Jim Kling

Although inflammatory bowel disease (IBD) affects primarily White patients, about one-quarter of cases are found in non-White racial and ethnic groups. Various factors have combined to lead to disparities in treatment and outcomes for non-Whites with IBD.

Ethnic and racial disparities, along with socioeconomic factors, were the subject of a presentation by Ruby Greywoode, MD, at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“Historical and present-day realities of racial inequity and factors that contribute to socioeconomic status [include] educational and housing policies, employment practices, and generational wealth. Addressing health disparities requires acknowledging these systemic factors,” said Dr. Greywoode, who is with Montefiore Medical Center in New York.

An important concept in discussing health disparity is social determinants of health, which refers to nonbiological factors that affect health and health outcomes. These are “the conditions in which people live, work, learn, and play that affect their health and their quality of life,” said Dr. Greywoode. 

Dr. Greywoode shared examples of social determinants that affect economic stability and financial worry. One study found that one in six IBD patients reported not taking their medications because of cost considerations. A survey of about 900 adults showed that 1 in 4 delayed medical care – half of those because of cost; patients who delayed care were 2.5 times more likely to report an IBD flare in the previous year.

Another important issue is food insecurity. Other presenters at the session emphasized the importance of high-quality nutrition in IBD, and Dr. Greywoode presented one survey showing that only 9% of patients who had both food security and social support reported cost-related medication nonadherence. Among those that had either food insecurity or poor social support, 12% reported cost-related medication nonadherence, but the proportion jumped to 57% among patients who had both food insecurity and lack of social support.

Session comoderator Kelly Issokson noted that socioeconomic factors often interfere with adoption of healthy diets. Whole foods and plant-based foods are expensive, and the financial pressures of the COVID-19 epidemic have made that worse. “Millions of people are slipping into poverty and food insecurity. This is one of the things she highlighted as factors in medication nonadherence,” said Ms. Issokson, who is the clinical nutritional coordinator at the digestive disease clinic at Cedars-Sinai Medical Center in Los Angeles.

Dr. Greywoode also described studies that looked at race, socioeconomic status, and IBD outcomes. A review from 2013 showed disparities among Whites, African Americans, and Hispanics with respect to undergoing ulcerative colitis–related colectomy and Crohn’s disease–related bowel resection. Ulcerative colitis patients on Medicaid had 230% greater in-patient mortality, compared with patients with private insurance, even after adjustment for multiple confounders.

But inequities are not static. “Since this publication, we have numerous other studies drawing conclusions that sometimes agree with and sometimes conflict with it. My belief is that health disparities in IBD will continue to be an active area of research. We know that it takes vigilance to identify, track, and address any disparities when they do arise,” said Dr. Greywoode.

Dr. Greywoode also noted that phenotypic differences based on race and ethnicity influence disparities. She showed results from a meta-analysis that found a difference in the frequency of perianal Crohn’s disease by race and ethnicity; the highest frequency occurred in Black patients (31%), followed by Asians (22%), Whites (14%), and Hispanics (13%). Another study showed that African American patients with Crohn’s disease were more likely to develop a new abscess (adjusted odds ratio, 2.27; 95% confidence interval, 1.31-3.93) or anal fissure (aOR, 1.76; 95% CI, 1.01-3.07), and were also more likely to be initiated on an anti–tumor necrosis factor drug (aOR, 1.85; 95% CI, 1.09-3.14).

Those differences underscore the need to recognize that IBD is not just a disease for White patients. “As we move forward in IBD research, we recognize that individuals of European ancestry are not the only ones who have IBD. There is a growing diverse racial and ethnic population with IBD,” said Dr. Greywoode.

She noted that, in the United States, it is estimated that about one in four adult patients are non-Hispanic African American, Hispanic, Asians, or other ethnicities. Nevertheless, Whites are overrepresented among participants in IBD clinical trials. Some trials are composed of as much as 95% White patients, and sometimes race isn’t even listed. “It’s unclear if [race/ethnicity data are] not collected or not deemed important, but we know that what is not collected is not measured, and what is not measured can’t be evaluated, either to praise or constructively criticize,” said Dr. Greywoode.

Fortunately, there are efforts in place to improve representation in clinical trials. There has been a mandate for almost 3 decades that federally funded research must include racial and ethnic minorities who have been traditionally underrepresented. The Food and Drug Administration has also provided guidance to industry to improve diversity in clinical trial participation, and industry groups have developed strategies, including improved representation among investigators and related early-career development programs. At the community and independent health care practice levels, clinical trial networks encourage patient participation with regulatory and data management support to bolster practices with insufficient resources.

Underrepresentation in clinical trials resonated with comoderator Tina Aswani Omprakash, who is a patient advocate and a master’s in public health student at the Icahn School of Medicine at Mount Sinai, New York. She called for greater awareness among physicians that IBD can occur among people of all backgrounds. “[Providers] would look at me and [say]: ‘There’s no way that, as a South Asian woman, you have that kind of disease.’ There’s that lack of believability,” said Ms. Aswani Omprakash.

Greater recognition of the diversity of patients, as well as the phenotypic differences found among ethnicities, could also inform clinical trial participation and, ultimately, more personalized medicine. “We have to look at these things, observe how they’re affecting populations differently, so that we can have proper medication solutions,” said Ms. Aswani Omprakash.

Dr. Greywoode and Ms. Issokson have no relevant financial disclosures. Ms. Aswani Omprakash has consulted for Genentech, AbbVie, Janssen, and Arena.

The AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. The AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

Updated Feb. 17, 2021.
 

Although inflammatory bowel disease (IBD) affects primarily White patients, about one-quarter of cases are found in non-White racial and ethnic groups. Various factors have combined to lead to disparities in treatment and outcomes for non-Whites with IBD.

Ethnic and racial disparities, along with socioeconomic factors, were the subject of a presentation by Ruby Greywoode, MD, at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“Historical and present-day realities of racial inequity and factors that contribute to socioeconomic status [include] educational and housing policies, employment practices, and generational wealth. Addressing health disparities requires acknowledging these systemic factors,” said Dr. Greywoode, who is with Montefiore Medical Center in New York.

An important concept in discussing health disparity is social determinants of health, which refers to nonbiological factors that affect health and health outcomes. These are “the conditions in which people live, work, learn, and play that affect their health and their quality of life,” said Dr. Greywoode. 

Dr. Greywoode shared examples of social determinants that affect economic stability and financial worry. One study found that one in six IBD patients reported not taking their medications because of cost considerations. A survey of about 900 adults showed that 1 in 4 delayed medical care – half of those because of cost; patients who delayed care were 2.5 times more likely to report an IBD flare in the previous year.

Another important issue is food insecurity. Other presenters at the session emphasized the importance of high-quality nutrition in IBD, and Dr. Greywoode presented one survey showing that only 9% of patients who had both food security and social support reported cost-related medication nonadherence. Among those that had either food insecurity or poor social support, 12% reported cost-related medication nonadherence, but the proportion jumped to 57% among patients who had both food insecurity and lack of social support.

Session comoderator Kelly Issokson noted that socioeconomic factors often interfere with adoption of healthy diets. Whole foods and plant-based foods are expensive, and the financial pressures of the COVID-19 epidemic have made that worse. “Millions of people are slipping into poverty and food insecurity. This is one of the things she highlighted as factors in medication nonadherence,” said Ms. Issokson, who is the clinical nutritional coordinator at the digestive disease clinic at Cedars-Sinai Medical Center in Los Angeles.

Dr. Greywoode also described studies that looked at race, socioeconomic status, and IBD outcomes. A review from 2013 showed disparities among Whites, African Americans, and Hispanics with respect to undergoing ulcerative colitis–related colectomy and Crohn’s disease–related bowel resection. Ulcerative colitis patients on Medicaid had 230% greater in-patient mortality, compared with patients with private insurance, even after adjustment for multiple confounders.

But inequities are not static. “Since this publication, we have numerous other studies drawing conclusions that sometimes agree with and sometimes conflict with it. My belief is that health disparities in IBD will continue to be an active area of research. We know that it takes vigilance to identify, track, and address any disparities when they do arise,” said Dr. Greywoode.

Dr. Greywoode also noted that phenotypic differences based on race and ethnicity influence disparities. She showed results from a meta-analysis that found a difference in the frequency of perianal Crohn’s disease by race and ethnicity; the highest frequency occurred in Black patients (31%), followed by Asians (22%), Whites (14%), and Hispanics (13%). Another study showed that African American patients with Crohn’s disease were more likely to develop a new abscess (adjusted odds ratio, 2.27; 95% confidence interval, 1.31-3.93) or anal fissure (aOR, 1.76; 95% CI, 1.01-3.07), and were also more likely to be initiated on an anti–tumor necrosis factor drug (aOR, 1.85; 95% CI, 1.09-3.14).

Those differences underscore the need to recognize that IBD is not just a disease for White patients. “As we move forward in IBD research, we recognize that individuals of European ancestry are not the only ones who have IBD. There is a growing diverse racial and ethnic population with IBD,” said Dr. Greywoode.

She noted that, in the United States, it is estimated that about one in four adult patients are non-Hispanic African American, Hispanic, Asians, or other ethnicities. Nevertheless, Whites are overrepresented among participants in IBD clinical trials. Some trials are composed of as much as 95% White patients, and sometimes race isn’t even listed. “It’s unclear if [race/ethnicity data are] not collected or not deemed important, but we know that what is not collected is not measured, and what is not measured can’t be evaluated, either to praise or constructively criticize,” said Dr. Greywoode.

Fortunately, there are efforts in place to improve representation in clinical trials. There has been a mandate for almost 3 decades that federally funded research must include racial and ethnic minorities who have been traditionally underrepresented. The Food and Drug Administration has also provided guidance to industry to improve diversity in clinical trial participation, and industry groups have developed strategies, including improved representation among investigators and related early-career development programs. At the community and independent health care practice levels, clinical trial networks encourage patient participation with regulatory and data management support to bolster practices with insufficient resources.

Underrepresentation in clinical trials resonated with comoderator Tina Aswani Omprakash, who is a patient advocate and a master’s in public health student at the Icahn School of Medicine at Mount Sinai, New York. She called for greater awareness among physicians that IBD can occur among people of all backgrounds. “[Providers] would look at me and [say]: ‘There’s no way that, as a South Asian woman, you have that kind of disease.’ There’s that lack of believability,” said Ms. Aswani Omprakash.

Greater recognition of the diversity of patients, as well as the phenotypic differences found among ethnicities, could also inform clinical trial participation and, ultimately, more personalized medicine. “We have to look at these things, observe how they’re affecting populations differently, so that we can have proper medication solutions,” said Ms. Aswani Omprakash.

Dr. Greywoode and Ms. Issokson have no relevant financial disclosures. Ms. Aswani Omprakash has consulted for Genentech, AbbVie, Janssen, and Arena.

The AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. The AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

Updated Feb. 17, 2021.
 

Although inflammatory bowel disease (IBD) affects primarily White patients, about one-quarter of cases are found in non-White racial and ethnic groups. Various factors have combined to lead to disparities in treatment and outcomes for non-Whites with IBD.

Ethnic and racial disparities, along with socioeconomic factors, were the subject of a presentation by Ruby Greywoode, MD, at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“Historical and present-day realities of racial inequity and factors that contribute to socioeconomic status [include] educational and housing policies, employment practices, and generational wealth. Addressing health disparities requires acknowledging these systemic factors,” said Dr. Greywoode, who is with Montefiore Medical Center in New York.

An important concept in discussing health disparity is social determinants of health, which refers to nonbiological factors that affect health and health outcomes. These are “the conditions in which people live, work, learn, and play that affect their health and their quality of life,” said Dr. Greywoode. 

Dr. Greywoode shared examples of social determinants that affect economic stability and financial worry. One study found that one in six IBD patients reported not taking their medications because of cost considerations. A survey of about 900 adults showed that 1 in 4 delayed medical care – half of those because of cost; patients who delayed care were 2.5 times more likely to report an IBD flare in the previous year.

Another important issue is food insecurity. Other presenters at the session emphasized the importance of high-quality nutrition in IBD, and Dr. Greywoode presented one survey showing that only 9% of patients who had both food security and social support reported cost-related medication nonadherence. Among those that had either food insecurity or poor social support, 12% reported cost-related medication nonadherence, but the proportion jumped to 57% among patients who had both food insecurity and lack of social support.

