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FDA calls for market removal of ranitidine
A problem with both branded and generic over-the-counter and prescription forms, from the market.
The NDMA contamination does not stem from a manufacturing concern, but rather the levels have been found to increase over time depending on how the ranitidine is stored.
In particular, the FDA found through product testing that the NDMA impurity developed over time when the ranitidine was stored above room temperature.
“The testing also showed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA,” FDA said in a statement announcing the call for product withdrawal.
The FDA has been investigating NDMA contamination since September 2019 when the agency first announced the contamination in ranitidine. Manufacturers have been withdrawing their products from the market since the first reports of contamination surfaced. Despite these recalls, there were still ranitidine products on the market, according to an FDA spokesperson, necessitating the further action taken by the agency.
In addition to products being removed from the market, FDA is asking consumers to discard any ranitidine products they may have.
“There are still questions about how the impurity is formed in ranitidine over time during storage,” Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, said during an April 1 conference call with reporters announcing the withdrawal request. “For example, what impact does the drug packaging have on the development or the specific formulation have on the development of NDMA.”
She said the issue may be fixable over time, and the agency is open to reformulations that demonstrate that ranitidine is stable over time and under various storage conditions.
Dr. Woodcock stressed that the products at the point of manufacture do not have unacceptable levels of NDMA.
“This is a market withdrawal, this is not a recall because technically the products are okay. They met all their specs,” she said. “It is only when they are subjected generally to heat stress do they manifest higher levels” of NDMA.
“Clearly, we can’t have products on the market that if they are stored under conditions consumers might store them under that they would become unacceptable.”
Dr. Woodcock said FDA is not withdrawing approvals for the products, but manufacturers would need to show the product remains stable under normal storage conditions.
This article was updated 4/7/20.
A problem with both branded and generic over-the-counter and prescription forms, from the market.
The NDMA contamination does not stem from a manufacturing concern, but rather the levels have been found to increase over time depending on how the ranitidine is stored.
In particular, the FDA found through product testing that the NDMA impurity developed over time when the ranitidine was stored above room temperature.
“The testing also showed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA,” FDA said in a statement announcing the call for product withdrawal.
The FDA has been investigating NDMA contamination since September 2019 when the agency first announced the contamination in ranitidine. Manufacturers have been withdrawing their products from the market since the first reports of contamination surfaced. Despite these recalls, there were still ranitidine products on the market, according to an FDA spokesperson, necessitating the further action taken by the agency.
In addition to products being removed from the market, FDA is asking consumers to discard any ranitidine products they may have.
“There are still questions about how the impurity is formed in ranitidine over time during storage,” Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, said during an April 1 conference call with reporters announcing the withdrawal request. “For example, what impact does the drug packaging have on the development or the specific formulation have on the development of NDMA.”
She said the issue may be fixable over time, and the agency is open to reformulations that demonstrate that ranitidine is stable over time and under various storage conditions.
Dr. Woodcock stressed that the products at the point of manufacture do not have unacceptable levels of NDMA.
“This is a market withdrawal, this is not a recall because technically the products are okay. They met all their specs,” she said. “It is only when they are subjected generally to heat stress do they manifest higher levels” of NDMA.
“Clearly, we can’t have products on the market that if they are stored under conditions consumers might store them under that they would become unacceptable.”
Dr. Woodcock said FDA is not withdrawing approvals for the products, but manufacturers would need to show the product remains stable under normal storage conditions.
This article was updated 4/7/20.
A problem with both branded and generic over-the-counter and prescription forms, from the market.
The NDMA contamination does not stem from a manufacturing concern, but rather the levels have been found to increase over time depending on how the ranitidine is stored.
In particular, the FDA found through product testing that the NDMA impurity developed over time when the ranitidine was stored above room temperature.
“The testing also showed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA,” FDA said in a statement announcing the call for product withdrawal.
The FDA has been investigating NDMA contamination since September 2019 when the agency first announced the contamination in ranitidine. Manufacturers have been withdrawing their products from the market since the first reports of contamination surfaced. Despite these recalls, there were still ranitidine products on the market, according to an FDA spokesperson, necessitating the further action taken by the agency.
In addition to products being removed from the market, FDA is asking consumers to discard any ranitidine products they may have.
“There are still questions about how the impurity is formed in ranitidine over time during storage,” Janet Woodcock, MD, director of the FDA Center for Drug Evaluation and Research, said during an April 1 conference call with reporters announcing the withdrawal request. “For example, what impact does the drug packaging have on the development or the specific formulation have on the development of NDMA.”
She said the issue may be fixable over time, and the agency is open to reformulations that demonstrate that ranitidine is stable over time and under various storage conditions.
Dr. Woodcock stressed that the products at the point of manufacture do not have unacceptable levels of NDMA.
“This is a market withdrawal, this is not a recall because technically the products are okay. They met all their specs,” she said. “It is only when they are subjected generally to heat stress do they manifest higher levels” of NDMA.
“Clearly, we can’t have products on the market that if they are stored under conditions consumers might store them under that they would become unacceptable.”
Dr. Woodcock said FDA is not withdrawing approvals for the products, but manufacturers would need to show the product remains stable under normal storage conditions.
This article was updated 4/7/20.
Microbiome studies may require correction for PPI use
Microbiome studies should be correcting statistics to account for proton pump inhibitor (PPI) use, according to a leading expert.
After antibiotics, PPIs are the leading cause of microbiome variance in both research and general populations, and these alterations could have a range of consequences, reported Rinse K. Weersma, MD, PhD, of the University of Groningen (the Netherlands).
About 20% of people are taking a PPI, Dr. Weersma said at the annual Gut Microbiota for Health World Summit, noting that, in countries such as the United States and the United Kingdom, this figure may be higher.
“There’s chronic use of proton pump inhibitors in the population on a massive scale,” Dr. Weersma said.
To complicate matters, estimates suggest that 25%-70% of people who are taking PPIs have no appropriate indication. While this issue is partly because of increasing over-the-counter usage, physicians are also contributing to the problem by prescribing PPIs without adequate follow-up.
“The number of people using proton pump inhibitors is steadily increasing,” Dr. Weersma said. “The number of people getting them prescribed is relatively stable. The problem is, we never stop.”
According to Dr. Weersma, a growing body of research shows that PPI use may increase the risk of developing other conditions. Although many of these relationships are correlative, some are now widely accepted as causal. Most notable and clinically relevant, Dr. Weersma said, are enteric infections. Clostridioides difficile–associated diarrhea, for instance, is 65% more common among PPI users.
While the mechanisms behind this susceptibility to infection are uncertain, Dr. Weersma suggested that the most likely cause is “oralization” of the gut microbiome caused by loss of the acid barrier, which introduces upper gastrointestinal bacteria, or oral bacteria, into the lower intestines.
Perhaps more relevant to clinical trials, PPIs may also influence the safety and efficacy of drugs.
“There is a lot of interaction between the gut microbiome and a lot of drugs,” Dr. Weersma said at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility. “We really don’t know a lot about this at the moment.”
He went on to explain that bidirectional interactions between drugs and the microbiome may actually present clinical opportunities.
“This is a field that people currently call pharmacomicrobiomics,” Dr. Weersma said. “This is very intriguing, of course, because everyone knows about pharmacogenomics ... which lets you stratify your patients, but you cannot intervene; you cannot change your genetic background to increase efficacy or avoid toxicity. But in fact, with the microbiome, we could modulate the microbiome and improve bioavailability, for example.”
Conversely, Dr. Weersma pointed out that PPI use may be interfering with drug efficacy to a life-altering degree.
He cited a recent study by Chalabi and colleagues, which found that PPI use affected responses to immune checkpoint inhibitors (Ann Oncol. 2020 Jan 16. doi: 10.1016/j.annonc.2020.01.006). Among 169 patients with lung cancer who were treated with atezolizumab, overall survival was significantly lower in PPI users (9.6 vs. 14.5 months; P = .001).
A number of other clinical implications are also possible, Dr. Weersma said, although these require further investigation. For example, a 2019 study by Stark and colleagues suggested that childhood use of PPIs may increase obesity risk.
“[There are] no microbiome data here,” Dr. Weersma said, “but it makes you think.”
While considering the downsides of PPIs, Dr. Weersma also emphasized their importance in clinical practice. “[Proton pump inhibitors] are very great drugs. They are cheap, they are safe, they are very effective. So if you have evidence-based indications to use proton pump inhibitors, you should definitely use them and not stop them.”
Dr. Weersma called for responsible use of PPIs, and suggested that clinicians need to prepare for pushback from patients, who, after stopping PPIs, may experience a temporary resurgence of symptoms because of acid rebound.
“You have to make them aware [of acid rebound],” Dr. Weersma said. “Say: ‘Wait 2 or 3 weeks and this rebound is gone.’ We should say that way, way, way more often.”
But clinicians shouldn’t bear the burden of responsible usage alone, Dr. Weersma said.
“There’s a role for clinicians, patients, and regulatory bodies also, to think about the massive use of proton pump inhibitors now and in the future.”
In the discussion that followed the presentation, a summit attendee brought up the realities of clinical practice before PPIs, when patients frequently had gastrointestinal bleeding secondary to nonsteroidal anti-inflammatory use. In response, Dr. Weersma again emphasized that PPIs play a critical role for many patients. After once more encouraging responsible use, Dr. Weersma expressed concern about the risks involved in conveying his message; not only to the medical community, but also to the general public.
“This is a very difficult message [to deliver],” Dr. Weersma said. “In the Netherlands this was taken up by the media and the news, so my email inbox exploded. It’s difficult to get this nuance right.”
Dr. Weersma disclosed relationships with Takeda, Johnson & Johnson, Ferring, and others.
Microbiome studies should be correcting statistics to account for proton pump inhibitor (PPI) use, according to a leading expert.
After antibiotics, PPIs are the leading cause of microbiome variance in both research and general populations, and these alterations could have a range of consequences, reported Rinse K. Weersma, MD, PhD, of the University of Groningen (the Netherlands).
About 20% of people are taking a PPI, Dr. Weersma said at the annual Gut Microbiota for Health World Summit, noting that, in countries such as the United States and the United Kingdom, this figure may be higher.
“There’s chronic use of proton pump inhibitors in the population on a massive scale,” Dr. Weersma said.
To complicate matters, estimates suggest that 25%-70% of people who are taking PPIs have no appropriate indication. While this issue is partly because of increasing over-the-counter usage, physicians are also contributing to the problem by prescribing PPIs without adequate follow-up.
“The number of people using proton pump inhibitors is steadily increasing,” Dr. Weersma said. “The number of people getting them prescribed is relatively stable. The problem is, we never stop.”
According to Dr. Weersma, a growing body of research shows that PPI use may increase the risk of developing other conditions. Although many of these relationships are correlative, some are now widely accepted as causal. Most notable and clinically relevant, Dr. Weersma said, are enteric infections. Clostridioides difficile–associated diarrhea, for instance, is 65% more common among PPI users.
While the mechanisms behind this susceptibility to infection are uncertain, Dr. Weersma suggested that the most likely cause is “oralization” of the gut microbiome caused by loss of the acid barrier, which introduces upper gastrointestinal bacteria, or oral bacteria, into the lower intestines.
Perhaps more relevant to clinical trials, PPIs may also influence the safety and efficacy of drugs.
“There is a lot of interaction between the gut microbiome and a lot of drugs,” Dr. Weersma said at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility. “We really don’t know a lot about this at the moment.”
He went on to explain that bidirectional interactions between drugs and the microbiome may actually present clinical opportunities.
“This is a field that people currently call pharmacomicrobiomics,” Dr. Weersma said. “This is very intriguing, of course, because everyone knows about pharmacogenomics ... which lets you stratify your patients, but you cannot intervene; you cannot change your genetic background to increase efficacy or avoid toxicity. But in fact, with the microbiome, we could modulate the microbiome and improve bioavailability, for example.”
Conversely, Dr. Weersma pointed out that PPI use may be interfering with drug efficacy to a life-altering degree.
He cited a recent study by Chalabi and colleagues, which found that PPI use affected responses to immune checkpoint inhibitors (Ann Oncol. 2020 Jan 16. doi: 10.1016/j.annonc.2020.01.006). Among 169 patients with lung cancer who were treated with atezolizumab, overall survival was significantly lower in PPI users (9.6 vs. 14.5 months; P = .001).
A number of other clinical implications are also possible, Dr. Weersma said, although these require further investigation. For example, a 2019 study by Stark and colleagues suggested that childhood use of PPIs may increase obesity risk.
“[There are] no microbiome data here,” Dr. Weersma said, “but it makes you think.”
While considering the downsides of PPIs, Dr. Weersma also emphasized their importance in clinical practice. “[Proton pump inhibitors] are very great drugs. They are cheap, they are safe, they are very effective. So if you have evidence-based indications to use proton pump inhibitors, you should definitely use them and not stop them.”
Dr. Weersma called for responsible use of PPIs, and suggested that clinicians need to prepare for pushback from patients, who, after stopping PPIs, may experience a temporary resurgence of symptoms because of acid rebound.
“You have to make them aware [of acid rebound],” Dr. Weersma said. “Say: ‘Wait 2 or 3 weeks and this rebound is gone.’ We should say that way, way, way more often.”
But clinicians shouldn’t bear the burden of responsible usage alone, Dr. Weersma said.
“There’s a role for clinicians, patients, and regulatory bodies also, to think about the massive use of proton pump inhibitors now and in the future.”
In the discussion that followed the presentation, a summit attendee brought up the realities of clinical practice before PPIs, when patients frequently had gastrointestinal bleeding secondary to nonsteroidal anti-inflammatory use. In response, Dr. Weersma again emphasized that PPIs play a critical role for many patients. After once more encouraging responsible use, Dr. Weersma expressed concern about the risks involved in conveying his message; not only to the medical community, but also to the general public.
“This is a very difficult message [to deliver],” Dr. Weersma said. “In the Netherlands this was taken up by the media and the news, so my email inbox exploded. It’s difficult to get this nuance right.”
Dr. Weersma disclosed relationships with Takeda, Johnson & Johnson, Ferring, and others.
Microbiome studies should be correcting statistics to account for proton pump inhibitor (PPI) use, according to a leading expert.
