mostly White and tended to be wealthier than the general population, so the findings may not apply to everyone, Dr. Wesselink says. Although the researchers saw some similarities between participants with income above $100,000 a year and those who earned less, socioeconomic status plays an important role in environmental exposures – including heat – so the results may not hold among lower-income populations, Dr. Wesselink says.

Dr. Wesselink and her colleagues published their findings in the journal Epidemiology.

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

Summer heat is notorious for making the strain of pregnancy worse. But for many pregnant people, sweltering temperatures are much worse than a sweaty annoyance.

New research shows that the risk of miscarriage rises sharply as the mercury climbs. In late August, for example, the risk of losing a pregnancy is 44% higher than in February, according to the findings.

“One of our hypotheses is that heat may trigger miscarriage, which is something that we are now exploring further,” says Amelia Wesselink, PhD, an assistant professor of epidemiology at Boston University School of Public Health, who led the study team. “Our next step is to dig into drivers of this seasonal pattern.”

She and her colleagues analyzed seasonal differences and pregnancy outcomes for over 12,000 women. Spontaneous abortion rates peaked in late August, especially for those living in the southern and midwestern United States.

Spontaneous abortion was defined as miscarriage, chemical pregnancy (a very early miscarriage where the embryo stops growing), or blighted ovum (the embryo stops developing or never develops).

From 2013 to 2020, 12,197 women living in the United States and Canada were followed for up to 1 year using Pregnancy Study Online (PRESTO), an internet-based fertility study from the Boston University School of Public Health. Those in the study answered questions about their income, education, race/ethnicity, and lifestyle, as well as follow-up questions about their pregnancy and/or loss of pregnancy.

Most of the people studied were non-Hispanic White (86%) and had at least a college degree (79%). Almost half earned more than $100,000 annually (47%). Those seeking fertility treatments were excluded from the study.

Half of the women (6,104) said they conceived in the first 12 months of trying to get pregnant, and almost one in five (19.5%) of those who conceived miscarried.

The risk of miscarriage was 44% higher in late August than it was in late February, the month with the lowest rate of lost pregnancies. This trend was almost exclusively seen for pregnancies in their first 8 weeks. The risk of miscarriage increased 31% in late August for pregnancies at any stage.

The link between miscarriage and extreme heat was strongest in the South and Midwest, with peaks in late August and early September, respectively.

“We know so little about the causes of miscarriage that it’s difficult to tie seasonal variation in risk to any particular cause,” says David Savitz, PhD, a professor of epidemiology and obstetrics, gynecology & pediatrics at Brown University, Providence, R.I., who helped conduct the study. “Exposures vary by summer, including a lower risk of respiratory infection in the warm season, changes in diet and physical activity, and physical factors such as temperature and sunlight.”

But another expert warned that extreme heat may not be the only culprit in summer’s observed miscarriage rates.

“You need to be careful when linking summer months to miscarriage, as women may pursue more outdoor activities during summer,” says Saifuddin Ahmed PhD, a researcher at Johns Hopkins Bloomberg School of Public Health, Baltimore.

Although the paper suggested physical activity may play a role in miscarriage frequency, no analysis supported this claim, Dr. Ahmed says.

Also, participants in the study were mostly White and tended to be wealthier than the general population, so the findings may not apply to everyone, Dr. Wesselink says. Although the researchers saw some similarities between participants with income above $100,000 a year and those who earned less, socioeconomic status plays an important role in environmental exposures – including heat – so the results may not hold among lower-income populations, Dr. Wesselink says.

Dr. Wesselink and her colleagues published their findings in the journal Epidemiology.

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

Amazon is working with the Fred Hutchinson Cancer Research Center to develop cancer vaccines in a new clinical trial.

The trial is aimed at finding “personalized vaccines” to treat breast cancer and melanoma. The phase 1 trial is recruiting 20 people over the age of 18 to study the safety of the vaccines, according to CNBC.

The Fred Hutchinson Cancer Research Center and University of Washington Cancer Consortium are listed as the researchers of the clinical trial, and Amazon is listed as a collaborator, according to a filing on the ClinicalTrials.gov database.

“Amazon is contributing scientific and machine learning expertise to a partnership with Fred Hutch to explore the development of a personalized treatment for certain forms of cancer,” an Amazon spokesperson told CNBC.

“It’s very early, but Fred Hutch recently received permission from the U.S. Food and Drug Administration to proceed with a phase 1 clinical trial, and it’s unclear whether it will be successful,” the spokesperson said. “This will be a long, multiyear process – should it progress, we would be open to working with other organizations in health care and life sciences that might also be interested in similar efforts.”

In recent years, Amazon has grown its presence in the health care industry, CNBC reported. The company launched an online pharmacy in 2020, developed a telehealth service called Amazon Care, and released its own COVID-19 test during the pandemic.

A research and development group inside Amazon, known as Grand Challenge, oversaw the company’s early cancer vaccine effort, according to Business Insider. It’s now under the purview of a cancer research team that reports to Robert Williams, the company’s vice president of devices.