Session comoderator Kelly Issokson noted that socioeconomic factors often interfere with adoption of healthy diets. Whole foods and plant-based foods are expensive, and the financial pressures of the COVID-19 epidemic have made that worse. “Millions of people are slipping into poverty and food insecurity. This is one of the things she highlighted as factors in medication nonadherence,” said Ms. Issokson, who is the clinical nutritional coordinator at the digestive disease clinic at Cedars-Sinai Medical Center in Los Angeles.

Dr. Greywoode also described studies that looked at race, socioeconomic status, and IBD outcomes. A review from 2013 showed disparities among Whites, African Americans, and Hispanics with respect to undergoing ulcerative colitis–related colectomy and Crohn’s disease–related bowel resection. Ulcerative colitis patients on Medicaid had 230% greater in-patient mortality, compared with patients with private insurance, even after adjustment for multiple confounders.

But inequities are not static. “Since this publication, we have numerous other studies drawing conclusions that sometimes agree with and sometimes conflict with it. My belief is that health disparities in IBD will continue to be an active area of research. We know that it takes vigilance to identify, track, and address any disparities when they do arise,” said Dr. Greywoode.

Dr. Greywoode also noted that phenotypic differences based on race and ethnicity influence disparities. She showed results from a meta-analysis that found a difference in the frequency of perianal Crohn’s disease by race and ethnicity; the highest frequency occurred in Black patients (31%), followed by Asians (22%), Whites (14%), and Hispanics (13%). Another study showed that African American patients with Crohn’s disease were more likely to develop a new abscess (adjusted odds ratio, 2.27; 95% confidence interval, 1.31-3.93) or anal fissure (aOR, 1.76; 95% CI, 1.01-3.07), and were also more likely to be initiated on an anti–tumor necrosis factor drug (aOR, 1.85; 95% CI, 1.09-3.14).

Those differences underscore the need to recognize that IBD is not just a disease for White patients. “As we move forward in IBD research, we recognize that individuals of European ancestry are not the only ones who have IBD. There is a growing diverse racial and ethnic population with IBD,” said Dr. Greywoode.

She noted that, in the United States, it is estimated that about one in four adult patients are non-Hispanic African American, Hispanic, Asians, or other ethnicities. Nevertheless, Whites are overrepresented among participants in IBD clinical trials. Some trials are composed of as much as 95% White patients, and sometimes race isn’t even listed. “It’s unclear if [race/ethnicity data are] not collected or not deemed important, but we know that what is not collected is not measured, and what is not measured can’t be evaluated, either to praise or constructively criticize,” said Dr. Greywoode.

Fortunately, there are efforts in place to improve representation in clinical trials. There has been a mandate for almost 3 decades that federally funded research must include racial and ethnic minorities who have been traditionally underrepresented. The Food and Drug Administration has also provided guidance to industry to improve diversity in clinical trial participation, and industry groups have developed strategies, including improved representation among investigators and related early-career development programs. At the community and independent health care practice levels, clinical trial networks encourage patient participation with regulatory and data management support to bolster practices with insufficient resources.

Underrepresentation in clinical trials resonated with comoderator Tina Aswani Omprakash, who is a patient advocate and a master’s in public health student at the Icahn School of Medicine at Mount Sinai, New York. She called for greater awareness among physicians that IBD can occur among people of all backgrounds. “[Providers] would look at me and [say]: ‘There’s no way that, as a South Asian woman, you have that kind of disease.’ There’s that lack of believability,” said Ms. Aswani Omprakash.

Greater recognition of the diversity of patients, as well as the phenotypic differences found among ethnicities, could also inform clinical trial participation and, ultimately, more personalized medicine. “We have to look at these things, observe how they’re affecting populations differently, so that we can have proper medication solutions,” said Ms. Aswani Omprakash.

Dr. Greywoode and Ms. Issokson have no relevant financial disclosures. Ms. Aswani Omprakash has consulted for Genentech, AbbVie, Janssen, and Arena.

The AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. The AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

Updated Feb. 17, 2021.
 

Multicenter and population cohort studies suggest that patients with inflammatory bowel disease (IBD) are not at unique risk of contracting COVID-19 or experiencing worse outcomes, with the exception of a few risk factors such as corticosteroid use and combination therapy that appear tied to greater risk of hospitalization and mortality. The findings line up well with previous experience with infectious disease and are reassuring, but they also underscore the need to taper steroids and de-escalate from combination therapy, when possible.

“There is not a clear increased risk of getting COVID-19 among IBD patients compared to the general population, and that seems to hold even if you look at certain medication types, [even] if patients are on immunosuppressives like thiopurines or anti-TNF [anti–tumor necrosis factor] drugs,” Ryan C. Ungaro, MD, said in an interview. Dr. Ungaro, who is with the Icahn School of Medicine at Mount Sinai, New York, discussed IBD and COVID-19 risks at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

This article was updated Jan. 27, 2021.

Multicenter and population cohort studies suggest that patients with inflammatory bowel disease (IBD) are not at unique risk of contracting COVID-19 or experiencing worse outcomes, with the exception of a few risk factors such as corticosteroid use and combination therapy that appear tied to greater risk of hospitalization and mortality. The findings line up well with previous experience with infectious disease and are reassuring, but they also underscore the need to taper steroids and de-escalate from combination therapy, when possible.

“There is not a clear increased risk of getting COVID-19 among IBD patients compared to the general population, and that seems to hold even if you look at certain medication types, [even] if patients are on immunosuppressives like thiopurines or anti-TNF [anti–tumor necrosis factor] drugs,” Ryan C. Ungaro, MD, said in an interview. Dr. Ungaro, who is with the Icahn School of Medicine at Mount Sinai, New York, discussed IBD and COVID-19 risks at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

This article was updated Jan. 27, 2021.

Multicenter and population cohort studies suggest that patients with inflammatory bowel disease (IBD) are not at unique risk of contracting COVID-19 or experiencing worse outcomes, with the exception of a few risk factors such as corticosteroid use and combination therapy that appear tied to greater risk of hospitalization and mortality. The findings line up well with previous experience with infectious disease and are reassuring, but they also underscore the need to taper steroids and de-escalate from combination therapy, when possible.

“There is not a clear increased risk of getting COVID-19 among IBD patients compared to the general population, and that seems to hold even if you look at certain medication types, [even] if patients are on immunosuppressives like thiopurines or anti-TNF [anti–tumor necrosis factor] drugs,” Ryan C. Ungaro, MD, said in an interview. Dr. Ungaro, who is with the Icahn School of Medicine at Mount Sinai, New York, discussed IBD and COVID-19 risks at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

This article was updated Jan. 27, 2021.

The COVID-19 pandemic led to a drastic reduction in lung cancer screening, but the rate of decline was similar between Whites and non-Whites and between rural and nonrural populations. All groups saw their rates of lung cancer screening (LCS) return to near prepandemic levels by June 2020, according to a new analysis of two academic and two community imaging sites in North Carolina.

The study was led by Louise Henderson, PhD, of the Lineberger Comprehensive Cancer Center, and M. Patricia Rivera, MD, FCCP, of the department of medicine, division of pulmonary disease and critical care medicine, both at the University of North Carolina at Chapel Hill. The findings appeared online in Chest.

“I am [not] surprised by the decline, but I am certainly reassured,” Abbie Begnaud, MD, FCCP, said in an interview. Dr. Begnaud is assistant professor of medicine at the University of Minnesota, Minneapolis. She was not involved in the study.

The COVID-19 pandemic led to a drastic reduction in lung cancer screening, but the rate of decline was similar between Whites and non-Whites and between rural and nonrural populations. All groups saw their rates of lung cancer screening (LCS) return to near prepandemic levels by June 2020, according to a new analysis of two academic and two community imaging sites in North Carolina.

The study was led by Louise Henderson, PhD, of the Lineberger Comprehensive Cancer Center, and M. Patricia Rivera, MD, FCCP, of the department of medicine, division of pulmonary disease and critical care medicine, both at the University of North Carolina at Chapel Hill. The findings appeared online in Chest.

“I am [not] surprised by the decline, but I am certainly reassured,” Abbie Begnaud, MD, FCCP, said in an interview. Dr. Begnaud is assistant professor of medicine at the University of Minnesota, Minneapolis. She was not involved in the study.

The COVID-19 pandemic led to a drastic reduction in lung cancer screening, but the rate of decline was similar between Whites and non-Whites and between rural and nonrural populations. All groups saw their rates of lung cancer screening (LCS) return to near prepandemic levels by June 2020, according to a new analysis of two academic and two community imaging sites in North Carolina.

The study was led by Louise Henderson, PhD, of the Lineberger Comprehensive Cancer Center, and M. Patricia Rivera, MD, FCCP, of the department of medicine, division of pulmonary disease and critical care medicine, both at the University of North Carolina at Chapel Hill. The findings appeared online in Chest.

“I am [not] surprised by the decline, but I am certainly reassured,” Abbie Begnaud, MD, FCCP, said in an interview. Dr. Begnaud is assistant professor of medicine at the University of Minnesota, Minneapolis. She was not involved in the study.

Until now, the neurological manifestations of COVID-19 have been believed to be a result of direct damage to nerve cells. However, a new study suggests that the virus might actually damage the brain’s small blood vessels rather than nerve cells themselves.

A postmortem analysis found abnormalities in the brains of a small sample of patients with COVID-19, suggesting inflammation and vascular damage to the brain stem and olfactory bulb. The findings add further weight to previous research into neurological complications from COVID-19, according to Anna Cervantes, MD. Dr. Cervantes is assistant professor of neurology at the Boston University and has been studying the neurological effects of COVID-19, though she was not involved in this study. “I can tell from my personal experience, and things we’ve published on and the literature that’s out there – there are patients that are having complications like stroke that aren’t even critically ill from COVID. We’re seeing that not in just the acute setting, but also in a delayed fashion. Even though most of the coagulopathy is largely venous and probably microvascular, this does affect the brain through a myriad of ways,” Dr. Cervantes said.

The research was published online Jan. 12 in the New England Journal of Medicine. Myoung‑Hwa Lee, PhD, was the lead author.

The study included high resolution magnetic resonance imaging and histopathological examination of 13 individuals with a median age of 50 years. Among 10 patients with brain alterations, the researchers conducted further studies in 5 individuals using multiplex fluorescence imaging and chromogenic immunostaining in all 10.

The team conducted conventional histopathology on the brains of 18 individuals. Fourteen had a history of chronic illness, including diabetes, and hypertension, and 11 had died unexpectedly or been found dead. Magnetic resonance microscopy revealed punctuate hypo-intensities in nine subjects, indicating microvascular injury and fibrinogen leakage. Histopathology using fluorescence imaging showed the same features. Collagen IV immunostaining showed thinning of the basal lamina of the endothelial cells in five patients. Ten patients had congested blood vessels and surrounding fibrinogen leakage, but comparatively intact vasculature. The researchers interpreted linear hypo-intensities as micro-hemorrhages.

The researchers found little perivascular inflammation, and no vascular occlusion. Thirteen subjects had perivascular-activated microglia, macrophage infiltrates, and hypertrophic astrocytes. Eight had CD3+ and CD8+ T cells in the perivascular spaces and in lumens next to endothelial cells, which could help explain vascular injury.

The researchers found no evidence of the SARS-CoV-2 virus itself, despite efforts using polymerase chain reaction with multiple primer sets, RNA sequencing within the brain, or RNA in situ hybridization and immunostaining. Subjects may have cleared the virus by the time they died, or viral copy numbers could have been below the detection limit of the assays.

The researchers also obtained a convenience sample of subjects who had died from COVID-19. Magnetic resonance microscopy, histopathology, and immunohistochemical analysis of sections revealed microvascular injury in the brain and olfactory bulb, despite no evidence of viral infection. The authors stressed that they could not draw conclusions about the neurological features of COVID-19 because of a lack of clinical information.

Dr. Cervantes noted that limitation: “We’re seeing a lot of patients with encephalopathy or alterations in their mental status. A lot of things can cause that, and some are common in patients who are critically ill, like medications and metabolic derangement.”