After antibiotics, PPIs are the leading cause of microbiome variance in both research and general populations, and these alterations could have a range of consequences, reported Rinse K. Weersma, MD, PhD, of the University of Groningen (the Netherlands).
About 20% of people are taking a PPI, Dr. Weersma said at the annual Gut Microbiota for Health World Summit, noting that, in countries such as the United States and the United Kingdom, this figure may be higher.
“There’s chronic use of proton pump inhibitors in the population on a massive scale,” Dr. Weersma said.
To complicate matters, estimates suggest that 25%-70% of people who are taking PPIs have no appropriate indication. While this issue is partly because of increasing over-the-counter usage, physicians are also contributing to the problem by prescribing PPIs without adequate follow-up.
“The number of people using proton pump inhibitors is steadily increasing,” Dr. Weersma said. “The number of people getting them prescribed is relatively stable. The problem is, we never stop.”
According to Dr. Weersma, a growing body of research shows that PPI use may increase the risk of developing other conditions. Although many of these relationships are correlative, some are now widely accepted as causal. Most notable and clinically relevant, Dr. Weersma said, are enteric infections. Clostridioides difficile–associated diarrhea, for instance, is 65% more common among PPI users.
While the mechanisms behind this susceptibility to infection are uncertain, Dr. Weersma suggested that the most likely cause is “oralization” of the gut microbiome caused by loss of the acid barrier, which introduces upper gastrointestinal bacteria, or oral bacteria, into the lower intestines.
Perhaps more relevant to clinical trials, PPIs may also influence the safety and efficacy of drugs.
“There is a lot of interaction between the gut microbiome and a lot of drugs,” Dr. Weersma said at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility. “We really don’t know a lot about this at the moment.”
He went on to explain that bidirectional interactions between drugs and the microbiome may actually present clinical opportunities.
“This is a field that people currently call pharmacomicrobiomics,” Dr. Weersma said. “This is very intriguing, of course, because everyone knows about pharmacogenomics ... which lets you stratify your patients, but you cannot intervene; you cannot change your genetic background to increase efficacy or avoid toxicity. But in fact, with the microbiome, we could modulate the microbiome and improve bioavailability, for example.”
Conversely, Dr. Weersma pointed out that PPI use may be interfering with drug efficacy to a life-altering degree.
He cited a recent study by Chalabi and colleagues, which found that PPI use affected responses to immune checkpoint inhibitors (Ann Oncol. 2020 Jan 16. doi: 10.1016/j.annonc.2020.01.006). Among 169 patients with lung cancer who were treated with atezolizumab, overall survival was significantly lower in PPI users (9.6 vs. 14.5 months; P = .001).
A number of other clinical implications are also possible, Dr. Weersma said, although these require further investigation. For example, a 2019 study by Stark and colleagues suggested that childhood use of PPIs may increase obesity risk.
“[There are] no microbiome data here,” Dr. Weersma said, “but it makes you think.”
While considering the downsides of PPIs, Dr. Weersma also emphasized their importance in clinical practice. “[Proton pump inhibitors] are very great drugs. They are cheap, they are safe, they are very effective. So if you have evidence-based indications to use proton pump inhibitors, you should definitely use them and not stop them.”
Dr. Weersma called for responsible use of PPIs, and suggested that clinicians need to prepare for pushback from patients, who, after stopping PPIs, may experience a temporary resurgence of symptoms because of acid rebound.
“You have to make them aware [of acid rebound],” Dr. Weersma said. “Say: ‘Wait 2 or 3 weeks and this rebound is gone.’ We should say that way, way, way more often.”
But clinicians shouldn’t bear the burden of responsible usage alone, Dr. Weersma said.
“There’s a role for clinicians, patients, and regulatory bodies also, to think about the massive use of proton pump inhibitors now and in the future.”
In the discussion that followed the presentation, a summit attendee brought up the realities of clinical practice before PPIs, when patients frequently had gastrointestinal bleeding secondary to nonsteroidal anti-inflammatory use. In response, Dr. Weersma again emphasized that PPIs play a critical role for many patients. After once more encouraging responsible use, Dr. Weersma expressed concern about the risks involved in conveying his message; not only to the medical community, but also to the general public.
“This is a very difficult message [to deliver],” Dr. Weersma said. “In the Netherlands this was taken up by the media and the news, so my email inbox exploded. It’s difficult to get this nuance right.”
Dr. Weersma disclosed relationships with Takeda, Johnson & Johnson, Ferring, and others.
EXPERT ANALYSIS FROM GMFH 2020
GERD symptoms affect one in three Americans
For most patients, proton pump inhibitors do not control symptoms of gastroesophageal reflux disease, according to the findings of a large population-based survey study.
In all, 31% of respondents reported gastroesophageal reflux disease (GERD) symptoms within the past week, and 54% of those on proton pump inhibitors (PPIs) had breakthrough symptoms, said Sean D. Delshad, MD, MBA. In all, 54% of patients on PPIs for GERD reported having breakthrough symptoms of heartburn or regurgitation. Novel treatments are needed for patients with PPI-refractory symptoms of GERD, he and his associates wrote in Gastroenterology.
Prior population-based U.S. studies have reported a lower prevalence (16%-28%) of weekly or monthly GERD symptoms, noted Dr. Delshad of the Cedars-Sinai Center for Outcomes Research and Education in Los Angeles. However, the study cohorts do not reflect current U.S. demographics — two were 82%-90% white and the third was 43% African American. The most recent data also were collected approximately 15 years ago, the researchers noted.
For the study, they deployed a mobile app that guides users through an automated, online assessment of GI symptoms called AEGIS. Respondents were asked to select any GERD symptoms they had ever experienced and any symptoms they had experienced in the past week. Options included heartburn, acid reflux, gastroesophageal reflux, abdominal pain, bloating or gas, constipation, diarrhea, disrupted swallowing, fecal incontinence, nausea and vomiting, and “no symptoms.” All 71,812 respondents were recruited by a research firm and surveyed during a 3-week period in 2015.
In all, 44% of respondents reported having ever had heartburn, acid reflux, or gastroesophageal reflux, and 31% reported having GERD symptoms in the past week. In all, 55% of respondents who had ever experienced GERD symptoms were on PPIs, 24% were on histamine2 receptor blockers, and 24% were on antacid agents.
Among more than 3,000 participants on daily PPIs, 54% had persistent symptoms of GERD, which compares with the results of prior community-based studies, the investigators wrote. Current GERD symptoms and PPI-refractory GERD were especially prevalent among women, non-Hispanic whites, and individuals with comorbidities such as irritable bowel syndrome, diabetes, Crohn’s disease, and endometriosis.
In an adjusted analysis, Latinos were 2.44 times more likely to have PPI-refractory GERD ,compared with non-Hispanic whites. “The reason behind this finding is unclear but may be secondary to physiologic or even cultural etiologies,” the researchers wrote.
The more independent and functional middle-aged and older adults are more likely to respond to online surveys. Furthermore, although incentives were used to reduce participation bias, calling the tool a “GI Survey” could have made those with GI symptoms more likely to respond. The survey also did not assess if respondents were taking PPIs correctly or if they had made behavioral changes to mitigate GERD.
This study was sponsored by Ironwood Pharmaceuticals, whose bile acid sequestrant IW-3718 is in late-phase development as an add-on to PPI therapy for patients with persistent GERD. Dr. Delshad reported having no relevant conflicts of interest, but two coinvestigators disclosed consulting relationships with Ironwood Pharmaceuticals.
SOURCE: Delshad SD et al. Gastroenterology. 2019 Dec 10. doi: 10.1053/j.gastro.2019.12.014.
Heartburn is a common symptom and is ubiquitously attributed to gastroesophageal reflux disease (GERD) among patients and clinicians. However, it is important to note that although most patients with GERD do have heartburn and/or regurgitation, many patients with these symptoms do not have GERD.
When the authors used a more precise definition of GERD based on the modified Montreal classification, they found that only 18% of the study population met the criteria for the disease. This is similar to prevalence of GERD reported in North America by other studies. The authors also found that, among patients on daily proton pump inhibitors (PPIs), 54% still reported persistent reflux symptoms.
Although this highlights the need for future research into developing other therapeutic modalities for GERD (such as bile acid sequestrants), most of the patients that are “PPI refractory” have lack of response because of a functional esophageal disorder. This is highlighted by the similar risk factors for functional heartburn and the PPI-refractory group in this study: younger individuals, women, and participants with irritable bowel syndrome.
Dhyanesh A. Patel, MD, is an assistant professor of medicine at the Center for Esophageal Disorders, Vanderbilt University Medical Center, Nashville, Tenn. He reported that he has no conflicts of interest.
Heartburn is a common symptom and is ubiquitously attributed to gastroesophageal reflux disease (GERD) among patients and clinicians. However, it is important to note that although most patients with GERD do have heartburn and/or regurgitation, many patients with these symptoms do not have GERD.
When the authors used a more precise definition of GERD based on the modified Montreal classification, they found that only 18% of the study population met the criteria for the disease. This is similar to prevalence of GERD reported in North America by other studies. The authors also found that, among patients on daily proton pump inhibitors (PPIs), 54% still reported persistent reflux symptoms.
Although this highlights the need for future research into developing other therapeutic modalities for GERD (such as bile acid sequestrants), most of the patients that are “PPI refractory” have lack of response because of a functional esophageal disorder. This is highlighted by the similar risk factors for functional heartburn and the PPI-refractory group in this study: younger individuals, women, and participants with irritable bowel syndrome.
Dhyanesh A. Patel, MD, is an assistant professor of medicine at the Center for Esophageal Disorders, Vanderbilt University Medical Center, Nashville, Tenn. He reported that he has no conflicts of interest.
Heartburn is a common symptom and is ubiquitously attributed to gastroesophageal reflux disease (GERD) among patients and clinicians. However, it is important to note that although most patients with GERD do have heartburn and/or regurgitation, many patients with these symptoms do not have GERD.
When the authors used a more precise definition of GERD based on the modified Montreal classification, they found that only 18% of the study population met the criteria for the disease. This is similar to prevalence of GERD reported in North America by other studies. The authors also found that, among patients on daily proton pump inhibitors (PPIs), 54% still reported persistent reflux symptoms.
Although this highlights the need for future research into developing other therapeutic modalities for GERD (such as bile acid sequestrants), most of the patients that are “PPI refractory” have lack of response because of a functional esophageal disorder. This is highlighted by the similar risk factors for functional heartburn and the PPI-refractory group in this study: younger individuals, women, and participants with irritable bowel syndrome.
Dhyanesh A. Patel, MD, is an assistant professor of medicine at the Center for Esophageal Disorders, Vanderbilt University Medical Center, Nashville, Tenn. He reported that he has no conflicts of interest.
For most patients, proton pump inhibitors do not control symptoms of gastroesophageal reflux disease, according to the findings of a large population-based survey study.
In all, 31% of respondents reported gastroesophageal reflux disease (GERD) symptoms within the past week, and 54% of those on proton pump inhibitors (PPIs) had breakthrough symptoms, said Sean D. Delshad, MD, MBA. In all, 54% of patients on PPIs for GERD reported having breakthrough symptoms of heartburn or regurgitation. Novel treatments are needed for patients with PPI-refractory symptoms of GERD, he and his associates wrote in Gastroenterology.
Prior population-based U.S. studies have reported a lower prevalence (16%-28%) of weekly or monthly GERD symptoms, noted Dr. Delshad of the Cedars-Sinai Center for Outcomes Research and Education in Los Angeles. However, the study cohorts do not reflect current U.S. demographics — two were 82%-90% white and the third was 43% African American. The most recent data also were collected approximately 15 years ago, the researchers noted.
For the study, they deployed a mobile app that guides users through an automated, online assessment of GI symptoms called AEGIS. Respondents were asked to select any GERD symptoms they had ever experienced and any symptoms they had experienced in the past week. Options included heartburn, acid reflux, gastroesophageal reflux, abdominal pain, bloating or gas, constipation, diarrhea, disrupted swallowing, fecal incontinence, nausea and vomiting, and “no symptoms.” All 71,812 respondents were recruited by a research firm and surveyed during a 3-week period in 2015.
In all, 44% of respondents reported having ever had heartburn, acid reflux, or gastroesophageal reflux, and 31% reported having GERD symptoms in the past week. In all, 55% of respondents who had ever experienced GERD symptoms were on PPIs, 24% were on histamine2 receptor blockers, and 24% were on antacid agents.
Among more than 3,000 participants on daily PPIs, 54% had persistent symptoms of GERD, which compares with the results of prior community-based studies, the investigators wrote. Current GERD symptoms and PPI-refractory GERD were especially prevalent among women, non-Hispanic whites, and individuals with comorbidities such as irritable bowel syndrome, diabetes, Crohn’s disease, and endometriosis.
In an adjusted analysis, Latinos were 2.44 times more likely to have PPI-refractory GERD ,compared with non-Hispanic whites. “The reason behind this finding is unclear but may be secondary to physiologic or even cultural etiologies,” the researchers wrote.
The more independent and functional middle-aged and older adults are more likely to respond to online surveys. Furthermore, although incentives were used to reduce participation bias, calling the tool a “GI Survey” could have made those with GI symptoms more likely to respond. The survey also did not assess if respondents were taking PPIs correctly or if they had made behavioral changes to mitigate GERD.
This study was sponsored by Ironwood Pharmaceuticals, whose bile acid sequestrant IW-3718 is in late-phase development as an add-on to PPI therapy for patients with persistent GERD. Dr. Delshad reported having no relevant conflicts of interest, but two coinvestigators disclosed consulting relationships with Ironwood Pharmaceuticals.
SOURCE: Delshad SD et al. Gastroenterology. 2019 Dec 10. doi: 10.1053/j.gastro.2019.12.014.
For most patients, proton pump inhibitors do not control symptoms of gastroesophageal reflux disease, according to the findings of a large population-based survey study.
In all, 31% of respondents reported gastroesophageal reflux disease (GERD) symptoms within the past week, and 54% of those on proton pump inhibitors (PPIs) had breakthrough symptoms, said Sean D. Delshad, MD, MBA. In all, 54% of patients on PPIs for GERD reported having breakthrough symptoms of heartburn or regurgitation. Novel treatments are needed for patients with PPI-refractory symptoms of GERD, he and his associates wrote in Gastroenterology.
