Conference Coverage

Researchers are trying to understand how e-cigarette use affects pregnancy and birth outcomes. This question may become more relevant as younger vapers, among whom the devices gained considerable popularity, start having children.

Limited emerging data from animal experiments and human epidemiologic studies suggest that vaping may have negative effects on fertility and pregnancy. “Even if these impacts are less severe than conventional smoking, we really should be thinking about alternate options that may be safer for our patients than inhalation of this aerosol,” said Blair J. Wylie, MD, MPH, a maternal-fetal medicine physician at Beth Israel Deaconess Medical Center in Boston.

Dr. Wylie reviewed what is known about vaping, including chemicals other than nicotine that have been detected in vape aerosols, and pregnancy at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

“There’s a lot we don’t know,” she said. “These products were only introduced recently, in 2003. They are marketed aggressively to our youth and have gained tremendous popularity among that population. And it’s only a matter of time, I think, before we see a lot of use in our own patient population.”

In a separate study presented at the ACOG meeting, Nicole Izhakoff, a researcher at Florida International University, Miami, and colleagues evaluated the association between e-cigarette use during pregnancy and unfavorable birth outcomes, such as preterm birth, low birth weight, or extended hospital stay for the newborn.

The investigators used 2016-2017 survey data from the Pregnancy Risk Assessment Monitoring System. In all, 71,940 women completed the survey, including 859 who reported e-cigarette use during pregnancy.

After adjusting for age, race, ethnicity, insurance, maternal education, prenatal care, abuse during pregnancy, and complications during pregnancy, the researchers estimated that the odds of an unfavorable birth outcome were 62% greater among women who used e-cigarettes during pregnancy, compared with those who did not.

The researchers lacked information about simultaneous use of alcohol, traditional tobacco, or other drugs, however.

“Physicians of all subspecialties, especially those of obstetrics-gynecology and pediatrics, need to increase the implementation of screening for past or current e-cigarette use in at-risk patients,” Ms. Izhakoff and coauthors concluded. “Further research regarding the long-term health effects of e-cigarettes is warranted.”

Dr. Wylie coauthored another study related to this topic that was published online May 24, 2021, in the Journal of Maternal-Fetal & Neonatal Medicine.

The researchers examined birth weights of children whose mothers use e-cigarettes alone, those whose mothers used both e-cigarettes and conventional cigarettes, and those whose mothers smoked conventional cigarettes only. Their estimates were imprecise, but signaled that e-cigarette use may reduce birth weight. The use of e-cigarettes alone appeared to have less of an impact on birth weight than the dual use of conventional cigarettes and e-cigarettes did.

Dr. Wylie cautioned that outcomes like birth weight are “pretty crude measures of whether an exposure is okay or not in pregnancy. Many of these toxins that we know that are in the aerosols can cause harm, but they may not be reflected in the absolute value of the birth weight.”

In addition, clinicians should avoid focusing on the wrong question when caring for patients.

“I think the wrong question is: Is vaping safer than smoking?” Dr. Wylie said in an interview. “Metals are going into your lungs. Plastics are going into your lungs. It is hard for me to think that we are going to identify that as our champion smoking cessation strategy in pregnancy.”
 

Rapidly changing landscape

Answering the question of which is safer is a challenge anyway because researchers likely have incomplete information about who vapes, who smokes, and who does both.

Still, the new research illustrates that “people are starting to think about this and beginning to do some analysis that is really hypothesis generating at this point,” Dr. Wylie said. Such studies may prompt clinicians to ask their patients about e-cigarette use. “Marijuana is sort of a similar thing where patients’ perception of safety, because things are legal, can lead to use during pregnancy without ... letting their care teams know,” she said. “Things are changing so rapidly in terms of what’s available to people to use that we need to stay on top of that as obstetricians and ask the right questions and try to understand what the risks are and potential benefits.”

Dr. Wylie is an obstetric consultant to the New England Pediatric Environmental Health Specialty Unit, which is where she heard pediatricians discussing widespread e-cigarette use among youth. It occurred to her that some of these teens eventually would be seeing obstetricians. She also saw parallels to prior research she conducted that focused on household air pollution or cooking from wood-burning fires in Africa.

“What is frightening, I think, about these electronic cigarettes is that you’re heating this liquid to extraordinarily high temperatures to create the vapor,” and the extreme heat vaporizes plastics and metals as well as nicotine, Dr. Wylie said.

An ACOG committee opinion discusses approaches to smoking and vaping cessation such as counseling, behavioral therapy, and medication.

The publication also lists a host of elements have been isolated from vape aerosol, including “carbonyl compounds (formaldehyde, acetaldehyde, acetone, and acrolein); volatile organic compounds (benzene and toluene); nitrosamines; particulate matter; and heavy metals such as copper, lead, zinc, and tin.”

In addition to the nicotine in e-cigarette liquids, which is harmful in itself, there is “all of this other company that it keeps,” including solvent byproducts, known carcinogens, and lung irritants, Dr. Wylie said. Fine particulate matter “can land in the small airways and cause inflammation, even translocate into the systemic circulation and cause systemic inflammation.”

The use of flavoring “likely alters perceptions of harm” and contributes to the popularity of vaping, Dr. Wylie noted. At the same time, the use of flavoring also has little regulatory oversight. Flavors usually are approved for marketing based on safety for ingestion, but that may not translate into safety for inhalation.
 

Parsing the health effects

People who vape have increased cough, wheezing, and phlegm production, compared with people who do not vape. Vaping also may worsen underlying lung disease like asthma. Lung function on spirometry decreases after e-cigarette use, studies have shown.

In 2019, researchers described e-cigarette or vaping product use–related acute lung injury (EVALI), which has caused more than 60 deaths in the United States. The condition may be related to vitamin E acetate, a component that had been used in some liquids used by patients with EVALI.

And the nicotine in e-cigarettes can accelerate atherogenesis and affect blood pressure, heart rate, and arterial stiffness.

Initially introduced as a smoking cessation tool, e-cigarettes now often are used on their own or in addition to cigarettes, rather than strictly for smoking cessation.

A Cochrane review suggests that e-cigarettes may be more effective than other approaches to smoking cessation. But “the effect is modest at best,” Dr. Wylie said. Among 100 people attempting to quit cigarette smoking, there might four to six more quitters with the use of e-cigarettes as a smoking cessation intervention, compared with other approaches.

Animal models provide other reasons for caution. One experiment in mice showed that exposure to e-cigarette aerosol impaired implantation and fetal health. The results suggest “that there might be some negative impacts across generations,” Dr. Wylie said.

Another study has suggested the possibility that women who currently use e-cigarettes may have slightly diminished fecundability. The results were not statistically significant, but the study “gives us pause about whether there could be some impact on early pregnancy and fertility,” Dr. Wylie said.

In mouse models, prenatal exposure to e-cigarette aerosol has decreased fetal weight and length, altered neurodevelopment and neuroregulatory gene expression, and increased proinflammatory cytokines. E-cigarette aerosol also has caused birth defects in zebrafish and facial clefting in frogs. Whether and how these data relate to human pregnancy is unclear.

While e-cigarette ads may convey a sense of style and harmlessness, clinicians have reasons to worry about the effects. “We have to be a little bit more cautious when we are talking about this with our patients,” Dr. Wylie said.

Dr. Wylie had no relevant financial disclosures. She is a Society for Maternal-Fetal Medicine board member and receives grant support related to research of household air pollution and pregnancy, prenatal pesticide exposure, preeclampsia in low income settings, and malaria during pregnancy. Ms. Izhakoff and coauthors had no disclosures.

jremaly@mdedge.com

Researchers are trying to understand how e-cigarette use affects pregnancy and birth outcomes. This question may become more relevant as younger vapers, among whom the devices gained considerable popularity, start having children.

Limited emerging data from animal experiments and human epidemiologic studies suggest that vaping may have negative effects on fertility and pregnancy. “Even if these impacts are less severe than conventional smoking, we really should be thinking about alternate options that may be safer for our patients than inhalation of this aerosol,” said Blair J. Wylie, MD, MPH, a maternal-fetal medicine physician at Beth Israel Deaconess Medical Center in Boston.

Dr. Wylie reviewed what is known about vaping, including chemicals other than nicotine that have been detected in vape aerosols, and pregnancy at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

“There’s a lot we don’t know,” she said. “These products were only introduced recently, in 2003. They are marketed aggressively to our youth and have gained tremendous popularity among that population. And it’s only a matter of time, I think, before we see a lot of use in our own patient population.”

In a separate study presented at the ACOG meeting, Nicole Izhakoff, a researcher at Florida International University, Miami, and colleagues evaluated the association between e-cigarette use during pregnancy and unfavorable birth outcomes, such as preterm birth, low birth weight, or extended hospital stay for the newborn.

The investigators used 2016-2017 survey data from the Pregnancy Risk Assessment Monitoring System. In all, 71,940 women completed the survey, including 859 who reported e-cigarette use during pregnancy.

After adjusting for age, race, ethnicity, insurance, maternal education, prenatal care, abuse during pregnancy, and complications during pregnancy, the researchers estimated that the odds of an unfavorable birth outcome were 62% greater among women who used e-cigarettes during pregnancy, compared with those who did not.

The researchers lacked information about simultaneous use of alcohol, traditional tobacco, or other drugs, however.

“Physicians of all subspecialties, especially those of obstetrics-gynecology and pediatrics, need to increase the implementation of screening for past or current e-cigarette use in at-risk patients,” Ms. Izhakoff and coauthors concluded. “Further research regarding the long-term health effects of e-cigarettes is warranted.”

Dr. Wylie coauthored another study related to this topic that was published online May 24, 2021, in the Journal of Maternal-Fetal & Neonatal Medicine.

The researchers examined birth weights of children whose mothers use e-cigarettes alone, those whose mothers used both e-cigarettes and conventional cigarettes, and those whose mothers smoked conventional cigarettes only. Their estimates were imprecise, but signaled that e-cigarette use may reduce birth weight. The use of e-cigarettes alone appeared to have less of an impact on birth weight than the dual use of conventional cigarettes and e-cigarettes did.

Dr. Wylie cautioned that outcomes like birth weight are “pretty crude measures of whether an exposure is okay or not in pregnancy. Many of these toxins that we know that are in the aerosols can cause harm, but they may not be reflected in the absolute value of the birth weight.”

In addition, clinicians should avoid focusing on the wrong question when caring for patients.

“I think the wrong question is: Is vaping safer than smoking?” Dr. Wylie said in an interview. “Metals are going into your lungs. Plastics are going into your lungs. It is hard for me to think that we are going to identify that as our champion smoking cessation strategy in pregnancy.”
 

Rapidly changing landscape

Answering the question of which is safer is a challenge anyway because researchers likely have incomplete information about who vapes, who smokes, and who does both.

Still, the new research illustrates that “people are starting to think about this and beginning to do some analysis that is really hypothesis generating at this point,” Dr. Wylie said. Such studies may prompt clinicians to ask their patients about e-cigarette use. “Marijuana is sort of a similar thing where patients’ perception of safety, because things are legal, can lead to use during pregnancy without ... letting their care teams know,” she said. “Things are changing so rapidly in terms of what’s available to people to use that we need to stay on top of that as obstetricians and ask the right questions and try to understand what the risks are and potential benefits.”

Dr. Wylie is an obstetric consultant to the New England Pediatric Environmental Health Specialty Unit, which is where she heard pediatricians discussing widespread e-cigarette use among youth. It occurred to her that some of these teens eventually would be seeing obstetricians. She also saw parallels to prior research she conducted that focused on household air pollution or cooking from wood-burning fires in Africa.

“What is frightening, I think, about these electronic cigarettes is that you’re heating this liquid to extraordinarily high temperatures to create the vapor,” and the extreme heat vaporizes plastics and metals as well as nicotine, Dr. Wylie said.

An ACOG committee opinion discusses approaches to smoking and vaping cessation such as counseling, behavioral therapy, and medication.

The publication also lists a host of elements have been isolated from vape aerosol, including “carbonyl compounds (formaldehyde, acetaldehyde, acetone, and acrolein); volatile organic compounds (benzene and toluene); nitrosamines; particulate matter; and heavy metals such as copper, lead, zinc, and tin.”

In addition to the nicotine in e-cigarette liquids, which is harmful in itself, there is “all of this other company that it keeps,” including solvent byproducts, known carcinogens, and lung irritants, Dr. Wylie said. Fine particulate matter “can land in the small airways and cause inflammation, even translocate into the systemic circulation and cause systemic inflammation.”

The use of flavoring “likely alters perceptions of harm” and contributes to the popularity of vaping, Dr. Wylie noted. At the same time, the use of flavoring also has little regulatory oversight. Flavors usually are approved for marketing based on safety for ingestion, but that may not translate into safety for inhalation.
 

Parsing the health effects

People who vape have increased cough, wheezing, and phlegm production, compared with people who do not vape. Vaping also may worsen underlying lung disease like asthma. Lung function on spirometry decreases after e-cigarette use, studies have shown.

In 2019, researchers described e-cigarette or vaping product use–related acute lung injury (EVALI), which has caused more than 60 deaths in the United States. The condition may be related to vitamin E acetate, a component that had been used in some liquids used by patients with EVALI.

And the nicotine in e-cigarettes can accelerate atherogenesis and affect blood pressure, heart rate, and arterial stiffness.

Initially introduced as a smoking cessation tool, e-cigarettes now often are used on their own or in addition to cigarettes, rather than strictly for smoking cessation.

A Cochrane review suggests that e-cigarettes may be more effective than other approaches to smoking cessation. But “the effect is modest at best,” Dr. Wylie said. Among 100 people attempting to quit cigarette smoking, there might four to six more quitters with the use of e-cigarettes as a smoking cessation intervention, compared with other approaches.

Animal models provide other reasons for caution. One experiment in mice showed that exposure to e-cigarette aerosol impaired implantation and fetal health. The results suggest “that there might be some negative impacts across generations,” Dr. Wylie said.

Another study has suggested the possibility that women who currently use e-cigarettes may have slightly diminished fecundability. The results were not statistically significant, but the study “gives us pause about whether there could be some impact on early pregnancy and fertility,” Dr. Wylie said.

In mouse models, prenatal exposure to e-cigarette aerosol has decreased fetal weight and length, altered neurodevelopment and neuroregulatory gene expression, and increased proinflammatory cytokines. E-cigarette aerosol also has caused birth defects in zebrafish and facial clefting in frogs. Whether and how these data relate to human pregnancy is unclear.

While e-cigarette ads may convey a sense of style and harmlessness, clinicians have reasons to worry about the effects. “We have to be a little bit more cautious when we are talking about this with our patients,” Dr. Wylie said.

Dr. Wylie had no relevant financial disclosures. She is a Society for Maternal-Fetal Medicine board member and receives grant support related to research of household air pollution and pregnancy, prenatal pesticide exposure, preeclampsia in low income settings, and malaria during pregnancy. Ms. Izhakoff and coauthors had no disclosures.

jremaly@mdedge.com

Researchers are trying to understand how e-cigarette use affects pregnancy and birth outcomes. This question may become more relevant as younger vapers, among whom the devices gained considerable popularity, start having children.

Limited emerging data from animal experiments and human epidemiologic studies suggest that vaping may have negative effects on fertility and pregnancy. “Even if these impacts are less severe than conventional smoking, we really should be thinking about alternate options that may be safer for our patients than inhalation of this aerosol,” said Blair J. Wylie, MD, MPH, a maternal-fetal medicine physician at Beth Israel Deaconess Medical Center in Boston.

Dr. Wylie reviewed what is known about vaping, including chemicals other than nicotine that have been detected in vape aerosols, and pregnancy at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

“There’s a lot we don’t know,” she said. “These products were only introduced recently, in 2003. They are marketed aggressively to our youth and have gained tremendous popularity among that population. And it’s only a matter of time, I think, before we see a lot of use in our own patient population.”

In a separate study presented at the ACOG meeting, Nicole Izhakoff, a researcher at Florida International University, Miami, and colleagues evaluated the association between e-cigarette use during pregnancy and unfavorable birth outcomes, such as preterm birth, low birth weight, or extended hospital stay for the newborn.

The investigators used 2016-2017 survey data from the Pregnancy Risk Assessment Monitoring System. In all, 71,940 women completed the survey, including 859 who reported e-cigarette use during pregnancy.

After adjusting for age, race, ethnicity, insurance, maternal education, prenatal care, abuse during pregnancy, and complications during pregnancy, the researchers estimated that the odds of an unfavorable birth outcome were 62% greater among women who used e-cigarettes during pregnancy, compared with those who did not.

The researchers lacked information about simultaneous use of alcohol, traditional tobacco, or other drugs, however.

“Physicians of all subspecialties, especially those of obstetrics-gynecology and pediatrics, need to increase the implementation of screening for past or current e-cigarette use in at-risk patients,” Ms. Izhakoff and coauthors concluded. “Further research regarding the long-term health effects of e-cigarettes is warranted.”

Dr. Wylie coauthored another study related to this topic that was published online May 24, 2021, in the Journal of Maternal-Fetal & Neonatal Medicine.

The researchers examined birth weights of children whose mothers use e-cigarettes alone, those whose mothers used both e-cigarettes and conventional cigarettes, and those whose mothers smoked conventional cigarettes only. Their estimates were imprecise, but signaled that e-cigarette use may reduce birth weight. The use of e-cigarettes alone appeared to have less of an impact on birth weight than the dual use of conventional cigarettes and e-cigarettes did.

Dr. Wylie cautioned that outcomes like birth weight are “pretty crude measures of whether an exposure is okay or not in pregnancy. Many of these toxins that we know that are in the aerosols can cause harm, but they may not be reflected in the absolute value of the birth weight.”

In addition, clinicians should avoid focusing on the wrong question when caring for patients.

“I think the wrong question is: Is vaping safer than smoking?” Dr. Wylie said in an interview. “Metals are going into your lungs. Plastics are going into your lungs. It is hard for me to think that we are going to identify that as our champion smoking cessation strategy in pregnancy.”
 

Rapidly changing landscape

Answering the question of which is safer is a challenge anyway because researchers likely have incomplete information about who vapes, who smokes, and who does both.

Still, the new research illustrates that “people are starting to think about this and beginning to do some analysis that is really hypothesis generating at this point,” Dr. Wylie said. Such studies may prompt clinicians to ask their patients about e-cigarette use. “Marijuana is sort of a similar thing where patients’ perception of safety, because things are legal, can lead to use during pregnancy without ... letting their care teams know,” she said. “Things are changing so rapidly in terms of what’s available to people to use that we need to stay on top of that as obstetricians and ask the right questions and try to understand what the risks are and potential benefits.”

Dr. Wylie is an obstetric consultant to the New England Pediatric Environmental Health Specialty Unit, which is where she heard pediatricians discussing widespread e-cigarette use among youth. It occurred to her that some of these teens eventually would be seeing obstetricians. She also saw parallels to prior research she conducted that focused on household air pollution or cooking from wood-burning fires in Africa.

“What is frightening, I think, about these electronic cigarettes is that you’re heating this liquid to extraordinarily high temperatures to create the vapor,” and the extreme heat vaporizes plastics and metals as well as nicotine, Dr. Wylie said.

An ACOG committee opinion discusses approaches to smoking and vaping cessation such as counseling, behavioral therapy, and medication.