Still, the findings could help to inform future medical management. “There’s going to be a large number of patients who don’t have really bad pulmonary disease but still may have encephalopathy. So if there is small vessel involvement because of inflammation that we might not necessarily catch in a lumbar puncture or routine imaging, there’s still somebody we can make better (using) steroids. Having more information on what’s happening on a pathophysiologic level and on pathology is really helpful.”

The study was supported by internal funds from the National Institute of Neurological Disorders and Stroke. Dr. Cervantes has no relevant financial disclosures.

Until now, the neurological manifestations of COVID-19 have been believed to be a result of direct damage to nerve cells. However, a new study suggests that the virus might actually damage the brain’s small blood vessels rather than nerve cells themselves.

A postmortem analysis found abnormalities in the brains of a small sample of patients with COVID-19, suggesting inflammation and vascular damage to the brain stem and olfactory bulb. The findings add further weight to previous research into neurological complications from COVID-19, according to Anna Cervantes, MD. Dr. Cervantes is assistant professor of neurology at the Boston University and has been studying the neurological effects of COVID-19, though she was not involved in this study. “I can tell from my personal experience, and things we’ve published on and the literature that’s out there – there are patients that are having complications like stroke that aren’t even critically ill from COVID. We’re seeing that not in just the acute setting, but also in a delayed fashion. Even though most of the coagulopathy is largely venous and probably microvascular, this does affect the brain through a myriad of ways,” Dr. Cervantes said.

The research was published online Jan. 12 in the New England Journal of Medicine. Myoung‑Hwa Lee, PhD, was the lead author.

The study included high resolution magnetic resonance imaging and histopathological examination of 13 individuals with a median age of 50 years. Among 10 patients with brain alterations, the researchers conducted further studies in 5 individuals using multiplex fluorescence imaging and chromogenic immunostaining in all 10.

The team conducted conventional histopathology on the brains of 18 individuals. Fourteen had a history of chronic illness, including diabetes, and hypertension, and 11 had died unexpectedly or been found dead. Magnetic resonance microscopy revealed punctuate hypo-intensities in nine subjects, indicating microvascular injury and fibrinogen leakage. Histopathology using fluorescence imaging showed the same features. Collagen IV immunostaining showed thinning of the basal lamina of the endothelial cells in five patients. Ten patients had congested blood vessels and surrounding fibrinogen leakage, but comparatively intact vasculature. The researchers interpreted linear hypo-intensities as micro-hemorrhages.

The researchers found little perivascular inflammation, and no vascular occlusion. Thirteen subjects had perivascular-activated microglia, macrophage infiltrates, and hypertrophic astrocytes. Eight had CD3+ and CD8+ T cells in the perivascular spaces and in lumens next to endothelial cells, which could help explain vascular injury.

The researchers found no evidence of the SARS-CoV-2 virus itself, despite efforts using polymerase chain reaction with multiple primer sets, RNA sequencing within the brain, or RNA in situ hybridization and immunostaining. Subjects may have cleared the virus by the time they died, or viral copy numbers could have been below the detection limit of the assays.

The researchers also obtained a convenience sample of subjects who had died from COVID-19. Magnetic resonance microscopy, histopathology, and immunohistochemical analysis of sections revealed microvascular injury in the brain and olfactory bulb, despite no evidence of viral infection. The authors stressed that they could not draw conclusions about the neurological features of COVID-19 because of a lack of clinical information.

Dr. Cervantes noted that limitation: “We’re seeing a lot of patients with encephalopathy or alterations in their mental status. A lot of things can cause that, and some are common in patients who are critically ill, like medications and metabolic derangement.”

Still, the findings could help to inform future medical management. “There’s going to be a large number of patients who don’t have really bad pulmonary disease but still may have encephalopathy. So if there is small vessel involvement because of inflammation that we might not necessarily catch in a lumbar puncture or routine imaging, there’s still somebody we can make better (using) steroids. Having more information on what’s happening on a pathophysiologic level and on pathology is really helpful.”

The study was supported by internal funds from the National Institute of Neurological Disorders and Stroke. Dr. Cervantes has no relevant financial disclosures.

Until now, the neurological manifestations of COVID-19 have been believed to be a result of direct damage to nerve cells. However, a new study suggests that the virus might actually damage the brain’s small blood vessels rather than nerve cells themselves.

A postmortem analysis found abnormalities in the brains of a small sample of patients with COVID-19, suggesting inflammation and vascular damage to the brain stem and olfactory bulb. The findings add further weight to previous research into neurological complications from COVID-19, according to Anna Cervantes, MD. Dr. Cervantes is assistant professor of neurology at the Boston University and has been studying the neurological effects of COVID-19, though she was not involved in this study. “I can tell from my personal experience, and things we’ve published on and the literature that’s out there – there are patients that are having complications like stroke that aren’t even critically ill from COVID. We’re seeing that not in just the acute setting, but also in a delayed fashion. Even though most of the coagulopathy is largely venous and probably microvascular, this does affect the brain through a myriad of ways,” Dr. Cervantes said.

The research was published online Jan. 12 in the New England Journal of Medicine. Myoung‑Hwa Lee, PhD, was the lead author.

The study included high resolution magnetic resonance imaging and histopathological examination of 13 individuals with a median age of 50 years. Among 10 patients with brain alterations, the researchers conducted further studies in 5 individuals using multiplex fluorescence imaging and chromogenic immunostaining in all 10.

The team conducted conventional histopathology on the brains of 18 individuals. Fourteen had a history of chronic illness, including diabetes, and hypertension, and 11 had died unexpectedly or been found dead. Magnetic resonance microscopy revealed punctuate hypo-intensities in nine subjects, indicating microvascular injury and fibrinogen leakage. Histopathology using fluorescence imaging showed the same features. Collagen IV immunostaining showed thinning of the basal lamina of the endothelial cells in five patients. Ten patients had congested blood vessels and surrounding fibrinogen leakage, but comparatively intact vasculature. The researchers interpreted linear hypo-intensities as micro-hemorrhages.

The researchers found little perivascular inflammation, and no vascular occlusion. Thirteen subjects had perivascular-activated microglia, macrophage infiltrates, and hypertrophic astrocytes. Eight had CD3+ and CD8+ T cells in the perivascular spaces and in lumens next to endothelial cells, which could help explain vascular injury.

The researchers found no evidence of the SARS-CoV-2 virus itself, despite efforts using polymerase chain reaction with multiple primer sets, RNA sequencing within the brain, or RNA in situ hybridization and immunostaining. Subjects may have cleared the virus by the time they died, or viral copy numbers could have been below the detection limit of the assays.

The researchers also obtained a convenience sample of subjects who had died from COVID-19. Magnetic resonance microscopy, histopathology, and immunohistochemical analysis of sections revealed microvascular injury in the brain and olfactory bulb, despite no evidence of viral infection. The authors stressed that they could not draw conclusions about the neurological features of COVID-19 because of a lack of clinical information.

Dr. Cervantes noted that limitation: “We’re seeing a lot of patients with encephalopathy or alterations in their mental status. A lot of things can cause that, and some are common in patients who are critically ill, like medications and metabolic derangement.”

Still, the findings could help to inform future medical management. “There’s going to be a large number of patients who don’t have really bad pulmonary disease but still may have encephalopathy. So if there is small vessel involvement because of inflammation that we might not necessarily catch in a lumbar puncture or routine imaging, there’s still somebody we can make better (using) steroids. Having more information on what’s happening on a pathophysiologic level and on pathology is really helpful.”

The study was supported by internal funds from the National Institute of Neurological Disorders and Stroke. Dr. Cervantes has no relevant financial disclosures.

Malpractice lawsuits related to colonoscopy continue to pose challenges for practitioners, and a new analysis reveals that errors related to sedation are more likely to be awarded to plaintiffs. Primary care physicians and surgeons are often codefendants, which emphasizes the importance of interdisciplinary care in colonoscopy.

Cases involving informed consent were more likely to be ruled for the defendant, while those tied to medication error favored the plaintiff, according to an analysis of cases from the Westlaw legal database. The study, led by Krishan S. Patel and Sushil Ahlawat of Rutgers New Jersey Medical School, Newark, was published in the Journal of Clinical Gastroenterology.

According to the authors, 55% of physicians face a malpractice suit at some point in their careers, and gastroenterology ranks as the sixth most common specialty named in malpractice suits. Every year, about 13% of gastroenterologists confront malpractice allegations, and colonoscopy is the most common reason.

The researchers searched the Westlaw legal database for malpractice cases involving colonoscopy or sigmoidoscopy, identifying 305 cases between 1980 and 2017. The average patient age was 54.9 years, and 52.8% of cases were brought by female patients. The most cases were from New York (21.0%), followed by California (13.4%), Pennsylvania (13.1%), Massachusetts (12.5%), and New Jersey (7.9%). Gastroenterologists were named in 71.1% of cases, internists in 25.6%, and surgeons in 14.8%.

A little more than half (51.8%) of cases were ruled in favor of the defendant, and 25% for the plaintiff; 17% were settled, and 6% had a mixed outcome. Payouts ranged from $30,000 to $500,000,000, with a median of $995,000.

There were multiple causes of litigation listed in 83.6% of cases. The most frequent causes were delayed treatment (65.9%), delayed diagnosis (65.6%), procedural error/negligence (44.3%), and failure to refer/reorder tests (25.6%).

Of 135 cases alleging procedural negligence, 90 (67%) named perforation. Among 79 cases that cited a failure to refer and order appropriate tests, 97% claimed the defendant missed a cancerous lesion. In cases alleging missed cancers, 31% were in the cecum, and 23% in the anus.

A logistic regression analysis of factors associated with a verdict for the defendant found “lack of informed consent” to be an independent predictor of defendant verdict (odds ratio, 4.05; P = .004). “Medication error” was associated with reduced defendant success (OR, 0.17; P=.023). There were nonsignificant trends between reduced odds of a verdict for the defendant and lawsuits that named “delay in diagnosis” (OR, 0.35; P = .060) and “failure to refer” (OR, 0.51; P = .074).

The authors sound a dire note about the number of malpractice suits brought against gastroenterologists, but Lawrence Kosinski, MD, is more sanguine. He notes that gastroenterologists have low insurance premiums, compared with other specialties, but recognizes that colonoscopies are a significant source of risk.

Dr. Kosinski, who is chief medical officer at SonarMD and formerly a managing partner at the Illinois Gastroenterology Group, said in an interview that the study is revealing. “It comes out in the article: Acts of omission are more dangerous to the physician than acts of commission. Not finding that cancer, not acting on that malignant polyp, not pursuing it, is much more likely to get you in trouble than taking it off and perforating a colon,” said Dr. Kosinski, who was not involved in the study.

To gastroenterologists seeking to reduce their risks, he offered advice: You shouldn’t assume that the patient has read the information provided. Risks of anesthesia and the procedure should be directly communicated. It’s also important to document the procedure, including pictures of the cecum and rectal retroflexion. Finally, don’t rush. “This isn’t a race. Clean the colon, make sure you don’t miss something. If that person pops up in 3 years with a cancer, someone may go after you,” said Dr. Kosinski.

No source of funding was disclosed. Dr. Kosinski has no relevant financial disclosures.

Malpractice lawsuits related to colonoscopy continue to pose challenges for practitioners, and a new analysis reveals that errors related to sedation are more likely to be awarded to plaintiffs. Primary care physicians and surgeons are often codefendants, which emphasizes the importance of interdisciplinary care in colonoscopy.

Cases involving informed consent were more likely to be ruled for the defendant, while those tied to medication error favored the plaintiff, according to an analysis of cases from the Westlaw legal database. The study, led by Krishan S. Patel and Sushil Ahlawat of Rutgers New Jersey Medical School, Newark, was published in the Journal of Clinical Gastroenterology.

According to the authors, 55% of physicians face a malpractice suit at some point in their careers, and gastroenterology ranks as the sixth most common specialty named in malpractice suits. Every year, about 13% of gastroenterologists confront malpractice allegations, and colonoscopy is the most common reason.