Prior population-based U.S. studies have reported a lower prevalence (16%-28%) of weekly or monthly GERD symptoms, noted Dr. Delshad of the Cedars-Sinai Center for Outcomes Research and Education in Los Angeles. However, the study cohorts do not reflect current U.S. demographics — two were 82%-90% white and the third was 43% African American. The most recent data also were collected approximately 15 years ago, the researchers noted.
For the study, they deployed a mobile app that guides users through an automated, online assessment of GI symptoms called AEGIS. Respondents were asked to select any GERD symptoms they had ever experienced and any symptoms they had experienced in the past week. Options included heartburn, acid reflux, gastroesophageal reflux, abdominal pain, bloating or gas, constipation, diarrhea, disrupted swallowing, fecal incontinence, nausea and vomiting, and “no symptoms.” All 71,812 respondents were recruited by a research firm and surveyed during a 3-week period in 2015.
In all, 44% of respondents reported having ever had heartburn, acid reflux, or gastroesophageal reflux, and 31% reported having GERD symptoms in the past week. In all, 55% of respondents who had ever experienced GERD symptoms were on PPIs, 24% were on histamine2 receptor blockers, and 24% were on antacid agents.
Among more than 3,000 participants on daily PPIs, 54% had persistent symptoms of GERD, which compares with the results of prior community-based studies, the investigators wrote. Current GERD symptoms and PPI-refractory GERD were especially prevalent among women, non-Hispanic whites, and individuals with comorbidities such as irritable bowel syndrome, diabetes, Crohn’s disease, and endometriosis.
In an adjusted analysis, Latinos were 2.44 times more likely to have PPI-refractory GERD ,compared with non-Hispanic whites. “The reason behind this finding is unclear but may be secondary to physiologic or even cultural etiologies,” the researchers wrote.
The more independent and functional middle-aged and older adults are more likely to respond to online surveys. Furthermore, although incentives were used to reduce participation bias, calling the tool a “GI Survey” could have made those with GI symptoms more likely to respond. The survey also did not assess if respondents were taking PPIs correctly or if they had made behavioral changes to mitigate GERD.
This study was sponsored by Ironwood Pharmaceuticals, whose bile acid sequestrant IW-3718 is in late-phase development as an add-on to PPI therapy for patients with persistent GERD. Dr. Delshad reported having no relevant conflicts of interest, but two coinvestigators disclosed consulting relationships with Ironwood Pharmaceuticals.
SOURCE: Delshad SD et al. Gastroenterology. 2019 Dec 10. doi: 10.1053/j.gastro.2019.12.014.
FROM GASTROENTEROLOGY
COVID-19 update: Transmission 5% or less among close contacts
The transmission rate of coronavirus disease 2019 (COVID-19) was 1%-5% among 38,000 Chinese people in close contact with infected patients, according to the chief epidemiologist of the Chinese Centers for Disease Control and Prevention, Beijing, Zunyou Wu, MD, PhD, who gave an update on the epidemic at the Conference on Retroviruses & Opportunistic Infections.
The rate of spread to family members – the driver of the infection in China – was 10% early in the outbreak, but fell to 3% with quicker recognition and isolation. The overall numbers are lower than might have been expected, and an important insight for clinicians trying to contain the outbreak in the United States.
, but their ability to spread the infection dropped after that, Dr. Wu and others said at a special COVID-19 session at the meeting, which was scheduled to be in Boston, but was held online instead because of concerns about spreading the virus. The session has been posted.
Transmission from presymptomatic people is rare. Shedding persists to some degree for 7-12 days in mild/moderate cases, but 2 weeks or more in severe cases.
Dr. Wu said the numbers in China are moving in the right direction, which means that containment efforts there have worked.
The virus emerged in Wuhan, the capital of Hubei province in central China, in connection with a wildlife food market in December 2019. Bats are thought to be the reservoir, with perhaps an intermediate step between civet cats and raccoon dogs. Officials shut down the market.
Essentially, the entire population of China, more than a billion people, was told to stay home for 10 days to interrupt the transmission cycle after the virus spread throughout the country in a few weeks, and almost 60 million people in Hubei were put behind a cordon sanitaire, where they have been for 50 days and will remain “for a while,” Dr. Wu said.
It’s led to a steep drop in new cases and deaths in China since mid-February; both are now more common outside China than inside, and international numbers are lower than they were at the peak in China.
Meanwhile, there’s been no evidence of perinatal transmission; the virus has not been detected in amniotic fluid, cord blood, neonatal throat swabs, or breast milk. Maternal morbidity appears to be similar to uninfected women. “The data around pregnancy are reassuring,” said John Brooks, MD, chief medical officers for HIV/AIDS prevention at the Centers for Disease Control and Prevention, Atlanta, who has been involved with CDC’s containment efforts.
There’s no data yet for immunocompromised people, but for people with HIV, he said, “we think the risk of severe illness would be greater” with lower CD4 counts and unsuppressed viral loads. “People living with HIV should take precautions against this new virus,” including having at least a 30-day supply of HIV medications; keeping up flu and pneumonia vaccinations; and having a care plan if quarantined. Setting up telemedicine might be a good idea.
The usual incubation period for COVID-19 is 4-6 days but can be longer. Recovery time is about 2 weeks in mild cases and 3-6 weeks in more severe cases. People who die do so within 2 months of symptom onset.
The most common symptoms among hospitalized patients in China are fever, dry cough, fatigue, and headache. Truly asymptomatic cases are not common; most go on to develop symptoms. There have been reports of diarrhea before other symptoms by a day or two, but it’s probably a red herring. The virus has been isolated from stool, but there is no evidence of fecal-oral transmission, Dr. Wu said.
Eighty percent of COVID-19 cases are mild or moderate and most patients recover spontaneously, especially middle aged and younger people. There is no meaningful difference in distribution between the sexes.
There are limited pediatric data perhaps due to underreporting, “but we know [children] experience milder illness than adults,” the CDC’s Dr. Brooks said.
He pegged the latest case fatality estimate at 0.5% to 3.5%, which is considerably higher than seasonal flu, but might well drop as more mild cases are detected and added to the denominator, he said.
For now, death rates top 5% in adults over 60 years old and climb further with increasing age, approaching 16% in people 80 years or older. Patients with hypertension, diabetes, cardiovascular disease, and chronic respiratory illness are at increased risk. The ultimate cause of death is acute respiratory distress syndrome, said Ralph Baric, PhD, a coronavirus expert and epidemiology professor at the University of North Carolina, Chapel Hill, who also presented at the meeting.
Several drug and vaccine candidates are under study for the infection. An intriguing possibility is that angiotensin converting enzyme (ACE) inhibitors might help. Hypertension is a known risk factor for severe infection; the virus makes use of ACE receptor pathways to infect airway epithelial cells; and there have been reports of ACE inhibitors having effect against the virus that caused severe acute respiratory syndrome (SARS), another coronavirus outbreak in 2003.
“I think it’s a very good idea to go back and re-explore use of these drugs,” Dr. Baric said.
The presenters didn’t have any relevant disclosures.
The transmission rate of coronavirus disease 2019 (COVID-19) was 1%-5% among 38,000 Chinese people in close contact with infected patients, according to the chief epidemiologist of the Chinese Centers for Disease Control and Prevention, Beijing, Zunyou Wu, MD, PhD, who gave an update on the epidemic at the Conference on Retroviruses & Opportunistic Infections.
The rate of spread to family members – the driver of the infection in China – was 10% early in the outbreak, but fell to 3% with quicker recognition and isolation. The overall numbers are lower than might have been expected, and an important insight for clinicians trying to contain the outbreak in the United States.
, but their ability to spread the infection dropped after that, Dr. Wu and others said at a special COVID-19 session at the meeting, which was scheduled to be in Boston, but was held online instead because of concerns about spreading the virus. The session has been posted.
Transmission from presymptomatic people is rare. Shedding persists to some degree for 7-12 days in mild/moderate cases, but 2 weeks or more in severe cases.
Dr. Wu said the numbers in China are moving in the right direction, which means that containment efforts there have worked.
The virus emerged in Wuhan, the capital of Hubei province in central China, in connection with a wildlife food market in December 2019. Bats are thought to be the reservoir, with perhaps an intermediate step between civet cats and raccoon dogs. Officials shut down the market.
Essentially, the entire population of China, more than a billion people, was told to stay home for 10 days to interrupt the transmission cycle after the virus spread throughout the country in a few weeks, and almost 60 million people in Hubei were put behind a cordon sanitaire, where they have been for 50 days and will remain “for a while,” Dr. Wu said.
It’s led to a steep drop in new cases and deaths in China since mid-February; both are now more common outside China than inside, and international numbers are lower than they were at the peak in China.
Meanwhile, there’s been no evidence of perinatal transmission; the virus has not been detected in amniotic fluid, cord blood, neonatal throat swabs, or breast milk. Maternal morbidity appears to be similar to uninfected women. “The data around pregnancy are reassuring,” said John Brooks, MD, chief medical officers for HIV/AIDS prevention at the Centers for Disease Control and Prevention, Atlanta, who has been involved with CDC’s containment efforts.
There’s no data yet for immunocompromised people, but for people with HIV, he said, “we think the risk of severe illness would be greater” with lower CD4 counts and unsuppressed viral loads. “People living with HIV should take precautions against this new virus,” including having at least a 30-day supply of HIV medications; keeping up flu and pneumonia vaccinations; and having a care plan if quarantined. Setting up telemedicine might be a good idea.
The usual incubation period for COVID-19 is 4-6 days but can be longer. Recovery time is about 2 weeks in mild cases and 3-6 weeks in more severe cases. People who die do so within 2 months of symptom onset.
The most common symptoms among hospitalized patients in China are fever, dry cough, fatigue, and headache. Truly asymptomatic cases are not common; most go on to develop symptoms. There have been reports of diarrhea before other symptoms by a day or two, but it’s probably a red herring. The virus has been isolated from stool, but there is no evidence of fecal-oral transmission, Dr. Wu said.
Eighty percent of COVID-19 cases are mild or moderate and most patients recover spontaneously, especially middle aged and younger people. There is no meaningful difference in distribution between the sexes.
There are limited pediatric data perhaps due to underreporting, “but we know [children] experience milder illness than adults,” the CDC’s Dr. Brooks said.
He pegged the latest case fatality estimate at 0.5% to 3.5%, which is considerably higher than seasonal flu, but might well drop as more mild cases are detected and added to the denominator, he said.
For now, death rates top 5% in adults over 60 years old and climb further with increasing age, approaching 16% in people 80 years or older. Patients with hypertension, diabetes, cardiovascular disease, and chronic respiratory illness are at increased risk. The ultimate cause of death is acute respiratory distress syndrome, said Ralph Baric, PhD, a coronavirus expert and epidemiology professor at the University of North Carolina, Chapel Hill, who also presented at the meeting.
Several drug and vaccine candidates are under study for the infection. An intriguing possibility is that angiotensin converting enzyme (ACE) inhibitors might help. Hypertension is a known risk factor for severe infection; the virus makes use of ACE receptor pathways to infect airway epithelial cells; and there have been reports of ACE inhibitors having effect against the virus that caused severe acute respiratory syndrome (SARS), another coronavirus outbreak in 2003.
“I think it’s a very good idea to go back and re-explore use of these drugs,” Dr. Baric said.
The presenters didn’t have any relevant disclosures.
The transmission rate of coronavirus disease 2019 (COVID-19) was 1%-5% among 38,000 Chinese people in close contact with infected patients, according to the chief epidemiologist of the Chinese Centers for Disease Control and Prevention, Beijing, Zunyou Wu, MD, PhD, who gave an update on the epidemic at the Conference on Retroviruses & Opportunistic Infections.
The rate of spread to family members – the driver of the infection in China – was 10% early in the outbreak, but fell to 3% with quicker recognition and isolation. The overall numbers are lower than might have been expected, and an important insight for clinicians trying to contain the outbreak in the United States.
, but their ability to spread the infection dropped after that, Dr. Wu and others said at a special COVID-19 session at the meeting, which was scheduled to be in Boston, but was held online instead because of concerns about spreading the virus. The session has been posted.
Transmission from presymptomatic people is rare. Shedding persists to some degree for 7-12 days in mild/moderate cases, but 2 weeks or more in severe cases.
Dr. Wu said the numbers in China are moving in the right direction, which means that containment efforts there have worked.
The virus emerged in Wuhan, the capital of Hubei province in central China, in connection with a wildlife food market in December 2019. Bats are thought to be the reservoir, with perhaps an intermediate step between civet cats and raccoon dogs. Officials shut down the market.
Essentially, the entire population of China, more than a billion people, was told to stay home for 10 days to interrupt the transmission cycle after the virus spread throughout the country in a few weeks, and almost 60 million people in Hubei were put behind a cordon sanitaire, where they have been for 50 days and will remain “for a while,” Dr. Wu said.
It’s led to a steep drop in new cases and deaths in China since mid-February; both are now more common outside China than inside, and international numbers are lower than they were at the peak in China.
Meanwhile, there’s been no evidence of perinatal transmission; the virus has not been detected in amniotic fluid, cord blood, neonatal throat swabs, or breast milk. Maternal morbidity appears to be similar to uninfected women. “The data around pregnancy are reassuring,” said John Brooks, MD, chief medical officers for HIV/AIDS prevention at the Centers for Disease Control and Prevention, Atlanta, who has been involved with CDC’s containment efforts.
There’s no data yet for immunocompromised people, but for people with HIV, he said, “we think the risk of severe illness would be greater” with lower CD4 counts and unsuppressed viral loads. “People living with HIV should take precautions against this new virus,” including having at least a 30-day supply of HIV medications; keeping up flu and pneumonia vaccinations; and having a care plan if quarantined. Setting up telemedicine might be a good idea.
The usual incubation period for COVID-19 is 4-6 days but can be longer. Recovery time is about 2 weeks in mild cases and 3-6 weeks in more severe cases. People who die do so within 2 months of symptom onset.