The study was first posted on ClinicalTrials.gov in October 2021 and began recruiting patients on June 9, according to the filing. The phase 1 trial is expected to run through November 2023.

The phase 1 trial will study the safety of personalized vaccines to treat patients with late-stage melanoma or hormone receptor-positive HER2-negative breast cancer which has either spread to other parts of the body or doesn’t respond to treatment.

More information about the study can be found on ClinicalTrials.gov under the identifier NCT05098210.

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

Amazon is working with the Fred Hutchinson Cancer Research Center to develop cancer vaccines in a new clinical trial.

The trial is aimed at finding “personalized vaccines” to treat breast cancer and melanoma. The phase 1 trial is recruiting 20 people over the age of 18 to study the safety of the vaccines, according to CNBC.

The Fred Hutchinson Cancer Research Center and University of Washington Cancer Consortium are listed as the researchers of the clinical trial, and Amazon is listed as a collaborator, according to a filing on the ClinicalTrials.gov database.

“Amazon is contributing scientific and machine learning expertise to a partnership with Fred Hutch to explore the development of a personalized treatment for certain forms of cancer,” an Amazon spokesperson told CNBC.

“It’s very early, but Fred Hutch recently received permission from the U.S. Food and Drug Administration to proceed with a phase 1 clinical trial, and it’s unclear whether it will be successful,” the spokesperson said. “This will be a long, multiyear process – should it progress, we would be open to working with other organizations in health care and life sciences that might also be interested in similar efforts.”

In recent years, Amazon has grown its presence in the health care industry, CNBC reported. The company launched an online pharmacy in 2020, developed a telehealth service called Amazon Care, and released its own COVID-19 test during the pandemic.

A research and development group inside Amazon, known as Grand Challenge, oversaw the company’s early cancer vaccine effort, according to Business Insider. It’s now under the purview of a cancer research team that reports to Robert Williams, the company’s vice president of devices.

The study was first posted on ClinicalTrials.gov in October 2021 and began recruiting patients on June 9, according to the filing. The phase 1 trial is expected to run through November 2023.

The phase 1 trial will study the safety of personalized vaccines to treat patients with late-stage melanoma or hormone receptor-positive HER2-negative breast cancer which has either spread to other parts of the body or doesn’t respond to treatment.

More information about the study can be found on ClinicalTrials.gov under the identifier NCT05098210.

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

Amazon is working with the Fred Hutchinson Cancer Research Center to develop cancer vaccines in a new clinical trial.

The trial is aimed at finding “personalized vaccines” to treat breast cancer and melanoma. The phase 1 trial is recruiting 20 people over the age of 18 to study the safety of the vaccines, according to CNBC.

The Fred Hutchinson Cancer Research Center and University of Washington Cancer Consortium are listed as the researchers of the clinical trial, and Amazon is listed as a collaborator, according to a filing on the ClinicalTrials.gov database.

“Amazon is contributing scientific and machine learning expertise to a partnership with Fred Hutch to explore the development of a personalized treatment for certain forms of cancer,” an Amazon spokesperson told CNBC.

“It’s very early, but Fred Hutch recently received permission from the U.S. Food and Drug Administration to proceed with a phase 1 clinical trial, and it’s unclear whether it will be successful,” the spokesperson said. “This will be a long, multiyear process – should it progress, we would be open to working with other organizations in health care and life sciences that might also be interested in similar efforts.”

In recent years, Amazon has grown its presence in the health care industry, CNBC reported. The company launched an online pharmacy in 2020, developed a telehealth service called Amazon Care, and released its own COVID-19 test during the pandemic.

A research and development group inside Amazon, known as Grand Challenge, oversaw the company’s early cancer vaccine effort, according to Business Insider. It’s now under the purview of a cancer research team that reports to Robert Williams, the company’s vice president of devices.

The study was first posted on ClinicalTrials.gov in October 2021 and began recruiting patients on June 9, according to the filing. The phase 1 trial is expected to run through November 2023.

The phase 1 trial will study the safety of personalized vaccines to treat patients with late-stage melanoma or hormone receptor-positive HER2-negative breast cancer which has either spread to other parts of the body or doesn’t respond to treatment.

More information about the study can be found on ClinicalTrials.gov under the identifier NCT05098210.

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

A cost-saving, stepwise approach to treating diabetic macular edema was as effective and at least as safe as what’s been the standard approach, which jumps straight to the costlier treatment, in a head-to-head, multicenter, U.S. randomized trial of the two regimens that included 312 eyes in 270 adults with type 1 or type 2 diabetes.

The findings validate a treatment regimen for diabetic macular edema that’s already common in U.S. practice based on requirements by many health insurance providers because of the money it saves.

The step-therapy approach studied involves starting off-label treatment with the relatively inexpensive agent bevacizumab (Avastin), followed by a switch to the much pricier aflibercept (Eylea) when patients don’t adequately respond, following a prespecified algorithm that applies four criteria to determine when patients need to change agents.