The researchers searched the Westlaw legal database for malpractice cases involving colonoscopy or sigmoidoscopy, identifying 305 cases between 1980 and 2017. The average patient age was 54.9 years, and 52.8% of cases were brought by female patients. The most cases were from New York (21.0%), followed by California (13.4%), Pennsylvania (13.1%), Massachusetts (12.5%), and New Jersey (7.9%). Gastroenterologists were named in 71.1% of cases, internists in 25.6%, and surgeons in 14.8%.

A little more than half (51.8%) of cases were ruled in favor of the defendant, and 25% for the plaintiff; 17% were settled, and 6% had a mixed outcome. Payouts ranged from $30,000 to $500,000,000, with a median of $995,000.

There were multiple causes of litigation listed in 83.6% of cases. The most frequent causes were delayed treatment (65.9%), delayed diagnosis (65.6%), procedural error/negligence (44.3%), and failure to refer/reorder tests (25.6%).

Of 135 cases alleging procedural negligence, 90 (67%) named perforation. Among 79 cases that cited a failure to refer and order appropriate tests, 97% claimed the defendant missed a cancerous lesion. In cases alleging missed cancers, 31% were in the cecum, and 23% in the anus.

A logistic regression analysis of factors associated with a verdict for the defendant found “lack of informed consent” to be an independent predictor of defendant verdict (odds ratio, 4.05; P = .004). “Medication error” was associated with reduced defendant success (OR, 0.17; P=.023). There were nonsignificant trends between reduced odds of a verdict for the defendant and lawsuits that named “delay in diagnosis” (OR, 0.35; P = .060) and “failure to refer” (OR, 0.51; P = .074).

The authors sound a dire note about the number of malpractice suits brought against gastroenterologists, but Lawrence Kosinski, MD, is more sanguine. He notes that gastroenterologists have low insurance premiums, compared with other specialties, but recognizes that colonoscopies are a significant source of risk.

Dr. Kosinski, who is chief medical officer at SonarMD and formerly a managing partner at the Illinois Gastroenterology Group, said in an interview that the study is revealing. “It comes out in the article: Acts of omission are more dangerous to the physician than acts of commission. Not finding that cancer, not acting on that malignant polyp, not pursuing it, is much more likely to get you in trouble than taking it off and perforating a colon,” said Dr. Kosinski, who was not involved in the study.

To gastroenterologists seeking to reduce their risks, he offered advice: You shouldn’t assume that the patient has read the information provided. Risks of anesthesia and the procedure should be directly communicated. It’s also important to document the procedure, including pictures of the cecum and rectal retroflexion. Finally, don’t rush. “This isn’t a race. Clean the colon, make sure you don’t miss something. If that person pops up in 3 years with a cancer, someone may go after you,” said Dr. Kosinski.

No source of funding was disclosed. Dr. Kosinski has no relevant financial disclosures.

Malpractice lawsuits related to colonoscopy continue to pose challenges for practitioners, and a new analysis reveals that errors related to sedation are more likely to be awarded to plaintiffs. Primary care physicians and surgeons are often codefendants, which emphasizes the importance of interdisciplinary care in colonoscopy.

Cases involving informed consent were more likely to be ruled for the defendant, while those tied to medication error favored the plaintiff, according to an analysis of cases from the Westlaw legal database. The study, led by Krishan S. Patel and Sushil Ahlawat of Rutgers New Jersey Medical School, Newark, was published in the Journal of Clinical Gastroenterology.

According to the authors, 55% of physicians face a malpractice suit at some point in their careers, and gastroenterology ranks as the sixth most common specialty named in malpractice suits. Every year, about 13% of gastroenterologists confront malpractice allegations, and colonoscopy is the most common reason.

The researchers searched the Westlaw legal database for malpractice cases involving colonoscopy or sigmoidoscopy, identifying 305 cases between 1980 and 2017. The average patient age was 54.9 years, and 52.8% of cases were brought by female patients. The most cases were from New York (21.0%), followed by California (13.4%), Pennsylvania (13.1%), Massachusetts (12.5%), and New Jersey (7.9%). Gastroenterologists were named in 71.1% of cases, internists in 25.6%, and surgeons in 14.8%.

A little more than half (51.8%) of cases were ruled in favor of the defendant, and 25% for the plaintiff; 17% were settled, and 6% had a mixed outcome. Payouts ranged from $30,000 to $500,000,000, with a median of $995,000.

There were multiple causes of litigation listed in 83.6% of cases. The most frequent causes were delayed treatment (65.9%), delayed diagnosis (65.6%), procedural error/negligence (44.3%), and failure to refer/reorder tests (25.6%).

Of 135 cases alleging procedural negligence, 90 (67%) named perforation. Among 79 cases that cited a failure to refer and order appropriate tests, 97% claimed the defendant missed a cancerous lesion. In cases alleging missed cancers, 31% were in the cecum, and 23% in the anus.

A logistic regression analysis of factors associated with a verdict for the defendant found “lack of informed consent” to be an independent predictor of defendant verdict (odds ratio, 4.05; P = .004). “Medication error” was associated with reduced defendant success (OR, 0.17; P=.023). There were nonsignificant trends between reduced odds of a verdict for the defendant and lawsuits that named “delay in diagnosis” (OR, 0.35; P = .060) and “failure to refer” (OR, 0.51; P = .074).

The authors sound a dire note about the number of malpractice suits brought against gastroenterologists, but Lawrence Kosinski, MD, is more sanguine. He notes that gastroenterologists have low insurance premiums, compared with other specialties, but recognizes that colonoscopies are a significant source of risk.

Dr. Kosinski, who is chief medical officer at SonarMD and formerly a managing partner at the Illinois Gastroenterology Group, said in an interview that the study is revealing. “It comes out in the article: Acts of omission are more dangerous to the physician than acts of commission. Not finding that cancer, not acting on that malignant polyp, not pursuing it, is much more likely to get you in trouble than taking it off and perforating a colon,” said Dr. Kosinski, who was not involved in the study.

To gastroenterologists seeking to reduce their risks, he offered advice: You shouldn’t assume that the patient has read the information provided. Risks of anesthesia and the procedure should be directly communicated. It’s also important to document the procedure, including pictures of the cecum and rectal retroflexion. Finally, don’t rush. “This isn’t a race. Clean the colon, make sure you don’t miss something. If that person pops up in 3 years with a cancer, someone may go after you,” said Dr. Kosinski.

No source of funding was disclosed. Dr. Kosinski has no relevant financial disclosures.

An update of the U.S. Preventive Services Task Force recommendation for hepatitis B screening shows little change from the 2014 version, but some wonder if it should have gone farther than a risk-based approach.

The recommendation, which was published in JAMA, reinforces that screening should be conducted among adolescents and adults who are at increased risk of hepatitis B virus (HBV) infection. The USPSTF named six categories of individuals at increased risk of infection: Persons born in countries with a 2% or higher prevalence of hepatitis B, such as Asia, Africa, the Pacific Islands, and some areas of South America; unvaccinated individuals born in the United States to parents from regions with a very high prevalence of HBV (≥8%); HIV-positive individuals; those who use injected drugs; men who have sex with men; and people who live with people who have HBV or who have HBV-infected sexual partners. It also recommended that pregnant women be screened for HBV infection during their first prenatal visit.

“I view the updated recommendations as an important document because it validates the importance of HBV screening, and the Grade B recommendation supports mandated insurance coverage for the screening test,” said Joseph Lim, MD, who is a professor of medicine at Yale University and director of the Yale Viral Hepatitis Program, both in New Haven, Conn.

Still, the recommendation could have gone further. Notably absent from the USPSTF document, yet featured in recommendations from the Centers for Disease Control and Prevention and the American Association for the Study of Liver Disease, are patients who have diabetes, are on immunosuppressive therapy, or have elevated liver enzymes or liver disease. Furthermore, a single-center study found that, among physicians administering immunosuppressive therapy, a setting in which HBV reactivation is a concern, there were low rates of screening for HBV infection, and the physicians did not reliably identify high-risk patients.

“This may also be viewed as a lost opportunity. Evidence suggests that risk factor–based screening is ineffective for the identification of chronic conditions such as hepatitis B. Risk factor–based screening is difficult to implement across health systems and exacerbates the burden on community-based organizations that are motivated to address viral hepatitis. It may further exacerbate labeling, stigma, and discrimination within already marginalized communities that are deemed to be at high risk,” said Dr. Lim.

A similar view was expressed by Avegail Flores, MD, medical director of liver transplantation at the Michael E. DeBakey Veterans Affairs Medical Center and assistant professor of medicine at Baylor College of Medicine, both in Houston. “This is a good launching point, and with further evidence provided, hopefully it will also bring in a broader conversation about other persons who are at risk but not included in these criteria.” Neither Dr. Lim nor Dr. Flores were involved in the study.

She noted that resistance to universal screening may be caused by the relatively low prevalence of hepatitis B infection in the United States. However, the CDC estimates that only about 61% of people infected with HBV are aware of it. “I don’t think we have done a good job screening those who are at risk,” said Dr. Flores.

Universal screening could help, but would have a low yield. Dr. Flores suggested expansion into other at-risk groups, such as Baby Boomers. With respect to other risk groups that could be stigmatized or discriminated against, Dr. Flores recalled her medical school days when some students went directly into underserved communities to provide information and screening services. “We have to think of creative ways of how to reach out to people, not just relying on the usual physician-patient relationship.”

The issue is especially timely because the World Health Organization has declared a target to reduce new hepatitis B infections by 90% by 2030, and that will require addressing gaps in diagnosis. “That’s why these recommendations are so consequential. We are at a critical juncture in terms of global hepatitis elimination efforts. There is a time sensitive need to have multistakeholder engagement in ensuring that all aspects of the care cascade are addressed. Because of the central role of screening and diagnosis, it’s of critical importance that organizations such as USPSTF are in alignment with other organizations that have already issued clear guidance on who should be screened. It is (my) hope that further examination of the evidence-base will further support broadening USPSTF guidance to include a larger group of at-risk individuals, or ideally a universal screening strategy,” said Dr. Lim.

The recommendation’s authors received travel reimbursement for their involvement, and one author reported receiving grants and personal fees from Healthwise. Dr. Flores has no relevant financial disclosures. Dr. Lim is a member of the American Association for the Study of Liver Disease’s Viral Hepatitis Elimination Task Force.

SOURCE: U.S. Preventive Services Task Force. JAMA. 2020 Dec 15. doi: 10.1001/jama.2020.22980.

Updated Jan. 20, 2021

An update of the U.S. Preventive Services Task Force recommendation for hepatitis B screening shows little change from the 2014 version, but some wonder if it should have gone farther than a risk-based approach.

The recommendation, which was published in JAMA, reinforces that screening should be conducted among adolescents and adults who are at increased risk of hepatitis B virus (HBV) infection. The USPSTF named six categories of individuals at increased risk of infection: Persons born in countries with a 2% or higher prevalence of hepatitis B, such as Asia, Africa, the Pacific Islands, and some areas of South America; unvaccinated individuals born in the United States to parents from regions with a very high prevalence of HBV (≥8%); HIV-positive individuals; those who use injected drugs; men who have sex with men; and people who live with people who have HBV or who have HBV-infected sexual partners. It also recommended that pregnant women be screened for HBV infection during their first prenatal visit.

“I view the updated recommendations as an important document because it validates the importance of HBV screening, and the Grade B recommendation supports mandated insurance coverage for the screening test,” said Joseph Lim, MD, who is a professor of medicine at Yale University and director of the Yale Viral Hepatitis Program, both in New Haven, Conn.

Still, the recommendation could have gone further. Notably absent from the USPSTF document, yet featured in recommendations from the Centers for Disease Control and Prevention and the American Association for the Study of Liver Disease, are patients who have diabetes, are on immunosuppressive therapy, or have elevated liver enzymes or liver disease. Furthermore, a single-center study found that, among physicians administering immunosuppressive therapy, a setting in which HBV reactivation is a concern, there were low rates of screening for HBV infection, and the physicians did not reliably identify high-risk patients.

“This may also be viewed as a lost opportunity. Evidence suggests that risk factor–based screening is ineffective for the identification of chronic conditions such as hepatitis B. Risk factor–based screening is difficult to implement across health systems and exacerbates the burden on community-based organizations that are motivated to address viral hepatitis. It may further exacerbate labeling, stigma, and discrimination within already marginalized communities that are deemed to be at high risk,” said Dr. Lim.