The most common symptoms among hospitalized patients in China are fever, dry cough, fatigue, and headache. Truly asymptomatic cases are not common; most go on to develop symptoms. There have been reports of diarrhea before other symptoms by a day or two, but it’s probably a red herring. The virus has been isolated from stool, but there is no evidence of fecal-oral transmission, Dr. Wu said.
Eighty percent of COVID-19 cases are mild or moderate and most patients recover spontaneously, especially middle aged and younger people. There is no meaningful difference in distribution between the sexes.
There are limited pediatric data perhaps due to underreporting, “but we know [children] experience milder illness than adults,” the CDC’s Dr. Brooks said.
He pegged the latest case fatality estimate at 0.5% to 3.5%, which is considerably higher than seasonal flu, but might well drop as more mild cases are detected and added to the denominator, he said.
For now, death rates top 5% in adults over 60 years old and climb further with increasing age, approaching 16% in people 80 years or older. Patients with hypertension, diabetes, cardiovascular disease, and chronic respiratory illness are at increased risk. The ultimate cause of death is acute respiratory distress syndrome, said Ralph Baric, PhD, a coronavirus expert and epidemiology professor at the University of North Carolina, Chapel Hill, who also presented at the meeting.
Several drug and vaccine candidates are under study for the infection. An intriguing possibility is that angiotensin converting enzyme (ACE) inhibitors might help. Hypertension is a known risk factor for severe infection; the virus makes use of ACE receptor pathways to infect airway epithelial cells; and there have been reports of ACE inhibitors having effect against the virus that caused severe acute respiratory syndrome (SARS), another coronavirus outbreak in 2003.
“I think it’s a very good idea to go back and re-explore use of these drugs,” Dr. Baric said.
The presenters didn’t have any relevant disclosures.
FROM CROI 2020
Some infected patients could show COVID-19 symptoms after quarantine
Although a 14-day quarantine after exposure to novel coronavirus is “well supported” by evidence, some infected individuals will not become symptomatic until after that period, according to authors of a recent analysis published in Annals of Internal Medicine.
Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will develop symptoms by day 12 of the infection, which is within the 14-day period of active monitoring currently recommended by the Centers for Disease Control and Prevention, the authors wrote.
However, an estimated 101 out of 10,000 cases could become symptomatic after the end of that 14-day monitoring period, they cautioned.
“Our analyses do not preclude that estimate from being higher,” said the investigators, led by Stephen A. Lauer, PhD, MD, of Johns Hopkins Bloomberg School of Public Health, Baltimore.
The analysis, based on 181 confirmed cases of coronavirus disease 2019 (COVID-19) that were documented outside of the outbreak epicenter, Wuhan, China, makes “more conservative assumptions” about the window of symptom onset and potential for continued exposure, compared with analyses in previous studies, the researchers wrote.
The estimated incubation period for SARS-CoV-2 in the 181-patient study was a median of 5.1 days, which is comparable with previous estimates based on COVID-19 cases outside of Wuhan and consistent with other known human coronavirus diseases, such as SARS, which had a reported mean incubation period of 5 days, Dr. Lauer and colleagues noted.
Symptoms developed within 11.5 days for 97.5% of patients in the study.
Whether it’s acceptable to have 101 out of 10,000 cases becoming symptomatic beyond the recommended quarantine window depends on two factors, according to the authors. The first is the expected infection risk in the population that is being monitored, and the second is “judgment about the cost of missing cases,” wrote the authors.
In an interview, Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau, Oceanside, N.Y., said that in practical terms, the results suggest that the majority of patients with COVID-19 will be identified within 14 days, with an “outside chance” of an infected individual leaving quarantine and transmitting virus for a short period of time before becoming symptomatic.
“I think the proper message to give those patients [who are asymptomatic upon leaving quarantine] is, ‘after 14 days, we’re pretty sure you’re out of the woods, but should you get any symptoms, immediately requarantine yourself and seek medical care,” he said.
Study coauthor Kyra H. Grantz, a doctoral graduate student at the Johns Hopkins Bloomberg School of Public Health, said that extending a quarantine beyond 14 days might be considered in the highest-risk scenarios, though the benefits of doing so would have to be weighed against the costs to public health and to the individuals under quarantine.
“Our estimate of the incubation period definitely supports the 14-day recommendation that the CDC has been using,” she said in an interview.
Dr. Grantz emphasized that the estimate of 101 out of 10,000 cases developing symptoms after day 14 of active monitoring – representing the 99th percentile of cases – assumes the “most conservative, worst-case scenario” in a population that is fully infected.
“If you’re looking at a following a cohort of 1,000 people whom you think may have been exposed, only a certain percentage will be infected, and only a certain percentage of those will even develop symptoms – before we get to this idea of how many people would we miss,” she said.
The study was supported by the Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, and the Alexander von Humboldt Foundation. Four authors reported disclosures related to those entities, and the remaining five reported no conflicts of interest.
SOURCE: Lauer SA et al. Ann Intern Med. 2020 Mar 9. doi:10.1101/2020.02.02.20020016.
Although a 14-day quarantine after exposure to novel coronavirus is “well supported” by evidence, some infected individuals will not become symptomatic until after that period, according to authors of a recent analysis published in Annals of Internal Medicine.
Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will develop symptoms by day 12 of the infection, which is within the 14-day period of active monitoring currently recommended by the Centers for Disease Control and Prevention, the authors wrote.
However, an estimated 101 out of 10,000 cases could become symptomatic after the end of that 14-day monitoring period, they cautioned.
“Our analyses do not preclude that estimate from being higher,” said the investigators, led by Stephen A. Lauer, PhD, MD, of Johns Hopkins Bloomberg School of Public Health, Baltimore.
The analysis, based on 181 confirmed cases of coronavirus disease 2019 (COVID-19) that were documented outside of the outbreak epicenter, Wuhan, China, makes “more conservative assumptions” about the window of symptom onset and potential for continued exposure, compared with analyses in previous studies, the researchers wrote.
The estimated incubation period for SARS-CoV-2 in the 181-patient study was a median of 5.1 days, which is comparable with previous estimates based on COVID-19 cases outside of Wuhan and consistent with other known human coronavirus diseases, such as SARS, which had a reported mean incubation period of 5 days, Dr. Lauer and colleagues noted.
Symptoms developed within 11.5 days for 97.5% of patients in the study.
Whether it’s acceptable to have 101 out of 10,000 cases becoming symptomatic beyond the recommended quarantine window depends on two factors, according to the authors. The first is the expected infection risk in the population that is being monitored, and the second is “judgment about the cost of missing cases,” wrote the authors.
In an interview, Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau, Oceanside, N.Y., said that in practical terms, the results suggest that the majority of patients with COVID-19 will be identified within 14 days, with an “outside chance” of an infected individual leaving quarantine and transmitting virus for a short period of time before becoming symptomatic.
“I think the proper message to give those patients [who are asymptomatic upon leaving quarantine] is, ‘after 14 days, we’re pretty sure you’re out of the woods, but should you get any symptoms, immediately requarantine yourself and seek medical care,” he said.
Study coauthor Kyra H. Grantz, a doctoral graduate student at the Johns Hopkins Bloomberg School of Public Health, said that extending a quarantine beyond 14 days might be considered in the highest-risk scenarios, though the benefits of doing so would have to be weighed against the costs to public health and to the individuals under quarantine.
“Our estimate of the incubation period definitely supports the 14-day recommendation that the CDC has been using,” she said in an interview.
Dr. Grantz emphasized that the estimate of 101 out of 10,000 cases developing symptoms after day 14 of active monitoring – representing the 99th percentile of cases – assumes the “most conservative, worst-case scenario” in a population that is fully infected.
“If you’re looking at a following a cohort of 1,000 people whom you think may have been exposed, only a certain percentage will be infected, and only a certain percentage of those will even develop symptoms – before we get to this idea of how many people would we miss,” she said.
The study was supported by the Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, and the Alexander von Humboldt Foundation. Four authors reported disclosures related to those entities, and the remaining five reported no conflicts of interest.
SOURCE: Lauer SA et al. Ann Intern Med. 2020 Mar 9. doi:10.1101/2020.02.02.20020016.
Although a 14-day quarantine after exposure to novel coronavirus is “well supported” by evidence, some infected individuals will not become symptomatic until after that period, according to authors of a recent analysis published in Annals of Internal Medicine.
Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will develop symptoms by day 12 of the infection, which is within the 14-day period of active monitoring currently recommended by the Centers for Disease Control and Prevention, the authors wrote.
However, an estimated 101 out of 10,000 cases could become symptomatic after the end of that 14-day monitoring period, they cautioned.
“Our analyses do not preclude that estimate from being higher,” said the investigators, led by Stephen A. Lauer, PhD, MD, of Johns Hopkins Bloomberg School of Public Health, Baltimore.
The analysis, based on 181 confirmed cases of coronavirus disease 2019 (COVID-19) that were documented outside of the outbreak epicenter, Wuhan, China, makes “more conservative assumptions” about the window of symptom onset and potential for continued exposure, compared with analyses in previous studies, the researchers wrote.
The estimated incubation period for SARS-CoV-2 in the 181-patient study was a median of 5.1 days, which is comparable with previous estimates based on COVID-19 cases outside of Wuhan and consistent with other known human coronavirus diseases, such as SARS, which had a reported mean incubation period of 5 days, Dr. Lauer and colleagues noted.
Symptoms developed within 11.5 days for 97.5% of patients in the study.
Whether it’s acceptable to have 101 out of 10,000 cases becoming symptomatic beyond the recommended quarantine window depends on two factors, according to the authors. The first is the expected infection risk in the population that is being monitored, and the second is “judgment about the cost of missing cases,” wrote the authors.
In an interview, Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau, Oceanside, N.Y., said that in practical terms, the results suggest that the majority of patients with COVID-19 will be identified within 14 days, with an “outside chance” of an infected individual leaving quarantine and transmitting virus for a short period of time before becoming symptomatic.
“I think the proper message to give those patients [who are asymptomatic upon leaving quarantine] is, ‘after 14 days, we’re pretty sure you’re out of the woods, but should you get any symptoms, immediately requarantine yourself and seek medical care,” he said.
Study coauthor Kyra H. Grantz, a doctoral graduate student at the Johns Hopkins Bloomberg School of Public Health, said that extending a quarantine beyond 14 days might be considered in the highest-risk scenarios, though the benefits of doing so would have to be weighed against the costs to public health and to the individuals under quarantine.
“Our estimate of the incubation period definitely supports the 14-day recommendation that the CDC has been using,” she said in an interview.
Dr. Grantz emphasized that the estimate of 101 out of 10,000 cases developing symptoms after day 14 of active monitoring – representing the 99th percentile of cases – assumes the “most conservative, worst-case scenario” in a population that is fully infected.
“If you’re looking at a following a cohort of 1,000 people whom you think may have been exposed, only a certain percentage will be infected, and only a certain percentage of those will even develop symptoms – before we get to this idea of how many people would we miss,” she said.
The study was supported by the Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, and the Alexander von Humboldt Foundation. Four authors reported disclosures related to those entities, and the remaining five reported no conflicts of interest.
SOURCE: Lauer SA et al. Ann Intern Med. 2020 Mar 9. doi:10.1101/2020.02.02.20020016.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical point: Some individuals who are infected with the novel coronavirus could become symptomatic after the active 14-day quarantine period.
Major finding: The median incubation period was 5.1 days, with 97.5% of patients developing symptoms within 11.5 days, implying that 101 of every 10,000 cases (99th percentile) would develop symptoms beyond the quarantine period.
Study details: Analysis of 181 confirmed COVID-19 cases identified outside of the outbreak epicenter, Wuhan, China.
Disclosures: The study was supported by the U.S. Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, and the Alexander von Humboldt Foundation. Four authors reported disclosures related to those entities, and the remaining five reported no conflicts of interest.
Source: Lauer SA et al. Ann Intern Med. 2020 Mar 9. doi: 10.1101/2020.02.02.20020016.
CMS issues guidance on containing spread of coronavirus
The first guidance document, “Guidance for Infection Control and Prevention Concerning Coronavirus Disease (COVID-19): FAQs and Considerations for Patient Triage, Placement and Hospital Discharge,” issued March 4, provides some basic guidance, including identifying which patients are at risk, how facilities should screen for COVID-19, how facilities should monitor or restrict health care facility staff, and other recommendations for infection prevention and control.
“Hospitals should identify visitors and patients at risk for having COVID-19 infection before or immediately upon arrival to the healthcare facility,” the guidance document notes. “For patients, implement respiratory hygiene and cough etiquette (i.e., placing a face mask over the patient’s nose and mouth if that has not already been done) and isolate the patient in an examination room with the door closed. If the patient cannot be immediately moved to an examination room, ensure they are not allowed to wait among other patients seeking care.”
The document offers further information regarding the care of patients and provides numerous links to existing guidance from the Centers for Disease Control and Prevention.
The second document, “Guidance for Infection Control and Prevention of Coronavirus Disease 2019 (COVID-19) in Nursing Homes,” issued the same day, provides information on how to limit and monitor visitors as well as monitor and restrict health staff. It details when to transfer residents with suspected or confirmed coronavirus infection, and when a nursing home should accept a resident diagnosed with COVID-19.
Facilities “should contact their local health department if they have questions or suspect a resident of a nursing home has COVID-19,” the document states. “Per CDC, prompt detection, triage and isolation of potentially infectious patients are essential to prevent unnecessary exposure among patients, healthcare personnel, and visitors at the facility.”
The CMS also announced that it is suspending all nonemergency survey activity.
“CMS is suspending nonemergency inspections across the country, allowing inspectors to turn their focus on the most serious health and safety threats like infectious diseases and abuse,” the agency stated in a March 4 memo. “This shift in approach will also allow inspectors to focus on addressing the spread of ... COVID-19. CMS is issuing this memorandum to State Survey Agencies to provide important guidelines for the inspection process in situations in which a COVID-19 is suspected.”
In a statement, CMS Administrator Seema Verma said these actions “represent a call to action across the health care system. All health care providers must immediately review their procedures to ensure compliance with CMS’ infection control requirements, as well as the guidelines from the Centers for Disease Control and Prevention.”