These new findings build on a 2016 study that compared aflibercept monotherapy with bevacizumab monotherapy and showed that after 2 years of treatment aflibercept produced clearly better outcomes.

The new trial findings “are particularly relevant given the increasing frequency of insurers mandating step therapy with bevacizumab before the use of other drugs” such as aflibercept, noted Chirag D. Jhaveri, MD, and colleagues in the study published online in the New England Journal of Medicine.
 

Opportunity for ‘substantial cost reductions’

Jhaveri, a retina surgeon in Austin, Texas, and associates note that, based on Medicare reimbursement rates of $1,830 for a single dose of aflibercept and $70 for one dose of bevacizumab, starting treatment with bevacizumab could produce “substantial cost reductions for the health care system.”

The authors of an accompanying editorial agree. Step therapy that starts with bevacizumab would probably result in “substantial” cost savings, and the findings document “similar outcomes” from the two tested regimens based on improvements in visual acuity and changes in the thickness measurement of the central retina during the 2-year trial, write David C. Musch, PhD, and Emily Y. Chew, MD.

Dr. Musch, a professor and ophthalmology epidemiologist at the University of Michigan in Ann Arbor, and Dr. Chew, director of the Division of Epidemiology and Clinical Applications at the National Eye Institute in Bethesda, Md., also laud the “rigorous” study for its design and conduct that was “beyond reproach,” and for producing evidence that “applies well to clinical practice.”

The only potential drawback to the step-therapy approach, they write, is that people with diabetes often have “numerous coexisting conditions that make it more difficult for them to adhere to frequent follow-up visits,” a key element of the tested step-care protocol, which mandated follow-up visits every 4 weeks during the first year and every 4-16 weeks during the second year.
 

312 eyes of 270 patients

The new trial, organized by the DRCR Retinal Network and the Jaeb Center for Health Research in Tampa, Fla., ran at 54 U.S. sites from December 2017 to November 2019. The study randomized 158 eyes in 137 patients to aflibercept monotherapy, and 154 eyes in 133 patients to the step-care regimen (both eyes were treated in several patients in each group, with each eye receiving a different regimen). Participants were around 60 years old, 48% were women, and 95% had type 2 diabetes.

To be eligible for enrollment, patients had at least one eye with a best-corrected visual-acuity letter score of 24-69 on an Electronic Early Treatment Diabetic Retinopathy Study chart (ranges from 0 to 100, with higher values indicating better visual acuity), which corresponds to Snellen chart values of 20/320-20/50, readings that encompass most patients with diabetic macular edema, noted study authors Adam R. Glassman and Jennifer K. Sun, MD, in an interview.

“Very few patients with diabetic macular edema have vision due to this alone that is worse than 20/320, which meets criteria for legal blindness,” said Dr. Glassman, who is executive director of the Jaeb Center for Health Research, and Dr. Sun, who is chief of the center for clinical eye research and trials at the Joslin Diabetes Center in Boston and chair of the DRCR Retinal Network.

The primary outcome was time-averaged change in visual-acuity letter score from baseline to 2 years, which improved by an average of 15.0 letters in the aflibercept monotherapy group and an average of 14.0 letters in the step-therapy group, an adjusted difference of 0.8 letters, which was not significant. An improvement from baseline of at least 15 letters occurred in 53% of the eyes in the aflibercept monotherapy group and in 58% of those who had step therapy, and 77% of eyes in both groups had improvements of at least 10 letters.  

Central retinal thickness dropped from baseline by an average of 192 mcm with aflibercept monotherapy and 198 mcm with step therapy. The average number of total treatments (by intravitreous injection) was 14.6 in the aflibercept monotherapy group and 16.1 in the step-therapy group. After the first 24 weeks of the study, 39% of eyes in the step-therapy group had switched from bevacizumab to aflibercept injections; after 1 year, 60% of eyes had switched; and by study end, after 2 years, 70% had changed.

The bevacizumab-first group also showed at least comparable if not better safety, with similar rates of prespecified ocular events in both groups, but with a significantly lower rate of serious systemic adverse events, which occurred in 52% of the eyes treated with aflibercept only and 36% of eyes that began treatment on bevacizumab. Serious systemic adverse events occurred in 43% of patients who had two eyes treated as part of the trial.
 

‘Bevacizumab first was noninferior’

The team that designed the trial opted for a superiority design rather than a noninferiority trial and powered the study based on the presumption that aflibercept monotherapy would prove superior, said Dr. Glassman and Dr. Sun. “We feel that the clinical interpretation of these results will be similar to the interpretation if we had conducted a noninferiority study, and we found that bevacizumab first was noninferior to aflibercept monotherapy,” they maintained in an interview.

Dr. Glassman and Dr. Sun said they and their coauthors are now analyzing the results to try to find patient characteristics that could identify eyes most likely to respond to the bevacizumab-first approach. “It would be clinically valuable” to use the results to identify characteristics that could help guide clinicians’ treatment approach and enhance patient counseling, they said.