A similar view was expressed by Avegail Flores, MD, medical director of liver transplantation at the Michael E. DeBakey Veterans Affairs Medical Center and assistant professor of medicine at Baylor College of Medicine, both in Houston. “This is a good launching point, and with further evidence provided, hopefully it will also bring in a broader conversation about other persons who are at risk but not included in these criteria.” Neither Dr. Lim nor Dr. Flores were involved in the study.

She noted that resistance to universal screening may be caused by the relatively low prevalence of hepatitis B infection in the United States. However, the CDC estimates that only about 61% of people infected with HBV are aware of it. “I don’t think we have done a good job screening those who are at risk,” said Dr. Flores.

Universal screening could help, but would have a low yield. Dr. Flores suggested expansion into other at-risk groups, such as Baby Boomers. With respect to other risk groups that could be stigmatized or discriminated against, Dr. Flores recalled her medical school days when some students went directly into underserved communities to provide information and screening services. “We have to think of creative ways of how to reach out to people, not just relying on the usual physician-patient relationship.”

The issue is especially timely because the World Health Organization has declared a target to reduce new hepatitis B infections by 90% by 2030, and that will require addressing gaps in diagnosis. “That’s why these recommendations are so consequential. We are at a critical juncture in terms of global hepatitis elimination efforts. There is a time sensitive need to have multistakeholder engagement in ensuring that all aspects of the care cascade are addressed. Because of the central role of screening and diagnosis, it’s of critical importance that organizations such as USPSTF are in alignment with other organizations that have already issued clear guidance on who should be screened. It is (my) hope that further examination of the evidence-base will further support broadening USPSTF guidance to include a larger group of at-risk individuals, or ideally a universal screening strategy,” said Dr. Lim.

The recommendation’s authors received travel reimbursement for their involvement, and one author reported receiving grants and personal fees from Healthwise. Dr. Flores has no relevant financial disclosures. Dr. Lim is a member of the American Association for the Study of Liver Disease’s Viral Hepatitis Elimination Task Force.

SOURCE: U.S. Preventive Services Task Force. JAMA. 2020 Dec 15. doi: 10.1001/jama.2020.22980.

Updated Jan. 20, 2021

An update of the U.S. Preventive Services Task Force recommendation for hepatitis B screening shows little change from the 2014 version, but some wonder if it should have gone farther than a risk-based approach.

The recommendation, which was published in JAMA, reinforces that screening should be conducted among adolescents and adults who are at increased risk of hepatitis B virus (HBV) infection. The USPSTF named six categories of individuals at increased risk of infection: Persons born in countries with a 2% or higher prevalence of hepatitis B, such as Asia, Africa, the Pacific Islands, and some areas of South America; unvaccinated individuals born in the United States to parents from regions with a very high prevalence of HBV (≥8%); HIV-positive individuals; those who use injected drugs; men who have sex with men; and people who live with people who have HBV or who have HBV-infected sexual partners. It also recommended that pregnant women be screened for HBV infection during their first prenatal visit.

“I view the updated recommendations as an important document because it validates the importance of HBV screening, and the Grade B recommendation supports mandated insurance coverage for the screening test,” said Joseph Lim, MD, who is a professor of medicine at Yale University and director of the Yale Viral Hepatitis Program, both in New Haven, Conn.

Still, the recommendation could have gone further. Notably absent from the USPSTF document, yet featured in recommendations from the Centers for Disease Control and Prevention and the American Association for the Study of Liver Disease, are patients who have diabetes, are on immunosuppressive therapy, or have elevated liver enzymes or liver disease. Furthermore, a single-center study found that, among physicians administering immunosuppressive therapy, a setting in which HBV reactivation is a concern, there were low rates of screening for HBV infection, and the physicians did not reliably identify high-risk patients.

“This may also be viewed as a lost opportunity. Evidence suggests that risk factor–based screening is ineffective for the identification of chronic conditions such as hepatitis B. Risk factor–based screening is difficult to implement across health systems and exacerbates the burden on community-based organizations that are motivated to address viral hepatitis. It may further exacerbate labeling, stigma, and discrimination within already marginalized communities that are deemed to be at high risk,” said Dr. Lim.

A similar view was expressed by Avegail Flores, MD, medical director of liver transplantation at the Michael E. DeBakey Veterans Affairs Medical Center and assistant professor of medicine at Baylor College of Medicine, both in Houston. “This is a good launching point, and with further evidence provided, hopefully it will also bring in a broader conversation about other persons who are at risk but not included in these criteria.” Neither Dr. Lim nor Dr. Flores were involved in the study.

She noted that resistance to universal screening may be caused by the relatively low prevalence of hepatitis B infection in the United States. However, the CDC estimates that only about 61% of people infected with HBV are aware of it. “I don’t think we have done a good job screening those who are at risk,” said Dr. Flores.

Universal screening could help, but would have a low yield. Dr. Flores suggested expansion into other at-risk groups, such as Baby Boomers. With respect to other risk groups that could be stigmatized or discriminated against, Dr. Flores recalled her medical school days when some students went directly into underserved communities to provide information and screening services. “We have to think of creative ways of how to reach out to people, not just relying on the usual physician-patient relationship.”

The issue is especially timely because the World Health Organization has declared a target to reduce new hepatitis B infections by 90% by 2030, and that will require addressing gaps in diagnosis. “That’s why these recommendations are so consequential. We are at a critical juncture in terms of global hepatitis elimination efforts. There is a time sensitive need to have multistakeholder engagement in ensuring that all aspects of the care cascade are addressed. Because of the central role of screening and diagnosis, it’s of critical importance that organizations such as USPSTF are in alignment with other organizations that have already issued clear guidance on who should be screened. It is (my) hope that further examination of the evidence-base will further support broadening USPSTF guidance to include a larger group of at-risk individuals, or ideally a universal screening strategy,” said Dr. Lim.

The recommendation’s authors received travel reimbursement for their involvement, and one author reported receiving grants and personal fees from Healthwise. Dr. Flores has no relevant financial disclosures. Dr. Lim is a member of the American Association for the Study of Liver Disease’s Viral Hepatitis Elimination Task Force.

SOURCE: U.S. Preventive Services Task Force. JAMA. 2020 Dec 15. doi: 10.1001/jama.2020.22980.

Updated Jan. 20, 2021

In patients who undergo resection of pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy, reduction in tumor size between diagnosis and surgery is associated with improved survival, according to a new single-center, retrospective analysis. The researchers compared tumor size as measured by endoscopic ultrasound (EUS) and found that a threshold of 47% or greater reduction in tumor size at resection was associated with a doubling in the 3-year survival rate.

The study, led by Rohit Das, MD, of the University of Pittsburgh Medical Center, was published in Clinical Gastroenterology and Hepatology.

The research represents only a small percentage of patients since most diagnosed with PDAC have locally advanced or metastatic disease that rules out surgery. Still, the work puts more emphasis on measuring tumor size while performing EUS, according to Robert Jay Sealock, MD, who is an assistant professor of medicine at Baylor College of Medicine, Houston.

“This is some helpful information that you can relay to the patient, saying that you have a significant decrease in the size of the tumor based on your initial EUS, and your chance of 3- to 5-year survival is going to be a lot higher, compared to somebody that didn’t have that tumor regression. Most of these patients will undergo an EUS anyway, and you’ll commonly if not always measure the tumor size while you’re in there. Now you can apply this information that you already have to give the patients some additional information if they do undergo surgery,” said Dr. Sealock, who was not involved in the research.

Previous efforts to prognosticate postsurgical survival focused on overall tumor burden using multidetector CT (MDCT), carbohydrate antigen 19-9 (CA19-9) levels, and histologic examination following surgery, but all suffer from various limitations. MDCT is not always accurate in its measurement of tumor size, other conditions can also raise CA19-9 levels, and pathologic findings are subjective because sometimes the amount of tumor before neoadjuvant therapy is uncertain.

The researchers mapped survival statistics to EUS and pathologic findings for 340 treatment-naive and 365 neoadjuvant-treated PDAC patients at the University of Pittsburgh Medical Center. They used a 200 patient cohort from the same center who had been treated with neoadjuvant therapy for validation.

Pathology examination revealed that, in the treatment-naive group, 71% of tumors were larger than the size determined during EUS. In 9% of cases there was no change in size (EUS versus pathology T-staging Pearson correlation coefficient, 0.586; P < .001). A similar analysis of MDCT showed a weaker correlation. There was no correlation between preoperative EUS/MDCT findings and postoperative pathology among patients who received neoadjuvant therapy.

In the neoadjuvant therapy group, tumor size was reduced in 31%, was unchanged in 53%, and actually grew in 16%. Three-year overall survival was highest in the reduced group (50%), and lower in the unchanged (37%) and tumor-growth (34%) groups. At 5 years, overall survival was 31%, 19%, and 16%, respectively (P = .003). Compared with those whose tumor size remained the same or grew, those with reduced tumor size had higher 3-year overall survival (50% vs. 33%) and 5-year overall survival (31% vs. 18%; P < .001).

The researchers used recursive positioning to identify the optimal threshold for tumor reduction, and found that a 47% or greater reduction was associated with 67% overall survival at 3 years and 47% at 5 years, compared with 32% and 16% for those with smaller reduction or tumors that maintained or increased in size (P < .001).

The researchers noted that, although their study is large, it remains retrospective in design. Another limitation they cited was that not all patients received the same neoadjuvant therapy. Furthermore, both EUS and pathologic evaluation can be subjective, and it can be difficult to correct for that.

“While additional studies are required, incorporating preoperative EUS and postoperative pathologic tumor size measurements into the standard evaluation of neoadjuvant-treated PDAC patients may guide subsequent management in the adjuvant setting,” the researchers concluded.

The study was funded in part by the National Pancreas Foundation, Sky Foundation, and the Pittsburgh Liver Research Center at the University of Pittsburgh. One author disclosed receiving an honorarium from Foundation Medicine, but the rest reported having nothing to disclose. Dr. Sealock has no relevant financial disclosures.

SOURCE: Das R et al. Clin Gastroenterol Hepatol. 2020 Dec 2. doi: 10.1016/j.cgh.2020.11.041.

In patients who undergo resection of pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy, reduction in tumor size between diagnosis and surgery is associated with improved survival, according to a new single-center, retrospective analysis. The researchers compared tumor size as measured by endoscopic ultrasound (EUS) and found that a threshold of 47% or greater reduction in tumor size at resection was associated with a doubling in the 3-year survival rate.

The study, led by Rohit Das, MD, of the University of Pittsburgh Medical Center, was published in Clinical Gastroenterology and Hepatology.

The research represents only a small percentage of patients since most diagnosed with PDAC have locally advanced or metastatic disease that rules out surgery. Still, the work puts more emphasis on measuring tumor size while performing EUS, according to Robert Jay Sealock, MD, who is an assistant professor of medicine at Baylor College of Medicine, Houston.

“This is some helpful information that you can relay to the patient, saying that you have a significant decrease in the size of the tumor based on your initial EUS, and your chance of 3- to 5-year survival is going to be a lot higher, compared to somebody that didn’t have that tumor regression. Most of these patients will undergo an EUS anyway, and you’ll commonly if not always measure the tumor size while you’re in there. Now you can apply this information that you already have to give the patients some additional information if they do undergo surgery,” said Dr. Sealock, who was not involved in the research.

Previous efforts to prognosticate postsurgical survival focused on overall tumor burden using multidetector CT (MDCT), carbohydrate antigen 19-9 (CA19-9) levels, and histologic examination following surgery, but all suffer from various limitations. MDCT is not always accurate in its measurement of tumor size, other conditions can also raise CA19-9 levels, and pathologic findings are subjective because sometimes the amount of tumor before neoadjuvant therapy is uncertain.

The researchers mapped survival statistics to EUS and pathologic findings for 340 treatment-naive and 365 neoadjuvant-treated PDAC patients at the University of Pittsburgh Medical Center. They used a 200 patient cohort from the same center who had been treated with neoadjuvant therapy for validation.