The first guidance document, “Guidance for Infection Control and Prevention Concerning Coronavirus Disease (COVID-19): FAQs and Considerations for Patient Triage, Placement and Hospital Discharge,” issued March 4, provides some basic guidance, including identifying which patients are at risk, how facilities should screen for COVID-19, how facilities should monitor or restrict health care facility staff, and other recommendations for infection prevention and control.
“Hospitals should identify visitors and patients at risk for having COVID-19 infection before or immediately upon arrival to the healthcare facility,” the guidance document notes. “For patients, implement respiratory hygiene and cough etiquette (i.e., placing a face mask over the patient’s nose and mouth if that has not already been done) and isolate the patient in an examination room with the door closed. If the patient cannot be immediately moved to an examination room, ensure they are not allowed to wait among other patients seeking care.”
The document offers further information regarding the care of patients and provides numerous links to existing guidance from the Centers for Disease Control and Prevention.
The second document, “Guidance for Infection Control and Prevention of Coronavirus Disease 2019 (COVID-19) in Nursing Homes,” issued the same day, provides information on how to limit and monitor visitors as well as monitor and restrict health staff. It details when to transfer residents with suspected or confirmed coronavirus infection, and when a nursing home should accept a resident diagnosed with COVID-19.
Facilities “should contact their local health department if they have questions or suspect a resident of a nursing home has COVID-19,” the document states. “Per CDC, prompt detection, triage and isolation of potentially infectious patients are essential to prevent unnecessary exposure among patients, healthcare personnel, and visitors at the facility.”
The CMS also announced that it is suspending all nonemergency survey activity.
“CMS is suspending nonemergency inspections across the country, allowing inspectors to turn their focus on the most serious health and safety threats like infectious diseases and abuse,” the agency stated in a March 4 memo. “This shift in approach will also allow inspectors to focus on addressing the spread of ... COVID-19. CMS is issuing this memorandum to State Survey Agencies to provide important guidelines for the inspection process in situations in which a COVID-19 is suspected.”
In a statement, CMS Administrator Seema Verma said these actions “represent a call to action across the health care system. All health care providers must immediately review their procedures to ensure compliance with CMS’ infection control requirements, as well as the guidelines from the Centers for Disease Control and Prevention.”
The first guidance document, “Guidance for Infection Control and Prevention Concerning Coronavirus Disease (COVID-19): FAQs and Considerations for Patient Triage, Placement and Hospital Discharge,” issued March 4, provides some basic guidance, including identifying which patients are at risk, how facilities should screen for COVID-19, how facilities should monitor or restrict health care facility staff, and other recommendations for infection prevention and control.
“Hospitals should identify visitors and patients at risk for having COVID-19 infection before or immediately upon arrival to the healthcare facility,” the guidance document notes. “For patients, implement respiratory hygiene and cough etiquette (i.e., placing a face mask over the patient’s nose and mouth if that has not already been done) and isolate the patient in an examination room with the door closed. If the patient cannot be immediately moved to an examination room, ensure they are not allowed to wait among other patients seeking care.”
The document offers further information regarding the care of patients and provides numerous links to existing guidance from the Centers for Disease Control and Prevention.
The second document, “Guidance for Infection Control and Prevention of Coronavirus Disease 2019 (COVID-19) in Nursing Homes,” issued the same day, provides information on how to limit and monitor visitors as well as monitor and restrict health staff. It details when to transfer residents with suspected or confirmed coronavirus infection, and when a nursing home should accept a resident diagnosed with COVID-19.
Facilities “should contact their local health department if they have questions or suspect a resident of a nursing home has COVID-19,” the document states. “Per CDC, prompt detection, triage and isolation of potentially infectious patients are essential to prevent unnecessary exposure among patients, healthcare personnel, and visitors at the facility.”
The CMS also announced that it is suspending all nonemergency survey activity.
“CMS is suspending nonemergency inspections across the country, allowing inspectors to turn their focus on the most serious health and safety threats like infectious diseases and abuse,” the agency stated in a March 4 memo. “This shift in approach will also allow inspectors to focus on addressing the spread of ... COVID-19. CMS is issuing this memorandum to State Survey Agencies to provide important guidelines for the inspection process in situations in which a COVID-19 is suspected.”
In a statement, CMS Administrator Seema Verma said these actions “represent a call to action across the health care system. All health care providers must immediately review their procedures to ensure compliance with CMS’ infection control requirements, as well as the guidelines from the Centers for Disease Control and Prevention.”
Esophageal length ratio predicts hiatal hernia recurrence
A new ratio based on manometric esophageal length in relation to patient height could offer an objective means of preoperatively identifying shortened esophagus, which could improve surgical planning and outcomes with hiatal hernia repair, according to investigators.
In a retrospective analysis, patients with a lower manometric esophageal length-to-height (MELH) ratio had a higher rate of hiatal hernia recurrence, reported lead author Pooja Lal, MD, of the Cleveland Clinic, and colleagues.
A short esophagus increases tension at the gastroesophageal junction, which may necessitate a lengthening procedure in addition to hiatal hernia repair, the investigators wrote in the Journal of Clinical Gastroenterology. As lengthening may require additional expertise, preoperative knowledge of a short esophagus is beneficial; however, until this point, short esophagus could only be identified intraoperatively. Since previous attempts to define short esophagus were confounded by patient height, the investigators devised the MELH ratio to account for this variable.
The investigators evaluated data from 245 patients who underwent hiatal hernia repair by Nissen fundoplication, of whom 157 also underwent esophageal lengthening with a Collis gastroplasty. The decision to perform a Collis gastroplasty was made intraoperatively if a patient did not have at least 2-3 cm of intra-abdominal esophageal length with minimal tension.
For all patients, the MELH ratio was determined by dividing manometric esophageal length by patient height (both in centimeters).
On average, patients who needed a Collis gastroplasty had a shorter esophagus (20.2 vs. 22.4 cm; P less than .001) and a lower MELH ratio (0.12 vs. 0.13; P less than .001).
Multivariable hazard regression showed that regardless of surgical approach, for every 0.01 U-increment increase in MELH ratio, risk of hernia recurrence decreased by 33% (hazard ratio, 0.67; P less than .001). In contrast, regardless of MELH ratio, repair without Collis was associated with a 500% increased risk of recurrence (HR, 6.1; P less than .001). Over 5 years, the benefit of Collis gastroplasty translated to a significantly lower rate of both hernia recurrence (18% vs. 55%; P less than .001) and reoperations for recurrence (0% vs. 10%; P less than .001).
“We suggest that surgeons and gastroenterologists calculate the MELH ratio before repair of a hiatal hernia, and be cognizant of patients with a shortened esophagus,” the investigators concluded. “An esophageal lengthening procedure such as a Collis gastroplasty may reduce the risk of hernia recurrence and reoperation for recurrence, especially for patients with a MELH ratio less than 0.12.”The investigators reported no conflicts of interest.
SOURCE: Lal P et al. J Clin Gastroenterol. 2020 Jan 20. doi: 10.1097/MCG.0000000000001316.
A new ratio based on manometric esophageal length in relation to patient height could offer an objective means of preoperatively identifying shortened esophagus, which could improve surgical planning and outcomes with hiatal hernia repair, according to investigators.
In a retrospective analysis, patients with a lower manometric esophageal length-to-height (MELH) ratio had a higher rate of hiatal hernia recurrence, reported lead author Pooja Lal, MD, of the Cleveland Clinic, and colleagues.
A short esophagus increases tension at the gastroesophageal junction, which may necessitate a lengthening procedure in addition to hiatal hernia repair, the investigators wrote in the Journal of Clinical Gastroenterology. As lengthening may require additional expertise, preoperative knowledge of a short esophagus is beneficial; however, until this point, short esophagus could only be identified intraoperatively. Since previous attempts to define short esophagus were confounded by patient height, the investigators devised the MELH ratio to account for this variable.
The investigators evaluated data from 245 patients who underwent hiatal hernia repair by Nissen fundoplication, of whom 157 also underwent esophageal lengthening with a Collis gastroplasty. The decision to perform a Collis gastroplasty was made intraoperatively if a patient did not have at least 2-3 cm of intra-abdominal esophageal length with minimal tension.
For all patients, the MELH ratio was determined by dividing manometric esophageal length by patient height (both in centimeters).
On average, patients who needed a Collis gastroplasty had a shorter esophagus (20.2 vs. 22.4 cm; P less than .001) and a lower MELH ratio (0.12 vs. 0.13; P less than .001).
Multivariable hazard regression showed that regardless of surgical approach, for every 0.01 U-increment increase in MELH ratio, risk of hernia recurrence decreased by 33% (hazard ratio, 0.67; P less than .001). In contrast, regardless of MELH ratio, repair without Collis was associated with a 500% increased risk of recurrence (HR, 6.1; P less than .001). Over 5 years, the benefit of Collis gastroplasty translated to a significantly lower rate of both hernia recurrence (18% vs. 55%; P less than .001) and reoperations for recurrence (0% vs. 10%; P less than .001).
“We suggest that surgeons and gastroenterologists calculate the MELH ratio before repair of a hiatal hernia, and be cognizant of patients with a shortened esophagus,” the investigators concluded. “An esophageal lengthening procedure such as a Collis gastroplasty may reduce the risk of hernia recurrence and reoperation for recurrence, especially for patients with a MELH ratio less than 0.12.”The investigators reported no conflicts of interest.
SOURCE: Lal P et al. J Clin Gastroenterol. 2020 Jan 20. doi: 10.1097/MCG.0000000000001316.
A new ratio based on manometric esophageal length in relation to patient height could offer an objective means of preoperatively identifying shortened esophagus, which could improve surgical planning and outcomes with hiatal hernia repair, according to investigators.
In a retrospective analysis, patients with a lower manometric esophageal length-to-height (MELH) ratio had a higher rate of hiatal hernia recurrence, reported lead author Pooja Lal, MD, of the Cleveland Clinic, and colleagues.
A short esophagus increases tension at the gastroesophageal junction, which may necessitate a lengthening procedure in addition to hiatal hernia repair, the investigators wrote in the Journal of Clinical Gastroenterology. As lengthening may require additional expertise, preoperative knowledge of a short esophagus is beneficial; however, until this point, short esophagus could only be identified intraoperatively. Since previous attempts to define short esophagus were confounded by patient height, the investigators devised the MELH ratio to account for this variable.
The investigators evaluated data from 245 patients who underwent hiatal hernia repair by Nissen fundoplication, of whom 157 also underwent esophageal lengthening with a Collis gastroplasty. The decision to perform a Collis gastroplasty was made intraoperatively if a patient did not have at least 2-3 cm of intra-abdominal esophageal length with minimal tension.
For all patients, the MELH ratio was determined by dividing manometric esophageal length by patient height (both in centimeters).
On average, patients who needed a Collis gastroplasty had a shorter esophagus (20.2 vs. 22.4 cm; P less than .001) and a lower MELH ratio (0.12 vs. 0.13; P less than .001).
Multivariable hazard regression showed that regardless of surgical approach, for every 0.01 U-increment increase in MELH ratio, risk of hernia recurrence decreased by 33% (hazard ratio, 0.67; P less than .001). In contrast, regardless of MELH ratio, repair without Collis was associated with a 500% increased risk of recurrence (HR, 6.1; P less than .001). Over 5 years, the benefit of Collis gastroplasty translated to a significantly lower rate of both hernia recurrence (18% vs. 55%; P less than .001) and reoperations for recurrence (0% vs. 10%; P less than .001).
“We suggest that surgeons and gastroenterologists calculate the MELH ratio before repair of a hiatal hernia, and be cognizant of patients with a shortened esophagus,” the investigators concluded. “An esophageal lengthening procedure such as a Collis gastroplasty may reduce the risk of hernia recurrence and reoperation for recurrence, especially for patients with a MELH ratio less than 0.12.”The investigators reported no conflicts of interest.
SOURCE: Lal P et al. J Clin Gastroenterol. 2020 Jan 20. doi: 10.1097/MCG.0000000000001316.
FROM THE JOURNAL OF CLINICAL GASTROENTEROLOGY
Trial of epicutaneous immunotherapy in eosinophilic esophagitis
For children with milk-induced eosinophilic esophagitis (EoE), 9 months of epicutaneous immunotherapy (EPIT) with Viaskin Milk did not significantly improve eosinophil counts or symptoms, compared with placebo, according to the results of an intention-to-treat analysis of a randomized, double-blinded pilot study.
Average maximum eosinophil counts were 50.1 per high-power field in the Viaskin Milk group versus 48.2 in the placebo group, said Jonathan M. Spergel, MD, of the Children’s Hospital of Philadelphia and associates. However, in the per-protocol analysis, the seven patients who received Viaskin Milk had mean eosinophil counts of 25.6 per high-power field, compared with 95.0 for the two children who received placebo (P = .038). Moreover, 47% of patients had fewer than 15 eosinophils per high-power field after an additional 11 months of open-label treatment with Viaskin Milk. Taken together, the findings justify larger, multicenter studies to evaluate EPIT for treating EoE and other non-IgE mediated food diseases, Dr. Spergel and associates wrote in Clinical Gastroenterology and Hepatology.
EoE results from an immune response to specific food allergens, including milk. Classic symptoms include difficulty feeding and failure to thrive in infants, abdominal pain in young children, and dysphagia in older children and adults. Definitive diagnosis requires an esophageal biopsy with an eosinophil count of 15 or more cells per high-power field. “There are no approved therapies [for eosinophilic esophagitis] beyond avoidance of the allergen(s) or treatment of inflammation,” the investigators wrote.
In prior studies, exposure to EPIT was found to mitigate eosinophilic gastrointestinal disease in mice and pigs. In humans, milk is the most common dietary cause of eosinophilic esophagitis. Accordingly, Viaskin Milk is an EPIT containing an allergen extract of milk that is administered epicutaneously using a specialized delivery system. To evaluate its use for the treatment of pediatric milk-induced EoE (at least 15 eosinophils per high-power frame despite at least 2 months of high-dose proton pump–inhibitor therapy at 1-2 mg/kg twice daily), the researchers randomly assigned 20 children on a 3:1 basis to receive either Viaskin Milk or placebo for 9 months. Patients and investigators were double-blinded for this phase of the study, during most of which patients abstained from milk. Toward the end of the 9 months, patients resumed consuming milk and continued doing so if their upper endoscopy biopsy showed resolution of EoE (eosinophil count less than 15 per high-power field).