The publication also lists a host of elements have been isolated from vape aerosol, including “carbonyl compounds (formaldehyde, acetaldehyde, acetone, and acrolein); volatile organic compounds (benzene and toluene); nitrosamines; particulate matter; and heavy metals such as copper, lead, zinc, and tin.”

In addition to the nicotine in e-cigarette liquids, which is harmful in itself, there is “all of this other company that it keeps,” including solvent byproducts, known carcinogens, and lung irritants, Dr. Wylie said. Fine particulate matter “can land in the small airways and cause inflammation, even translocate into the systemic circulation and cause systemic inflammation.”

The use of flavoring “likely alters perceptions of harm” and contributes to the popularity of vaping, Dr. Wylie noted. At the same time, the use of flavoring also has little regulatory oversight. Flavors usually are approved for marketing based on safety for ingestion, but that may not translate into safety for inhalation.
 

Parsing the health effects

People who vape have increased cough, wheezing, and phlegm production, compared with people who do not vape. Vaping also may worsen underlying lung disease like asthma. Lung function on spirometry decreases after e-cigarette use, studies have shown.

In 2019, researchers described e-cigarette or vaping product use–related acute lung injury (EVALI), which has caused more than 60 deaths in the United States. The condition may be related to vitamin E acetate, a component that had been used in some liquids used by patients with EVALI.

And the nicotine in e-cigarettes can accelerate atherogenesis and affect blood pressure, heart rate, and arterial stiffness.

Initially introduced as a smoking cessation tool, e-cigarettes now often are used on their own or in addition to cigarettes, rather than strictly for smoking cessation.

A Cochrane review suggests that e-cigarettes may be more effective than other approaches to smoking cessation. But “the effect is modest at best,” Dr. Wylie said. Among 100 people attempting to quit cigarette smoking, there might four to six more quitters with the use of e-cigarettes as a smoking cessation intervention, compared with other approaches.

Animal models provide other reasons for caution. One experiment in mice showed that exposure to e-cigarette aerosol impaired implantation and fetal health. The results suggest “that there might be some negative impacts across generations,” Dr. Wylie said.

Another study has suggested the possibility that women who currently use e-cigarettes may have slightly diminished fecundability. The results were not statistically significant, but the study “gives us pause about whether there could be some impact on early pregnancy and fertility,” Dr. Wylie said.

In mouse models, prenatal exposure to e-cigarette aerosol has decreased fetal weight and length, altered neurodevelopment and neuroregulatory gene expression, and increased proinflammatory cytokines. E-cigarette aerosol also has caused birth defects in zebrafish and facial clefting in frogs. Whether and how these data relate to human pregnancy is unclear.

While e-cigarette ads may convey a sense of style and harmlessness, clinicians have reasons to worry about the effects. “We have to be a little bit more cautious when we are talking about this with our patients,” Dr. Wylie said.

Dr. Wylie had no relevant financial disclosures. She is a Society for Maternal-Fetal Medicine board member and receives grant support related to research of household air pollution and pregnancy, prenatal pesticide exposure, preeclampsia in low income settings, and malaria during pregnancy. Ms. Izhakoff and coauthors had no disclosures.

jremaly@mdedge.com

Gastrointestinal symptoms and chronic fatigue may persist months after the COVID-19 virus infection resolves, results of a recent cohort-controlled study suggest.

About 5 months after SARS-CoV-2 infection, relative risks of loose stools, somatization, and chronic fatigue were increased by approximately two- to three fold, compared to individuals who had not been infected, according to study results presented at the annual Digestive Disease Week® (DDW).

These longer-term consequences of SARS-CoV-2 appeared to be more severe in patients who had experienced diarrhea during the acute infection, according to investigator Daniele Noviello, MD, a second-year resident in gastroenterology and hepatology at the University of Milan.

This is the first cohort-controlled study that specifically investigates gastrointestinal symptoms and somatoform disorders, Dr. Noviello said in a virtual presentation of the results.

“Based on our data, chronic fatigue, gastrointestinal, and somatoform symptoms may have a common postinfectious origin, and they should be investigated in the follow-up of SARS-CoV-2 patients,” he said.
 

Links between SARS-CoV-2 and gastrointestinal symptoms

Gastrointestinal symptoms are known to be relatively common during acute infection. According to Dr. Noviello, the most frequent gastrointestinal symptom associated with SARS-CoV-2 is diarrhea, occurring in 4% to nearly 40% of patients in case series to date.

However, data on the longer-term gastrointestinal impacts of SARS-CoV-2 remain scarce.

In one noncontrolled cohort study in China, loss of appetite, nausea, acid reflux, and diarrhea were seen in 15%-24% of patients 3 months after the infection, Dr. Noviello said. In another cohort study in China, diarrhea and vomiting were reported in 5% of patients 6 months after infection.

In any case, it is known that viral, bacterial, and protozoal infections of the gastrointestinal tract are a risk factor for development of functional disorders including irritable bowel syndrome (IBS), functional dyspepsia, and chronic fatigue, according to Dr. Noviello.

Accordingly, the results of the present study suggest that SARS-CoV-2 also “may affect the brain-gut axis in the long term,” Dr. Noviello and coauthors wrote in an abstract of the study.

It is plausible that SARS-CoV-2 infection could be a trigger for longer-term gastrointestinal symptoms, especially given the previous evidence linking infections and IBS symptoms, or postinfectious IBS, said Juan Pablo Stefanolo, MD, a physician with the neurogastroenterology and motility section, Hospital de Clínicas José de San Martín, Buenos Aires University.

“If it is demonstrated [that SARS-CoV-2 infection is a trigger], the microbiota-gut-brain axis concept in IBS pathophysiology is reinforced,” Dr. Stefanolo said in an interview.

In the meantime, practitioners may want to take into account COVID-19 infection history in the evaluation of a patient with IBS-like symptoms and, in case of a known positive COVID-19 result in an IBS patient, be aware of the possibility of symptom exacerbation, Dr. Stefanolo said.
 

Pandemic in Italy: Unique study opportunity

The severe outbreak in the Milan region early in the COVID-19 pandemic provided a “unique opportunity” to assess the long-term impact of infection on gastrointestinal and extraintestinal somatoform symptoms, said Dr. Noviello.

The investigators sent an online questionnaire to patients who had a molecular diagnosis of SARS-CoV-2 infection by nasal swab between February and April of 2020. To form a control group, they also sent questionnaires to hospital employees and health care providers who had tested negative over that same time period.

In all, 378 questionnaires were completed by 177 SARS-CoV-2–positive individuals and 201 controls. The SARS-CoV-2–positive patients were somewhat older (about 44 years vs. 40 years for controls), were less often female (40% vs. 61%), had a lower education level, and smoked less than did controls, according to the investigators.

A mean of 4.8 months had elapsed between the time of SARS-CoV-2 infection and when the questionnaires were compiled, said Dr. Noviello.

In the acute phase, diarrhea was the most common gastrointestinal symptom among virus-positive individuals, occurring in about 50% compared to 20% of controls (P < .001), data show. Other symptoms reported by 40% of SARS-CoV-2–infected individuals included fever, dyspnea, loss of smell or taste, weight loss, myalgia, arthralgia, and asthenia in the acute phase controls in the acute phase, Dr. Noviello said.
 

Persistent gastrointestinal symptoms after SARS-CoV-2

Persistent symptoms included loose stools, as measured by the Bristol Stool scale, occurring in 17.8% of SARS-CoV-2–positive individuals, but only 9.3% of the SARS-CoV-2–negative controls, according to Dr. Noviello, with an adjusted risk ratio of 1.88 (95% confidence interval, 0.99-3.54).

Chronic fatigue symptoms, as measured by the Structured Assessment of Gastrointestinal Symptoms questionnaire, were reported by about 30% of SARS-CoV-2–positive patients and about 15% of controls, for an adjusted risk ratio of 2.24 (95% CI, 1.48-3.37), according to Dr. Noviello’s presentation.

The mean t-score on the Symptom Checklist–12 for somatoform disorders was higher for the virus-positive patients compared to controls, according to Dr. Noviello. The scores were 54.6 and 50.5, respectively, with an adjusted score difference of 3.6 (95% CI, 1.0-6.2).

The longer-term sequelae of SARS-CoV-2 infection might be more severe in individuals who experienced diarrhea during acute infection, according to Dr. Noviello. In a post hoc analysis, reports of irritable bowel syndrome and loose stools were significantly higher in SARS-CoV-2–infected individuals who had diarrhea in the acute phase compared to those who did not experience diarrhea, he said.

Somatoform disorder scores were significantly higher, and reports of headache, back pain, and chronic fatigue were significantly more common, in individuals who had diarrhea at the time of SARS-CoV-2 infection, he added.

Dr. Noviello and coauthors reported no competing interests related to the study. Dr. Stefanolo had no disclosures to report.
 

Gastrointestinal symptoms and chronic fatigue may persist months after the COVID-19 virus infection resolves, results of a recent cohort-controlled study suggest.

About 5 months after SARS-CoV-2 infection, relative risks of loose stools, somatization, and chronic fatigue were increased by approximately two- to three fold, compared to individuals who had not been infected, according to study results presented at the annual Digestive Disease Week® (DDW).

These longer-term consequences of SARS-CoV-2 appeared to be more severe in patients who had experienced diarrhea during the acute infection, according to investigator Daniele Noviello, MD, a second-year resident in gastroenterology and hepatology at the University of Milan.

This is the first cohort-controlled study that specifically investigates gastrointestinal symptoms and somatoform disorders, Dr. Noviello said in a virtual presentation of the results.

“Based on our data, chronic fatigue, gastrointestinal, and somatoform symptoms may have a common postinfectious origin, and they should be investigated in the follow-up of SARS-CoV-2 patients,” he said.
 

Links between SARS-CoV-2 and gastrointestinal symptoms

Gastrointestinal symptoms are known to be relatively common during acute infection. According to Dr. Noviello, the most frequent gastrointestinal symptom associated with SARS-CoV-2 is diarrhea, occurring in 4% to nearly 40% of patients in case series to date.

However, data on the longer-term gastrointestinal impacts of SARS-CoV-2 remain scarce.

In one noncontrolled cohort study in China, loss of appetite, nausea, acid reflux, and diarrhea were seen in 15%-24% of patients 3 months after the infection, Dr. Noviello said. In another cohort study in China, diarrhea and vomiting were reported in 5% of patients 6 months after infection.

In any case, it is known that viral, bacterial, and protozoal infections of the gastrointestinal tract are a risk factor for development of functional disorders including irritable bowel syndrome (IBS), functional dyspepsia, and chronic fatigue, according to Dr. Noviello.

Accordingly, the results of the present study suggest that SARS-CoV-2 also “may affect the brain-gut axis in the long term,” Dr. Noviello and coauthors wrote in an abstract of the study.

It is plausible that SARS-CoV-2 infection could be a trigger for longer-term gastrointestinal symptoms, especially given the previous evidence linking infections and IBS symptoms, or postinfectious IBS, said Juan Pablo Stefanolo, MD, a physician with the neurogastroenterology and motility section, Hospital de Clínicas José de San Martín, Buenos Aires University.

“If it is demonstrated [that SARS-CoV-2 infection is a trigger], the microbiota-gut-brain axis concept in IBS pathophysiology is reinforced,” Dr. Stefanolo said in an interview.

In the meantime, practitioners may want to take into account COVID-19 infection history in the evaluation of a patient with IBS-like symptoms and, in case of a known positive COVID-19 result in an IBS patient, be aware of the possibility of symptom exacerbation, Dr. Stefanolo said.
 

Pandemic in Italy: Unique study opportunity

The severe outbreak in the Milan region early in the COVID-19 pandemic provided a “unique opportunity” to assess the long-term impact of infection on gastrointestinal and extraintestinal somatoform symptoms, said Dr. Noviello.

The investigators sent an online questionnaire to patients who had a molecular diagnosis of SARS-CoV-2 infection by nasal swab between February and April of 2020. To form a control group, they also sent questionnaires to hospital employees and health care providers who had tested negative over that same time period.

In all, 378 questionnaires were completed by 177 SARS-CoV-2–positive individuals and 201 controls. The SARS-CoV-2–positive patients were somewhat older (about 44 years vs. 40 years for controls), were less often female (40% vs. 61%), had a lower education level, and smoked less than did controls, according to the investigators.

A mean of 4.8 months had elapsed between the time of SARS-CoV-2 infection and when the questionnaires were compiled, said Dr. Noviello.

In the acute phase, diarrhea was the most common gastrointestinal symptom among virus-positive individuals, occurring in about 50% compared to 20% of controls (P < .001), data show. Other symptoms reported by 40% of SARS-CoV-2–infected individuals included fever, dyspnea, loss of smell or taste, weight loss, myalgia, arthralgia, and asthenia in the acute phase controls in the acute phase, Dr. Noviello said.
 

Persistent gastrointestinal symptoms after SARS-CoV-2

Persistent symptoms included loose stools, as measured by the Bristol Stool scale, occurring in 17.8% of SARS-CoV-2–positive individuals, but only 9.3% of the SARS-CoV-2–negative controls, according to Dr. Noviello, with an adjusted risk ratio of 1.88 (95% confidence interval, 0.99-3.54).

Chronic fatigue symptoms, as measured by the Structured Assessment of Gastrointestinal Symptoms questionnaire, were reported by about 30% of SARS-CoV-2–positive patients and about 15% of controls, for an adjusted risk ratio of 2.24 (95% CI, 1.48-3.37), according to Dr. Noviello’s presentation.

The mean t-score on the Symptom Checklist–12 for somatoform disorders was higher for the virus-positive patients compared to controls, according to Dr. Noviello. The scores were 54.6 and 50.5, respectively, with an adjusted score difference of 3.6 (95% CI, 1.0-6.2).

The longer-term sequelae of SARS-CoV-2 infection might be more severe in individuals who experienced diarrhea during acute infection, according to Dr. Noviello. In a post hoc analysis, reports of irritable bowel syndrome and loose stools were significantly higher in SARS-CoV-2–infected individuals who had diarrhea in the acute phase compared to those who did not experience diarrhea, he said.

Somatoform disorder scores were significantly higher, and reports of headache, back pain, and chronic fatigue were significantly more common, in individuals who had diarrhea at the time of SARS-CoV-2 infection, he added.

Dr. Noviello and coauthors reported no competing interests related to the study. Dr. Stefanolo had no disclosures to report.
 

Gastrointestinal symptoms and chronic fatigue may persist months after the COVID-19 virus infection resolves, results of a recent cohort-controlled study suggest.

About 5 months after SARS-CoV-2 infection, relative risks of loose stools, somatization, and chronic fatigue were increased by approximately two- to three fold, compared to individuals who had not been infected, according to study results presented at the annual Digestive Disease Week® (DDW).

These longer-term consequences of SARS-CoV-2 appeared to be more severe in patients who had experienced diarrhea during the acute infection, according to investigator Daniele Noviello, MD, a second-year resident in gastroenterology and hepatology at the University of Milan.

This is the first cohort-controlled study that specifically investigates gastrointestinal symptoms and somatoform disorders, Dr. Noviello said in a virtual presentation of the results.

“Based on our data, chronic fatigue, gastrointestinal, and somatoform symptoms may have a common postinfectious origin, and they should be investigated in the follow-up of SARS-CoV-2 patients,” he said.
 

Links between SARS-CoV-2 and gastrointestinal symptoms

Gastrointestinal symptoms are known to be relatively common during acute infection. According to Dr. Noviello, the most frequent gastrointestinal symptom associated with SARS-CoV-2 is diarrhea, occurring in 4% to nearly 40% of patients in case series to date.

However, data on the longer-term gastrointestinal impacts of SARS-CoV-2 remain scarce.

In one noncontrolled cohort study in China, loss of appetite, nausea, acid reflux, and diarrhea were seen in 15%-24% of patients 3 months after the infection, Dr. Noviello said. In another cohort study in China, diarrhea and vomiting were reported in 5% of patients 6 months after infection.

In any case, it is known that viral, bacterial, and protozoal infections of the gastrointestinal tract are a risk factor for development of functional disorders including irritable bowel syndrome (IBS), functional dyspepsia, and chronic fatigue, according to Dr. Noviello.

Accordingly, the results of the present study suggest that SARS-CoV-2 also “may affect the brain-gut axis in the long term,” Dr. Noviello and coauthors wrote in an abstract of the study.

It is plausible that SARS-CoV-2 infection could be a trigger for longer-term gastrointestinal symptoms, especially given the previous evidence linking infections and IBS symptoms, or postinfectious IBS, said Juan Pablo Stefanolo, MD, a physician with the neurogastroenterology and motility section, Hospital de Clínicas José de San Martín, Buenos Aires University.

“If it is demonstrated [that SARS-CoV-2 infection is a trigger], the microbiota-gut-brain axis concept in IBS pathophysiology is reinforced,” Dr. Stefanolo said in an interview.

In the meantime, practitioners may want to take into account COVID-19 infection history in the evaluation of a patient with IBS-like symptoms and, in case of a known positive COVID-19 result in an IBS patient, be aware of the possibility of symptom exacerbation, Dr. Stefanolo said.
 

Pandemic in Italy: Unique study opportunity

The severe outbreak in the Milan region early in the COVID-19 pandemic provided a “unique opportunity” to assess the long-term impact of infection on gastrointestinal and extraintestinal somatoform symptoms, said Dr. Noviello.

The investigators sent an online questionnaire to patients who had a molecular diagnosis of SARS-CoV-2 infection by nasal swab between February and April of 2020. To form a control group, they also sent questionnaires to hospital employees and health care providers who had tested negative over that same time period.

In all, 378 questionnaires were completed by 177 SARS-CoV-2–positive individuals and 201 controls. The SARS-CoV-2–positive patients were somewhat older (about 44 years vs. 40 years for controls), were less often female (40% vs. 61%), had a lower education level, and smoked less than did controls, according to the investigators.

A mean of 4.8 months had elapsed between the time of SARS-CoV-2 infection and when the questionnaires were compiled, said Dr. Noviello.

In the acute phase, diarrhea was the most common gastrointestinal symptom among virus-positive individuals, occurring in about 50% compared to 20% of controls (P < .001), data show. Other symptoms reported by 40% of SARS-CoV-2–infected individuals included fever, dyspnea, loss of smell or taste, weight loss, myalgia, arthralgia, and asthenia in the acute phase controls in the acute phase, Dr. Noviello said.
 

Persistent gastrointestinal symptoms after SARS-CoV-2

Persistent symptoms included loose stools, as measured by the Bristol Stool scale, occurring in 17.8% of SARS-CoV-2–positive individuals, but only 9.3% of the SARS-CoV-2–negative controls, according to Dr. Noviello, with an adjusted risk ratio of 1.88 (95% confidence interval, 0.99-3.54).

Chronic fatigue symptoms, as measured by the Structured Assessment of Gastrointestinal Symptoms questionnaire, were reported by about 30% of SARS-CoV-2–positive patients and about 15% of controls, for an adjusted risk ratio of 2.24 (95% CI, 1.48-3.37), according to Dr. Noviello’s presentation.

The mean t-score on the Symptom Checklist–12 for somatoform disorders was higher for the virus-positive patients compared to controls, according to Dr. Noviello. The scores were 54.6 and 50.5, respectively, with an adjusted score difference of 3.6 (95% CI, 1.0-6.2).