Pathology examination revealed that, in the treatment-naive group, 71% of tumors were larger than the size determined during EUS. In 9% of cases there was no change in size (EUS versus pathology T-staging Pearson correlation coefficient, 0.586; P < .001). A similar analysis of MDCT showed a weaker correlation. There was no correlation between preoperative EUS/MDCT findings and postoperative pathology among patients who received neoadjuvant therapy.

In the neoadjuvant therapy group, tumor size was reduced in 31%, was unchanged in 53%, and actually grew in 16%. Three-year overall survival was highest in the reduced group (50%), and lower in the unchanged (37%) and tumor-growth (34%) groups. At 5 years, overall survival was 31%, 19%, and 16%, respectively (P = .003). Compared with those whose tumor size remained the same or grew, those with reduced tumor size had higher 3-year overall survival (50% vs. 33%) and 5-year overall survival (31% vs. 18%; P < .001).

The researchers used recursive positioning to identify the optimal threshold for tumor reduction, and found that a 47% or greater reduction was associated with 67% overall survival at 3 years and 47% at 5 years, compared with 32% and 16% for those with smaller reduction or tumors that maintained or increased in size (P < .001).

The researchers noted that, although their study is large, it remains retrospective in design. Another limitation they cited was that not all patients received the same neoadjuvant therapy. Furthermore, both EUS and pathologic evaluation can be subjective, and it can be difficult to correct for that.

“While additional studies are required, incorporating preoperative EUS and postoperative pathologic tumor size measurements into the standard evaluation of neoadjuvant-treated PDAC patients may guide subsequent management in the adjuvant setting,” the researchers concluded.

The study was funded in part by the National Pancreas Foundation, Sky Foundation, and the Pittsburgh Liver Research Center at the University of Pittsburgh. One author disclosed receiving an honorarium from Foundation Medicine, but the rest reported having nothing to disclose. Dr. Sealock has no relevant financial disclosures.

SOURCE: Das R et al. Clin Gastroenterol Hepatol. 2020 Dec 2. doi: 10.1016/j.cgh.2020.11.041.

In patients who undergo resection of pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy, reduction in tumor size between diagnosis and surgery is associated with improved survival, according to a new single-center, retrospective analysis. The researchers compared tumor size as measured by endoscopic ultrasound (EUS) and found that a threshold of 47% or greater reduction in tumor size at resection was associated with a doubling in the 3-year survival rate.

The study, led by Rohit Das, MD, of the University of Pittsburgh Medical Center, was published in Clinical Gastroenterology and Hepatology.

The research represents only a small percentage of patients since most diagnosed with PDAC have locally advanced or metastatic disease that rules out surgery. Still, the work puts more emphasis on measuring tumor size while performing EUS, according to Robert Jay Sealock, MD, who is an assistant professor of medicine at Baylor College of Medicine, Houston.

“This is some helpful information that you can relay to the patient, saying that you have a significant decrease in the size of the tumor based on your initial EUS, and your chance of 3- to 5-year survival is going to be a lot higher, compared to somebody that didn’t have that tumor regression. Most of these patients will undergo an EUS anyway, and you’ll commonly if not always measure the tumor size while you’re in there. Now you can apply this information that you already have to give the patients some additional information if they do undergo surgery,” said Dr. Sealock, who was not involved in the research.

Previous efforts to prognosticate postsurgical survival focused on overall tumor burden using multidetector CT (MDCT), carbohydrate antigen 19-9 (CA19-9) levels, and histologic examination following surgery, but all suffer from various limitations. MDCT is not always accurate in its measurement of tumor size, other conditions can also raise CA19-9 levels, and pathologic findings are subjective because sometimes the amount of tumor before neoadjuvant therapy is uncertain.

The researchers mapped survival statistics to EUS and pathologic findings for 340 treatment-naive and 365 neoadjuvant-treated PDAC patients at the University of Pittsburgh Medical Center. They used a 200 patient cohort from the same center who had been treated with neoadjuvant therapy for validation.

Pathology examination revealed that, in the treatment-naive group, 71% of tumors were larger than the size determined during EUS. In 9% of cases there was no change in size (EUS versus pathology T-staging Pearson correlation coefficient, 0.586; P < .001). A similar analysis of MDCT showed a weaker correlation. There was no correlation between preoperative EUS/MDCT findings and postoperative pathology among patients who received neoadjuvant therapy.

In the neoadjuvant therapy group, tumor size was reduced in 31%, was unchanged in 53%, and actually grew in 16%. Three-year overall survival was highest in the reduced group (50%), and lower in the unchanged (37%) and tumor-growth (34%) groups. At 5 years, overall survival was 31%, 19%, and 16%, respectively (P = .003). Compared with those whose tumor size remained the same or grew, those with reduced tumor size had higher 3-year overall survival (50% vs. 33%) and 5-year overall survival (31% vs. 18%; P < .001).

The researchers used recursive positioning to identify the optimal threshold for tumor reduction, and found that a 47% or greater reduction was associated with 67% overall survival at 3 years and 47% at 5 years, compared with 32% and 16% for those with smaller reduction or tumors that maintained or increased in size (P < .001).

The researchers noted that, although their study is large, it remains retrospective in design. Another limitation they cited was that not all patients received the same neoadjuvant therapy. Furthermore, both EUS and pathologic evaluation can be subjective, and it can be difficult to correct for that.

“While additional studies are required, incorporating preoperative EUS and postoperative pathologic tumor size measurements into the standard evaluation of neoadjuvant-treated PDAC patients may guide subsequent management in the adjuvant setting,” the researchers concluded.

The study was funded in part by the National Pancreas Foundation, Sky Foundation, and the Pittsburgh Liver Research Center at the University of Pittsburgh. One author disclosed receiving an honorarium from Foundation Medicine, but the rest reported having nothing to disclose. Dr. Sealock has no relevant financial disclosures.

SOURCE: Das R et al. Clin Gastroenterol Hepatol. 2020 Dec 2. doi: 10.1016/j.cgh.2020.11.041.

Among patients taking direct oral anticoagulants (DOACs), elective endoscopy procedures carry a risk of bleeding and thromboembolic events similar to that seen in those receiving vitamin K antagonists (VKAs), according to a multicenter, prospective observational study conducted at 12 Spanish academic and community centers.

DOACs have several advantages over VKAs, including more predictable pharmacokinetic profiles and fewer food and drug interactions, but they have not been well studied in the elective endoscopy setting. Some previous studies suggested a lower risk with DOACs than with VKAs, but they were retrospective or based on administrative databases.

It also remains unclear when anticoagulant therapy should be resumed following high-risk procedures. The new study, which was led by Enrique Rodríguez de Santiago of Universidad de Alcalá (Spain) and published in Clinical Gastroenterology and Hepatology, suggested that early resumption may be safe. “It certainly showed there was an acceptable rate of clinically significant rate of bleeding for patients on anticoagulants, and the thing I appreciated the most was that there was no statistically significant difference in terms of bleeding depending on when you resumed the anticoagulant,” said Robert Jay Sealock, MD, assistant professor of medicine at Baylor College of Medicine in Houston. Dr. Sealock was not involved in the study.

The researchers examined data from 1,623 patients who underwent 1,874 endoscopic procedures. Among these patients, 62.7% were taking VKAs, and 37.3% were taking DOACs; 58.9% were men, and the mean age was 74.2 years. Overall, 75.5% were on anticoagulant therapy for atrial fibrillation.

The most common procedures were colonoscopy (68.3%) and esophagogastroduodenoscopy (27.3%).

Within 30 days, The risk of bleeding was similar between patients taking VKAs (6.2%; 95% confidence interval, 4.8-7.8%) and DOACs (6.7%; 95% CI, 4.9-9%). This was true regardless of intervention and site. Overall, 1.4% of subjects experienced a thromboembolic event (95% CI, 0.9-2.1%), and there was no significant difference between the VKA group (1.3%; 95% CI, 0.8-2.2%) and the DOAC group (1.5%; 95% CI, 0.8-2.8%).

Clinically significant gastrointestinal bleeding occurred in 6.4% of subjects (95% CI, 5.3-7.7%); 2.7% of clinically significant gastrointestinal bleeding events were intraprocedural and 4.1% were delayed. The lowest risk of bleeding occurred with diagnostic endoscopy (1.1%) and biopsy (2.2%). The risk of bleeding for high-risk procedures was 11.5% (95% CI, 9.4-14%).

The overall mortality was 1.4%, with two deaths related to thromboembolic events, both in the DOAC group. The other deaths were considered to be unrelated to the procedure or periprocedural interruption of anticoagulants.

The researchers also examined the timing of anticoagulant resumption. Overall, 59.2% of subjects received bridging therapy, including 85% of the VKA group and 16% of the DOAC group (P < .001). This was not associated with increased endoscopy-related bleeding in either the VKA (3.3% with bridging therapy vs. 6.4% without; P = .14) or the DOAC group (8.3% vs. 6.4%; P = .48).

A total of 747 patients underwent a high-risk procedure, 46.3% of patients resumed anticoagulant therapy within 24 hours of the procedure, and 46.2% between 24 and 48 hours. After inverse probability of treatment weighting adjustment, a delay in anticoagulant resumption was not associated with a reduction in the frequency of postprocedural clinically significant gastrointestinal bleeding.

Still, the research left some questions unanswered. Most of the high-risk procedures were hot (41.8%) or cold snare polypectomies (39.8%). There weren’t enough data in the study to evaluate risk in patients undergoing other high-risk procedures such as balloon dilation for strictures, endoscopic ultrasound with fine-needle aspiration, and sphincterotomy. “That’s one group that we still don’t really have enough data about, particularly those patients who are on DOACs,” said Dr. Sealock.

The study also found a high number of patients on bridging therapy. “It highlighted the fact that we probably use bridging therapy too much in patients undergoing endoscopy,” said Dr. Sealock. He recommended using tools that generate recommendations for bridging therapy and timing for withholding and resuming anticoagulants based on procedure and patient characteristics.

SOURCE: de Santiago ER et al. Clin Gastroenterol Hepatol. 2020 Dec 03. doi: 10.1016/j.cgh.2020.11.037.

Among patients taking direct oral anticoagulants (DOACs), elective endoscopy procedures carry a risk of bleeding and thromboembolic events similar to that seen in those receiving vitamin K antagonists (VKAs), according to a multicenter, prospective observational study conducted at 12 Spanish academic and community centers.

DOACs have several advantages over VKAs, including more predictable pharmacokinetic profiles and fewer food and drug interactions, but they have not been well studied in the elective endoscopy setting. Some previous studies suggested a lower risk with DOACs than with VKAs, but they were retrospective or based on administrative databases.

It also remains unclear when anticoagulant therapy should be resumed following high-risk procedures. The new study, which was led by Enrique Rodríguez de Santiago of Universidad de Alcalá (Spain) and published in Clinical Gastroenterology and Hepatology, suggested that early resumption may be safe. “It certainly showed there was an acceptable rate of clinically significant rate of bleeding for patients on anticoagulants, and the thing I appreciated the most was that there was no statistically significant difference in terms of bleeding depending on when you resumed the anticoagulant,” said Robert Jay Sealock, MD, assistant professor of medicine at Baylor College of Medicine in Houston. Dr. Sealock was not involved in the study.

The researchers examined data from 1,623 patients who underwent 1,874 endoscopic procedures. Among these patients, 62.7% were taking VKAs, and 37.3% were taking DOACs; 58.9% were men, and the mean age was 74.2 years. Overall, 75.5% were on anticoagulant therapy for atrial fibrillation.

The most common procedures were colonoscopy (68.3%) and esophagogastroduodenoscopy (27.3%).

Within 30 days, The risk of bleeding was similar between patients taking VKAs (6.2%; 95% confidence interval, 4.8-7.8%) and DOACs (6.7%; 95% CI, 4.9-9%). This was true regardless of intervention and site. Overall, 1.4% of subjects experienced a thromboembolic event (95% CI, 0.9-2.1%), and there was no significant difference between the VKA group (1.3%; 95% CI, 0.8-2.2%) and the DOAC group (1.5%; 95% CI, 0.8-2.8%).