In the intention-to-treat analysis, Viaskin Milk did not meet the primary endpoint of the difference in least squares mean compared with placebo (8.6; 95% confidence interval, –35.36 to 52.56). Symptom scores also were similar between groups. In contrast, at the end of the 11-month, open-label period, 9 of 19 evaluable patients had eosinophil biopsy counts of fewer than 15 per high-power field, for a response rate of 47%. “The number of adverse events did not differ significantly between the Viaskin Milk and placebo groups,” the researchers added.
Protocol violations might explain why EPIT failed to meet the primary endpoint in the intention-to-treat analysis, they wrote. “For example, the patients on the active therapy wanted to ingest more milk, while the patients in the placebo group wanted less milk,” they reported. “Three patients in the active therapy went on binge milk diets drinking 4 to 8 times the amount of milk compared with baseline.” The use of proton pump inhibitors also was inconsistent between groups, they added. “The major limitation in the [per-protocol] population was the small sample size of this pilot study, raising the possibility of false-positive results.”
The study was funded by DBV Technologies and by the Children’s Hospital of Philadelphia Eosinophilic Esophagitis Family Fund. Dr. Spergel disclosed consulting agreements, grants funding, and stock equity with DBV Technologies. Three coinvestigators also disclosed ties to DBV. The remaining five coinvestigators reported having no conflicts of interest.
SOURCE: Spergel JM et al. Clin Gastroenterol Hepatol. 2019 May 14. doi: 10.1016/j.cgh.2019.05.014.
Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease that is primarily triggered by food antigens. Though many patients can be treated with dietary elimination or pharmacologic therapies, when foods are added back, elimination diets are not followed, or medications stopped, the disease will flare. Further, unlike some other atopic conditions, patients with EoE do not “grow out of it.” A true cure for EoE has been elusive. In this study by Spergel and colleagues, they build on intriguing data from animal models showing induction of immune tolerance to food antigens with epicutaneous immunotherapy (EPIT).
The investigators conducted a proof-of-concept, double-blind, placebo-controlled randomized trial of epicutaneous desensitization with a milk patch in children with EoE who had milk as a confirmed dietary trigger. The primary intention-to-treat results showed that there was no difference between placebo and active patches for decreasing esophageal eosinophil counts. However, in the small set of patients who were able to adhere fully to the protocol, the per-protocol analysis suggested that there was a lower eosinophil count with active treatment. Additionally, in an 11-month, open-label extension, there were patients who maintained histologic response (less than 15 eosinophils/hpf) after reintroducing milk.
These data suggest that EPIT potentially can desensitize milk-triggered EoE patients and that this treatment method should be pursued in future studies, with protocol alterations based on lessons learned regarding adherence in this study. Should this line of investigation be successful, then EoE patients who have milk as their EoE trigger, and who undergo successful desensitization with mild reintroduction while maintaining disease remission, may be able to be deemed cured.
Evan S. Dellon, MD, MPH, professor of medicine and epidemiology, division of gastroenterology and hepatology, University of North Carolina at Chapel Hill. He has received research funding from and consulted for Adare, Allakos, GSK, Celgene/Receptos, and Shire/Takeda among other pharmaceutical companies.
Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease that is primarily triggered by food antigens. Though many patients can be treated with dietary elimination or pharmacologic therapies, when foods are added back, elimination diets are not followed, or medications stopped, the disease will flare. Further, unlike some other atopic conditions, patients with EoE do not “grow out of it.” A true cure for EoE has been elusive. In this study by Spergel and colleagues, they build on intriguing data from animal models showing induction of immune tolerance to food antigens with epicutaneous immunotherapy (EPIT).
The investigators conducted a proof-of-concept, double-blind, placebo-controlled randomized trial of epicutaneous desensitization with a milk patch in children with EoE who had milk as a confirmed dietary trigger. The primary intention-to-treat results showed that there was no difference between placebo and active patches for decreasing esophageal eosinophil counts. However, in the small set of patients who were able to adhere fully to the protocol, the per-protocol analysis suggested that there was a lower eosinophil count with active treatment. Additionally, in an 11-month, open-label extension, there were patients who maintained histologic response (less than 15 eosinophils/hpf) after reintroducing milk.
These data suggest that EPIT potentially can desensitize milk-triggered EoE patients and that this treatment method should be pursued in future studies, with protocol alterations based on lessons learned regarding adherence in this study. Should this line of investigation be successful, then EoE patients who have milk as their EoE trigger, and who undergo successful desensitization with mild reintroduction while maintaining disease remission, may be able to be deemed cured.
Evan S. Dellon, MD, MPH, professor of medicine and epidemiology, division of gastroenterology and hepatology, University of North Carolina at Chapel Hill. He has received research funding from and consulted for Adare, Allakos, GSK, Celgene/Receptos, and Shire/Takeda among other pharmaceutical companies.
Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease that is primarily triggered by food antigens. Though many patients can be treated with dietary elimination or pharmacologic therapies, when foods are added back, elimination diets are not followed, or medications stopped, the disease will flare. Further, unlike some other atopic conditions, patients with EoE do not “grow out of it.” A true cure for EoE has been elusive. In this study by Spergel and colleagues, they build on intriguing data from animal models showing induction of immune tolerance to food antigens with epicutaneous immunotherapy (EPIT).
The investigators conducted a proof-of-concept, double-blind, placebo-controlled randomized trial of epicutaneous desensitization with a milk patch in children with EoE who had milk as a confirmed dietary trigger. The primary intention-to-treat results showed that there was no difference between placebo and active patches for decreasing esophageal eosinophil counts. However, in the small set of patients who were able to adhere fully to the protocol, the per-protocol analysis suggested that there was a lower eosinophil count with active treatment. Additionally, in an 11-month, open-label extension, there were patients who maintained histologic response (less than 15 eosinophils/hpf) after reintroducing milk.
These data suggest that EPIT potentially can desensitize milk-triggered EoE patients and that this treatment method should be pursued in future studies, with protocol alterations based on lessons learned regarding adherence in this study. Should this line of investigation be successful, then EoE patients who have milk as their EoE trigger, and who undergo successful desensitization with mild reintroduction while maintaining disease remission, may be able to be deemed cured.
Evan S. Dellon, MD, MPH, professor of medicine and epidemiology, division of gastroenterology and hepatology, University of North Carolina at Chapel Hill. He has received research funding from and consulted for Adare, Allakos, GSK, Celgene/Receptos, and Shire/Takeda among other pharmaceutical companies.
For children with milk-induced eosinophilic esophagitis (EoE), 9 months of epicutaneous immunotherapy (EPIT) with Viaskin Milk did not significantly improve eosinophil counts or symptoms, compared with placebo, according to the results of an intention-to-treat analysis of a randomized, double-blinded pilot study.
Average maximum eosinophil counts were 50.1 per high-power field in the Viaskin Milk group versus 48.2 in the placebo group, said Jonathan M. Spergel, MD, of the Children’s Hospital of Philadelphia and associates. However, in the per-protocol analysis, the seven patients who received Viaskin Milk had mean eosinophil counts of 25.6 per high-power field, compared with 95.0 for the two children who received placebo (P = .038). Moreover, 47% of patients had fewer than 15 eosinophils per high-power field after an additional 11 months of open-label treatment with Viaskin Milk. Taken together, the findings justify larger, multicenter studies to evaluate EPIT for treating EoE and other non-IgE mediated food diseases, Dr. Spergel and associates wrote in Clinical Gastroenterology and Hepatology.
EoE results from an immune response to specific food allergens, including milk. Classic symptoms include difficulty feeding and failure to thrive in infants, abdominal pain in young children, and dysphagia in older children and adults. Definitive diagnosis requires an esophageal biopsy with an eosinophil count of 15 or more cells per high-power field. “There are no approved therapies [for eosinophilic esophagitis] beyond avoidance of the allergen(s) or treatment of inflammation,” the investigators wrote.
In prior studies, exposure to EPIT was found to mitigate eosinophilic gastrointestinal disease in mice and pigs. In humans, milk is the most common dietary cause of eosinophilic esophagitis. Accordingly, Viaskin Milk is an EPIT containing an allergen extract of milk that is administered epicutaneously using a specialized delivery system. To evaluate its use for the treatment of pediatric milk-induced EoE (at least 15 eosinophils per high-power frame despite at least 2 months of high-dose proton pump–inhibitor therapy at 1-2 mg/kg twice daily), the researchers randomly assigned 20 children on a 3:1 basis to receive either Viaskin Milk or placebo for 9 months. Patients and investigators were double-blinded for this phase of the study, during most of which patients abstained from milk. Toward the end of the 9 months, patients resumed consuming milk and continued doing so if their upper endoscopy biopsy showed resolution of EoE (eosinophil count less than 15 per high-power field).
In the intention-to-treat analysis, Viaskin Milk did not meet the primary endpoint of the difference in least squares mean compared with placebo (8.6; 95% confidence interval, –35.36 to 52.56). Symptom scores also were similar between groups. In contrast, at the end of the 11-month, open-label period, 9 of 19 evaluable patients had eosinophil biopsy counts of fewer than 15 per high-power field, for a response rate of 47%. “The number of adverse events did not differ significantly between the Viaskin Milk and placebo groups,” the researchers added.
Protocol violations might explain why EPIT failed to meet the primary endpoint in the intention-to-treat analysis, they wrote. “For example, the patients on the active therapy wanted to ingest more milk, while the patients in the placebo group wanted less milk,” they reported. “Three patients in the active therapy went on binge milk diets drinking 4 to 8 times the amount of milk compared with baseline.” The use of proton pump inhibitors also was inconsistent between groups, they added. “The major limitation in the [per-protocol] population was the small sample size of this pilot study, raising the possibility of false-positive results.”
The study was funded by DBV Technologies and by the Children’s Hospital of Philadelphia Eosinophilic Esophagitis Family Fund. Dr. Spergel disclosed consulting agreements, grants funding, and stock equity with DBV Technologies. Three coinvestigators also disclosed ties to DBV. The remaining five coinvestigators reported having no conflicts of interest.
SOURCE: Spergel JM et al. Clin Gastroenterol Hepatol. 2019 May 14. doi: 10.1016/j.cgh.2019.05.014.
For children with milk-induced eosinophilic esophagitis (EoE), 9 months of epicutaneous immunotherapy (EPIT) with Viaskin Milk did not significantly improve eosinophil counts or symptoms, compared with placebo, according to the results of an intention-to-treat analysis of a randomized, double-blinded pilot study.
Average maximum eosinophil counts were 50.1 per high-power field in the Viaskin Milk group versus 48.2 in the placebo group, said Jonathan M. Spergel, MD, of the Children’s Hospital of Philadelphia and associates. However, in the per-protocol analysis, the seven patients who received Viaskin Milk had mean eosinophil counts of 25.6 per high-power field, compared with 95.0 for the two children who received placebo (P = .038). Moreover, 47% of patients had fewer than 15 eosinophils per high-power field after an additional 11 months of open-label treatment with Viaskin Milk. Taken together, the findings justify larger, multicenter studies to evaluate EPIT for treating EoE and other non-IgE mediated food diseases, Dr. Spergel and associates wrote in Clinical Gastroenterology and Hepatology.
EoE results from an immune response to specific food allergens, including milk. Classic symptoms include difficulty feeding and failure to thrive in infants, abdominal pain in young children, and dysphagia in older children and adults. Definitive diagnosis requires an esophageal biopsy with an eosinophil count of 15 or more cells per high-power field. “There are no approved therapies [for eosinophilic esophagitis] beyond avoidance of the allergen(s) or treatment of inflammation,” the investigators wrote.
In prior studies, exposure to EPIT was found to mitigate eosinophilic gastrointestinal disease in mice and pigs. In humans, milk is the most common dietary cause of eosinophilic esophagitis. Accordingly, Viaskin Milk is an EPIT containing an allergen extract of milk that is administered epicutaneously using a specialized delivery system. To evaluate its use for the treatment of pediatric milk-induced EoE (at least 15 eosinophils per high-power frame despite at least 2 months of high-dose proton pump–inhibitor therapy at 1-2 mg/kg twice daily), the researchers randomly assigned 20 children on a 3:1 basis to receive either Viaskin Milk or placebo for 9 months. Patients and investigators were double-blinded for this phase of the study, during most of which patients abstained from milk. Toward the end of the 9 months, patients resumed consuming milk and continued doing so if their upper endoscopy biopsy showed resolution of EoE (eosinophil count less than 15 per high-power field).
In the intention-to-treat analysis, Viaskin Milk did not meet the primary endpoint of the difference in least squares mean compared with placebo (8.6; 95% confidence interval, –35.36 to 52.56). Symptom scores also were similar between groups. In contrast, at the end of the 11-month, open-label period, 9 of 19 evaluable patients had eosinophil biopsy counts of fewer than 15 per high-power field, for a response rate of 47%. “The number of adverse events did not differ significantly between the Viaskin Milk and placebo groups,” the researchers added.
Protocol violations might explain why EPIT failed to meet the primary endpoint in the intention-to-treat analysis, they wrote. “For example, the patients on the active therapy wanted to ingest more milk, while the patients in the placebo group wanted less milk,” they reported. “Three patients in the active therapy went on binge milk diets drinking 4 to 8 times the amount of milk compared with baseline.” The use of proton pump inhibitors also was inconsistent between groups, they added. “The major limitation in the [per-protocol] population was the small sample size of this pilot study, raising the possibility of false-positive results.”
The study was funded by DBV Technologies and by the Children’s Hospital of Philadelphia Eosinophilic Esophagitis Family Fund. Dr. Spergel disclosed consulting agreements, grants funding, and stock equity with DBV Technologies. Three coinvestigators also disclosed ties to DBV. The remaining five coinvestigators reported having no conflicts of interest.
SOURCE: Spergel JM et al. Clin Gastroenterol Hepatol. 2019 May 14. doi: 10.1016/j.cgh.2019.05.014.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Optimal management of Barrett’s esophagus without high-grade dysplasia
, according to the study, which was published in Clinical Gastroenterology and Hepatology.