The longer-term sequelae of SARS-CoV-2 infection might be more severe in individuals who experienced diarrhea during acute infection, according to Dr. Noviello. In a post hoc analysis, reports of irritable bowel syndrome and loose stools were significantly higher in SARS-CoV-2–infected individuals who had diarrhea in the acute phase compared to those who did not experience diarrhea, he said.

Somatoform disorder scores were significantly higher, and reports of headache, back pain, and chronic fatigue were significantly more common, in individuals who had diarrhea at the time of SARS-CoV-2 infection, he added.

Dr. Noviello and coauthors reported no competing interests related to the study. Dr. Stefanolo had no disclosures to report.
 

A 14-day course of hybrid therapy was as effective as 10-day bismuth quadruple therapy, but with fewer side effects, according to results of a randomized trial conducted in Taiwan.

“However, the former had fewer adverse events than the latter,” investigator Ping-I Hsu, MD, of An Nan Hospital, China Medical University, Taiwan said in a virtual presentation at the annual Digestive Disease Week® (DDW). Some patients in the trial received 14-day high-dose dual therapy, which also had a lower rate of adverse events but a lower eradication rate, compared with quadruple therapy, Dr. Hsu added.

This study confirms previous data showing that hybrid therapy has high eradication rates and a lower frequency of adverse events compared with bismuth quadruple therapy, noted Joseph Adrian L. Buensalido, MD, clinical associate professor of medicine in the division of infectious diseases at the University of the Philippines–Philippine General Hospital in Manila. “Clinicians and specialty/guideline groups may need to start looking at moving to first-line hybrid therapy as opposed to the traditional approach,” Dr. Buensalido said in an interview.
 

Current guidelines and data to date

An American College of Gastroenterology clinical guideline published in 2017 strongly recommends bismuth quadruple therapy, with a duration of 10-14 days, as a first-line treatment option. Hybrid therapy is conditionally recommended as a first-line option in the ACG guideline, while high-dose dual therapy is conditionally recommended as a salvage regimen.

In a prospective, randomized comparative study published in 2017, the eradication rates (93.9%) in patients receiving 14-day bismuth quadruple therapy (pantoprazole, bismuth subcitrate, tetracycline, and metronidazole) were comparable with eradication rates (92.8%) with 14-day hybrid therapy (dual therapy with pantoprazole plus amoxicillin for 7 days, followed by quadruple therapy with pantoprazole, amoxicillin, clarithromycin, and metronidazole for 7 days).

Quadruple therapy had a higher frequency of adverse events, at 55%, compared with 15.7% for hybrid therapy (P < .001). “Whether shortening the treatment duration of bismuth quadruple therapy from 14 days to 10 days can reduce the frequency of adverse effects remains unclear,” Dr. Hsu said in introductory comments to his study.
 

Comparing three approaches

In the multicenter, randomized, open-label superiority trial presented at DDW, Dr. Hsu and colleagues randomly assigned 600 Helicobacter pylori–infected participants in equal numbers to receive 14-day hybrid therapy, 14-day high-dose dual therapy, or 10-day bismuth quadruple therapy.

The hybrid therapy regimen consisted of rabeprazole 20 mg twice a day plus amoxicillin 1 g twice a day for 14 days, with clarithromycin 500 mg and metronidazole 500 mg twice a day in the final 7 days. The high-dose dual therapy regimen consisted of rabeprazole 20 mg and amoxicillin 750 mg four times a day for 14 days. The bismuth quadruple therapy regimen consisted of rabeprazole 20 mg twice a day, tripotassium dicitrato bismuthate 300 mg four times a day, tetracycline 500 mg twice a day, and metronidazole 250 mg four times a day for 10 days.

Investigators assessed H. pylori status 6 weeks following the end of therapy. In an intention-to-treat analysis, the hybrid therapy regimen yielded an eradication rate of 96.5%, which was comparable with the 93.5% eradication rate seen with bismuth quadruple therapy and was significantly higher than the 86.0% eradication rate seen with high-dose dual therapy (P < .001), according to Dr. Hsu. Similar efficacy outcomes were seen in per-protocol analysis.

The frequency of adverse events was lowest with high-dose dual therapy, at 13.0%, according to Dr. Hsu. That was significantly lower than the 25.5% frequency of adverse events with hybrid therapy. Bismuth quadruple therapy had a rate of 34.0%.
 

Antibiotic resistance results

Antibiotic resistance was most common for metronidazole, seen in approximately 28% of the quadruple-therapy group, 34% of the hybrid group, and 37% of the high-dose therapy groups. Clarithromycin resistance occurred in about 23% of quadruple therapy recipients, 16% of hybrid recipients, and 16% of high-dose therapy recipients. Amoxicillin and tetracycline resistance was rare, occurring in approximately 0%-3% of groups.

In the quadruple therapy arm, metronidazole resistance was associated with H. pylori eradication failure, according to Dr. Hsu. The eradication rate was about 96% for those subjects with no metronidazole resistance, and 88% for those with resistance (P = .05). Amoxicillin resistance, although rare in the study, independently predicted eradication failure of high-dose dual therapy, Dr. Hsu said. The eradication rate with high-dose dual therapy was 87.6% for individuals without amoxicillin resistance, and 40.0% in individuals with resistance, according to presented data.

The authors reported no financial disclosures related to their research. Dr. Buensalido has been a speaker for Unilab, BSV Bioscience, and Philcare Pharma, and has received sponsorship from Pfizer.

A 14-day course of hybrid therapy was as effective as 10-day bismuth quadruple therapy, but with fewer side effects, according to results of a randomized trial conducted in Taiwan.

“However, the former had fewer adverse events than the latter,” investigator Ping-I Hsu, MD, of An Nan Hospital, China Medical University, Taiwan said in a virtual presentation at the annual Digestive Disease Week® (DDW). Some patients in the trial received 14-day high-dose dual therapy, which also had a lower rate of adverse events but a lower eradication rate, compared with quadruple therapy, Dr. Hsu added.

This study confirms previous data showing that hybrid therapy has high eradication rates and a lower frequency of adverse events compared with bismuth quadruple therapy, noted Joseph Adrian L. Buensalido, MD, clinical associate professor of medicine in the division of infectious diseases at the University of the Philippines–Philippine General Hospital in Manila. “Clinicians and specialty/guideline groups may need to start looking at moving to first-line hybrid therapy as opposed to the traditional approach,” Dr. Buensalido said in an interview.
 

Current guidelines and data to date

An American College of Gastroenterology clinical guideline published in 2017 strongly recommends bismuth quadruple therapy, with a duration of 10-14 days, as a first-line treatment option. Hybrid therapy is conditionally recommended as a first-line option in the ACG guideline, while high-dose dual therapy is conditionally recommended as a salvage regimen.

In a prospective, randomized comparative study published in 2017, the eradication rates (93.9%) in patients receiving 14-day bismuth quadruple therapy (pantoprazole, bismuth subcitrate, tetracycline, and metronidazole) were comparable with eradication rates (92.8%) with 14-day hybrid therapy (dual therapy with pantoprazole plus amoxicillin for 7 days, followed by quadruple therapy with pantoprazole, amoxicillin, clarithromycin, and metronidazole for 7 days).

Quadruple therapy had a higher frequency of adverse events, at 55%, compared with 15.7% for hybrid therapy (P < .001). “Whether shortening the treatment duration of bismuth quadruple therapy from 14 days to 10 days can reduce the frequency of adverse effects remains unclear,” Dr. Hsu said in introductory comments to his study.
 

Comparing three approaches

In the multicenter, randomized, open-label superiority trial presented at DDW, Dr. Hsu and colleagues randomly assigned 600 Helicobacter pylori–infected participants in equal numbers to receive 14-day hybrid therapy, 14-day high-dose dual therapy, or 10-day bismuth quadruple therapy.

The hybrid therapy regimen consisted of rabeprazole 20 mg twice a day plus amoxicillin 1 g twice a day for 14 days, with clarithromycin 500 mg and metronidazole 500 mg twice a day in the final 7 days. The high-dose dual therapy regimen consisted of rabeprazole 20 mg and amoxicillin 750 mg four times a day for 14 days. The bismuth quadruple therapy regimen consisted of rabeprazole 20 mg twice a day, tripotassium dicitrato bismuthate 300 mg four times a day, tetracycline 500 mg twice a day, and metronidazole 250 mg four times a day for 10 days.

Investigators assessed H. pylori status 6 weeks following the end of therapy. In an intention-to-treat analysis, the hybrid therapy regimen yielded an eradication rate of 96.5%, which was comparable with the 93.5% eradication rate seen with bismuth quadruple therapy and was significantly higher than the 86.0% eradication rate seen with high-dose dual therapy (P < .001), according to Dr. Hsu. Similar efficacy outcomes were seen in per-protocol analysis.

The frequency of adverse events was lowest with high-dose dual therapy, at 13.0%, according to Dr. Hsu. That was significantly lower than the 25.5% frequency of adverse events with hybrid therapy. Bismuth quadruple therapy had a rate of 34.0%.
 

Antibiotic resistance results

Antibiotic resistance was most common for metronidazole, seen in approximately 28% of the quadruple-therapy group, 34% of the hybrid group, and 37% of the high-dose therapy groups. Clarithromycin resistance occurred in about 23% of quadruple therapy recipients, 16% of hybrid recipients, and 16% of high-dose therapy recipients. Amoxicillin and tetracycline resistance was rare, occurring in approximately 0%-3% of groups.

In the quadruple therapy arm, metronidazole resistance was associated with H. pylori eradication failure, according to Dr. Hsu. The eradication rate was about 96% for those subjects with no metronidazole resistance, and 88% for those with resistance (P = .05). Amoxicillin resistance, although rare in the study, independently predicted eradication failure of high-dose dual therapy, Dr. Hsu said. The eradication rate with high-dose dual therapy was 87.6% for individuals without amoxicillin resistance, and 40.0% in individuals with resistance, according to presented data.

The authors reported no financial disclosures related to their research. Dr. Buensalido has been a speaker for Unilab, BSV Bioscience, and Philcare Pharma, and has received sponsorship from Pfizer.

A 14-day course of hybrid therapy was as effective as 10-day bismuth quadruple therapy, but with fewer side effects, according to results of a randomized trial conducted in Taiwan.

“However, the former had fewer adverse events than the latter,” investigator Ping-I Hsu, MD, of An Nan Hospital, China Medical University, Taiwan said in a virtual presentation at the annual Digestive Disease Week® (DDW). Some patients in the trial received 14-day high-dose dual therapy, which also had a lower rate of adverse events but a lower eradication rate, compared with quadruple therapy, Dr. Hsu added.

This study confirms previous data showing that hybrid therapy has high eradication rates and a lower frequency of adverse events compared with bismuth quadruple therapy, noted Joseph Adrian L. Buensalido, MD, clinical associate professor of medicine in the division of infectious diseases at the University of the Philippines–Philippine General Hospital in Manila. “Clinicians and specialty/guideline groups may need to start looking at moving to first-line hybrid therapy as opposed to the traditional approach,” Dr. Buensalido said in an interview.
 

Current guidelines and data to date

An American College of Gastroenterology clinical guideline published in 2017 strongly recommends bismuth quadruple therapy, with a duration of 10-14 days, as a first-line treatment option. Hybrid therapy is conditionally recommended as a first-line option in the ACG guideline, while high-dose dual therapy is conditionally recommended as a salvage regimen.

In a prospective, randomized comparative study published in 2017, the eradication rates (93.9%) in patients receiving 14-day bismuth quadruple therapy (pantoprazole, bismuth subcitrate, tetracycline, and metronidazole) were comparable with eradication rates (92.8%) with 14-day hybrid therapy (dual therapy with pantoprazole plus amoxicillin for 7 days, followed by quadruple therapy with pantoprazole, amoxicillin, clarithromycin, and metronidazole for 7 days).

Quadruple therapy had a higher frequency of adverse events, at 55%, compared with 15.7% for hybrid therapy (P < .001). “Whether shortening the treatment duration of bismuth quadruple therapy from 14 days to 10 days can reduce the frequency of adverse effects remains unclear,” Dr. Hsu said in introductory comments to his study.
 

Comparing three approaches

In the multicenter, randomized, open-label superiority trial presented at DDW, Dr. Hsu and colleagues randomly assigned 600 Helicobacter pylori–infected participants in equal numbers to receive 14-day hybrid therapy, 14-day high-dose dual therapy, or 10-day bismuth quadruple therapy.

The hybrid therapy regimen consisted of rabeprazole 20 mg twice a day plus amoxicillin 1 g twice a day for 14 days, with clarithromycin 500 mg and metronidazole 500 mg twice a day in the final 7 days. The high-dose dual therapy regimen consisted of rabeprazole 20 mg and amoxicillin 750 mg four times a day for 14 days. The bismuth quadruple therapy regimen consisted of rabeprazole 20 mg twice a day, tripotassium dicitrato bismuthate 300 mg four times a day, tetracycline 500 mg twice a day, and metronidazole 250 mg four times a day for 10 days.

Investigators assessed H. pylori status 6 weeks following the end of therapy. In an intention-to-treat analysis, the hybrid therapy regimen yielded an eradication rate of 96.5%, which was comparable with the 93.5% eradication rate seen with bismuth quadruple therapy and was significantly higher than the 86.0% eradication rate seen with high-dose dual therapy (P < .001), according to Dr. Hsu. Similar efficacy outcomes were seen in per-protocol analysis.

The frequency of adverse events was lowest with high-dose dual therapy, at 13.0%, according to Dr. Hsu. That was significantly lower than the 25.5% frequency of adverse events with hybrid therapy. Bismuth quadruple therapy had a rate of 34.0%.
 

Antibiotic resistance results

Antibiotic resistance was most common for metronidazole, seen in approximately 28% of the quadruple-therapy group, 34% of the hybrid group, and 37% of the high-dose therapy groups. Clarithromycin resistance occurred in about 23% of quadruple therapy recipients, 16% of hybrid recipients, and 16% of high-dose therapy recipients. Amoxicillin and tetracycline resistance was rare, occurring in approximately 0%-3% of groups.

In the quadruple therapy arm, metronidazole resistance was associated with H. pylori eradication failure, according to Dr. Hsu. The eradication rate was about 96% for those subjects with no metronidazole resistance, and 88% for those with resistance (P = .05). Amoxicillin resistance, although rare in the study, independently predicted eradication failure of high-dose dual therapy, Dr. Hsu said. The eradication rate with high-dose dual therapy was 87.6% for individuals without amoxicillin resistance, and 40.0% in individuals with resistance, according to presented data.

The authors reported no financial disclosures related to their research. Dr. Buensalido has been a speaker for Unilab, BSV Bioscience, and Philcare Pharma, and has received sponsorship from Pfizer.

For biologic-naive adults with moderate to severe Crohn’s disease, treatment with adalimumab or ustekinumab leads to similar outcomes, according to results of the head-to-head SEAVUE trial.

When lead author Bruce E. Sands, MD, of Icahn School of Medicine at Mount Sinai, New York, compared treatment arms, patients had similar rates of clinical remission at one year. All major secondary endpoints, such as endoscopic remission, were comparable, as were safety profiles, Dr. Sands reported at the annual Digestive Disease Week^® (DDW).

“From my perspective, this is an important study,” Dr. Sands wrote in a virtual chat following his presentation. “We need more head-to-head studies!”

Results from the SEAVUE trial come almost 2 years after Dr. Sands reported findings of another head-to-head IBD trial: VARSITY, which demonstrated the superiority of vedolizumab over adalimumab among patients with moderate to severe ulcerative colitis.

The multicenter, double-blinded SEAVUE trial involved 386 patients with biologic-naive Crohn’s disease who had failed corticosteroids or immunomodulators. All patients had Crohn’s Disease Activity Index (CDAI) scores ranging from 220 to 450 and had at least one ulcer detected at baseline ileocolonoscopy.

Participants were randomized in a 1:1 ratio to receive monotherapy with either subcutaneous adalimumab (citrate-free; 160 mg at baseline, 70 mg at week 2, then 40 mg every 2 weeks) or ustekinumab, which was given first intravenously at a dose of 6 mg/kg then subcutaneously at 90 mg every 8 weeks.

The primary endpoint was clinical remission at week 52, defined by a CDAI score less than 150. Major secondary endpoints included clinical response, corticosteroid-free remission, endoscopic remission, remission in patient-reported CDAI components, and clinical remission at week 16.

Results were statistically similar across all endpoints, with clinical remission at 1 year occurring in 64.9% and 61.0% of patients receiving ustekinumab and adalimumab, respectively (P = .417).

“Both treatments demonstrated rapid onset of action and robust endoscopy results,” Dr. Sands noted during his presentation; he reported comparable rates of endoscopic remission, at 28.5% and 30.7% for ustekinumab and adalimumab, respectively (P = .631).

Among secondary endpoints, ustekinumab demonstrated some superiority, with greater maintenance of clinical response at week 52 among patients with response at week 16 (88.6% vs. 78.0%; P = .016), greater reduction in liquid/soft stools in prior 7 days from baseline to week 52 (–19.9 vs. –16.2; P = .004), and greater reduction in sum number of liquid/soft stools and abdominal pain scores in prior 7 days from baseline to week 52 (–29.6 vs. –25.1; P = .013).

Safety metrics were similar between groups, and consistent with previous experience. Although the adalimumab group had a higher rate of discontinuation due to adverse events, this trend was not statistically significant (11.3% vs. 6.3%; P value not provided).
 

Don’t ignore discontinuation rates

Jordan E. Axelrad, MD, assistant professor of medicine at NYU and a clinician at the Inflammatory Bowel Disease Center at NYU Langone Health, New York, commended the SEAVUE trial for its head-to-head design, which is a first for biologics in Crohn’s disease.

“With newer drugs, there’s a critical need for head-to-head studies for us to understand where to position a lot of these agents,” he said in an interview. “[T]his was a good undifferentiated group to understand what’s the first biologic you should use in a patient with moderate-to-severe Crohn’s disease. The primary, major take-home is that [ustekinumab and adalimumab] are similarly effective.”

When asked about the slight superiority in minor secondary endpoints associated with ustekinumab, Dr. Axelrad suggested that rates of discontinuation deserve more attention.

“For me, maybe the major focus would be on the number of patients who stopped treatment,” Dr. Axelrad said, noting a higher rate of discontinuation in the adalimumab group. “Although that was just numerical, that to me is actually more important than [the minor secondary endpoints].” He also highlighted the lower injection burden associated with ustekinumab, which is given every 8 weeks, compared with every 2 weeks for adalimumab.

Ultimately, however, it’s unlikely that treatment sequencing will depend on these finer points, Dr. Axelrad suggested, and will instead come down to finances, especially with adalimumab biosimilars on the horizon, which may be the most cost-effective.

“A lot of the decision-making of where to position [ustekinumab in Crohn’s disease] is going to come down to the payer,” Dr. Axelrad said. “If there was a clear signal, providers such as myself would have a better leg to stand on, like we saw with VARSITY, where vedolizumab was clearly superior to adalimumab on multiple endpoints. We didn’t see that sort of robust signal here.”

The SEAVUE trial was supported by Janssen Scientific Affairs. Dr. Sands disclosed relationships with Janssen, AbbVie, Takeda, and others. Dr. Axelrad disclosed previous consulting fees from Janssen and research support from BioFire.

For biologic-naive adults with moderate to severe Crohn’s disease, treatment with adalimumab or ustekinumab leads to similar outcomes, according to results of the head-to-head SEAVUE trial.