Clinically significant gastrointestinal bleeding occurred in 6.4% of subjects (95% CI, 5.3-7.7%); 2.7% of clinically significant gastrointestinal bleeding events were intraprocedural and 4.1% were delayed. The lowest risk of bleeding occurred with diagnostic endoscopy (1.1%) and biopsy (2.2%). The risk of bleeding for high-risk procedures was 11.5% (95% CI, 9.4-14%).

The overall mortality was 1.4%, with two deaths related to thromboembolic events, both in the DOAC group. The other deaths were considered to be unrelated to the procedure or periprocedural interruption of anticoagulants.

The researchers also examined the timing of anticoagulant resumption. Overall, 59.2% of subjects received bridging therapy, including 85% of the VKA group and 16% of the DOAC group (P < .001). This was not associated with increased endoscopy-related bleeding in either the VKA (3.3% with bridging therapy vs. 6.4% without; P = .14) or the DOAC group (8.3% vs. 6.4%; P = .48).

A total of 747 patients underwent a high-risk procedure, 46.3% of patients resumed anticoagulant therapy within 24 hours of the procedure, and 46.2% between 24 and 48 hours. After inverse probability of treatment weighting adjustment, a delay in anticoagulant resumption was not associated with a reduction in the frequency of postprocedural clinically significant gastrointestinal bleeding.

Still, the research left some questions unanswered. Most of the high-risk procedures were hot (41.8%) or cold snare polypectomies (39.8%). There weren’t enough data in the study to evaluate risk in patients undergoing other high-risk procedures such as balloon dilation for strictures, endoscopic ultrasound with fine-needle aspiration, and sphincterotomy. “That’s one group that we still don’t really have enough data about, particularly those patients who are on DOACs,” said Dr. Sealock.

The study also found a high number of patients on bridging therapy. “It highlighted the fact that we probably use bridging therapy too much in patients undergoing endoscopy,” said Dr. Sealock. He recommended using tools that generate recommendations for bridging therapy and timing for withholding and resuming anticoagulants based on procedure and patient characteristics.

SOURCE: de Santiago ER et al. Clin Gastroenterol Hepatol. 2020 Dec 03. doi: 10.1016/j.cgh.2020.11.037.

Among patients taking direct oral anticoagulants (DOACs), elective endoscopy procedures carry a risk of bleeding and thromboembolic events similar to that seen in those receiving vitamin K antagonists (VKAs), according to a multicenter, prospective observational study conducted at 12 Spanish academic and community centers.

DOACs have several advantages over VKAs, including more predictable pharmacokinetic profiles and fewer food and drug interactions, but they have not been well studied in the elective endoscopy setting. Some previous studies suggested a lower risk with DOACs than with VKAs, but they were retrospective or based on administrative databases.

It also remains unclear when anticoagulant therapy should be resumed following high-risk procedures. The new study, which was led by Enrique Rodríguez de Santiago of Universidad de Alcalá (Spain) and published in Clinical Gastroenterology and Hepatology, suggested that early resumption may be safe. “It certainly showed there was an acceptable rate of clinically significant rate of bleeding for patients on anticoagulants, and the thing I appreciated the most was that there was no statistically significant difference in terms of bleeding depending on when you resumed the anticoagulant,” said Robert Jay Sealock, MD, assistant professor of medicine at Baylor College of Medicine in Houston. Dr. Sealock was not involved in the study.

The researchers examined data from 1,623 patients who underwent 1,874 endoscopic procedures. Among these patients, 62.7% were taking VKAs, and 37.3% were taking DOACs; 58.9% were men, and the mean age was 74.2 years. Overall, 75.5% were on anticoagulant therapy for atrial fibrillation.

The most common procedures were colonoscopy (68.3%) and esophagogastroduodenoscopy (27.3%).

Within 30 days, The risk of bleeding was similar between patients taking VKAs (6.2%; 95% confidence interval, 4.8-7.8%) and DOACs (6.7%; 95% CI, 4.9-9%). This was true regardless of intervention and site. Overall, 1.4% of subjects experienced a thromboembolic event (95% CI, 0.9-2.1%), and there was no significant difference between the VKA group (1.3%; 95% CI, 0.8-2.2%) and the DOAC group (1.5%; 95% CI, 0.8-2.8%).

Clinically significant gastrointestinal bleeding occurred in 6.4% of subjects (95% CI, 5.3-7.7%); 2.7% of clinically significant gastrointestinal bleeding events were intraprocedural and 4.1% were delayed. The lowest risk of bleeding occurred with diagnostic endoscopy (1.1%) and biopsy (2.2%). The risk of bleeding for high-risk procedures was 11.5% (95% CI, 9.4-14%).

The overall mortality was 1.4%, with two deaths related to thromboembolic events, both in the DOAC group. The other deaths were considered to be unrelated to the procedure or periprocedural interruption of anticoagulants.

The researchers also examined the timing of anticoagulant resumption. Overall, 59.2% of subjects received bridging therapy, including 85% of the VKA group and 16% of the DOAC group (P < .001). This was not associated with increased endoscopy-related bleeding in either the VKA (3.3% with bridging therapy vs. 6.4% without; P = .14) or the DOAC group (8.3% vs. 6.4%; P = .48).

A total of 747 patients underwent a high-risk procedure, 46.3% of patients resumed anticoagulant therapy within 24 hours of the procedure, and 46.2% between 24 and 48 hours. After inverse probability of treatment weighting adjustment, a delay in anticoagulant resumption was not associated with a reduction in the frequency of postprocedural clinically significant gastrointestinal bleeding.

Still, the research left some questions unanswered. Most of the high-risk procedures were hot (41.8%) or cold snare polypectomies (39.8%). There weren’t enough data in the study to evaluate risk in patients undergoing other high-risk procedures such as balloon dilation for strictures, endoscopic ultrasound with fine-needle aspiration, and sphincterotomy. “That’s one group that we still don’t really have enough data about, particularly those patients who are on DOACs,” said Dr. Sealock.

The study also found a high number of patients on bridging therapy. “It highlighted the fact that we probably use bridging therapy too much in patients undergoing endoscopy,” said Dr. Sealock. He recommended using tools that generate recommendations for bridging therapy and timing for withholding and resuming anticoagulants based on procedure and patient characteristics.

SOURCE: de Santiago ER et al. Clin Gastroenterol Hepatol. 2020 Dec 03. doi: 10.1016/j.cgh.2020.11.037.

Clostridioides difficile (C. diff) infection (CDI) is a pathogen of both humans and animals, and to control it will require an integrated approach that encompasses human health care, veterinary health care, environmental regulation, and public policy. That is the conclusion of a group led by Su-Chen Lim, MD, and Tom Riley, MD, of Edith Cowan University in Australia, who published a review in Clinical Microbiology and Infection.

CDI was generally considered a nuisance infection until the early 21st century, when a hypervirulent fluoroquinolone-resistant strain emerged in North America. The strain is now documented In the United States, Canada, and most countries in Europe.

Another new feature of CDI is increased evidence of community transmission, which was previously rare. This is defined as cases where the patient experienced symptom onset outside the hospital, and had no history of hospitalization in the previous 12 weeks or symptom onset within 48 hours of hospital admission. Community-associated CDI now accounts for 41% of U.S. cases, nearly 30% of Australian cases, and about 14% in Europe, according to recent studies.

Several features of CDI suggest a need for an integrated management plan. The preferred habitat of C. diff is the gastrointestinal track of mammals, and likely colonizes all mammalian neonates. Over time, colonization by other microbes likely crowd it out and prevent overgrowth. But widespread use of antimicrobials in animal production can lead to the creation of an environment resembling that of the neonate, allowing C. diff to expand. That has led to food animals becoming a major C. diff reservoir, and whole-genome studies showed that strains found in humans, food, animals, and the environment are closely related and sometimes genetically indistinguishable, suggesting transmission between humans and animals that may be attributable to contaminated food and environments.

The authors suggest that C. diff infection control should be guided by the One Health initiative, which seeks cooperation between physicians, osteopathic physicians, veterinarians, dentists, nurses, and other scientific and environmental disciplines. The goal is to enhance surveillance and interdisciplinary communication, as well as integrated policies. The authors note that C. diff is often thought of by physicians as primarily a hospital problem, who may be unaware of the increased prevalence of community-acquired disease. It is also a significant problem in agriculture, since as many as 50% of piglets succumb to the disease. Other studies have recently shown that asymptomatic carriers of toxigenic strains are likely to transmit the bacteria to C. diff-negative patients. Asymptomatic carriers cluster with symptomatic patients. In one Cleveland hospital, more than 25% of hospital-associated CDI cases were found to have been colonized prior to admission, suggesting that these were not true hospital-associated cases.

C. diff has been isolated from a wide range of sources, including food animals, meat, seafood, vegetables, household environments, and natural environments like rivers, lakes, and soil. About 20% of calves and 70% of piglets are colonized with C. diff. It has a high prevalence in meat products in the United States, but lower in the Europe, possibly because of different slaughtering practices.

The authors suggest that zoonotic C. diff spread is unlikely to be confined to any geographic region or population, and that widespread C. diff contamination is occurring through food or the environment. This could be occurring because spores can withstand cooking temperatures and disseminate through the air, and even through manure from food animals made into compost or fertilizer.

Veterinary efforts mimicking hospital measures have reduced animal CDI, but there are no rapid diagnostic tests for CDI in animals, making it challenging to control its spread in this context.

The authors call for enhanced antimicrobial stewardship in both human and animal settings, including banning of antimicrobial agents as growth promoters. This has been done in the United States and Europe, but not in Brazil, China, Canada, India, and Australia. They also call for research on inactivation of C. diff spores during waste treatment.

Even better, the authors suggest that vaccines should be developed and employed in both animals and humans. No such vaccine exists in animals, but Pfizer has one for humans in a phase 3 clinical trial, but it does not prevent colonization. Others are in development.

The epidemiology of CDI is an ongoing challenge, with emerging new strains and changing social and environmental conditions. “However, it is with the collaborative efforts of industry partners, policymakers, veterinarians, clinicians, and researchers that CDI needs to be approached, a perfect example of One Health. Opening an interdisciplinary dialogue to address CDI and One Health issues has to be the focus of future studies,” the authors concluded.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

SOURCE: SC Lim et al. Clinical Microbiology and Infection. 2020;26:85-863.

Clostridioides difficile (C. diff) infection (CDI) is a pathogen of both humans and animals, and to control it will require an integrated approach that encompasses human health care, veterinary health care, environmental regulation, and public policy. That is the conclusion of a group led by Su-Chen Lim, MD, and Tom Riley, MD, of Edith Cowan University in Australia, who published a review in Clinical Microbiology and Infection.

CDI was generally considered a nuisance infection until the early 21st century, when a hypervirulent fluoroquinolone-resistant strain emerged in North America. The strain is now documented In the United States, Canada, and most countries in Europe.

Another new feature of CDI is increased evidence of community transmission, which was previously rare. This is defined as cases where the patient experienced symptom onset outside the hospital, and had no history of hospitalization in the previous 12 weeks or symptom onset within 48 hours of hospital admission. Community-associated CDI now accounts for 41% of U.S. cases, nearly 30% of Australian cases, and about 14% in Europe, according to recent studies.

Several features of CDI suggest a need for an integrated management plan. The preferred habitat of C. diff is the gastrointestinal track of mammals, and likely colonizes all mammalian neonates. Over time, colonization by other microbes likely crowd it out and prevent overgrowth. But widespread use of antimicrobials in animal production can lead to the creation of an environment resembling that of the neonate, allowing C. diff to expand. That has led to food animals becoming a major C. diff reservoir, and whole-genome studies showed that strains found in humans, food, animals, and the environment are closely related and sometimes genetically indistinguishable, suggesting transmission between humans and animals that may be attributable to contaminated food and environments.

The authors suggest that C. diff infection control should be guided by the One Health initiative, which seeks cooperation between physicians, osteopathic physicians, veterinarians, dentists, nurses, and other scientific and environmental disciplines. The goal is to enhance surveillance and interdisciplinary communication, as well as integrated policies. The authors note that C. diff is often thought of by physicians as primarily a hospital problem, who may be unaware of the increased prevalence of community-acquired disease. It is also a significant problem in agriculture, since as many as 50% of piglets succumb to the disease. Other studies have recently shown that asymptomatic carriers of toxigenic strains are likely to transmit the bacteria to C. diff-negative patients. Asymptomatic carriers cluster with symptomatic patients. In one Cleveland hospital, more than 25% of hospital-associated CDI cases were found to have been colonized prior to admission, suggesting that these were not true hospital-associated cases.