The study received funding from the National Institutes of Health. Dr. Jhaveri has reported being a consultant for Genentech, Novartis, and Regenxbio. Dr. Glassman has reported receiving grants from Genentech and Regeneron. Dr. Sun has reported receiving grants from Boehringer Ingelheim, Janssen Biotech, KalVista, Optovue, and Physical Sciences, grants and travel support from Novartis and Novo Nordisk, travel support from Merck, writing support from Genentech, and equipment supplied by Adaptive Sensory and Boston Micromachines. Dr. Musch and Dr. Chew have reported no relevant financial relationships.

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

A cost-saving, stepwise approach to treating diabetic macular edema was as effective and at least as safe as what’s been the standard approach, which jumps straight to the costlier treatment, in a head-to-head, multicenter, U.S. randomized trial of the two regimens that included 312 eyes in 270 adults with type 1 or type 2 diabetes.

The findings validate a treatment regimen for diabetic macular edema that’s already common in U.S. practice based on requirements by many health insurance providers because of the money it saves.

The step-therapy approach studied involves starting off-label treatment with the relatively inexpensive agent bevacizumab (Avastin), followed by a switch to the much pricier aflibercept (Eylea) when patients don’t adequately respond, following a prespecified algorithm that applies four criteria to determine when patients need to change agents.

These new findings build on a 2016 study that compared aflibercept monotherapy with bevacizumab monotherapy and showed that after 2 years of treatment aflibercept produced clearly better outcomes.

The new trial findings “are particularly relevant given the increasing frequency of insurers mandating step therapy with bevacizumab before the use of other drugs” such as aflibercept, noted Chirag D. Jhaveri, MD, and colleagues in the study published online in the New England Journal of Medicine.
 

Opportunity for ‘substantial cost reductions’

Jhaveri, a retina surgeon in Austin, Texas, and associates note that, based on Medicare reimbursement rates of $1,830 for a single dose of aflibercept and $70 for one dose of bevacizumab, starting treatment with bevacizumab could produce “substantial cost reductions for the health care system.”

The authors of an accompanying editorial agree. Step therapy that starts with bevacizumab would probably result in “substantial” cost savings, and the findings document “similar outcomes” from the two tested regimens based on improvements in visual acuity and changes in the thickness measurement of the central retina during the 2-year trial, write David C. Musch, PhD, and Emily Y. Chew, MD.

Dr. Musch, a professor and ophthalmology epidemiologist at the University of Michigan in Ann Arbor, and Dr. Chew, director of the Division of Epidemiology and Clinical Applications at the National Eye Institute in Bethesda, Md., also laud the “rigorous” study for its design and conduct that was “beyond reproach,” and for producing evidence that “applies well to clinical practice.”

The only potential drawback to the step-therapy approach, they write, is that people with diabetes often have “numerous coexisting conditions that make it more difficult for them to adhere to frequent follow-up visits,” a key element of the tested step-care protocol, which mandated follow-up visits every 4 weeks during the first year and every 4-16 weeks during the second year.
 

312 eyes of 270 patients

The new trial, organized by the DRCR Retinal Network and the Jaeb Center for Health Research in Tampa, Fla., ran at 54 U.S. sites from December 2017 to November 2019. The study randomized 158 eyes in 137 patients to aflibercept monotherapy, and 154 eyes in 133 patients to the step-care regimen (both eyes were treated in several patients in each group, with each eye receiving a different regimen). Participants were around 60 years old, 48% were women, and 95% had type 2 diabetes.

To be eligible for enrollment, patients had at least one eye with a best-corrected visual-acuity letter score of 24-69 on an Electronic Early Treatment Diabetic Retinopathy Study chart (ranges from 0 to 100, with higher values indicating better visual acuity), which corresponds to Snellen chart values of 20/320-20/50, readings that encompass most patients with diabetic macular edema, noted study authors Adam R. Glassman and Jennifer K. Sun, MD, in an interview.

“Very few patients with diabetic macular edema have vision due to this alone that is worse than 20/320, which meets criteria for legal blindness,” said Dr. Glassman, who is executive director of the Jaeb Center for Health Research, and Dr. Sun, who is chief of the center for clinical eye research and trials at the Joslin Diabetes Center in Boston and chair of the DRCR Retinal Network.

The primary outcome was time-averaged change in visual-acuity letter score from baseline to 2 years, which improved by an average of 15.0 letters in the aflibercept monotherapy group and an average of 14.0 letters in the step-therapy group, an adjusted difference of 0.8 letters, which was not significant. An improvement from baseline of at least 15 letters occurred in 53% of the eyes in the aflibercept monotherapy group and in 58% of those who had step therapy, and 77% of eyes in both groups had improvements of at least 10 letters.  