When lead author Bruce E. Sands, MD, of Icahn School of Medicine at Mount Sinai, New York, compared treatment arms, patients had similar rates of clinical remission at one year. All major secondary endpoints, such as endoscopic remission, were comparable, as were safety profiles, Dr. Sands reported at the annual Digestive Disease Week^® (DDW).

“From my perspective, this is an important study,” Dr. Sands wrote in a virtual chat following his presentation. “We need more head-to-head studies!”

Results from the SEAVUE trial come almost 2 years after Dr. Sands reported findings of another head-to-head IBD trial: VARSITY, which demonstrated the superiority of vedolizumab over adalimumab among patients with moderate to severe ulcerative colitis.

The multicenter, double-blinded SEAVUE trial involved 386 patients with biologic-naive Crohn’s disease who had failed corticosteroids or immunomodulators. All patients had Crohn’s Disease Activity Index (CDAI) scores ranging from 220 to 450 and had at least one ulcer detected at baseline ileocolonoscopy.

Participants were randomized in a 1:1 ratio to receive monotherapy with either subcutaneous adalimumab (citrate-free; 160 mg at baseline, 70 mg at week 2, then 40 mg every 2 weeks) or ustekinumab, which was given first intravenously at a dose of 6 mg/kg then subcutaneously at 90 mg every 8 weeks.

The primary endpoint was clinical remission at week 52, defined by a CDAI score less than 150. Major secondary endpoints included clinical response, corticosteroid-free remission, endoscopic remission, remission in patient-reported CDAI components, and clinical remission at week 16.

Results were statistically similar across all endpoints, with clinical remission at 1 year occurring in 64.9% and 61.0% of patients receiving ustekinumab and adalimumab, respectively (P = .417).

“Both treatments demonstrated rapid onset of action and robust endoscopy results,” Dr. Sands noted during his presentation; he reported comparable rates of endoscopic remission, at 28.5% and 30.7% for ustekinumab and adalimumab, respectively (P = .631).

Among secondary endpoints, ustekinumab demonstrated some superiority, with greater maintenance of clinical response at week 52 among patients with response at week 16 (88.6% vs. 78.0%; P = .016), greater reduction in liquid/soft stools in prior 7 days from baseline to week 52 (–19.9 vs. –16.2; P = .004), and greater reduction in sum number of liquid/soft stools and abdominal pain scores in prior 7 days from baseline to week 52 (–29.6 vs. –25.1; P = .013).

Safety metrics were similar between groups, and consistent with previous experience. Although the adalimumab group had a higher rate of discontinuation due to adverse events, this trend was not statistically significant (11.3% vs. 6.3%; P value not provided).
 

Don’t ignore discontinuation rates

Jordan E. Axelrad, MD, assistant professor of medicine at NYU and a clinician at the Inflammatory Bowel Disease Center at NYU Langone Health, New York, commended the SEAVUE trial for its head-to-head design, which is a first for biologics in Crohn’s disease.

“With newer drugs, there’s a critical need for head-to-head studies for us to understand where to position a lot of these agents,” he said in an interview. “[T]his was a good undifferentiated group to understand what’s the first biologic you should use in a patient with moderate-to-severe Crohn’s disease. The primary, major take-home is that [ustekinumab and adalimumab] are similarly effective.”

When asked about the slight superiority in minor secondary endpoints associated with ustekinumab, Dr. Axelrad suggested that rates of discontinuation deserve more attention.

“For me, maybe the major focus would be on the number of patients who stopped treatment,” Dr. Axelrad said, noting a higher rate of discontinuation in the adalimumab group. “Although that was just numerical, that to me is actually more important than [the minor secondary endpoints].” He also highlighted the lower injection burden associated with ustekinumab, which is given every 8 weeks, compared with every 2 weeks for adalimumab.

Ultimately, however, it’s unlikely that treatment sequencing will depend on these finer points, Dr. Axelrad suggested, and will instead come down to finances, especially with adalimumab biosimilars on the horizon, which may be the most cost-effective.

“A lot of the decision-making of where to position [ustekinumab in Crohn’s disease] is going to come down to the payer,” Dr. Axelrad said. “If there was a clear signal, providers such as myself would have a better leg to stand on, like we saw with VARSITY, where vedolizumab was clearly superior to adalimumab on multiple endpoints. We didn’t see that sort of robust signal here.”

The SEAVUE trial was supported by Janssen Scientific Affairs. Dr. Sands disclosed relationships with Janssen, AbbVie, Takeda, and others. Dr. Axelrad disclosed previous consulting fees from Janssen and research support from BioFire.

For biologic-naive adults with moderate to severe Crohn’s disease, treatment with adalimumab or ustekinumab leads to similar outcomes, according to results of the head-to-head SEAVUE trial.

When lead author Bruce E. Sands, MD, of Icahn School of Medicine at Mount Sinai, New York, compared treatment arms, patients had similar rates of clinical remission at one year. All major secondary endpoints, such as endoscopic remission, were comparable, as were safety profiles, Dr. Sands reported at the annual Digestive Disease Week^® (DDW).

“From my perspective, this is an important study,” Dr. Sands wrote in a virtual chat following his presentation. “We need more head-to-head studies!”

Results from the SEAVUE trial come almost 2 years after Dr. Sands reported findings of another head-to-head IBD trial: VARSITY, which demonstrated the superiority of vedolizumab over adalimumab among patients with moderate to severe ulcerative colitis.

The multicenter, double-blinded SEAVUE trial involved 386 patients with biologic-naive Crohn’s disease who had failed corticosteroids or immunomodulators. All patients had Crohn’s Disease Activity Index (CDAI) scores ranging from 220 to 450 and had at least one ulcer detected at baseline ileocolonoscopy.

Participants were randomized in a 1:1 ratio to receive monotherapy with either subcutaneous adalimumab (citrate-free; 160 mg at baseline, 70 mg at week 2, then 40 mg every 2 weeks) or ustekinumab, which was given first intravenously at a dose of 6 mg/kg then subcutaneously at 90 mg every 8 weeks.

The primary endpoint was clinical remission at week 52, defined by a CDAI score less than 150. Major secondary endpoints included clinical response, corticosteroid-free remission, endoscopic remission, remission in patient-reported CDAI components, and clinical remission at week 16.

Results were statistically similar across all endpoints, with clinical remission at 1 year occurring in 64.9% and 61.0% of patients receiving ustekinumab and adalimumab, respectively (P = .417).

“Both treatments demonstrated rapid onset of action and robust endoscopy results,” Dr. Sands noted during his presentation; he reported comparable rates of endoscopic remission, at 28.5% and 30.7% for ustekinumab and adalimumab, respectively (P = .631).

Among secondary endpoints, ustekinumab demonstrated some superiority, with greater maintenance of clinical response at week 52 among patients with response at week 16 (88.6% vs. 78.0%; P = .016), greater reduction in liquid/soft stools in prior 7 days from baseline to week 52 (–19.9 vs. –16.2; P = .004), and greater reduction in sum number of liquid/soft stools and abdominal pain scores in prior 7 days from baseline to week 52 (–29.6 vs. –25.1; P = .013).

Safety metrics were similar between groups, and consistent with previous experience. Although the adalimumab group had a higher rate of discontinuation due to adverse events, this trend was not statistically significant (11.3% vs. 6.3%; P value not provided).
 

Don’t ignore discontinuation rates

Jordan E. Axelrad, MD, assistant professor of medicine at NYU and a clinician at the Inflammatory Bowel Disease Center at NYU Langone Health, New York, commended the SEAVUE trial for its head-to-head design, which is a first for biologics in Crohn’s disease.

“With newer drugs, there’s a critical need for head-to-head studies for us to understand where to position a lot of these agents,” he said in an interview. “[T]his was a good undifferentiated group to understand what’s the first biologic you should use in a patient with moderate-to-severe Crohn’s disease. The primary, major take-home is that [ustekinumab and adalimumab] are similarly effective.”

When asked about the slight superiority in minor secondary endpoints associated with ustekinumab, Dr. Axelrad suggested that rates of discontinuation deserve more attention.

“For me, maybe the major focus would be on the number of patients who stopped treatment,” Dr. Axelrad said, noting a higher rate of discontinuation in the adalimumab group. “Although that was just numerical, that to me is actually more important than [the minor secondary endpoints].” He also highlighted the lower injection burden associated with ustekinumab, which is given every 8 weeks, compared with every 2 weeks for adalimumab.

Ultimately, however, it’s unlikely that treatment sequencing will depend on these finer points, Dr. Axelrad suggested, and will instead come down to finances, especially with adalimumab biosimilars on the horizon, which may be the most cost-effective.

“A lot of the decision-making of where to position [ustekinumab in Crohn’s disease] is going to come down to the payer,” Dr. Axelrad said. “If there was a clear signal, providers such as myself would have a better leg to stand on, like we saw with VARSITY, where vedolizumab was clearly superior to adalimumab on multiple endpoints. We didn’t see that sort of robust signal here.”

The SEAVUE trial was supported by Janssen Scientific Affairs. Dr. Sands disclosed relationships with Janssen, AbbVie, Takeda, and others. Dr. Axelrad disclosed previous consulting fees from Janssen and research support from BioFire.

SER-109, an oral microbiome therapeutic, safely protects against Clostridioides difficile recurrence for up to 24 weeks, according to a recent phase 3 trial. Three days of treatment with purified Firmicutes spores reduced risk of recurrence by 54%, suggesting a sustained, clinically meaningful response, according to a multicenter study presented at this year’s Digestive Disease Week^® (DDW).

“Antibiotics targeted against C. difficile bacteria are necessary but insufficient to achieve a durable clinical response because they have no effect on C. difficile spores that germinate within a disrupted microbiome,” the investigators reported at the meeting.

“The manufacturing processes for SER-109 are designed to inactivate potential pathogens, while enriching for beneficial Firmicutes spores, which play a central role in inhibiting the cycle of C. difficile,” said Louis Y. Korman, MD, a gastroenterologist in Washington, who was lead author.
 

Extended data from ECOSPOR-III

The ECOSPOR-III trial involved 182 patients with at least three episodes of C. difficile infection in the previous 12 months. Patients underwent 10-21 days of antibiotic therapy with fidaxomicin or vancomycin to resolve symptoms before they were then randomized in a 1:1 ratio to receive either SER-109 (four capsules daily for 3 days) or placebo, with stratification by specific antibiotic and patient age (threshold of 65 years).

The primary objectives were safety and efficacy at 8 weeks. These results, which were previously reported at ACG 2020, showed a 68% relative risk reduction in the SER-109 group, and favorable safety data. The findings presented at DDW added to those earlier ones by providing safety and efficacy data extending to week 24. At this time point, patients treated with SER-109 had a 54% relative risk reduction in C. difficile recurrence. Recurrence rates were 21.3% and 47.3% for the treatment and placebo groups, respectively (P less than .001).

Patients 65 years and older benefited the most from SER-109 therapy, based on a relative risk reduction of 56% (P less than .001), versus a 49% relative risk reduction (lacking statistical significance) for patients younger than 65 years (P = .093). The specific antibiotic therapy patients received also appeared to impact outcomes. Patients treated with fidaxomicin had a 73% relative risk reduction (P = .009), compared with 48% for vancomycin (P = .006). Safety profiles were similar between study arms.

“By enriching for Firmicutes spores, SER-109 achieves high efficacy, while mitigating risk of transmitting infectious agents and represents a major paradigm shift in the clinical management of patients with recurrent C. difficile infection,” the investigators concluded, noting that “an open-label study for patients with recurrent C. difficile infection is currently enrolling.”
 

Microbiome restoration therapies

According to Sahil Khanna, MBBS, professor of medicine at Mayo Clinic, Rochester, Minn., these findings “advance the field” because they show a sustained response. “We know that microbiome restoration therapies help restore colonization resistance,” Dr. Khanna said in an interview, noting that they offer benefits comparable to fecal microbiota transplantation (FMT) without the downsides.

SER-109, an oral microbiome therapeutic, safely protects against Clostridioides difficile recurrence for up to 24 weeks, according to a recent phase 3 trial. Three days of treatment with purified Firmicutes spores reduced risk of recurrence by 54%, suggesting a sustained, clinically meaningful response, according to a multicenter study presented at this year’s Digestive Disease Week^® (DDW).

“Antibiotics targeted against C. difficile bacteria are necessary but insufficient to achieve a durable clinical response because they have no effect on C. difficile spores that germinate within a disrupted microbiome,” the investigators reported at the meeting.

“The manufacturing processes for SER-109 are designed to inactivate potential pathogens, while enriching for beneficial Firmicutes spores, which play a central role in inhibiting the cycle of C. difficile,” said Louis Y. Korman, MD, a gastroenterologist in Washington, who was lead author.
 

Extended data from ECOSPOR-III

The ECOSPOR-III trial involved 182 patients with at least three episodes of C. difficile infection in the previous 12 months. Patients underwent 10-21 days of antibiotic therapy with fidaxomicin or vancomycin to resolve symptoms before they were then randomized in a 1:1 ratio to receive either SER-109 (four capsules daily for 3 days) or placebo, with stratification by specific antibiotic and patient age (threshold of 65 years).

The primary objectives were safety and efficacy at 8 weeks. These results, which were previously reported at ACG 2020, showed a 68% relative risk reduction in the SER-109 group, and favorable safety data. The findings presented at DDW added to those earlier ones by providing safety and efficacy data extending to week 24. At this time point, patients treated with SER-109 had a 54% relative risk reduction in C. difficile recurrence. Recurrence rates were 21.3% and 47.3% for the treatment and placebo groups, respectively (P less than .001).

Patients 65 years and older benefited the most from SER-109 therapy, based on a relative risk reduction of 56% (P less than .001), versus a 49% relative risk reduction (lacking statistical significance) for patients younger than 65 years (P = .093). The specific antibiotic therapy patients received also appeared to impact outcomes. Patients treated with fidaxomicin had a 73% relative risk reduction (P = .009), compared with 48% for vancomycin (P = .006). Safety profiles were similar between study arms.

“By enriching for Firmicutes spores, SER-109 achieves high efficacy, while mitigating risk of transmitting infectious agents and represents a major paradigm shift in the clinical management of patients with recurrent C. difficile infection,” the investigators concluded, noting that “an open-label study for patients with recurrent C. difficile infection is currently enrolling.”
 

Microbiome restoration therapies

According to Sahil Khanna, MBBS, professor of medicine at Mayo Clinic, Rochester, Minn., these findings “advance the field” because they show a sustained response. “We know that microbiome restoration therapies help restore colonization resistance,” Dr. Khanna said in an interview, noting that they offer benefits comparable to fecal microbiota transplantation (FMT) without the downsides.

SER-109, an oral microbiome therapeutic, safely protects against Clostridioides difficile recurrence for up to 24 weeks, according to a recent phase 3 trial. Three days of treatment with purified Firmicutes spores reduced risk of recurrence by 54%, suggesting a sustained, clinically meaningful response, according to a multicenter study presented at this year’s Digestive Disease Week^® (DDW).

“Antibiotics targeted against C. difficile bacteria are necessary but insufficient to achieve a durable clinical response because they have no effect on C. difficile spores that germinate within a disrupted microbiome,” the investigators reported at the meeting.

“The manufacturing processes for SER-109 are designed to inactivate potential pathogens, while enriching for beneficial Firmicutes spores, which play a central role in inhibiting the cycle of C. difficile,” said Louis Y. Korman, MD, a gastroenterologist in Washington, who was lead author.
 

Extended data from ECOSPOR-III

The ECOSPOR-III trial involved 182 patients with at least three episodes of C. difficile infection in the previous 12 months. Patients underwent 10-21 days of antibiotic therapy with fidaxomicin or vancomycin to resolve symptoms before they were then randomized in a 1:1 ratio to receive either SER-109 (four capsules daily for 3 days) or placebo, with stratification by specific antibiotic and patient age (threshold of 65 years).

The primary objectives were safety and efficacy at 8 weeks. These results, which were previously reported at ACG 2020, showed a 68% relative risk reduction in the SER-109 group, and favorable safety data. The findings presented at DDW added to those earlier ones by providing safety and efficacy data extending to week 24. At this time point, patients treated with SER-109 had a 54% relative risk reduction in C. difficile recurrence. Recurrence rates were 21.3% and 47.3% for the treatment and placebo groups, respectively (P less than .001).

Patients 65 years and older benefited the most from SER-109 therapy, based on a relative risk reduction of 56% (P less than .001), versus a 49% relative risk reduction (lacking statistical significance) for patients younger than 65 years (P = .093). The specific antibiotic therapy patients received also appeared to impact outcomes. Patients treated with fidaxomicin had a 73% relative risk reduction (P = .009), compared with 48% for vancomycin (P = .006). Safety profiles were similar between study arms.

“By enriching for Firmicutes spores, SER-109 achieves high efficacy, while mitigating risk of transmitting infectious agents and represents a major paradigm shift in the clinical management of patients with recurrent C. difficile infection,” the investigators concluded, noting that “an open-label study for patients with recurrent C. difficile infection is currently enrolling.”
 

Microbiome restoration therapies

According to Sahil Khanna, MBBS, professor of medicine at Mayo Clinic, Rochester, Minn., these findings “advance the field” because they show a sustained response. “We know that microbiome restoration therapies help restore colonization resistance,” Dr. Khanna said in an interview, noting that they offer benefits comparable to fecal microbiota transplantation (FMT) without the downsides.

There is an unmet need to standardize outcomes that are reported in clinical trials of rosacea, according to authors of a new systematic review of rosacea treatment studies.

“Rosacea is a chronic dermatologic condition that affects 16 million Americans,” one of the study authors, Sarah A. Ibrahim, told this news organization after the annual conference of the American Society for Laser Medicine and Surgery. “The features of rosacea, such as inflammatory lesions, redness, burning sensations, and swelling, can have a negative impact on the quality of life for many patients. Additionally, patients with rosacea are at an increased risk for other conditions such as autoimmune diseases, like inflammatory bowel disease.”

In an effort led by principal investigator Murad Alam, MD, vice chair of the department of dermatology at Northwestern University, Chicago, Ms. Ibrahim conducted a systematic review to identify all outcomes that have previously been reported in clinical trials of rosacea, as part of the development of the core outcome set established by the Measurement of Priority Outcome Variables in Dermatologic Surgery (IMPROVED) group. “This has not been done before and is an important first step in understanding what outcomes should be measured in every future clinical study of rosacea,” said Ms. Ibrahim, a medical student at Northwestern University, and predoctoral research fellow in Northwestern’s department of dermatology.

The researchers limited their analysis to randomized, controlled trials of rosacea interventions published between 2010 and 2020 and categorized outcomes into domains based on similar themes.

A total of 58 studies were included in the systematic review, of which 7 (12%) evaluated laser-based interventions. The researchers identified 55 unique outcomes that encompassed eight domains: Quality of life, treatment effects, patient perception of health, clinical assessment, acceptance of care, laboratory assessment, physiological skin assessment, and patient satisfaction. Of the eight domains, clinical assessment-related outcomes were measured in all studies. Nontransient erythema was the most commonly reported outcome (43 studies, 78%), followed by inflammatory lesions (36 studies, 65%) and telangiectasia (22 studies, 40%).