Clinical guidelines recommend surveillance or treatment of patients with Barrett’s esophagus, a precursor lesion for esophageal adenocarcinoma, depending on the presence and grade of dysplasia. For high-grade dysplasia, guidelines recommend endoscopic eradication therapy. For low-grade dysplasia, the optimal strategy is unclear, said first study author Amir-Houshang Omidvari, MD, MPH, a researcher at Erasmus MC University Medical Center Rotterdam (the Netherlands) and colleagues. In addition, the ideal surveillance interval for patients with nondysplastic Barrett’s esophagus is unknown.
Simulated cohorts
To identify optimal management strategies, the investigators simulated cohorts of 60-year-old patients with Barrett’s esophagus in the United States using three independent population-based models. They followed each cohort until death or age 100 years. The study compared disease progression without surveillance or treatment with 78 management strategies. The cost-effectiveness analyses used a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY).
For low-grade dysplasia, the researchers assessed various surveillance intervals, endoscopic eradication therapy with confirmation of low-grade dysplasia by a repeat endoscopy after 2 months of high-dose acid suppression, and endoscopic eradication therapy without confirmatory testing. For nondysplastic Barrett’s esophagus, the researchers evaluated no surveillance and surveillance intervals of 1, 2, 3, 4, 5, or 10 years. The researchers made assumptions based on published data about rates of misdiagnosis, treatment efficacy, recurrence, complications, and other outcomes. They used Centers for Medicare & Medicaid Services reimbursement rates to evaluate costs. For all management strategies, the researchers assumed surveillance would stop at age 80 years.
In a simulated cohort of men with Barrett’s esophagus who did not receive surveillance or endoscopic eradication therapy, the models predicted an average esophageal adenocarcinoma cumulative incidence of 111 cases per 1,000 patients and mortality of 77 deaths per 1,000 patients, with a total cost of $5.7 million for their care. Management strategies “prevented 23%-75% of [esophageal adenocarcinoma] cases and decreased mortality by 31%-88% while increasing costs to $6.2-$17.3 million depending on the management strategy,” the authors said. The optimal cost-effective strategy – endoscopic eradication therapy for patients with low-grade dysplasia after endoscopic confirmation, and surveillance every 3 years for patients with nondysplastic Barrett’s esophagus – decreased esophageal adenocarcinoma incidence to 38 cases (–66%) and mortality to 15 deaths (–81%) per 1,000 patients, compared with natural history. This approach increased costs to $9.8 million and gained 358 QALYs.
The models predicted fewer esophageal adenocarcinoma cases in women without surveillance or treatment (75 cases per 1,000 patients). “Because of the higher incremental costs per QALY gained in women, the optimal strategy was surveillance every 5 years for [nondysplastic Barrett’s esophagus],” the researchers reported.
Avoiding misdiagnosis
“Despite the potential harms and cost of endoscopic therapy, [endoscopic eradication therapy of low-grade dysplasia] reduces the number of endoscopies required for surveillance ... because of prolonged surveillance intervals after successful treatment, and [it] generally prevents more [esophageal adenocarcinoma] cases than strategies using only surveillance,” wrote Dr. Omidvari and colleagues. Confirmation of low-grade dysplasia with repeat testing before treatment was more cost-effective than treatment without confirmatory testing. Although this approach requires one more endoscopy per patient, a decrease in inappropriate treatment of patients with false-positive low-grade dysplasia diagnoses compensates for the additional testing costs, they said.
The researchers noted that available data on long-term outcomes are limited. Nevertheless, the analysis may have important implications for patients with Barrett’s esophagus without dysplasia or with low-grade dysplasia, the authors said.
The National Institutes of Health/National Cancer Institute supported the study and provided funding for the authors.
SOURCE: Omidvari A-H et al. Clin Gastroenterol Hepatol. 2019 Dec 6. doi: 10.1016/j.cgh.2019.11.058.
, according to the study, which was published in Clinical Gastroenterology and Hepatology.
Clinical guidelines recommend surveillance or treatment of patients with Barrett’s esophagus, a precursor lesion for esophageal adenocarcinoma, depending on the presence and grade of dysplasia. For high-grade dysplasia, guidelines recommend endoscopic eradication therapy. For low-grade dysplasia, the optimal strategy is unclear, said first study author Amir-Houshang Omidvari, MD, MPH, a researcher at Erasmus MC University Medical Center Rotterdam (the Netherlands) and colleagues. In addition, the ideal surveillance interval for patients with nondysplastic Barrett’s esophagus is unknown.
Simulated cohorts
To identify optimal management strategies, the investigators simulated cohorts of 60-year-old patients with Barrett’s esophagus in the United States using three independent population-based models. They followed each cohort until death or age 100 years. The study compared disease progression without surveillance or treatment with 78 management strategies. The cost-effectiveness analyses used a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY).
For low-grade dysplasia, the researchers assessed various surveillance intervals, endoscopic eradication therapy with confirmation of low-grade dysplasia by a repeat endoscopy after 2 months of high-dose acid suppression, and endoscopic eradication therapy without confirmatory testing. For nondysplastic Barrett’s esophagus, the researchers evaluated no surveillance and surveillance intervals of 1, 2, 3, 4, 5, or 10 years. The researchers made assumptions based on published data about rates of misdiagnosis, treatment efficacy, recurrence, complications, and other outcomes. They used Centers for Medicare & Medicaid Services reimbursement rates to evaluate costs. For all management strategies, the researchers assumed surveillance would stop at age 80 years.
In a simulated cohort of men with Barrett’s esophagus who did not receive surveillance or endoscopic eradication therapy, the models predicted an average esophageal adenocarcinoma cumulative incidence of 111 cases per 1,000 patients and mortality of 77 deaths per 1,000 patients, with a total cost of $5.7 million for their care. Management strategies “prevented 23%-75% of [esophageal adenocarcinoma] cases and decreased mortality by 31%-88% while increasing costs to $6.2-$17.3 million depending on the management strategy,” the authors said. The optimal cost-effective strategy – endoscopic eradication therapy for patients with low-grade dysplasia after endoscopic confirmation, and surveillance every 3 years for patients with nondysplastic Barrett’s esophagus – decreased esophageal adenocarcinoma incidence to 38 cases (–66%) and mortality to 15 deaths (–81%) per 1,000 patients, compared with natural history. This approach increased costs to $9.8 million and gained 358 QALYs.
The models predicted fewer esophageal adenocarcinoma cases in women without surveillance or treatment (75 cases per 1,000 patients). “Because of the higher incremental costs per QALY gained in women, the optimal strategy was surveillance every 5 years for [nondysplastic Barrett’s esophagus],” the researchers reported.
Avoiding misdiagnosis
“Despite the potential harms and cost of endoscopic therapy, [endoscopic eradication therapy of low-grade dysplasia] reduces the number of endoscopies required for surveillance ... because of prolonged surveillance intervals after successful treatment, and [it] generally prevents more [esophageal adenocarcinoma] cases than strategies using only surveillance,” wrote Dr. Omidvari and colleagues. Confirmation of low-grade dysplasia with repeat testing before treatment was more cost-effective than treatment without confirmatory testing. Although this approach requires one more endoscopy per patient, a decrease in inappropriate treatment of patients with false-positive low-grade dysplasia diagnoses compensates for the additional testing costs, they said.
The researchers noted that available data on long-term outcomes are limited. Nevertheless, the analysis may have important implications for patients with Barrett’s esophagus without dysplasia or with low-grade dysplasia, the authors said.
The National Institutes of Health/National Cancer Institute supported the study and provided funding for the authors.
SOURCE: Omidvari A-H et al. Clin Gastroenterol Hepatol. 2019 Dec 6. doi: 10.1016/j.cgh.2019.11.058.
, according to the study, which was published in Clinical Gastroenterology and Hepatology.
Clinical guidelines recommend surveillance or treatment of patients with Barrett’s esophagus, a precursor lesion for esophageal adenocarcinoma, depending on the presence and grade of dysplasia. For high-grade dysplasia, guidelines recommend endoscopic eradication therapy. For low-grade dysplasia, the optimal strategy is unclear, said first study author Amir-Houshang Omidvari, MD, MPH, a researcher at Erasmus MC University Medical Center Rotterdam (the Netherlands) and colleagues. In addition, the ideal surveillance interval for patients with nondysplastic Barrett’s esophagus is unknown.
Simulated cohorts
To identify optimal management strategies, the investigators simulated cohorts of 60-year-old patients with Barrett’s esophagus in the United States using three independent population-based models. They followed each cohort until death or age 100 years. The study compared disease progression without surveillance or treatment with 78 management strategies. The cost-effectiveness analyses used a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY).
For low-grade dysplasia, the researchers assessed various surveillance intervals, endoscopic eradication therapy with confirmation of low-grade dysplasia by a repeat endoscopy after 2 months of high-dose acid suppression, and endoscopic eradication therapy without confirmatory testing. For nondysplastic Barrett’s esophagus, the researchers evaluated no surveillance and surveillance intervals of 1, 2, 3, 4, 5, or 10 years. The researchers made assumptions based on published data about rates of misdiagnosis, treatment efficacy, recurrence, complications, and other outcomes. They used Centers for Medicare & Medicaid Services reimbursement rates to evaluate costs. For all management strategies, the researchers assumed surveillance would stop at age 80 years.
In a simulated cohort of men with Barrett’s esophagus who did not receive surveillance or endoscopic eradication therapy, the models predicted an average esophageal adenocarcinoma cumulative incidence of 111 cases per 1,000 patients and mortality of 77 deaths per 1,000 patients, with a total cost of $5.7 million for their care. Management strategies “prevented 23%-75% of [esophageal adenocarcinoma] cases and decreased mortality by 31%-88% while increasing costs to $6.2-$17.3 million depending on the management strategy,” the authors said. The optimal cost-effective strategy – endoscopic eradication therapy for patients with low-grade dysplasia after endoscopic confirmation, and surveillance every 3 years for patients with nondysplastic Barrett’s esophagus – decreased esophageal adenocarcinoma incidence to 38 cases (–66%) and mortality to 15 deaths (–81%) per 1,000 patients, compared with natural history. This approach increased costs to $9.8 million and gained 358 QALYs.
The models predicted fewer esophageal adenocarcinoma cases in women without surveillance or treatment (75 cases per 1,000 patients). “Because of the higher incremental costs per QALY gained in women, the optimal strategy was surveillance every 5 years for [nondysplastic Barrett’s esophagus],” the researchers reported.
Avoiding misdiagnosis
“Despite the potential harms and cost of endoscopic therapy, [endoscopic eradication therapy of low-grade dysplasia] reduces the number of endoscopies required for surveillance ... because of prolonged surveillance intervals after successful treatment, and [it] generally prevents more [esophageal adenocarcinoma] cases than strategies using only surveillance,” wrote Dr. Omidvari and colleagues. Confirmation of low-grade dysplasia with repeat testing before treatment was more cost-effective than treatment without confirmatory testing. Although this approach requires one more endoscopy per patient, a decrease in inappropriate treatment of patients with false-positive low-grade dysplasia diagnoses compensates for the additional testing costs, they said.
The researchers noted that available data on long-term outcomes are limited. Nevertheless, the analysis may have important implications for patients with Barrett’s esophagus without dysplasia or with low-grade dysplasia, the authors said.
The National Institutes of Health/National Cancer Institute supported the study and provided funding for the authors.
SOURCE: Omidvari A-H et al. Clin Gastroenterol Hepatol. 2019 Dec 6. doi: 10.1016/j.cgh.2019.11.058.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Gastric electrical stimulation device may improve refractory vomiting
An implanted gastric electrical stimulation device significantly improved refractory vomiting but not quality of life in a randomized, multicenter, double-blind crossover trial of 172 patients.
After 4 months of electrical stimulation, frequency of vomiting was significantly improved from baseline in the intervention arm, compared with the control arm, in patients with both delayed (P less than .01) and normal (P = .05) gastric emptying. There was also an improvement in nausea with gastric stimulation. In contrast, there was no significant improvement in the coprimary endpoint of quality of life. Based on these findings, “a limited number of medically resistant patients may benefit from gastroelectric stimulation to relieve nausea and vomiting,” wrote Philippe Ducrotté, MD, of Rouen (France) University Hospital and associates in Gastroenterology.
High-frequency gastric electrical stimulation with the surgically implanted Enterra device is regarded as a treatment option for chronic refractory vomiting in patients with or without gastroparesis. However, only moderate evidence supports the use of this therapy, with level 1 evidence limited to a single study, according to the researchers. For the study, they enrolled 172 adults with at least 12 months of nausea or vomiting that was refractory to antiemetic or prokinetic therapy and was either idiopathic or related to type 1 or 2 diabetes mellitus or surgery (partial gastric resection or vagotomy). Symptoms “had to be severe enough to affect the general condition of the patient, including [causing] weight loss, or the need to change dietary intake to control diabetes,” said the researchers.
The study started with a 4-month run-in period, after which all patients had the device implanted and left off for one month. Patients in the intervention arm then had the device turned on and programmed at standard parameters (5 mA, 14 Hz, 330 micros, cycle on 0.1s, cycle off 5s). Both groups were assessed at 4 months, and 149 patients then crossed over to the other arm and were assessed again at 4 months. Vomiting was evaluated on a 5-point scale ranging from 0 (most severe) to 5 (symptom absent), while quality of life was assessed by means of the 36-question, self-administered Gastrointestinal Quality of Life Index (GIQLI).
During the intervention, 30.6% of patients reported at least a 1-point improvement on the vomiting frequency scale, while 53% reported no change. With the device turned off, 16.5% of patients reported an improvement in vomiting. During both phases of the trial, median vomiting frequency score was improved in the intervention arm compared with the control arm (P less than .001) in patients with (42%) and without (58%) diabetes. “Gastric emptying was not accelerated during the on period compared with the off period,” the investigators wrote.
A total of 133 (77%) patients in the study had gastroparesis. Most patients were women in their 40s who vomited several times per day. Among 45 device-related events, the most common was abdominal pain at the implantation site (62%), followed by “infectious problems” at the abdominal pouch level (36%) and hematoma (2%). Three of these events “were serious enough to prompt device removal,” the researchers wrote.