Central retinal thickness dropped from baseline by an average of 192 mcm with aflibercept monotherapy and 198 mcm with step therapy. The average number of total treatments (by intravitreous injection) was 14.6 in the aflibercept monotherapy group and 16.1 in the step-therapy group. After the first 24 weeks of the study, 39% of eyes in the step-therapy group had switched from bevacizumab to aflibercept injections; after 1 year, 60% of eyes had switched; and by study end, after 2 years, 70% had changed.

The bevacizumab-first group also showed at least comparable if not better safety, with similar rates of prespecified ocular events in both groups, but with a significantly lower rate of serious systemic adverse events, which occurred in 52% of the eyes treated with aflibercept only and 36% of eyes that began treatment on bevacizumab. Serious systemic adverse events occurred in 43% of patients who had two eyes treated as part of the trial.
 

‘Bevacizumab first was noninferior’

The team that designed the trial opted for a superiority design rather than a noninferiority trial and powered the study based on the presumption that aflibercept monotherapy would prove superior, said Dr. Glassman and Dr. Sun. “We feel that the clinical interpretation of these results will be similar to the interpretation if we had conducted a noninferiority study, and we found that bevacizumab first was noninferior to aflibercept monotherapy,” they maintained in an interview.

Dr. Glassman and Dr. Sun said they and their coauthors are now analyzing the results to try to find patient characteristics that could identify eyes most likely to respond to the bevacizumab-first approach. “It would be clinically valuable” to use the results to identify characteristics that could help guide clinicians’ treatment approach and enhance patient counseling, they said.

The study received funding from the National Institutes of Health. Dr. Jhaveri has reported being a consultant for Genentech, Novartis, and Regenxbio. Dr. Glassman has reported receiving grants from Genentech and Regeneron. Dr. Sun has reported receiving grants from Boehringer Ingelheim, Janssen Biotech, KalVista, Optovue, and Physical Sciences, grants and travel support from Novartis and Novo Nordisk, travel support from Merck, writing support from Genentech, and equipment supplied by Adaptive Sensory and Boston Micromachines. Dr. Musch and Dr. Chew have reported no relevant financial relationships.

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

A cost-saving, stepwise approach to treating diabetic macular edema was as effective and at least as safe as what’s been the standard approach, which jumps straight to the costlier treatment, in a head-to-head, multicenter, U.S. randomized trial of the two regimens that included 312 eyes in 270 adults with type 1 or type 2 diabetes.

The findings validate a treatment regimen for diabetic macular edema that’s already common in U.S. practice based on requirements by many health insurance providers because of the money it saves.

The step-therapy approach studied involves starting off-label treatment with the relatively inexpensive agent bevacizumab (Avastin), followed by a switch to the much pricier aflibercept (Eylea) when patients don’t adequately respond, following a prespecified algorithm that applies four criteria to determine when patients need to change agents.

These new findings build on a 2016 study that compared aflibercept monotherapy with bevacizumab monotherapy and showed that after 2 years of treatment aflibercept produced clearly better outcomes.

The new trial findings “are particularly relevant given the increasing frequency of insurers mandating step therapy with bevacizumab before the use of other drugs” such as aflibercept, noted Chirag D. Jhaveri, MD, and colleagues in the study published online in the New England Journal of Medicine.
 

Opportunity for ‘substantial cost reductions’

Jhaveri, a retina surgeon in Austin, Texas, and associates note that, based on Medicare reimbursement rates of $1,830 for a single dose of aflibercept and $70 for one dose of bevacizumab, starting treatment with bevacizumab could produce “substantial cost reductions for the health care system.”

The authors of an accompanying editorial agree. Step therapy that starts with bevacizumab would probably result in “substantial” cost savings, and the findings document “similar outcomes” from the two tested regimens based on improvements in visual acuity and changes in the thickness measurement of the central retina during the 2-year trial, write David C. Musch, PhD, and Emily Y. Chew, MD.

Dr. Musch, a professor and ophthalmology epidemiologist at the University of Michigan in Ann Arbor, and Dr. Chew, director of the Division of Epidemiology and Clinical Applications at the National Eye Institute in Bethesda, Md., also laud the “rigorous” study for its design and conduct that was “beyond reproach,” and for producing evidence that “applies well to clinical practice.”

The only potential drawback to the step-therapy approach, they write, is that people with diabetes often have “numerous coexisting conditions that make it more difficult for them to adhere to frequent follow-up visits,” a key element of the tested step-care protocol, which mandated follow-up visits every 4 weeks during the first year and every 4-16 weeks during the second year.
 

312 eyes of 270 patients

The new trial, organized by the DRCR Retinal Network and the Jaeb Center for Health Research in Tampa, Fla., ran at 54 U.S. sites from December 2017 to November 2019. The study randomized 158 eyes in 137 patients to aflibercept monotherapy, and 154 eyes in 133 patients to the step-care regimen (both eyes were treated in several patients in each group, with each eye receiving a different regimen). Participants were around 60 years old, 48% were women, and 95% had type 2 diabetes.