Outcomes pertaining to treatment effects such as adverse events were measured in 49 of the 55 studies (89%), while patient-reported outcomes were measured in 21 (38%). Quality of life and patient satisfaction were reported in 18 (33%) and 13 (24%) studies, respectively.

sruilk/shutterstock

“There were two main take-home messages of our study,” said Ms. Ibrahim, who presented the results at the meeting. “The first is that there is a wide range of outcomes that are reported in clinical trials of rosacea therapies. Second, that there is a need to standardize the outcomes that are reported in clinical trials of rosacea, in order to be able to combine the results from different studies to better understand which interventions for rosacea are most effective.”

She acknowledged certain limitations of the review, including that other trials related to the topic were not included. “Because of the date range and types of studies that we used to narrow down our search, it is possible that additional outcomes were reported in studies that were not included here,” she said.

“This is a very important study because rosacea is a very common condition and one that I have seen more frequently in clinic since the pandemic started,” said Omar Ibrahimi, PhD, MD, a dermatologist with the Connecticut Skin Institute in Stamford, who was asked to comment on the work. “One of the limitations with rosacea studies is that the studies done are often fairly small and the outcome measures are heterogenous. The current study by Ibrahim and coworkers does a wonderful job of highlighting the various outcomes measures used to measure the success of rosacea treatments with energy-based devices.”

This information, he added, “will be very useful for further research studies because it forms the basis for formulating a set of core outcome measures to judge treatment interventions with consensus input from a variety of key opinion leaders. This will prove to be valuable because if we can have a uniform set of outcome measures to judge rosacea treatments with then we will be able to compare the results from different studies better.”

Ms. Ibrahim and colleagues reported having no relevant financial disclosures. Dr. Ibrahimi disclosed that he has been a speaker for both Candela and Cutera and he is currently on the medical advisory board for Cutera.
 

dbrunk@mdedge.com

There is an unmet need to standardize outcomes that are reported in clinical trials of rosacea, according to authors of a new systematic review of rosacea treatment studies.

“Rosacea is a chronic dermatologic condition that affects 16 million Americans,” one of the study authors, Sarah A. Ibrahim, told this news organization after the annual conference of the American Society for Laser Medicine and Surgery. “The features of rosacea, such as inflammatory lesions, redness, burning sensations, and swelling, can have a negative impact on the quality of life for many patients. Additionally, patients with rosacea are at an increased risk for other conditions such as autoimmune diseases, like inflammatory bowel disease.”

In an effort led by principal investigator Murad Alam, MD, vice chair of the department of dermatology at Northwestern University, Chicago, Ms. Ibrahim conducted a systematic review to identify all outcomes that have previously been reported in clinical trials of rosacea, as part of the development of the core outcome set established by the Measurement of Priority Outcome Variables in Dermatologic Surgery (IMPROVED) group. “This has not been done before and is an important first step in understanding what outcomes should be measured in every future clinical study of rosacea,” said Ms. Ibrahim, a medical student at Northwestern University, and predoctoral research fellow in Northwestern’s department of dermatology.

The researchers limited their analysis to randomized, controlled trials of rosacea interventions published between 2010 and 2020 and categorized outcomes into domains based on similar themes.

A total of 58 studies were included in the systematic review, of which 7 (12%) evaluated laser-based interventions. The researchers identified 55 unique outcomes that encompassed eight domains: Quality of life, treatment effects, patient perception of health, clinical assessment, acceptance of care, laboratory assessment, physiological skin assessment, and patient satisfaction. Of the eight domains, clinical assessment-related outcomes were measured in all studies. Nontransient erythema was the most commonly reported outcome (43 studies, 78%), followed by inflammatory lesions (36 studies, 65%) and telangiectasia (22 studies, 40%).

Outcomes pertaining to treatment effects such as adverse events were measured in 49 of the 55 studies (89%), while patient-reported outcomes were measured in 21 (38%). Quality of life and patient satisfaction were reported in 18 (33%) and 13 (24%) studies, respectively.

sruilk/shutterstock

“There were two main take-home messages of our study,” said Ms. Ibrahim, who presented the results at the meeting. “The first is that there is a wide range of outcomes that are reported in clinical trials of rosacea therapies. Second, that there is a need to standardize the outcomes that are reported in clinical trials of rosacea, in order to be able to combine the results from different studies to better understand which interventions for rosacea are most effective.”

She acknowledged certain limitations of the review, including that other trials related to the topic were not included. “Because of the date range and types of studies that we used to narrow down our search, it is possible that additional outcomes were reported in studies that were not included here,” she said.

“This is a very important study because rosacea is a very common condition and one that I have seen more frequently in clinic since the pandemic started,” said Omar Ibrahimi, PhD, MD, a dermatologist with the Connecticut Skin Institute in Stamford, who was asked to comment on the work. “One of the limitations with rosacea studies is that the studies done are often fairly small and the outcome measures are heterogenous. The current study by Ibrahim and coworkers does a wonderful job of highlighting the various outcomes measures used to measure the success of rosacea treatments with energy-based devices.”

This information, he added, “will be very useful for further research studies because it forms the basis for formulating a set of core outcome measures to judge treatment interventions with consensus input from a variety of key opinion leaders. This will prove to be valuable because if we can have a uniform set of outcome measures to judge rosacea treatments with then we will be able to compare the results from different studies better.”

Ms. Ibrahim and colleagues reported having no relevant financial disclosures. Dr. Ibrahimi disclosed that he has been a speaker for both Candela and Cutera and he is currently on the medical advisory board for Cutera.
 

dbrunk@mdedge.com

There is an unmet need to standardize outcomes that are reported in clinical trials of rosacea, according to authors of a new systematic review of rosacea treatment studies.

“Rosacea is a chronic dermatologic condition that affects 16 million Americans,” one of the study authors, Sarah A. Ibrahim, told this news organization after the annual conference of the American Society for Laser Medicine and Surgery. “The features of rosacea, such as inflammatory lesions, redness, burning sensations, and swelling, can have a negative impact on the quality of life for many patients. Additionally, patients with rosacea are at an increased risk for other conditions such as autoimmune diseases, like inflammatory bowel disease.”

In an effort led by principal investigator Murad Alam, MD, vice chair of the department of dermatology at Northwestern University, Chicago, Ms. Ibrahim conducted a systematic review to identify all outcomes that have previously been reported in clinical trials of rosacea, as part of the development of the core outcome set established by the Measurement of Priority Outcome Variables in Dermatologic Surgery (IMPROVED) group. “This has not been done before and is an important first step in understanding what outcomes should be measured in every future clinical study of rosacea,” said Ms. Ibrahim, a medical student at Northwestern University, and predoctoral research fellow in Northwestern’s department of dermatology.

The researchers limited their analysis to randomized, controlled trials of rosacea interventions published between 2010 and 2020 and categorized outcomes into domains based on similar themes.

A total of 58 studies were included in the systematic review, of which 7 (12%) evaluated laser-based interventions. The researchers identified 55 unique outcomes that encompassed eight domains: Quality of life, treatment effects, patient perception of health, clinical assessment, acceptance of care, laboratory assessment, physiological skin assessment, and patient satisfaction. Of the eight domains, clinical assessment-related outcomes were measured in all studies. Nontransient erythema was the most commonly reported outcome (43 studies, 78%), followed by inflammatory lesions (36 studies, 65%) and telangiectasia (22 studies, 40%).

Outcomes pertaining to treatment effects such as adverse events were measured in 49 of the 55 studies (89%), while patient-reported outcomes were measured in 21 (38%). Quality of life and patient satisfaction were reported in 18 (33%) and 13 (24%) studies, respectively.

sruilk/shutterstock

“There were two main take-home messages of our study,” said Ms. Ibrahim, who presented the results at the meeting. “The first is that there is a wide range of outcomes that are reported in clinical trials of rosacea therapies. Second, that there is a need to standardize the outcomes that are reported in clinical trials of rosacea, in order to be able to combine the results from different studies to better understand which interventions for rosacea are most effective.”

She acknowledged certain limitations of the review, including that other trials related to the topic were not included. “Because of the date range and types of studies that we used to narrow down our search, it is possible that additional outcomes were reported in studies that were not included here,” she said.

“This is a very important study because rosacea is a very common condition and one that I have seen more frequently in clinic since the pandemic started,” said Omar Ibrahimi, PhD, MD, a dermatologist with the Connecticut Skin Institute in Stamford, who was asked to comment on the work. “One of the limitations with rosacea studies is that the studies done are often fairly small and the outcome measures are heterogenous. The current study by Ibrahim and coworkers does a wonderful job of highlighting the various outcomes measures used to measure the success of rosacea treatments with energy-based devices.”

This information, he added, “will be very useful for further research studies because it forms the basis for formulating a set of core outcome measures to judge treatment interventions with consensus input from a variety of key opinion leaders. This will prove to be valuable because if we can have a uniform set of outcome measures to judge rosacea treatments with then we will be able to compare the results from different studies better.”

Ms. Ibrahim and colleagues reported having no relevant financial disclosures. Dr. Ibrahimi disclosed that he has been a speaker for both Candela and Cutera and he is currently on the medical advisory board for Cutera.
 

dbrunk@mdedge.com

Proton pump inhibitor (PPI) use can safely be reduced by deprescribing efforts coupled with patient and clinician education, according to a retrospective study involving more than 4 million veterans.

After 1 year, the intervention was associated with a significant reduction in PPI use without worsening of acid-related diseases, reported lead author Jacob E. Kurlander, MD, of the University of Michigan, Ann Arbor, and the VA Ann Arbor Healthcare System’s Center for Clinical Management Research.

“There’s increasing interest in interventions to reduce PPI use,” Dr. Kurlander said during his virtual presentation at the annual Digestive Disease Week® (DDW). “Many of the interventions have come in the form of patient and provider education, like the Choosing Wisely campaign put out by the American Board of Internal Medicine. However, in rigorous studies, few interventions have actually proven effective, and many of these studies lack data on clinical outcomes, so it’s difficult to ascertain the real clinical benefits, or even harms.”

In an effort to address this gap, the investigators conducted a retrospective, difference-in-difference study spanning 10 years, from 2009 to 2019. The 1-year intervention, implemented in August 2013, included refill restrictions for PPIs without documented indication for long-term use, voiding of PPI prescriptions not filled within 6 months, a quick-order option for H2-receptor antagonists, reports to identify high-dose PPI prescribing, and patient and clinician education.

The intervention group consisted of 192,607-250,349 veterans in Veteran Integrated Service Network 17, whereas the control group consisted of 3,775,978-4,360,908 veterans in other service networks (ranges in population size are due to variations across 6-month intervals of analysis). For each 6-month interval, patients were included if they had at least two primary care visits within the past 2 years, and excluded if they received primary care at three other sites that joined the intervention site after initial implementation.

The investigators analyzed three main outcomes: Proportion of veterans dispensed a PPI prescription from the VA at any dose; incidence proportion of hospitalization for upper GI diseases, including upper GI bleeding other than from esophageal varices or angiodysplasia, as well as nonbleeding acid peptic disease; and rates of primary care visits, gastroenterology visits, and esophagogastroduodenoscopies (EGDs).

The analysis was divided into a preimplementation period, lasting approximately 5 years, and a postimplementation period with a similar duration. In the postimplementation period, the intervention group had a 5.9% relative reduction in PPI prescriptions, compared with the control group (P < .001). During the same period, the intervention site did not have a significant increase in the rate of patients hospitalized for upper GI diseases, primary care visits, GI clinic visits, or EGDs.

In a subgroup analysis of patients coprescribed PPIs during time at high-risk for upper GI bleeding (that is, when they possessed at least two high-risk medications, such as warfarin), there was a 4.6% relative reduction in time with PPI gastroprotection among the intervention group, compared with the control group (P = .003). In a second sensitivity analysis, hospitalization for upper GI diseases in high-risk patients at least 65 years of age was not significantly different between groups.

“[This] multicomponent PPI deprescribing program led to sustained reductions in PPI use,” Dr. Kurlander concluded. “However, this blunt intervention also reduced appropriate use of PPIs for gastroprotection, raising some concerns about clinical quality of care, but this did not appear to cause any measurable clinical harm in terms of hospitalizations for upper GI diseases.”
 

Debate around ‘unnecessary PPI use’

According to Philip O. Katz, MD, professor of medicine and director of motility laboratories at Weill Cornell Medicine, New York, the study “makes an attempt to do what others have tried in different ways, which is to develop a mechanism to help reduce or discontinue proton pump inhibitors when people believe they’re not indicated.”

Yet this latter element – appropriate indication – drives an ongoing debate.

“This is a very controversial area,” Dr. Katz said in an interview. “The concept of using the lowest effective dose of medication needed for a symptom or a disease is not new, but the push to reducing or eliminating ‘unnecessary PPI use’ is one that I believe should be carefully discussed, and that we have a clear understanding of what constitutes unnecessary use. And quite honestly, I’m willing to state that I don’t believe that’s been well defined.”

Dr. Katz, who recently coauthored an article about PPIs, suggested that more prospective research is needed to identify which patients need PPIs and which don’t.

“What we really need are more studies that look at who really needs [PPIs] long term,” Dr. Katz said, “as opposed to doing it ad hoc.”

The study was funded by the U.S. Department of Veterans Affairs and the National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest. Dr. Katz is a consultant for Phathom Pharma.

Proton pump inhibitor (PPI) use can safely be reduced by deprescribing efforts coupled with patient and clinician education, according to a retrospective study involving more than 4 million veterans.

After 1 year, the intervention was associated with a significant reduction in PPI use without worsening of acid-related diseases, reported lead author Jacob E. Kurlander, MD, of the University of Michigan, Ann Arbor, and the VA Ann Arbor Healthcare System’s Center for Clinical Management Research.

“There’s increasing interest in interventions to reduce PPI use,” Dr. Kurlander said during his virtual presentation at the annual Digestive Disease Week® (DDW). “Many of the interventions have come in the form of patient and provider education, like the Choosing Wisely campaign put out by the American Board of Internal Medicine. However, in rigorous studies, few interventions have actually proven effective, and many of these studies lack data on clinical outcomes, so it’s difficult to ascertain the real clinical benefits, or even harms.”

In an effort to address this gap, the investigators conducted a retrospective, difference-in-difference study spanning 10 years, from 2009 to 2019. The 1-year intervention, implemented in August 2013, included refill restrictions for PPIs without documented indication for long-term use, voiding of PPI prescriptions not filled within 6 months, a quick-order option for H2-receptor antagonists, reports to identify high-dose PPI prescribing, and patient and clinician education.

The intervention group consisted of 192,607-250,349 veterans in Veteran Integrated Service Network 17, whereas the control group consisted of 3,775,978-4,360,908 veterans in other service networks (ranges in population size are due to variations across 6-month intervals of analysis). For each 6-month interval, patients were included if they had at least two primary care visits within the past 2 years, and excluded if they received primary care at three other sites that joined the intervention site after initial implementation.

The investigators analyzed three main outcomes: Proportion of veterans dispensed a PPI prescription from the VA at any dose; incidence proportion of hospitalization for upper GI diseases, including upper GI bleeding other than from esophageal varices or angiodysplasia, as well as nonbleeding acid peptic disease; and rates of primary care visits, gastroenterology visits, and esophagogastroduodenoscopies (EGDs).

The analysis was divided into a preimplementation period, lasting approximately 5 years, and a postimplementation period with a similar duration. In the postimplementation period, the intervention group had a 5.9% relative reduction in PPI prescriptions, compared with the control group (P < .001). During the same period, the intervention site did not have a significant increase in the rate of patients hospitalized for upper GI diseases, primary care visits, GI clinic visits, or EGDs.

In a subgroup analysis of patients coprescribed PPIs during time at high-risk for upper GI bleeding (that is, when they possessed at least two high-risk medications, such as warfarin), there was a 4.6% relative reduction in time with PPI gastroprotection among the intervention group, compared with the control group (P = .003). In a second sensitivity analysis, hospitalization for upper GI diseases in high-risk patients at least 65 years of age was not significantly different between groups.

“[This] multicomponent PPI deprescribing program led to sustained reductions in PPI use,” Dr. Kurlander concluded. “However, this blunt intervention also reduced appropriate use of PPIs for gastroprotection, raising some concerns about clinical quality of care, but this did not appear to cause any measurable clinical harm in terms of hospitalizations for upper GI diseases.”
 

Debate around ‘unnecessary PPI use’

According to Philip O. Katz, MD, professor of medicine and director of motility laboratories at Weill Cornell Medicine, New York, the study “makes an attempt to do what others have tried in different ways, which is to develop a mechanism to help reduce or discontinue proton pump inhibitors when people believe they’re not indicated.”

Yet this latter element – appropriate indication – drives an ongoing debate.

“This is a very controversial area,” Dr. Katz said in an interview. “The concept of using the lowest effective dose of medication needed for a symptom or a disease is not new, but the push to reducing or eliminating ‘unnecessary PPI use’ is one that I believe should be carefully discussed, and that we have a clear understanding of what constitutes unnecessary use. And quite honestly, I’m willing to state that I don’t believe that’s been well defined.”

Dr. Katz, who recently coauthored an article about PPIs, suggested that more prospective research is needed to identify which patients need PPIs and which don’t.

“What we really need are more studies that look at who really needs [PPIs] long term,” Dr. Katz said, “as opposed to doing it ad hoc.”

The study was funded by the U.S. Department of Veterans Affairs and the National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest. Dr. Katz is a consultant for Phathom Pharma.

Proton pump inhibitor (PPI) use can safely be reduced by deprescribing efforts coupled with patient and clinician education, according to a retrospective study involving more than 4 million veterans.

After 1 year, the intervention was associated with a significant reduction in PPI use without worsening of acid-related diseases, reported lead author Jacob E. Kurlander, MD, of the University of Michigan, Ann Arbor, and the VA Ann Arbor Healthcare System’s Center for Clinical Management Research.

“There’s increasing interest in interventions to reduce PPI use,” Dr. Kurlander said during his virtual presentation at the annual Digestive Disease Week® (DDW). “Many of the interventions have come in the form of patient and provider education, like the Choosing Wisely campaign put out by the American Board of Internal Medicine. However, in rigorous studies, few interventions have actually proven effective, and many of these studies lack data on clinical outcomes, so it’s difficult to ascertain the real clinical benefits, or even harms.”

In an effort to address this gap, the investigators conducted a retrospective, difference-in-difference study spanning 10 years, from 2009 to 2019. The 1-year intervention, implemented in August 2013, included refill restrictions for PPIs without documented indication for long-term use, voiding of PPI prescriptions not filled within 6 months, a quick-order option for H2-receptor antagonists, reports to identify high-dose PPI prescribing, and patient and clinician education.

The intervention group consisted of 192,607-250,349 veterans in Veteran Integrated Service Network 17, whereas the control group consisted of 3,775,978-4,360,908 veterans in other service networks (ranges in population size are due to variations across 6-month intervals of analysis). For each 6-month interval, patients were included if they had at least two primary care visits within the past 2 years, and excluded if they received primary care at three other sites that joined the intervention site after initial implementation.

The investigators analyzed three main outcomes: Proportion of veterans dispensed a PPI prescription from the VA at any dose; incidence proportion of hospitalization for upper GI diseases, including upper GI bleeding other than from esophageal varices or angiodysplasia, as well as nonbleeding acid peptic disease; and rates of primary care visits, gastroenterology visits, and esophagogastroduodenoscopies (EGDs).