The French government funded the study. The investigators reported having no conflicts of interest. They dedicated the paper to the memory of Dr. Ducrotté, who died during the course of the study.
*This story was updated on January 13, 2020.
SOURCE: Ducrotté P et al. Gastroenterology. 2019 Oct 1. https://doi.org/10.1053/j.gastro.2019.10.018
Use of gastric electric stimulation is a controversial therapy for gastroparesis. The Enterra Gastric Electric Stimulator System received FDA approval under a Humanitarian Device Exemption in 2000 considering the device to be safe and of probable benefit. Enterra had been shown to decrease vomiting frequency in patients with medication refractory gastroparesis. Subsequent studies performed for approval for efficacy did not meet their predefined endpoint. Some physicians use this as treatment for their patients with refractory gastroparesis under the HDE and with institutional review board approval; many physicians do not.
The article by the French group brings support for gastric electric stimulation in a double blind study that showed gastric stimulation significantly reduced nausea and vomiting, both in diabetic and nondiabetic patients and in both those with delayed and normal gastric emptying.
The NIH Gastroparesis Clinical Research Consortium recently reported the symptom response with gastric stimulation for clinical care of patients with gastroparesis, compared with those who did not receive this treatment. In this observational study in multiple practice settings, 15% of patients with symptoms of gastroparesis in the NIH registry underwent gastric stimulation. Patients with more severe overall symptoms were more likely to improve symptomatically over 48 weeks, primarily because of reduction in nausea severity.
In the last 5 years, pyloromyotomy for gastroparesis has reemerged as a treatment for gastroparesis, especially when performed endoscopically (G-POEM or POP). Multiple studies, primarily single-center studies, support this treatment in improving gastroparesis symptoms and gastric emptying, though placebo-controlled studies have not been performed.
When should one perform gastric electric stimulation versus pyloromyotomy? At our center, we perform both stimulator placement and pyloromyotomy procedures in patients with refractory gastroparesis symptoms with delayed gastric emptying. We find that patients with refractory symptoms of gastroparesis undergoing stimulator placement, pyloromyotomy, or combined stimulator with pyloromyotomy each had improvement of their gastroparesis symptoms. Gastric stimulation and combined stimulator with pyloromyotomy improved nausea/vomiting, whereas pyloromyotomy alone tended to improve early satiety and postprandial fullness.
Presently, our clinical protocol for patients with refractory gastroparesis (not responding to metoclopramide, domperidone, granisetron patch, mirtazapine) is the following:
- If nausea and vomiting are particularly severe, we proceed with gastric stimulation.
- If gastric emptying is significantly delayed especially with symptoms of early satiety, patients undergo pyloromyotomy.
- If patients have significant nausea and vomiting with markedly delayed gastric emptying, patients get both stimulator placement and pyloromyotomy.
Studies are currently being performed to evaluate this type of patient-oriented management approach.
Henry P. Parkman, MD, gastroenterologist, gastroenterology section, Temple University, Philadelphia. He has no conflicts of interest.
Use of gastric electric stimulation is a controversial therapy for gastroparesis. The Enterra Gastric Electric Stimulator System received FDA approval under a Humanitarian Device Exemption in 2000 considering the device to be safe and of probable benefit. Enterra had been shown to decrease vomiting frequency in patients with medication refractory gastroparesis. Subsequent studies performed for approval for efficacy did not meet their predefined endpoint. Some physicians use this as treatment for their patients with refractory gastroparesis under the HDE and with institutional review board approval; many physicians do not.
The article by the French group brings support for gastric electric stimulation in a double blind study that showed gastric stimulation significantly reduced nausea and vomiting, both in diabetic and nondiabetic patients and in both those with delayed and normal gastric emptying.
The NIH Gastroparesis Clinical Research Consortium recently reported the symptom response with gastric stimulation for clinical care of patients with gastroparesis, compared with those who did not receive this treatment. In this observational study in multiple practice settings, 15% of patients with symptoms of gastroparesis in the NIH registry underwent gastric stimulation. Patients with more severe overall symptoms were more likely to improve symptomatically over 48 weeks, primarily because of reduction in nausea severity.
In the last 5 years, pyloromyotomy for gastroparesis has reemerged as a treatment for gastroparesis, especially when performed endoscopically (G-POEM or POP). Multiple studies, primarily single-center studies, support this treatment in improving gastroparesis symptoms and gastric emptying, though placebo-controlled studies have not been performed.
When should one perform gastric electric stimulation versus pyloromyotomy? At our center, we perform both stimulator placement and pyloromyotomy procedures in patients with refractory gastroparesis symptoms with delayed gastric emptying. We find that patients with refractory symptoms of gastroparesis undergoing stimulator placement, pyloromyotomy, or combined stimulator with pyloromyotomy each had improvement of their gastroparesis symptoms. Gastric stimulation and combined stimulator with pyloromyotomy improved nausea/vomiting, whereas pyloromyotomy alone tended to improve early satiety and postprandial fullness.
Presently, our clinical protocol for patients with refractory gastroparesis (not responding to metoclopramide, domperidone, granisetron patch, mirtazapine) is the following:
- If nausea and vomiting are particularly severe, we proceed with gastric stimulation.
- If gastric emptying is significantly delayed especially with symptoms of early satiety, patients undergo pyloromyotomy.
- If patients have significant nausea and vomiting with markedly delayed gastric emptying, patients get both stimulator placement and pyloromyotomy.
Studies are currently being performed to evaluate this type of patient-oriented management approach.
Henry P. Parkman, MD, gastroenterologist, gastroenterology section, Temple University, Philadelphia. He has no conflicts of interest.
Use of gastric electric stimulation is a controversial therapy for gastroparesis. The Enterra Gastric Electric Stimulator System received FDA approval under a Humanitarian Device Exemption in 2000 considering the device to be safe and of probable benefit. Enterra had been shown to decrease vomiting frequency in patients with medication refractory gastroparesis. Subsequent studies performed for approval for efficacy did not meet their predefined endpoint. Some physicians use this as treatment for their patients with refractory gastroparesis under the HDE and with institutional review board approval; many physicians do not.
The article by the French group brings support for gastric electric stimulation in a double blind study that showed gastric stimulation significantly reduced nausea and vomiting, both in diabetic and nondiabetic patients and in both those with delayed and normal gastric emptying.
The NIH Gastroparesis Clinical Research Consortium recently reported the symptom response with gastric stimulation for clinical care of patients with gastroparesis, compared with those who did not receive this treatment. In this observational study in multiple practice settings, 15% of patients with symptoms of gastroparesis in the NIH registry underwent gastric stimulation. Patients with more severe overall symptoms were more likely to improve symptomatically over 48 weeks, primarily because of reduction in nausea severity.
In the last 5 years, pyloromyotomy for gastroparesis has reemerged as a treatment for gastroparesis, especially when performed endoscopically (G-POEM or POP). Multiple studies, primarily single-center studies, support this treatment in improving gastroparesis symptoms and gastric emptying, though placebo-controlled studies have not been performed.
When should one perform gastric electric stimulation versus pyloromyotomy? At our center, we perform both stimulator placement and pyloromyotomy procedures in patients with refractory gastroparesis symptoms with delayed gastric emptying. We find that patients with refractory symptoms of gastroparesis undergoing stimulator placement, pyloromyotomy, or combined stimulator with pyloromyotomy each had improvement of their gastroparesis symptoms. Gastric stimulation and combined stimulator with pyloromyotomy improved nausea/vomiting, whereas pyloromyotomy alone tended to improve early satiety and postprandial fullness.
Presently, our clinical protocol for patients with refractory gastroparesis (not responding to metoclopramide, domperidone, granisetron patch, mirtazapine) is the following:
- If nausea and vomiting are particularly severe, we proceed with gastric stimulation.
- If gastric emptying is significantly delayed especially with symptoms of early satiety, patients undergo pyloromyotomy.
- If patients have significant nausea and vomiting with markedly delayed gastric emptying, patients get both stimulator placement and pyloromyotomy.
Studies are currently being performed to evaluate this type of patient-oriented management approach.
Henry P. Parkman, MD, gastroenterologist, gastroenterology section, Temple University, Philadelphia. He has no conflicts of interest.
An implanted gastric electrical stimulation device significantly improved refractory vomiting but not quality of life in a randomized, multicenter, double-blind crossover trial of 172 patients.
After 4 months of electrical stimulation, frequency of vomiting was significantly improved from baseline in the intervention arm, compared with the control arm, in patients with both delayed (P less than .01) and normal (P = .05) gastric emptying. There was also an improvement in nausea with gastric stimulation. In contrast, there was no significant improvement in the coprimary endpoint of quality of life. Based on these findings, “a limited number of medically resistant patients may benefit from gastroelectric stimulation to relieve nausea and vomiting,” wrote Philippe Ducrotté, MD, of Rouen (France) University Hospital and associates in Gastroenterology.
High-frequency gastric electrical stimulation with the surgically implanted Enterra device is regarded as a treatment option for chronic refractory vomiting in patients with or without gastroparesis. However, only moderate evidence supports the use of this therapy, with level 1 evidence limited to a single study, according to the researchers. For the study, they enrolled 172 adults with at least 12 months of nausea or vomiting that was refractory to antiemetic or prokinetic therapy and was either idiopathic or related to type 1 or 2 diabetes mellitus or surgery (partial gastric resection or vagotomy). Symptoms “had to be severe enough to affect the general condition of the patient, including [causing] weight loss, or the need to change dietary intake to control diabetes,” said the researchers.
The study started with a 4-month run-in period, after which all patients had the device implanted and left off for one month. Patients in the intervention arm then had the device turned on and programmed at standard parameters (5 mA, 14 Hz, 330 micros, cycle on 0.1s, cycle off 5s). Both groups were assessed at 4 months, and 149 patients then crossed over to the other arm and were assessed again at 4 months. Vomiting was evaluated on a 5-point scale ranging from 0 (most severe) to 5 (symptom absent), while quality of life was assessed by means of the 36-question, self-administered Gastrointestinal Quality of Life Index (GIQLI).
During the intervention, 30.6% of patients reported at least a 1-point improvement on the vomiting frequency scale, while 53% reported no change. With the device turned off, 16.5% of patients reported an improvement in vomiting. During both phases of the trial, median vomiting frequency score was improved in the intervention arm compared with the control arm (P less than .001) in patients with (42%) and without (58%) diabetes. “Gastric emptying was not accelerated during the on period compared with the off period,” the investigators wrote.
A total of 133 (77%) patients in the study had gastroparesis. Most patients were women in their 40s who vomited several times per day. Among 45 device-related events, the most common was abdominal pain at the implantation site (62%), followed by “infectious problems” at the abdominal pouch level (36%) and hematoma (2%). Three of these events “were serious enough to prompt device removal,” the researchers wrote.
The French government funded the study. The investigators reported having no conflicts of interest. They dedicated the paper to the memory of Dr. Ducrotté, who died during the course of the study.
*This story was updated on January 13, 2020.
SOURCE: Ducrotté P et al. Gastroenterology. 2019 Oct 1. https://doi.org/10.1053/j.gastro.2019.10.018
An implanted gastric electrical stimulation device significantly improved refractory vomiting but not quality of life in a randomized, multicenter, double-blind crossover trial of 172 patients.
After 4 months of electrical stimulation, frequency of vomiting was significantly improved from baseline in the intervention arm, compared with the control arm, in patients with both delayed (P less than .01) and normal (P = .05) gastric emptying. There was also an improvement in nausea with gastric stimulation. In contrast, there was no significant improvement in the coprimary endpoint of quality of life. Based on these findings, “a limited number of medically resistant patients may benefit from gastroelectric stimulation to relieve nausea and vomiting,” wrote Philippe Ducrotté, MD, of Rouen (France) University Hospital and associates in Gastroenterology.
High-frequency gastric electrical stimulation with the surgically implanted Enterra device is regarded as a treatment option for chronic refractory vomiting in patients with or without gastroparesis. However, only moderate evidence supports the use of this therapy, with level 1 evidence limited to a single study, according to the researchers. For the study, they enrolled 172 adults with at least 12 months of nausea or vomiting that was refractory to antiemetic or prokinetic therapy and was either idiopathic or related to type 1 or 2 diabetes mellitus or surgery (partial gastric resection or vagotomy). Symptoms “had to be severe enough to affect the general condition of the patient, including [causing] weight loss, or the need to change dietary intake to control diabetes,” said the researchers.
The study started with a 4-month run-in period, after which all patients had the device implanted and left off for one month. Patients in the intervention arm then had the device turned on and programmed at standard parameters (5 mA, 14 Hz, 330 micros, cycle on 0.1s, cycle off 5s). Both groups were assessed at 4 months, and 149 patients then crossed over to the other arm and were assessed again at 4 months. Vomiting was evaluated on a 5-point scale ranging from 0 (most severe) to 5 (symptom absent), while quality of life was assessed by means of the 36-question, self-administered Gastrointestinal Quality of Life Index (GIQLI).
During the intervention, 30.6% of patients reported at least a 1-point improvement on the vomiting frequency scale, while 53% reported no change. With the device turned off, 16.5% of patients reported an improvement in vomiting. During both phases of the trial, median vomiting frequency score was improved in the intervention arm compared with the control arm (P less than .001) in patients with (42%) and without (58%) diabetes. “Gastric emptying was not accelerated during the on period compared with the off period,” the investigators wrote.
A total of 133 (77%) patients in the study had gastroparesis. Most patients were women in their 40s who vomited several times per day. Among 45 device-related events, the most common was abdominal pain at the implantation site (62%), followed by “infectious problems” at the abdominal pouch level (36%) and hematoma (2%). Three of these events “were serious enough to prompt device removal,” the researchers wrote.
The French government funded the study. The investigators reported having no conflicts of interest. They dedicated the paper to the memory of Dr. Ducrotté, who died during the course of the study.
*This story was updated on January 13, 2020.
SOURCE: Ducrotté P et al. Gastroenterology. 2019 Oct 1. https://doi.org/10.1053/j.gastro.2019.10.018
FROM GASTROENTEROLOGY