To be eligible for enrollment, patients had at least one eye with a best-corrected visual-acuity letter score of 24-69 on an Electronic Early Treatment Diabetic Retinopathy Study chart (ranges from 0 to 100, with higher values indicating better visual acuity), which corresponds to Snellen chart values of 20/320-20/50, readings that encompass most patients with diabetic macular edema, noted study authors Adam R. Glassman and Jennifer K. Sun, MD, in an interview.

“Very few patients with diabetic macular edema have vision due to this alone that is worse than 20/320, which meets criteria for legal blindness,” said Dr. Glassman, who is executive director of the Jaeb Center for Health Research, and Dr. Sun, who is chief of the center for clinical eye research and trials at the Joslin Diabetes Center in Boston and chair of the DRCR Retinal Network.

The primary outcome was time-averaged change in visual-acuity letter score from baseline to 2 years, which improved by an average of 15.0 letters in the aflibercept monotherapy group and an average of 14.0 letters in the step-therapy group, an adjusted difference of 0.8 letters, which was not significant. An improvement from baseline of at least 15 letters occurred in 53% of the eyes in the aflibercept monotherapy group and in 58% of those who had step therapy, and 77% of eyes in both groups had improvements of at least 10 letters.  

Central retinal thickness dropped from baseline by an average of 192 mcm with aflibercept monotherapy and 198 mcm with step therapy. The average number of total treatments (by intravitreous injection) was 14.6 in the aflibercept monotherapy group and 16.1 in the step-therapy group. After the first 24 weeks of the study, 39% of eyes in the step-therapy group had switched from bevacizumab to aflibercept injections; after 1 year, 60% of eyes had switched; and by study end, after 2 years, 70% had changed.

The bevacizumab-first group also showed at least comparable if not better safety, with similar rates of prespecified ocular events in both groups, but with a significantly lower rate of serious systemic adverse events, which occurred in 52% of the eyes treated with aflibercept only and 36% of eyes that began treatment on bevacizumab. Serious systemic adverse events occurred in 43% of patients who had two eyes treated as part of the trial.
 

‘Bevacizumab first was noninferior’

The team that designed the trial opted for a superiority design rather than a noninferiority trial and powered the study based on the presumption that aflibercept monotherapy would prove superior, said Dr. Glassman and Dr. Sun. “We feel that the clinical interpretation of these results will be similar to the interpretation if we had conducted a noninferiority study, and we found that bevacizumab first was noninferior to aflibercept monotherapy,” they maintained in an interview.

Dr. Glassman and Dr. Sun said they and their coauthors are now analyzing the results to try to find patient characteristics that could identify eyes most likely to respond to the bevacizumab-first approach. “It would be clinically valuable” to use the results to identify characteristics that could help guide clinicians’ treatment approach and enhance patient counseling, they said.

The study received funding from the National Institutes of Health. Dr. Jhaveri has reported being a consultant for Genentech, Novartis, and Regenxbio. Dr. Glassman has reported receiving grants from Genentech and Regeneron. Dr. Sun has reported receiving grants from Boehringer Ingelheim, Janssen Biotech, KalVista, Optovue, and Physical Sciences, grants and travel support from Novartis and Novo Nordisk, travel support from Merck, writing support from Genentech, and equipment supplied by Adaptive Sensory and Boston Micromachines. Dr. Musch and Dr. Chew have reported no relevant financial relationships.

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

Interventional echocardiographers have become an increasingly critical part of the structural heart team but may be paying the price in terms of radiation exposure, a new study suggests.

Results showed that interventional echocardiographers receive threefold higher head-level radiation doses than interventional cardiologists during left atrial appendage occlusion (LAAO) closures and 11-fold higher doses during mitral valve transcatheter edge-to-edge repair (TEER).

“Over the last 5-10 years there’s been exponential growth in these two procedures, TEER and LAAO, and while that’s been very exciting, I think there hasn’t been as much research into how to protect these individuals,” lead author David A. McNamara, MD, MPH, Spectrum Health, Grand Rapids, Mich., told this news organization. 

The study was published  in JAMA Network Open.

Previous studies have focused largely on radiation exposure and mitigation efforts during coronary interventions, but the room set-up for LAAO and TEER and shielding techniques to mitigate radiation exposure are vastly different, he noted.

A 2017 study reported that radiation exposure was significantly higher for imaging specialists than structural heart specialists and varied by procedure type.

For the current study, Dr. McNamara, an echocardiographer by training, and colleagues collected data from 30 consecutive LAAO and 30 consecutive TEER procedures performed at their institution between July 2016 and January 2018.

Interventional imagers, interventional cardiologists, and sonographers all wore a lead skirt, apron, and thyroid collar, as well as a dosimeter to collect radiation data.

Interventional cardiologists stood immediately adjacent to the procedure table and used a ceiling-mounted, upper-body lead shield and a lower-body shield extending from the table to the floor. The echocardiographer stood at the patient’s head and used a mobile accessory shield raised to a height that allowed the imager to extend their arms over the shield to manipulate a transesophageal echocardiogram probe throughout the case.