The analysis was divided into a preimplementation period, lasting approximately 5 years, and a postimplementation period with a similar duration. In the postimplementation period, the intervention group had a 5.9% relative reduction in PPI prescriptions, compared with the control group (P < .001). During the same period, the intervention site did not have a significant increase in the rate of patients hospitalized for upper GI diseases, primary care visits, GI clinic visits, or EGDs.

In a subgroup analysis of patients coprescribed PPIs during time at high-risk for upper GI bleeding (that is, when they possessed at least two high-risk medications, such as warfarin), there was a 4.6% relative reduction in time with PPI gastroprotection among the intervention group, compared with the control group (P = .003). In a second sensitivity analysis, hospitalization for upper GI diseases in high-risk patients at least 65 years of age was not significantly different between groups.

“[This] multicomponent PPI deprescribing program led to sustained reductions in PPI use,” Dr. Kurlander concluded. “However, this blunt intervention also reduced appropriate use of PPIs for gastroprotection, raising some concerns about clinical quality of care, but this did not appear to cause any measurable clinical harm in terms of hospitalizations for upper GI diseases.”
 

Debate around ‘unnecessary PPI use’

According to Philip O. Katz, MD, professor of medicine and director of motility laboratories at Weill Cornell Medicine, New York, the study “makes an attempt to do what others have tried in different ways, which is to develop a mechanism to help reduce or discontinue proton pump inhibitors when people believe they’re not indicated.”

Yet this latter element – appropriate indication – drives an ongoing debate.

“This is a very controversial area,” Dr. Katz said in an interview. “The concept of using the lowest effective dose of medication needed for a symptom or a disease is not new, but the push to reducing or eliminating ‘unnecessary PPI use’ is one that I believe should be carefully discussed, and that we have a clear understanding of what constitutes unnecessary use. And quite honestly, I’m willing to state that I don’t believe that’s been well defined.”

Dr. Katz, who recently coauthored an article about PPIs, suggested that more prospective research is needed to identify which patients need PPIs and which don’t.

“What we really need are more studies that look at who really needs [PPIs] long term,” Dr. Katz said, “as opposed to doing it ad hoc.”

The study was funded by the U.S. Department of Veterans Affairs and the National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest. Dr. Katz is a consultant for Phathom Pharma.

While liver transplant outcomes were historically poor in people coinfected with HIV and hepatitis C virus (HCV), they have improved significantly in the era of direct-acting antiviral (DAA) therapy, a recent analysis of U.S. organ transplant data showed.

The availability of highly potent DAA therapy should change how transplant specialists view patients coinfected with HIV/HCV who need a liver transplant, according to researcher Jennifer Wang, MD, chief gastroenterology fellow at the University of Chicago, who presented the results of the analysis at the annual Digestive Disease Week® (DDW). Cumulative graft survival rates since the introduction of DAAs are comparable between transplant recipients with HIV/HCV coinfection and recipients who are both HIV and HCV negative, according to the study.

“Having hepatitis C no longer confers worse patient survival in the DAA era, and this is the main takeaway from our study,” Dr. Wang said.

The study also showed that the number of liver transplants among HIV-infected patients has increased over the past 4-5 years. However, the absolute number remains low at 64 cases in 2019, or less than 1% of all liver transplants that year, and only about one-third of those HIV-positive recipients had HCV coinfection, according to Dr. Wang.

Moreover, relatively few centers are performing liver transplants for patients who are HIV/HCV coinfected, and there is significant geographic variation in where the procedures are done, she said in her presentation.
 

Reassuring data that should prompt referral

Taken together, these results should offer reassurance to transplant centers that patients coinfected with HIV/HCV are no longer at increased risk for poor outcomes after transplantation, said Christine M. Durand, MD, associate professor of medicine at Johns Hopkins University, Baltimore.

“The additional call for action should be beyond the transplantation community to ensure that referrals for liver transplant are where they should be,” Dr. Durand said in an interview.

“With a number of only 64 transplants a year, we’re not doing enough, and there are more patients that could benefit from liver transplants,” added Dr. Durand, who is principal investigator of HOPE in Action, a prospective, multicenter, clinical trial evaluating the safety and survival outcomes of HIV-positive deceased donor liver transplants in HIV-positive recipients.
 

Impact of the HOPE Act

Liver transplantation for HIV-positive patients has increased since the signing of the HIV Organ Policy Equity (HOPE) Act in 2013, according to Dr. Wang.

The HOPE act expanded the donor pool to include HIV-positive deceased donors, which not only increased the donor supply overall, but specifically helped HIV-positive individuals, who experience a higher rate of waiting-list mortality, according to a review on the topic authored by Dr. Durand and coauthors.

However, some transplant centers may be reluctant to do liver transplants in HIV-positive patients coinfected with HCV. That’s because, in previous studies that were conducted before the DAA era, outcomes after liver transplant in HIV/HCV-coinfected patients were inferior to those in patients with HIV but no HCV infection, Dr. Wang said.

Accordingly, Dr. Wang and colleagues analyzed Organ Procurement and Transplantation Network (OPTN) data on adult patients who underwent liver transplants between 2008 and 2019 to see if the introduction of DAAs had leveled the playing field for those with HCV coinfection.
 

Progress in a still-underserved population

The practice of liver transplant in the HIV population has been increasing since the HOPE Act, according to Dr. Wang.

Overall, out of 70,125 liver transplant recipients over the 2008-2019 period, 416 (0.6%) were HIV infected, the data show.

In 2014, 28 liver transplants (0.5%) were performed in HIV-infected individuals, which increased to 64 transplants (0.8%) in 2019, data show. Of those 64 HIV-positive liver transplant recipients in 2019, 23 (35.9%) were coinfected with HCV.

Graft survival has greatly improved, from a 3-year survival of only 58% in patients transplanted before the availability of DAAs to 82% in the DAA era, a difference that was statistically significant, Dr. Wang said.

In the DAA era, there was no significant difference in graft failure outcomes when comparing HIV/HCV-coinfected recipients with uninfected recipients, she added.

The largest proportion of liver transplantations in HIV/HCV-coinfected recipients have been done in OPTN Region 9 (New York), both in the pre- and post-DAA eras, according to Dr. Wang. Several regions have very low numbers or have performed no liver transplants in HIV/HCV-coinfected patients in either era.

“The number of transplant centers participating in liver transplant for coinfected patients is still quite low, so this is a very underserved patient population,” Dr. Wang said.

Dr. Wang provided no financial disclosures related to the research. Dr. Durand receives grants to the institution from Abbvie and GlaxoSmithKline and she receives honoraria from Gilead Sciences for serving on a grant review committee.

While liver transplant outcomes were historically poor in people coinfected with HIV and hepatitis C virus (HCV), they have improved significantly in the era of direct-acting antiviral (DAA) therapy, a recent analysis of U.S. organ transplant data showed.

The availability of highly potent DAA therapy should change how transplant specialists view patients coinfected with HIV/HCV who need a liver transplant, according to researcher Jennifer Wang, MD, chief gastroenterology fellow at the University of Chicago, who presented the results of the analysis at the annual Digestive Disease Week® (DDW). Cumulative graft survival rates since the introduction of DAAs are comparable between transplant recipients with HIV/HCV coinfection and recipients who are both HIV and HCV negative, according to the study.

“Having hepatitis C no longer confers worse patient survival in the DAA era, and this is the main takeaway from our study,” Dr. Wang said.

The study also showed that the number of liver transplants among HIV-infected patients has increased over the past 4-5 years. However, the absolute number remains low at 64 cases in 2019, or less than 1% of all liver transplants that year, and only about one-third of those HIV-positive recipients had HCV coinfection, according to Dr. Wang.

Moreover, relatively few centers are performing liver transplants for patients who are HIV/HCV coinfected, and there is significant geographic variation in where the procedures are done, she said in her presentation.
 

Reassuring data that should prompt referral

Taken together, these results should offer reassurance to transplant centers that patients coinfected with HIV/HCV are no longer at increased risk for poor outcomes after transplantation, said Christine M. Durand, MD, associate professor of medicine at Johns Hopkins University, Baltimore.

“The additional call for action should be beyond the transplantation community to ensure that referrals for liver transplant are where they should be,” Dr. Durand said in an interview.

“With a number of only 64 transplants a year, we’re not doing enough, and there are more patients that could benefit from liver transplants,” added Dr. Durand, who is principal investigator of HOPE in Action, a prospective, multicenter, clinical trial evaluating the safety and survival outcomes of HIV-positive deceased donor liver transplants in HIV-positive recipients.
 

Impact of the HOPE Act

Liver transplantation for HIV-positive patients has increased since the signing of the HIV Organ Policy Equity (HOPE) Act in 2013, according to Dr. Wang.

The HOPE act expanded the donor pool to include HIV-positive deceased donors, which not only increased the donor supply overall, but specifically helped HIV-positive individuals, who experience a higher rate of waiting-list mortality, according to a review on the topic authored by Dr. Durand and coauthors.

However, some transplant centers may be reluctant to do liver transplants in HIV-positive patients coinfected with HCV. That’s because, in previous studies that were conducted before the DAA era, outcomes after liver transplant in HIV/HCV-coinfected patients were inferior to those in patients with HIV but no HCV infection, Dr. Wang said.

Accordingly, Dr. Wang and colleagues analyzed Organ Procurement and Transplantation Network (OPTN) data on adult patients who underwent liver transplants between 2008 and 2019 to see if the introduction of DAAs had leveled the playing field for those with HCV coinfection.
 

Progress in a still-underserved population

The practice of liver transplant in the HIV population has been increasing since the HOPE Act, according to Dr. Wang.

Overall, out of 70,125 liver transplant recipients over the 2008-2019 period, 416 (0.6%) were HIV infected, the data show.

In 2014, 28 liver transplants (0.5%) were performed in HIV-infected individuals, which increased to 64 transplants (0.8%) in 2019, data show. Of those 64 HIV-positive liver transplant recipients in 2019, 23 (35.9%) were coinfected with HCV.

Graft survival has greatly improved, from a 3-year survival of only 58% in patients transplanted before the availability of DAAs to 82% in the DAA era, a difference that was statistically significant, Dr. Wang said.

In the DAA era, there was no significant difference in graft failure outcomes when comparing HIV/HCV-coinfected recipients with uninfected recipients, she added.

The largest proportion of liver transplantations in HIV/HCV-coinfected recipients have been done in OPTN Region 9 (New York), both in the pre- and post-DAA eras, according to Dr. Wang. Several regions have very low numbers or have performed no liver transplants in HIV/HCV-coinfected patients in either era.

“The number of transplant centers participating in liver transplant for coinfected patients is still quite low, so this is a very underserved patient population,” Dr. Wang said.

Dr. Wang provided no financial disclosures related to the research. Dr. Durand receives grants to the institution from Abbvie and GlaxoSmithKline and she receives honoraria from Gilead Sciences for serving on a grant review committee.

While liver transplant outcomes were historically poor in people coinfected with HIV and hepatitis C virus (HCV), they have improved significantly in the era of direct-acting antiviral (DAA) therapy, a recent analysis of U.S. organ transplant data showed.

The availability of highly potent DAA therapy should change how transplant specialists view patients coinfected with HIV/HCV who need a liver transplant, according to researcher Jennifer Wang, MD, chief gastroenterology fellow at the University of Chicago, who presented the results of the analysis at the annual Digestive Disease Week® (DDW). Cumulative graft survival rates since the introduction of DAAs are comparable between transplant recipients with HIV/HCV coinfection and recipients who are both HIV and HCV negative, according to the study.

“Having hepatitis C no longer confers worse patient survival in the DAA era, and this is the main takeaway from our study,” Dr. Wang said.

The study also showed that the number of liver transplants among HIV-infected patients has increased over the past 4-5 years. However, the absolute number remains low at 64 cases in 2019, or less than 1% of all liver transplants that year, and only about one-third of those HIV-positive recipients had HCV coinfection, according to Dr. Wang.

Moreover, relatively few centers are performing liver transplants for patients who are HIV/HCV coinfected, and there is significant geographic variation in where the procedures are done, she said in her presentation.
 

Reassuring data that should prompt referral

Taken together, these results should offer reassurance to transplant centers that patients coinfected with HIV/HCV are no longer at increased risk for poor outcomes after transplantation, said Christine M. Durand, MD, associate professor of medicine at Johns Hopkins University, Baltimore.

“The additional call for action should be beyond the transplantation community to ensure that referrals for liver transplant are where they should be,” Dr. Durand said in an interview.

“With a number of only 64 transplants a year, we’re not doing enough, and there are more patients that could benefit from liver transplants,” added Dr. Durand, who is principal investigator of HOPE in Action, a prospective, multicenter, clinical trial evaluating the safety and survival outcomes of HIV-positive deceased donor liver transplants in HIV-positive recipients.
 

Impact of the HOPE Act

Liver transplantation for HIV-positive patients has increased since the signing of the HIV Organ Policy Equity (HOPE) Act in 2013, according to Dr. Wang.

The HOPE act expanded the donor pool to include HIV-positive deceased donors, which not only increased the donor supply overall, but specifically helped HIV-positive individuals, who experience a higher rate of waiting-list mortality, according to a review on the topic authored by Dr. Durand and coauthors.

However, some transplant centers may be reluctant to do liver transplants in HIV-positive patients coinfected with HCV. That’s because, in previous studies that were conducted before the DAA era, outcomes after liver transplant in HIV/HCV-coinfected patients were inferior to those in patients with HIV but no HCV infection, Dr. Wang said.

Accordingly, Dr. Wang and colleagues analyzed Organ Procurement and Transplantation Network (OPTN) data on adult patients who underwent liver transplants between 2008 and 2019 to see if the introduction of DAAs had leveled the playing field for those with HCV coinfection.
 

Progress in a still-underserved population

The practice of liver transplant in the HIV population has been increasing since the HOPE Act, according to Dr. Wang.

Overall, out of 70,125 liver transplant recipients over the 2008-2019 period, 416 (0.6%) were HIV infected, the data show.

In 2014, 28 liver transplants (0.5%) were performed in HIV-infected individuals, which increased to 64 transplants (0.8%) in 2019, data show. Of those 64 HIV-positive liver transplant recipients in 2019, 23 (35.9%) were coinfected with HCV.

Graft survival has greatly improved, from a 3-year survival of only 58% in patients transplanted before the availability of DAAs to 82% in the DAA era, a difference that was statistically significant, Dr. Wang said.

In the DAA era, there was no significant difference in graft failure outcomes when comparing HIV/HCV-coinfected recipients with uninfected recipients, she added.

The largest proportion of liver transplantations in HIV/HCV-coinfected recipients have been done in OPTN Region 9 (New York), both in the pre- and post-DAA eras, according to Dr. Wang. Several regions have very low numbers or have performed no liver transplants in HIV/HCV-coinfected patients in either era.

“The number of transplant centers participating in liver transplant for coinfected patients is still quite low, so this is a very underserved patient population,” Dr. Wang said.

Dr. Wang provided no financial disclosures related to the research. Dr. Durand receives grants to the institution from Abbvie and GlaxoSmithKline and she receives honoraria from Gilead Sciences for serving on a grant review committee.

Greater severity of obstructive sleep apnea (OSA) is associated with a higher risk of contracting COVID-19, and positive airway pressure (PAP) treatment may counter that risk, according to a retrospective analysis from the records of Kaiser Permanente Southern California.

OSA patients often worry that PAP therapy might increase risk of severe COVID-19, said Dennis Hwang, MD, who presented the study at the American Thoracic Society’s virtual international conference (Abstract A1108). But the findings should be reassuring. “If you have obstructive sleep apnea, and you’re supposed to be using PAP, we recommend that you continue using PAP. It’s good for your overall wellness and reducing the risk of cardiovascular disease, but as it relates to COVID-19, it’s possible that it could protect. And there doesn’t appear to be any risk of increased severity of illness (with use of PAP),” Dr. Hwang said in an interview. He is medical director of sleep medicine for Kaiser Permanente San Bernardino County and cochair of sleep medicine for Kaiser Southern California.

He noted that the retrospective nature of the study makes it difficult to pin down whether PAP therapy is truly protective, “but I think there’s enough that we’ve been able conceptually to understand, to suggest that a direct causative relationship is possible,” said Dr. Hwang.

The results may imply that OSA patients should pay special attention to their OSA when there’s concern about exposure to an infectious agent like SARS-CoV-2. “The intermittent hypoxia at night, which can linger over to the day as increased sympathetic activity, increased heart rate. All of these are stresses to the body. So if you’re going to get infected, you want to start at a healthier level. You want to eliminate your sleep apnea to help reduce your risk of morbidity,” said Esra Tasali, MD, who was asked to comment on the study. Dr. Tasali is associate professor of medicine at the University of Chicago, and director of the Sleep Research Center there.

During the Q&A session after the talk, audience members asked about the timing of PAP use during COVID-19 infection, for example how often it was used during the asymptomatic phase of infection and if PAP has a positive effect. The data were not available, but “I think that the way to go is to understand this chronology,” said Dr. Tasali.

The researchers examined records between 2015 and 2020, using sleep study data, remotely collected daily PAP data, and electronic health records, all from Kaiser Permanente Southern California. Included subjects were adults who had enrolled before Feb. 1, 2020, and had sleep diagnostic or PAP data on record by March 1, 2020. The researchers analyzed PAP adherence between March 1, 2020, and the time of COVID-19 diagnosis, or until the study ended on July 31, 2020.

Patients were defined as being untreated (< 2 hours/night PAP), moderately treated (2-3.9 hours/night), or well treated (4 or more hours/night). Apnea hypopnea index (AHI) was used to determine severity. The analysis included 81,932 patients (39.8% were women, mean age was 54.0 years, 9.9% were Black, and 34.5% were Hispanic). A total of 1.7% of subjects without OSA experienced COVID-19 infection, compared to 1.8% with OSA; 0.3% with OSA were hospitalized and 0.07% underwent intensive care or died.

There were some differences between the two groups. The non-USA population was younger (mean age 47.0 vs. 54.5 years), was less likely to be men (44% vs. 60.3%), had a lower mean body mass index (30.4 vs. 34.3), had fewer comorbidities according to the Charleston Comorbidity Index (1.3 vs. 2.0), and were less likely to have hypertension (5.6% vs. 12.4%; P < .0001 for all).

Infection rates were higher in patients with more severe OSA. The rates in untreated mild, moderate, and severe OSA were 2%, 2%, and 2.4% respectively. The rate among all treated patients was 1.4% (P < .0001). Infection rates also dropped among patients with better treatment: untreated, 2.1%; moderately treated, 1.7%; and well treated, 1.3% (P < .0001).

Not having OSA was associated with a lower infection risk than was having OSA (odds ratio [OR], 0.82; 95% confidence interval, 0.70-0.96). Compared to untreated patients, there was lower infection risk in the moderately treated (OR, 0.82; 95% CI, 0.65-1.03) and well treated (OR, 0.68; 95% CI, 0.59-0.79) groups. Higher infection rates were associated with obesity, higher Charlson Comorbidity score (> 2; OR, 1.29; 95% CI, 1.09-1.53), Black (OR, 1.51; 95% CI, 1.24-1.84) and Hispanic ethnicities (OR, 2.23; 95% CI, 1.96-2.54), and Medicaid enrollment. Increasing age was associated with lower risk of infection, with each 5-year increment linked to reduced risk (OR, 0.88; 95% CI, 0.86-0.90). Dr. Hwang suggested that the age association may be because older individuals were more likely to follow social distancing and other precautions.

A multivariate analysis found that OSA was associated with infection risk according to OSA severity, including mild (OR, 1.21; 95% CI, 1.01-1.44), and moderate to severe (OR, 1.27; 95% CI, 1.07-1.51). There was no association between hospitalization rate or ICU admission/death and presence of OSA or PAP adherence in the data presented, but Dr. Hwang said that an updated analysis suggests that OSA may be associated with a risk of greater COVID-19 severity.

The control group was composed of individuals who had undergone sleep testing, but found to not have OSA. Still, they aren’t necessarily representative of the general population, since symptoms likely drove them to testing. A high percentage were also obese, and the average BMI was 30. “It’s certainly not a ‘normal population,’ but the advantage of what we did in terms of using this control group is that they underwent sleep testing, so they were proven to have no obstructive sleep apnea, whereas if we used a general population, we just don’t know,” said Dr. Hwang.

The study received technical and data support from Somnoware, and was funded by Kaiser Permanente. Dr. Tasali has no relevant financial disclosures.
 

Greater severity of obstructive sleep apnea (OSA) is associated with a higher risk of contracting COVID-19, and positive airway pressure (PAP) treatment may counter that risk, according to a retrospective analysis from the records of Kaiser Permanente Southern California.

OSA patients often worry that PAP therapy might increase risk of severe COVID-19, said Dennis Hwang, MD, who presented the study at the American Thoracic Society’s virtual international conference (Abstract A1108). But the findings should be reassuring. “If you have obstructive sleep apnea, and you’re supposed to be using PAP, we recommend that you continue using PAP. It’s good for your overall wellness and reducing the risk of cardiovascular disease, but as it relates to COVID-19, it’s possible that it could protect. And there doesn’t appear to be any risk of increased severity of illness (with use of PAP),” Dr. Hwang said in an interview. He is medical director of sleep medicine for Kaiser Permanente San Bernardino County and cochair of sleep medicine for Kaiser Southern California.

He noted that the retrospective nature of the study makes it difficult to pin down whether PAP therapy is truly protective, “but I think there’s enough that we’ve been able conceptually to understand, to suggest that a direct causative relationship is possible,” said Dr. Hwang.

The results may imply that OSA patients should pay special attention to their OSA when there’s concern about exposure to an infectious agent like SARS-CoV-2. “The intermittent hypoxia at night, which can linger over to the day as increased sympathetic activity, increased heart rate. All of these are stresses to the body. So if you’re going to get infected, you want to start at a healthier level. You want to eliminate your sleep apnea to help reduce your risk of morbidity,” said Esra Tasali, MD, who was asked to comment on the study. Dr. Tasali is associate professor of medicine at the University of Chicago, and director of the Sleep Research Center there.

During the Q&A session after the talk, audience members asked about the timing of PAP use during COVID-19 infection, for example how often it was used during the asymptomatic phase of infection and if PAP has a positive effect. The data were not available, but “I think that the way to go is to understand this chronology,” said Dr. Tasali.

The researchers examined records between 2015 and 2020, using sleep study data, remotely collected daily PAP data, and electronic health records, all from Kaiser Permanente Southern California. Included subjects were adults who had enrolled before Feb. 1, 2020, and had sleep diagnostic or PAP data on record by March 1, 2020. The researchers analyzed PAP adherence between March 1, 2020, and the time of COVID-19 diagnosis, or until the study ended on July 31, 2020.

Patients were defined as being untreated (< 2 hours/night PAP), moderately treated (2-3.9 hours/night), or well treated (4 or more hours/night). Apnea hypopnea index (AHI) was used to determine severity. The analysis included 81,932 patients (39.8% were women, mean age was 54.0 years, 9.9% were Black, and 34.5% were Hispanic). A total of 1.7% of subjects without OSA experienced COVID-19 infection, compared to 1.8% with OSA; 0.3% with OSA were hospitalized and 0.07% underwent intensive care or died.

There were some differences between the two groups. The non-USA population was younger (mean age 47.0 vs. 54.5 years), was less likely to be men (44% vs. 60.3%), had a lower mean body mass index (30.4 vs. 34.3), had fewer comorbidities according to the Charleston Comorbidity Index (1.3 vs. 2.0), and were less likely to have hypertension (5.6% vs. 12.4%; P < .0001 for all).

Infection rates were higher in patients with more severe OSA. The rates in untreated mild, moderate, and severe OSA were 2%, 2%, and 2.4% respectively. The rate among all treated patients was 1.4% (P < .0001). Infection rates also dropped among patients with better treatment: untreated, 2.1%; moderately treated, 1.7%; and well treated, 1.3% (P < .0001).

Not having OSA was associated with a lower infection risk than was having OSA (odds ratio [OR], 0.82; 95% confidence interval, 0.70-0.96). Compared to untreated patients, there was lower infection risk in the moderately treated (OR, 0.82; 95% CI, 0.65-1.03) and well treated (OR, 0.68; 95% CI, 0.59-0.79) groups. Higher infection rates were associated with obesity, higher Charlson Comorbidity score (> 2; OR, 1.29; 95% CI, 1.09-1.53), Black (OR, 1.51; 95% CI, 1.24-1.84) and Hispanic ethnicities (OR, 2.23; 95% CI, 1.96-2.54), and Medicaid enrollment. Increasing age was associated with lower risk of infection, with each 5-year increment linked to reduced risk (OR, 0.88; 95% CI, 0.86-0.90). Dr. Hwang suggested that the age association may be because older individuals were more likely to follow social distancing and other precautions.

A multivariate analysis found that OSA was associated with infection risk according to OSA severity, including mild (OR, 1.21; 95% CI, 1.01-1.44), and moderate to severe (OR, 1.27; 95% CI, 1.07-1.51). There was no association between hospitalization rate or ICU admission/death and presence of OSA or PAP adherence in the data presented, but Dr. Hwang said that an updated analysis suggests that OSA may be associated with a risk of greater COVID-19 severity.

The control group was composed of individuals who had undergone sleep testing, but found to not have OSA. Still, they aren’t necessarily representative of the general population, since symptoms likely drove them to testing. A high percentage were also obese, and the average BMI was 30. “It’s certainly not a ‘normal population,’ but the advantage of what we did in terms of using this control group is that they underwent sleep testing, so they were proven to have no obstructive sleep apnea, whereas if we used a general population, we just don’t know,” said Dr. Hwang.

The study received technical and data support from Somnoware, and was funded by Kaiser Permanente. Dr. Tasali has no relevant financial disclosures.
 

Greater severity of obstructive sleep apnea (OSA) is associated with a higher risk of contracting COVID-19, and positive airway pressure (PAP) treatment may counter that risk, according to a retrospective analysis from the records of Kaiser Permanente Southern California.

OSA patients often worry that PAP therapy might increase risk of severe COVID-19, said Dennis Hwang, MD, who presented the study at the American Thoracic Society’s virtual international conference (Abstract A1108). But the findings should be reassuring. “If you have obstructive sleep apnea, and you’re supposed to be using PAP, we recommend that you continue using PAP. It’s good for your overall wellness and reducing the risk of cardiovascular disease, but as it relates to COVID-19, it’s possible that it could protect. And there doesn’t appear to be any risk of increased severity of illness (with use of PAP),” Dr. Hwang said in an interview. He is medical director of sleep medicine for Kaiser Permanente San Bernardino County and cochair of sleep medicine for Kaiser Southern California.

He noted that the retrospective nature of the study makes it difficult to pin down whether PAP therapy is truly protective, “but I think there’s enough that we’ve been able conceptually to understand, to suggest that a direct causative relationship is possible,” said Dr. Hwang.

The results may imply that OSA patients should pay special attention to their OSA when there’s concern about exposure to an infectious agent like SARS-CoV-2. “The intermittent hypoxia at night, which can linger over to the day as increased sympathetic activity, increased heart rate. All of these are stresses to the body. So if you’re going to get infected, you want to start at a healthier level. You want to eliminate your sleep apnea to help reduce your risk of morbidity,” said Esra Tasali, MD, who was asked to comment on the study. Dr. Tasali is associate professor of medicine at the University of Chicago, and director of the Sleep Research Center there.

During the Q&A session after the talk, audience members asked about the timing of PAP use during COVID-19 infection, for example how often it was used during the asymptomatic phase of infection and if PAP has a positive effect. The data were not available, but “I think that the way to go is to understand this chronology,” said Dr. Tasali.

The researchers examined records between 2015 and 2020, using sleep study data, remotely collected daily PAP data, and electronic health records, all from Kaiser Permanente Southern California. Included subjects were adults who had enrolled before Feb. 1, 2020, and had sleep diagnostic or PAP data on record by March 1, 2020. The researchers analyzed PAP adherence between March 1, 2020, and the time of COVID-19 diagnosis, or until the study ended on July 31, 2020.

Patients were defined as being untreated (< 2 hours/night PAP), moderately treated (2-3.9 hours/night), or well treated (4 or more hours/night). Apnea hypopnea index (AHI) was used to determine severity. The analysis included 81,932 patients (39.8% were women, mean age was 54.0 years, 9.9% were Black, and 34.5% were Hispanic). A total of 1.7% of subjects without OSA experienced COVID-19 infection, compared to 1.8% with OSA; 0.3% with OSA were hospitalized and 0.07% underwent intensive care or died.

There were some differences between the two groups. The non-USA population was younger (mean age 47.0 vs. 54.5 years), was less likely to be men (44% vs. 60.3%), had a lower mean body mass index (30.4 vs. 34.3), had fewer comorbidities according to the Charleston Comorbidity Index (1.3 vs. 2.0), and were less likely to have hypertension (5.6% vs. 12.4%; P < .0001 for all).

Infection rates were higher in patients with more severe OSA. The rates in untreated mild, moderate, and severe OSA were 2%, 2%, and 2.4% respectively. The rate among all treated patients was 1.4% (P < .0001). Infection rates also dropped among patients with better treatment: untreated, 2.1%; moderately treated, 1.7%; and well treated, 1.3% (P < .0001).

Not having OSA was associated with a lower infection risk than was having OSA (odds ratio [OR], 0.82; 95% confidence interval, 0.70-0.96). Compared to untreated patients, there was lower infection risk in the moderately treated (OR, 0.82; 95% CI, 0.65-1.03) and well treated (OR, 0.68; 95% CI, 0.59-0.79) groups. Higher infection rates were associated with obesity, higher Charlson Comorbidity score (> 2; OR, 1.29; 95% CI, 1.09-1.53), Black (OR, 1.51; 95% CI, 1.24-1.84) and Hispanic ethnicities (OR, 2.23; 95% CI, 1.96-2.54), and Medicaid enrollment. Increasing age was associated with lower risk of infection, with each 5-year increment linked to reduced risk (OR, 0.88; 95% CI, 0.86-0.90). Dr. Hwang suggested that the age association may be because older individuals were more likely to follow social distancing and other precautions.

A multivariate analysis found that OSA was associated with infection risk according to OSA severity, including mild (OR, 1.21; 95% CI, 1.01-1.44), and moderate to severe (OR, 1.27; 95% CI, 1.07-1.51). There was no association between hospitalization rate or ICU admission/death and presence of OSA or PAP adherence in the data presented, but Dr. Hwang said that an updated analysis suggests that OSA may be associated with a risk of greater COVID-19 severity.

The control group was composed of individuals who had undergone sleep testing, but found to not have OSA. Still, they aren’t necessarily representative of the general population, since symptoms likely drove them to testing. A high percentage were also obese, and the average BMI was 30. “It’s certainly not a ‘normal population,’ but the advantage of what we did in terms of using this control group is that they underwent sleep testing, so they were proven to have no obstructive sleep apnea, whereas if we used a general population, we just don’t know,” said Dr. Hwang.

The study received technical and data support from Somnoware, and was funded by Kaiser Permanente. Dr. Tasali has no relevant financial disclosures.
 

William Lynes, MD, had a flourishing medical practice and a fulfilling family life with three children when he first attempted suicide in 1999 at age 45. By 2003, depression and two more suicide attempts led to his early retirement.

In a session at the recent virtual American Psychiatric Association (APA) 2021 annual meeting, Dr. Lynes talked about the challenges of dealing with depression while managing the stresses of a career in medicine. The session in which he spoke was called, “The Suicidal Physician: Narratives From a Physician Who Survived and the Physician Widow of One Who Did Not.”

By writing and speaking about his experiences, he says, he has been able to retain his identity as a physician and avoid obsessive thoughts about suicide. He hopes conversations like these help other physicians feel less alone and enable them to push past stigmas to get the help they need. He suspects they do. More than 600 people joined the APA session, and Dr. Lynes received dozens of thankful messages afterward.

“I love medicine, but intrinsically, the practice of medicine is stressful, and you can’t get away,” said Dr. Lynes, a retired urologist in Temecula, Calif. “As far as feedback, it made me feel like it’s something I should continue to do.”
 

A way to heal

For Dr. Lynes, his “downward spiral into darkness” began with a series of catastrophic medical events starting in 1998, when he came home from a family vacation in Mexico feeling unwell. He didn’t bother to do anything about it – typical of a physician, he says. Then one night he woke up shaking with chills and fever. Soon he was in the hospital with respiratory failure from septic shock.

Dr. Lynes spent 6 weeks in the intensive care unit, including 4 weeks on a ventilator. He underwent a tracheostomy. He lost 40 pounds and experienced ICU-related delirium. It was a terrifying time, he said. When he tried to return to work 10 months later, he didn’t feel as though he could function normally.

Having once been a driven doctor who worked long hours, he now doubted himself and dreaded giving patients bad news. Spontaneously, he tried to take his own life.

Afterward, he concealed what had happened from everyone except his wife and managed to resume his practice. However, he was unable to regain the enthusiasm he had once had for his work. Although he had experienced depression before, this time it was unrelenting.

He sought help from a psychiatrist, received a diagnosis of bipolar disorder, and began taking medication. Still, he struggled to fulfill his responsibilities. Then in April 2002, he had a snowboarding accident that caused multiple facial fractures and required five operations. When he returned to work this time, he felt like a failure but resisted asking colleagues for help.

A few months later, Dr. Lynes again attempted suicide, which led to another stay in the ICU and more time on a ventilator. Doctors told his family they didn’t think he would survive. When he recovered, he spent time as an inpatient in a psychiatric ward, where he received the first of a series of electroconvulsive therapy sessions. Compounding his anxiety and depression was the inability to come to terms with his life if he were not able to practice medicine.

The next fall, in September 2003, his third suicide attempt took place in his office on a weekend when no one was around. After locking the door, he looked at his reflection in the frame of his medical school diploma. The glass was cracked. “It was dark, it was black, it was cold,” he said. “I can remember seeing my reflection and thinking how disgusted I was.”

For years after that, Dr. Lynes struggled with his sense of self-worth. He hid from the medical system and dreaded doctors’ appointments. Finally in 2016, he found new meaning at a writing conference, where he met a fellow physician whose story was similar to his. She encouraged him to write about his experience. His essay was published in Annals of Internal Medicine that year. “Then I started speaking, and I feel like I’m a physician again,” he said. “That has really healed me quite a bit.”
 

Why physicians die by suicide

Working in health care can be extremely stressful, even in the best of times, said Michael Myers, MD, a psychiatrist at State University of New York, Brooklyn, and author of the book, “Why Physicians Die By Suicide: Lessons Learned From Their Families and Others Who Cared.”

Years of school and training culminate in a career in which demands are relentless. Societal expectations are high. Many doctors are perfectionists by nature, and physicians tend to feel intense pressure to compete for coveted positions.

Stress starts early in a medical career. A 2016 systematic review and meta-analysis of 183 studies from 43 countries showed that nearly 30% of medical students experienced symptoms of depression and that 11% reported suicidal thoughts, but only 15% sought help.

A 2015 review of 31 studies that involved residents showed that rates of depression remained close to 30% and that about three-quarters of trainees meet criteria for burnout, a type of emotional exhaustion and sense of inadequacy that can result from chronic stress at work.

The stress of medical training appears to be a direct cause of mental health struggles. Rates of depression are higher among those working to become physicians than among their peers of the same age, research shows. In addition, symptoms become more prevalent as people progress through their training.

The COVID-19 pandemic has added stress to an already stressful job. Of more than 2,300 physicians surveyed in August 2020 by the Physicians Foundation, a physicians advocacy organization, 50% indicated that they experienced excessive anger, tearfulness, or anxiety because of the way the pandemic affected their work; 30% felt hopeless or lacking purpose; and 8% had thoughts of self-harm related to the pandemic. Rates of burnout had risen from 40% in 2018 to 58%.

Those problems might be even more acute in places experiencing other types of crises. A 2020 study of 154 emergency department (ED) physicians in Libya, which is in the midst of a civil war, found that 65% were experiencing anxiety, 73% were showing signs of depression, and 68% felt emotionally exhausted.
 

Every story is different

It is unclear how common suicide is among physicians. One often-repeated estimate is that 300-400 physicians die by suicide each year, but no one is certain how that number was determined, said Dr. Myers, who organized the APA panel.

Studies on suicide are inconsistent, and trends are hard to pinpoint. Anecdotally, he has received just as many calls about physician suicides in the past year as he did before the pandemic started. “What I can tell you is that this is a serious subject,” Dr. Myers said. “And it’s not going away.”

Every person is different, and so is every death. Sometimes, career problems have nothing to do with a physician’s suicide, Dr. Myers said. When job stress does play a role, factors are often varied and complex.

After a 35-year career as a double board certified ED physician, Matthew Seaman, MD, retired in January 2017. The same month, a patient filed a complaint against him with the Washington State medical board, which led to an investigation and a lawsuit.

The case was hard on Dr. Seaman, who had continued to work night shifts throughout his career and had won a Hero Award from the American Board of Emergency Medicine, said his wife, Linda Seaman, MD, a family practitioner in Yakima, Wash., who also spoke on the APA panel.

Dr. Seaman said that 2 years after the investigation started, her husband was growing increasingly depressed. In 2019, he testified in a deposition. She said the plaintiff’s attorney “tried every way he could to shame Matt, humiliate Matt, make him believe he was a very bad doctor.” Three days later, he died by suicide at age 62.

Looking back at the year leading up to her husband’s death, Dr. Seaman recognizes multiple obstacles that interfered with her husband’s ability to get help, including frustrating interactions with psychiatrists and the couple’s insurance company.

His identity and experience as a physician also played a role. A couple of months before he died, she tried unsuccessfully to reach his psychiatrist, whose office suggested he go to the ED. However, because he worked as an ED doctor in their small town, he wouldn’t go. Dr. Seaman suspects he was wary of the stigma.

Burnout likely set him up to cave in after decades of work on the front lines, she added. Working in the ED exposes providers to horrific, traumatic cases every day, she said. Physicians learn to suppress their own emotions to deal with what they encounter. Stuffing their feelings can lead to posttraumatic stress. “You just perform,” she said. “You learn to do that.”
 

A real gift

Whenever Dr. Myers hears stories about doctors who died by suicide or who have written about their mental health struggles to help others, he contacts them. One goal of his own writing and of the conference sessions he organizes is to make it easier for others to share their own stories.

“I tell them, first of all, their courage and honesty is a real gift, and they’re saving lives,” he said. “There are so many suffering doctors out there who think that they’re the only one.”