The median fluoroscopy time was 9.2 minutes for LAAO and 20.9 minutes for TEER. The median air kerma was 164 mGy and 109 mGy, respectively.

Interventional echocardiographers received a median per case radiation dose of 10.6 µSv, compared with 2.1 µSv for interventional cardiologists. The result was similar for TEER (10.5 vs. 0.9 µSv) and LAAO (10.6 vs. 3.5 µSv; P < .001 for all).

The odds of interventional echocardiographers having a radiation dose greater than 20 µSV were 7.5 times greater than for interventional cardiologists (P < .001).

“It’s not the direction of the association, but really the magnitude is what surprised us,” observed Dr. McNamara.

The team was pleasantly surprised, he said, that sonographers, a “vastly understudied group,” received significantly lower median radiation doses than interventional imagers during LAAO (0.2 µSV) and TEER procedures (0.0 µSv; P < .001 for both).

The average distances from the radiation source were 26 cm (10.2 inches) for the echocardiographer, 36 cm (14.2 inches) for the interventional cardiologist, and 250 cm (8.2 feet) for the sonographer.

“These folks [sonographers] were much further away than both the physicians performing these cases, and that is what we hypothesize drove their very low rates, but that should also help inform our mitigation techniques for physicians and for all other cath lab members in the room,” Dr. McNamara said.

He noted that Spectrum Health has been at the forefront in terms of research into radiation exposure and mitigation, has good institutional radiation safety education, and used dose-lowering fluoroscopy systems (AlluraClarity, Philips) with real-time image noise reduction technology and a frame rate of 15 frames per second for the study. “So we’re hopeful that this actually represents a somewhat best-case scenario for what is being done at multiple institutions throughout the nation.”

Nevertheless, there is a huge amount of variability in radiation exposure, Dr. McNamara observed. “First and foremost, we really just have to identify our problem and highlight that this is something that needs some advocacy from our [professional] groups.”

Sunil Rao, MD, the newly minted president of the Society of Cardiovascular Angiography and Interventions (SCAI), said, “This is a really important study, because it expands the potential occupational hazards outside of what we traditionally think of as the team that does interventional procedures ... we have to recognize that the procedures we’re doing in the cath lab have changed.”

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

Interventional echocardiographers have become an increasingly critical part of the structural heart team but may be paying the price in terms of radiation exposure, a new study suggests.

Results showed that interventional echocardiographers receive threefold higher head-level radiation doses than interventional cardiologists during left atrial appendage occlusion (LAAO) closures and 11-fold higher doses during mitral valve transcatheter edge-to-edge repair (TEER).

“Over the last 5-10 years there’s been exponential growth in these two procedures, TEER and LAAO, and while that’s been very exciting, I think there hasn’t been as much research into how to protect these individuals,” lead author David A. McNamara, MD, MPH, Spectrum Health, Grand Rapids, Mich., told this news organization. 

The study was published  in JAMA Network Open.

Previous studies have focused largely on radiation exposure and mitigation efforts during coronary interventions, but the room set-up for LAAO and TEER and shielding techniques to mitigate radiation exposure are vastly different, he noted.

A 2017 study reported that radiation exposure was significantly higher for imaging specialists than structural heart specialists and varied by procedure type.

For the current study, Dr. McNamara, an echocardiographer by training, and colleagues collected data from 30 consecutive LAAO and 30 consecutive TEER procedures performed at their institution between July 2016 and January 2018.

Interventional imagers, interventional cardiologists, and sonographers all wore a lead skirt, apron, and thyroid collar, as well as a dosimeter to collect radiation data.

Interventional cardiologists stood immediately adjacent to the procedure table and used a ceiling-mounted, upper-body lead shield and a lower-body shield extending from the table to the floor. The echocardiographer stood at the patient’s head and used a mobile accessory shield raised to a height that allowed the imager to extend their arms over the shield to manipulate a transesophageal echocardiogram probe throughout the case.

The median fluoroscopy time was 9.2 minutes for LAAO and 20.9 minutes for TEER. The median air kerma was 164 mGy and 109 mGy, respectively.

Interventional echocardiographers received a median per case radiation dose of 10.6 µSv, compared with 2.1 µSv for interventional cardiologists. The result was similar for TEER (10.5 vs. 0.9 µSv) and LAAO (10.6 vs. 3.5 µSv; P < .001 for all).

The odds of interventional echocardiographers having a radiation dose greater than 20 µSV were 7.5 times greater than for interventional cardiologists (P < .001).

“It’s not the direction of the association, but really the magnitude is what surprised us,” observed Dr. McNamara.

The team was pleasantly surprised, he said, that sonographers, a “vastly understudied group,” received significantly lower median radiation doses than interventional imagers during LAAO (0.2 µSV) and TEER procedures (0.0 µSv; P < .001 for both).

The average distances from the radiation source were 26 cm (10.2 inches) for the echocardiographer, 36 cm (14.2 inches) for the interventional cardiologist, and 250 cm (8.2 feet) for the sonographer.

“These folks [sonographers] were much further away than both the physicians performing these cases, and that is what we hypothesize drove their very low rates, but that should also help inform our mitigation techniques for physicians and for all other cath lab members in the room,” Dr. McNamara said.

He noted that Spectrum Health has been at the forefront in terms of research into radiation exposure and mitigation, has good institutional radiation safety education, and used dose-lowering fluoroscopy systems (AlluraClarity, Philips) with real-time image noise reduction technology and a frame rate of 15 frames per second for the study. “So we’re hopeful that this actually represents a somewhat best-case scenario for what is being done at multiple institutions throughout the nation.”

Nevertheless, there is a huge amount of variability in radiation exposure, Dr. McNamara observed. “First and foremost, we really just have to identify our problem and highlight that this is something that needs some advocacy from our [professional] groups.”

Sunil Rao, MD, the newly minted president of the Society of Cardiovascular Angiography and Interventions (SCAI), said, “This is a really important study, because it expands the potential occupational hazards outside of what we traditionally think of as the team that does interventional procedures ... we have to recognize that the procedures we’re doing in the cath lab have changed.”

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

Interventional echocardiographers have become an increasingly critical part of the structural heart team but may be paying the price in terms of radiation exposure, a new study suggests.

Results showed that interventional echocardiographers receive threefold higher head-level radiation doses than interventional cardiologists during left atrial appendage occlusion (LAAO) closures and 11-fold higher doses during mitral valve transcatheter edge-to-edge repair (TEER).

“Over the last 5-10 years there’s been exponential growth in these two procedures, TEER and LAAO, and while that’s been very exciting, I think there hasn’t been as much research into how to protect these individuals,” lead author David A. McNamara, MD, MPH, Spectrum Health, Grand Rapids, Mich., told this news organization. 

The study was published  in JAMA Network Open.

Previous studies have focused largely on radiation exposure and mitigation efforts during coronary interventions, but the room set-up for LAAO and TEER and shielding techniques to mitigate radiation exposure are vastly different, he noted.

A 2017 study reported that radiation exposure was significantly higher for imaging specialists than structural heart specialists and varied by procedure type.

For the current study, Dr. McNamara, an echocardiographer by training, and colleagues collected data from 30 consecutive LAAO and 30 consecutive TEER procedures performed at their institution between July 2016 and January 2018.

Interventional imagers, interventional cardiologists, and sonographers all wore a lead skirt, apron, and thyroid collar, as well as a dosimeter to collect radiation data.

Interventional cardiologists stood immediately adjacent to the procedure table and used a ceiling-mounted, upper-body lead shield and a lower-body shield extending from the table to the floor. The echocardiographer stood at the patient’s head and used a mobile accessory shield raised to a height that allowed the imager to extend their arms over the shield to manipulate a transesophageal echocardiogram probe throughout the case.

The median fluoroscopy time was 9.2 minutes for LAAO and 20.9 minutes for TEER. The median air kerma was 164 mGy and 109 mGy, respectively.

Interventional echocardiographers received a median per case radiation dose of 10.6 µSv, compared with 2.1 µSv for interventional cardiologists. The result was similar for TEER (10.5 vs. 0.9 µSv) and LAAO (10.6 vs. 3.5 µSv; P < .001 for all).

The odds of interventional echocardiographers having a radiation dose greater than 20 µSV were 7.5 times greater than for interventional cardiologists (P < .001).

“It’s not the direction of the association, but really the magnitude is what surprised us,” observed Dr. McNamara.

The team was pleasantly surprised, he said, that sonographers, a “vastly understudied group,” received significantly lower median radiation doses than interventional imagers during LAAO (0.2 µSV) and TEER procedures (0.0 µSv; P < .001 for both).

The average distances from the radiation source were 26 cm (10.2 inches) for the echocardiographer, 36 cm (14.2 inches) for the interventional cardiologist, and 250 cm (8.2 feet) for the sonographer.

“These folks [sonographers] were much further away than both the physicians performing these cases, and that is what we hypothesize drove their very low rates, but that should also help inform our mitigation techniques for physicians and for all other cath lab members in the room,” Dr. McNamara said.

He noted that Spectrum Health has been at the forefront in terms of research into radiation exposure and mitigation, has good institutional radiation safety education, and used dose-lowering fluoroscopy systems (AlluraClarity, Philips) with real-time image noise reduction technology and a frame rate of 15 frames per second for the study. “So we’re hopeful that this actually represents a somewhat best-case scenario for what is being done at multiple institutions throughout the nation.”

Nevertheless, there is a huge amount of variability in radiation exposure, Dr. McNamara observed. “First and foremost, we really just have to identify our problem and highlight that this is something that needs some advocacy from our [professional] groups.”

Sunil Rao, MD, the newly minted president of the Society of Cardiovascular Angiography and Interventions (SCAI), said, “This is a really important study, because it expands the potential occupational hazards outside of what we traditionally think of as the team that does interventional procedures ... we have to recognize that the procedures we’re doing in the cath lab have changed.”

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