Public conversations such as those that occurred in the APA session also offer opportunities to share advice, including Dr. Myers’ recommendation that doctors be sure they have a primary care physician of their own.

Many don’t, he says, because they say they are too busy, they can treat their own symptoms, or they can self-refer to specialists when needed. But physicians don’t always recognize symptoms of depression in themselves, and when mental health problems arise, they may not seek help or treat themselves appropriately.

A primary care physician can be the first person to recognize a mental health problem and refer a patient for mental health care, said Dr. Myers, whose latest book, “Becoming a Doctors’ Doctor: A Memoir,” explores his experiences treating doctors with burnout and other mental health problems.

Whether they have a primary care doctor or not, he suggests that physicians talk to anyone they trust – a social worker, a religious leader, or a family member who can then help them find the right sort of care.

In the United States, around-the-clock help is available through the National Suicide Prevention Lifeline at 800-273-8255. A psychiatrist-run hotline specifically for physicians is available at 888-409-0141. “Reach out and get some help,” Dr. Myers said. “Just don’t do it alone.”

Dr. Lynes advocates setting boundaries between life and work. He has also benefited from writing about his experiences. A blog or a diary can help physicians process their feelings, he said. His 2016 essay marked a major turning point in his life, giving his life meaning in helping others.

“Since I wrote that article, I can’t tell you how much better I am,” he said. “Now, I’m not embarrassed to be around physicians. I actually consider myself a physician. I didn’t for many, many years. So, I’m doing pretty well.”
 

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

William Lynes, MD, had a flourishing medical practice and a fulfilling family life with three children when he first attempted suicide in 1999 at age 45. By 2003, depression and two more suicide attempts led to his early retirement.

In a session at the recent virtual American Psychiatric Association (APA) 2021 annual meeting, Dr. Lynes talked about the challenges of dealing with depression while managing the stresses of a career in medicine. The session in which he spoke was called, “The Suicidal Physician: Narratives From a Physician Who Survived and the Physician Widow of One Who Did Not.”

By writing and speaking about his experiences, he says, he has been able to retain his identity as a physician and avoid obsessive thoughts about suicide. He hopes conversations like these help other physicians feel less alone and enable them to push past stigmas to get the help they need. He suspects they do. More than 600 people joined the APA session, and Dr. Lynes received dozens of thankful messages afterward.

“I love medicine, but intrinsically, the practice of medicine is stressful, and you can’t get away,” said Dr. Lynes, a retired urologist in Temecula, Calif. “As far as feedback, it made me feel like it’s something I should continue to do.”
 

A way to heal

For Dr. Lynes, his “downward spiral into darkness” began with a series of catastrophic medical events starting in 1998, when he came home from a family vacation in Mexico feeling unwell. He didn’t bother to do anything about it – typical of a physician, he says. Then one night he woke up shaking with chills and fever. Soon he was in the hospital with respiratory failure from septic shock.

Dr. Lynes spent 6 weeks in the intensive care unit, including 4 weeks on a ventilator. He underwent a tracheostomy. He lost 40 pounds and experienced ICU-related delirium. It was a terrifying time, he said. When he tried to return to work 10 months later, he didn’t feel as though he could function normally.

Having once been a driven doctor who worked long hours, he now doubted himself and dreaded giving patients bad news. Spontaneously, he tried to take his own life.

Afterward, he concealed what had happened from everyone except his wife and managed to resume his practice. However, he was unable to regain the enthusiasm he had once had for his work. Although he had experienced depression before, this time it was unrelenting.

He sought help from a psychiatrist, received a diagnosis of bipolar disorder, and began taking medication. Still, he struggled to fulfill his responsibilities. Then in April 2002, he had a snowboarding accident that caused multiple facial fractures and required five operations. When he returned to work this time, he felt like a failure but resisted asking colleagues for help.

A few months later, Dr. Lynes again attempted suicide, which led to another stay in the ICU and more time on a ventilator. Doctors told his family they didn’t think he would survive. When he recovered, he spent time as an inpatient in a psychiatric ward, where he received the first of a series of electroconvulsive therapy sessions. Compounding his anxiety and depression was the inability to come to terms with his life if he were not able to practice medicine.

The next fall, in September 2003, his third suicide attempt took place in his office on a weekend when no one was around. After locking the door, he looked at his reflection in the frame of his medical school diploma. The glass was cracked. “It was dark, it was black, it was cold,” he said. “I can remember seeing my reflection and thinking how disgusted I was.”

For years after that, Dr. Lynes struggled with his sense of self-worth. He hid from the medical system and dreaded doctors’ appointments. Finally in 2016, he found new meaning at a writing conference, where he met a fellow physician whose story was similar to his. She encouraged him to write about his experience. His essay was published in Annals of Internal Medicine that year. “Then I started speaking, and I feel like I’m a physician again,” he said. “That has really healed me quite a bit.”
 

Why physicians die by suicide

Working in health care can be extremely stressful, even in the best of times, said Michael Myers, MD, a psychiatrist at State University of New York, Brooklyn, and author of the book, “Why Physicians Die By Suicide: Lessons Learned From Their Families and Others Who Cared.”

Years of school and training culminate in a career in which demands are relentless. Societal expectations are high. Many doctors are perfectionists by nature, and physicians tend to feel intense pressure to compete for coveted positions.

Stress starts early in a medical career. A 2016 systematic review and meta-analysis of 183 studies from 43 countries showed that nearly 30% of medical students experienced symptoms of depression and that 11% reported suicidal thoughts, but only 15% sought help.

A 2015 review of 31 studies that involved residents showed that rates of depression remained close to 30% and that about three-quarters of trainees meet criteria for burnout, a type of emotional exhaustion and sense of inadequacy that can result from chronic stress at work.

The stress of medical training appears to be a direct cause of mental health struggles. Rates of depression are higher among those working to become physicians than among their peers of the same age, research shows. In addition, symptoms become more prevalent as people progress through their training.

The COVID-19 pandemic has added stress to an already stressful job. Of more than 2,300 physicians surveyed in August 2020 by the Physicians Foundation, a physicians advocacy organization, 50% indicated that they experienced excessive anger, tearfulness, or anxiety because of the way the pandemic affected their work; 30% felt hopeless or lacking purpose; and 8% had thoughts of self-harm related to the pandemic. Rates of burnout had risen from 40% in 2018 to 58%.

Those problems might be even more acute in places experiencing other types of crises. A 2020 study of 154 emergency department (ED) physicians in Libya, which is in the midst of a civil war, found that 65% were experiencing anxiety, 73% were showing signs of depression, and 68% felt emotionally exhausted.
 

Every story is different

It is unclear how common suicide is among physicians. One often-repeated estimate is that 300-400 physicians die by suicide each year, but no one is certain how that number was determined, said Dr. Myers, who organized the APA panel.

Studies on suicide are inconsistent, and trends are hard to pinpoint. Anecdotally, he has received just as many calls about physician suicides in the past year as he did before the pandemic started. “What I can tell you is that this is a serious subject,” Dr. Myers said. “And it’s not going away.”

Every person is different, and so is every death. Sometimes, career problems have nothing to do with a physician’s suicide, Dr. Myers said. When job stress does play a role, factors are often varied and complex.

After a 35-year career as a double board certified ED physician, Matthew Seaman, MD, retired in January 2017. The same month, a patient filed a complaint against him with the Washington State medical board, which led to an investigation and a lawsuit.

The case was hard on Dr. Seaman, who had continued to work night shifts throughout his career and had won a Hero Award from the American Board of Emergency Medicine, said his wife, Linda Seaman, MD, a family practitioner in Yakima, Wash., who also spoke on the APA panel.

Dr. Seaman said that 2 years after the investigation started, her husband was growing increasingly depressed. In 2019, he testified in a deposition. She said the plaintiff’s attorney “tried every way he could to shame Matt, humiliate Matt, make him believe he was a very bad doctor.” Three days later, he died by suicide at age 62.

Looking back at the year leading up to her husband’s death, Dr. Seaman recognizes multiple obstacles that interfered with her husband’s ability to get help, including frustrating interactions with psychiatrists and the couple’s insurance company.

His identity and experience as a physician also played a role. A couple of months before he died, she tried unsuccessfully to reach his psychiatrist, whose office suggested he go to the ED. However, because he worked as an ED doctor in their small town, he wouldn’t go. Dr. Seaman suspects he was wary of the stigma.

Burnout likely set him up to cave in after decades of work on the front lines, she added. Working in the ED exposes providers to horrific, traumatic cases every day, she said. Physicians learn to suppress their own emotions to deal with what they encounter. Stuffing their feelings can lead to posttraumatic stress. “You just perform,” she said. “You learn to do that.”
 

A real gift

Whenever Dr. Myers hears stories about doctors who died by suicide or who have written about their mental health struggles to help others, he contacts them. One goal of his own writing and of the conference sessions he organizes is to make it easier for others to share their own stories.

“I tell them, first of all, their courage and honesty is a real gift, and they’re saving lives,” he said. “There are so many suffering doctors out there who think that they’re the only one.”

Public conversations such as those that occurred in the APA session also offer opportunities to share advice, including Dr. Myers’ recommendation that doctors be sure they have a primary care physician of their own.

Many don’t, he says, because they say they are too busy, they can treat their own symptoms, or they can self-refer to specialists when needed. But physicians don’t always recognize symptoms of depression in themselves, and when mental health problems arise, they may not seek help or treat themselves appropriately.

A primary care physician can be the first person to recognize a mental health problem and refer a patient for mental health care, said Dr. Myers, whose latest book, “Becoming a Doctors’ Doctor: A Memoir,” explores his experiences treating doctors with burnout and other mental health problems.

Whether they have a primary care doctor or not, he suggests that physicians talk to anyone they trust – a social worker, a religious leader, or a family member who can then help them find the right sort of care.

In the United States, around-the-clock help is available through the National Suicide Prevention Lifeline at 800-273-8255. A psychiatrist-run hotline specifically for physicians is available at 888-409-0141. “Reach out and get some help,” Dr. Myers said. “Just don’t do it alone.”

Dr. Lynes advocates setting boundaries between life and work. He has also benefited from writing about his experiences. A blog or a diary can help physicians process their feelings, he said. His 2016 essay marked a major turning point in his life, giving his life meaning in helping others.

“Since I wrote that article, I can’t tell you how much better I am,” he said. “Now, I’m not embarrassed to be around physicians. I actually consider myself a physician. I didn’t for many, many years. So, I’m doing pretty well.”
 

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

William Lynes, MD, had a flourishing medical practice and a fulfilling family life with three children when he first attempted suicide in 1999 at age 45. By 2003, depression and two more suicide attempts led to his early retirement.

In a session at the recent virtual American Psychiatric Association (APA) 2021 annual meeting, Dr. Lynes talked about the challenges of dealing with depression while managing the stresses of a career in medicine. The session in which he spoke was called, “The Suicidal Physician: Narratives From a Physician Who Survived and the Physician Widow of One Who Did Not.”

By writing and speaking about his experiences, he says, he has been able to retain his identity as a physician and avoid obsessive thoughts about suicide. He hopes conversations like these help other physicians feel less alone and enable them to push past stigmas to get the help they need. He suspects they do. More than 600 people joined the APA session, and Dr. Lynes received dozens of thankful messages afterward.

“I love medicine, but intrinsically, the practice of medicine is stressful, and you can’t get away,” said Dr. Lynes, a retired urologist in Temecula, Calif. “As far as feedback, it made me feel like it’s something I should continue to do.”
 

A way to heal

For Dr. Lynes, his “downward spiral into darkness” began with a series of catastrophic medical events starting in 1998, when he came home from a family vacation in Mexico feeling unwell. He didn’t bother to do anything about it – typical of a physician, he says. Then one night he woke up shaking with chills and fever. Soon he was in the hospital with respiratory failure from septic shock.

Dr. Lynes spent 6 weeks in the intensive care unit, including 4 weeks on a ventilator. He underwent a tracheostomy. He lost 40 pounds and experienced ICU-related delirium. It was a terrifying time, he said. When he tried to return to work 10 months later, he didn’t feel as though he could function normally.

Having once been a driven doctor who worked long hours, he now doubted himself and dreaded giving patients bad news. Spontaneously, he tried to take his own life.

Afterward, he concealed what had happened from everyone except his wife and managed to resume his practice. However, he was unable to regain the enthusiasm he had once had for his work. Although he had experienced depression before, this time it was unrelenting.

He sought help from a psychiatrist, received a diagnosis of bipolar disorder, and began taking medication. Still, he struggled to fulfill his responsibilities. Then in April 2002, he had a snowboarding accident that caused multiple facial fractures and required five operations. When he returned to work this time, he felt like a failure but resisted asking colleagues for help.

A few months later, Dr. Lynes again attempted suicide, which led to another stay in the ICU and more time on a ventilator. Doctors told his family they didn’t think he would survive. When he recovered, he spent time as an inpatient in a psychiatric ward, where he received the first of a series of electroconvulsive therapy sessions. Compounding his anxiety and depression was the inability to come to terms with his life if he were not able to practice medicine.

The next fall, in September 2003, his third suicide attempt took place in his office on a weekend when no one was around. After locking the door, he looked at his reflection in the frame of his medical school diploma. The glass was cracked. “It was dark, it was black, it was cold,” he said. “I can remember seeing my reflection and thinking how disgusted I was.”

For years after that, Dr. Lynes struggled with his sense of self-worth. He hid from the medical system and dreaded doctors’ appointments. Finally in 2016, he found new meaning at a writing conference, where he met a fellow physician whose story was similar to his. She encouraged him to write about his experience. His essay was published in Annals of Internal Medicine that year. “Then I started speaking, and I feel like I’m a physician again,” he said. “That has really healed me quite a bit.”
 

Why physicians die by suicide

Working in health care can be extremely stressful, even in the best of times, said Michael Myers, MD, a psychiatrist at State University of New York, Brooklyn, and author of the book, “Why Physicians Die By Suicide: Lessons Learned From Their Families and Others Who Cared.”

Years of school and training culminate in a career in which demands are relentless. Societal expectations are high. Many doctors are perfectionists by nature, and physicians tend to feel intense pressure to compete for coveted positions.

Stress starts early in a medical career. A 2016 systematic review and meta-analysis of 183 studies from 43 countries showed that nearly 30% of medical students experienced symptoms of depression and that 11% reported suicidal thoughts, but only 15% sought help.

A 2015 review of 31 studies that involved residents showed that rates of depression remained close to 30% and that about three-quarters of trainees meet criteria for burnout, a type of emotional exhaustion and sense of inadequacy that can result from chronic stress at work.

The stress of medical training appears to be a direct cause of mental health struggles. Rates of depression are higher among those working to become physicians than among their peers of the same age, research shows. In addition, symptoms become more prevalent as people progress through their training.

The COVID-19 pandemic has added stress to an already stressful job. Of more than 2,300 physicians surveyed in August 2020 by the Physicians Foundation, a physicians advocacy organization, 50% indicated that they experienced excessive anger, tearfulness, or anxiety because of the way the pandemic affected their work; 30% felt hopeless or lacking purpose; and 8% had thoughts of self-harm related to the pandemic. Rates of burnout had risen from 40% in 2018 to 58%.

Those problems might be even more acute in places experiencing other types of crises. A 2020 study of 154 emergency department (ED) physicians in Libya, which is in the midst of a civil war, found that 65% were experiencing anxiety, 73% were showing signs of depression, and 68% felt emotionally exhausted.
 

Every story is different

It is unclear how common suicide is among physicians. One often-repeated estimate is that 300-400 physicians die by suicide each year, but no one is certain how that number was determined, said Dr. Myers, who organized the APA panel.

Studies on suicide are inconsistent, and trends are hard to pinpoint. Anecdotally, he has received just as many calls about physician suicides in the past year as he did before the pandemic started. “What I can tell you is that this is a serious subject,” Dr. Myers said. “And it’s not going away.”

Every person is different, and so is every death. Sometimes, career problems have nothing to do with a physician’s suicide, Dr. Myers said. When job stress does play a role, factors are often varied and complex.

After a 35-year career as a double board certified ED physician, Matthew Seaman, MD, retired in January 2017. The same month, a patient filed a complaint against him with the Washington State medical board, which led to an investigation and a lawsuit.

The case was hard on Dr. Seaman, who had continued to work night shifts throughout his career and had won a Hero Award from the American Board of Emergency Medicine, said his wife, Linda Seaman, MD, a family practitioner in Yakima, Wash., who also spoke on the APA panel.

Dr. Seaman said that 2 years after the investigation started, her husband was growing increasingly depressed. In 2019, he testified in a deposition. She said the plaintiff’s attorney “tried every way he could to shame Matt, humiliate Matt, make him believe he was a very bad doctor.” Three days later, he died by suicide at age 62.

Looking back at the year leading up to her husband’s death, Dr. Seaman recognizes multiple obstacles that interfered with her husband’s ability to get help, including frustrating interactions with psychiatrists and the couple’s insurance company.

His identity and experience as a physician also played a role. A couple of months before he died, she tried unsuccessfully to reach his psychiatrist, whose office suggested he go to the ED. However, because he worked as an ED doctor in their small town, he wouldn’t go. Dr. Seaman suspects he was wary of the stigma.

Burnout likely set him up to cave in after decades of work on the front lines, she added. Working in the ED exposes providers to horrific, traumatic cases every day, she said. Physicians learn to suppress their own emotions to deal with what they encounter. Stuffing their feelings can lead to posttraumatic stress. “You just perform,” she said. “You learn to do that.”
 

A real gift

Whenever Dr. Myers hears stories about doctors who died by suicide or who have written about their mental health struggles to help others, he contacts them. One goal of his own writing and of the conference sessions he organizes is to make it easier for others to share their own stories.

“I tell them, first of all, their courage and honesty is a real gift, and they’re saving lives,” he said. “There are so many suffering doctors out there who think that they’re the only one.”

Public conversations such as those that occurred in the APA session also offer opportunities to share advice, including Dr. Myers’ recommendation that doctors be sure they have a primary care physician of their own.

Many don’t, he says, because they say they are too busy, they can treat their own symptoms, or they can self-refer to specialists when needed. But physicians don’t always recognize symptoms of depression in themselves, and when mental health problems arise, they may not seek help or treat themselves appropriately.

A primary care physician can be the first person to recognize a mental health problem and refer a patient for mental health care, said Dr. Myers, whose latest book, “Becoming a Doctors’ Doctor: A Memoir,” explores his experiences treating doctors with burnout and other mental health problems.

Whether they have a primary care doctor or not, he suggests that physicians talk to anyone they trust – a social worker, a religious leader, or a family member who can then help them find the right sort of care.

In the United States, around-the-clock help is available through the National Suicide Prevention Lifeline at 800-273-8255. A psychiatrist-run hotline specifically for physicians is available at 888-409-0141. “Reach out and get some help,” Dr. Myers said. “Just don’t do it alone.”

Dr. Lynes advocates setting boundaries between life and work. He has also benefited from writing about his experiences. A blog or a diary can help physicians process their feelings, he said. His 2016 essay marked a major turning point in his life, giving his life meaning in helping others.

“Since I wrote that article, I can’t tell you how much better I am,” he said. “Now, I’m not embarrassed to be around physicians. I actually consider myself a physician. I didn’t for many, many years. So, I’m doing pretty well.”
 

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