C. diff has been isolated from a wide range of sources, including food animals, meat, seafood, vegetables, household environments, and natural environments like rivers, lakes, and soil. About 20% of calves and 70% of piglets are colonized with C. diff. It has a high prevalence in meat products in the United States, but lower in the Europe, possibly because of different slaughtering practices.

The authors suggest that zoonotic C. diff spread is unlikely to be confined to any geographic region or population, and that widespread C. diff contamination is occurring through food or the environment. This could be occurring because spores can withstand cooking temperatures and disseminate through the air, and even through manure from food animals made into compost or fertilizer.

Veterinary efforts mimicking hospital measures have reduced animal CDI, but there are no rapid diagnostic tests for CDI in animals, making it challenging to control its spread in this context.

The authors call for enhanced antimicrobial stewardship in both human and animal settings, including banning of antimicrobial agents as growth promoters. This has been done in the United States and Europe, but not in Brazil, China, Canada, India, and Australia. They also call for research on inactivation of C. diff spores during waste treatment.

Even better, the authors suggest that vaccines should be developed and employed in both animals and humans. No such vaccine exists in animals, but Pfizer has one for humans in a phase 3 clinical trial, but it does not prevent colonization. Others are in development.

The epidemiology of CDI is an ongoing challenge, with emerging new strains and changing social and environmental conditions. “However, it is with the collaborative efforts of industry partners, policymakers, veterinarians, clinicians, and researchers that CDI needs to be approached, a perfect example of One Health. Opening an interdisciplinary dialogue to address CDI and One Health issues has to be the focus of future studies,” the authors concluded.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

SOURCE: SC Lim et al. Clinical Microbiology and Infection. 2020;26:85-863.

Clostridioides difficile (C. diff) infection (CDI) is a pathogen of both humans and animals, and to control it will require an integrated approach that encompasses human health care, veterinary health care, environmental regulation, and public policy. That is the conclusion of a group led by Su-Chen Lim, MD, and Tom Riley, MD, of Edith Cowan University in Australia, who published a review in Clinical Microbiology and Infection.

CDI was generally considered a nuisance infection until the early 21st century, when a hypervirulent fluoroquinolone-resistant strain emerged in North America. The strain is now documented In the United States, Canada, and most countries in Europe.

Another new feature of CDI is increased evidence of community transmission, which was previously rare. This is defined as cases where the patient experienced symptom onset outside the hospital, and had no history of hospitalization in the previous 12 weeks or symptom onset within 48 hours of hospital admission. Community-associated CDI now accounts for 41% of U.S. cases, nearly 30% of Australian cases, and about 14% in Europe, according to recent studies.

Several features of CDI suggest a need for an integrated management plan. The preferred habitat of C. diff is the gastrointestinal track of mammals, and likely colonizes all mammalian neonates. Over time, colonization by other microbes likely crowd it out and prevent overgrowth. But widespread use of antimicrobials in animal production can lead to the creation of an environment resembling that of the neonate, allowing C. diff to expand. That has led to food animals becoming a major C. diff reservoir, and whole-genome studies showed that strains found in humans, food, animals, and the environment are closely related and sometimes genetically indistinguishable, suggesting transmission between humans and animals that may be attributable to contaminated food and environments.

The authors suggest that C. diff infection control should be guided by the One Health initiative, which seeks cooperation between physicians, osteopathic physicians, veterinarians, dentists, nurses, and other scientific and environmental disciplines. The goal is to enhance surveillance and interdisciplinary communication, as well as integrated policies. The authors note that C. diff is often thought of by physicians as primarily a hospital problem, who may be unaware of the increased prevalence of community-acquired disease. It is also a significant problem in agriculture, since as many as 50% of piglets succumb to the disease. Other studies have recently shown that asymptomatic carriers of toxigenic strains are likely to transmit the bacteria to C. diff-negative patients. Asymptomatic carriers cluster with symptomatic patients. In one Cleveland hospital, more than 25% of hospital-associated CDI cases were found to have been colonized prior to admission, suggesting that these were not true hospital-associated cases.

C. diff has been isolated from a wide range of sources, including food animals, meat, seafood, vegetables, household environments, and natural environments like rivers, lakes, and soil. About 20% of calves and 70% of piglets are colonized with C. diff. It has a high prevalence in meat products in the United States, but lower in the Europe, possibly because of different slaughtering practices.

The authors suggest that zoonotic C. diff spread is unlikely to be confined to any geographic region or population, and that widespread C. diff contamination is occurring through food or the environment. This could be occurring because spores can withstand cooking temperatures and disseminate through the air, and even through manure from food animals made into compost or fertilizer.

Veterinary efforts mimicking hospital measures have reduced animal CDI, but there are no rapid diagnostic tests for CDI in animals, making it challenging to control its spread in this context.

The authors call for enhanced antimicrobial stewardship in both human and animal settings, including banning of antimicrobial agents as growth promoters. This has been done in the United States and Europe, but not in Brazil, China, Canada, India, and Australia. They also call for research on inactivation of C. diff spores during waste treatment.

Even better, the authors suggest that vaccines should be developed and employed in both animals and humans. No such vaccine exists in animals, but Pfizer has one for humans in a phase 3 clinical trial, but it does not prevent colonization. Others are in development.

The epidemiology of CDI is an ongoing challenge, with emerging new strains and changing social and environmental conditions. “However, it is with the collaborative efforts of industry partners, policymakers, veterinarians, clinicians, and researchers that CDI needs to be approached, a perfect example of One Health. Opening an interdisciplinary dialogue to address CDI and One Health issues has to be the focus of future studies,” the authors concluded.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

SOURCE: SC Lim et al. Clinical Microbiology and Infection. 2020;26:85-863.

Clostridioides difficile (C. diff) infection (CDI) is a pathogen of both humans and animals, and to control it will require an integrated approach that encompasses human health care, veterinary health care, environmental regulation, and public policy. That is the conclusion of a group led by Su-Chen Lim, MD, and Tom Riley, MD, of Edith Cowan University in Australia, who published a review in Clinical Microbiology and Infection.

CDI was generally considered a nuisance infection until the early 21st century, when a hypervirulent fluoroquinolone-resistant strain emerged in North America. The strain is now documented In the United States, Canada, and most countries in Europe.

Another new feature of CDI is increased evidence of community transmission, which was previously rare. This is defined as cases where the patient experienced symptom onset outside the hospital, and had no history of hospitalization in the previous 12 weeks or symptom onset within 48 hours of hospital admission. Community-associated CDI now accounts for 41% of U.S. cases, nearly 30% of Australian cases, and about 14% in Europe, according to recent studies.

Several features of CDI suggest a need for an integrated management plan. The preferred habitat of C. diff is the gastrointestinal track of mammals, and likely colonizes all mammalian neonates. Over time, colonization by other microbes likely crowd it out and prevent overgrowth. But widespread use of antimicrobials in animal production can lead to the creation of an environment resembling that of the neonate, allowing C. diff to expand. That has led to food animals becoming a major C. diff reservoir, and whole-genome studies showed that strains found in humans, food, animals, and the environment are closely related and sometimes genetically indistinguishable, suggesting transmission between humans and animals that may be attributable to contaminated food and environments.

The authors suggest that C. diff infection control should be guided by the One Health initiative, which seeks cooperation between physicians, osteopathic physicians, veterinarians, dentists, nurses, and other scientific and environmental disciplines. The goal is to enhance surveillance and interdisciplinary communication, as well as integrated policies. The authors note that C. diff is often thought of by physicians as primarily a hospital problem, who may be unaware of the increased prevalence of community-acquired disease. It is also a significant problem in agriculture, since as many as 50% of piglets succumb to the disease. Other studies have recently shown that asymptomatic carriers of toxigenic strains are likely to transmit the bacteria to C. diff-negative patients. Asymptomatic carriers cluster with symptomatic patients. In one Cleveland hospital, more than 25% of hospital-associated CDI cases were found to have been colonized prior to admission, suggesting that these were not true hospital-associated cases.

C. diff has been isolated from a wide range of sources, including food animals, meat, seafood, vegetables, household environments, and natural environments like rivers, lakes, and soil. About 20% of calves and 70% of piglets are colonized with C. diff. It has a high prevalence in meat products in the United States, but lower in the Europe, possibly because of different slaughtering practices.

The authors suggest that zoonotic C. diff spread is unlikely to be confined to any geographic region or population, and that widespread C. diff contamination is occurring through food or the environment. This could be occurring because spores can withstand cooking temperatures and disseminate through the air, and even through manure from food animals made into compost or fertilizer.

Veterinary efforts mimicking hospital measures have reduced animal CDI, but there are no rapid diagnostic tests for CDI in animals, making it challenging to control its spread in this context.

The authors call for enhanced antimicrobial stewardship in both human and animal settings, including banning of antimicrobial agents as growth promoters. This has been done in the United States and Europe, but not in Brazil, China, Canada, India, and Australia. They also call for research on inactivation of C. diff spores during waste treatment.

Even better, the authors suggest that vaccines should be developed and employed in both animals and humans. No such vaccine exists in animals, but Pfizer has one for humans in a phase 3 clinical trial, but it does not prevent colonization. Others are in development.

The epidemiology of CDI is an ongoing challenge, with emerging new strains and changing social and environmental conditions. “However, it is with the collaborative efforts of industry partners, policymakers, veterinarians, clinicians, and researchers that CDI needs to be approached, a perfect example of One Health. Opening an interdisciplinary dialogue to address CDI and One Health issues has to be the focus of future studies,” the authors concluded.

SOURCE: SC Lim et al. Clinical Microbiology and Infection. 2020;26:85-863.

Clostridioides difficile (C. diff) infection (CDI) is a pathogen of both humans and animals, and to control it will require an integrated approach that encompasses human health care, veterinary health care, environmental regulation, and public policy. That is the conclusion of a group led by Su-Chen Lim, MD, and Tom Riley, MD, of Edith Cowan University in Australia, who published a review in Clinical Microbiology and Infection.

CDI was generally considered a nuisance infection until the early 21st century, when a hypervirulent fluoroquinolone-resistant strain emerged in North America. The strain is now documented In the United States, Canada, and most countries in Europe.

Another new feature of CDI is increased evidence of community transmission, which was previously rare. This is defined as cases where the patient experienced symptom onset outside the hospital, and had no history of hospitalization in the previous 12 weeks or symptom onset within 48 hours of hospital admission. Community-associated CDI now accounts for 41% of U.S. cases, nearly 30% of Australian cases, and about 14% in Europe, according to recent studies.

Several features of CDI suggest a need for an integrated management plan. The preferred habitat of C. diff is the gastrointestinal track of mammals, and likely colonizes all mammalian neonates. Over time, colonization by other microbes likely crowd it out and prevent overgrowth. But widespread use of antimicrobials in animal production can lead to the creation of an environment resembling that of the neonate, allowing C. diff to expand. That has led to food animals becoming a major C. diff reservoir, and whole-genome studies showed that strains found in humans, food, animals, and the environment are closely related and sometimes genetically indistinguishable, suggesting transmission between humans and animals that may be attributable to contaminated food and environments.

The authors suggest that C. diff infection control should be guided by the One Health initiative, which seeks cooperation between physicians, osteopathic physicians, veterinarians, dentists, nurses, and other scientific and environmental disciplines. The goal is to enhance surveillance and interdisciplinary communication, as well as integrated policies. The authors note that C. diff is often thought of by physicians as primarily a hospital problem, who may be unaware of the increased prevalence of community-acquired disease. It is also a significant problem in agriculture, since as many as 50% of piglets succumb to the disease. Other studies have recently shown that asymptomatic carriers of toxigenic strains are likely to transmit the bacteria to C. diff-negative patients. Asymptomatic carriers cluster with symptomatic patients. In one Cleveland hospital, more than 25% of hospital-associated CDI cases were found to have been colonized prior to admission, suggesting that these were not true hospital-associated cases.

C. diff has been isolated from a wide range of sources, including food animals, meat, seafood, vegetables, household environments, and natural environments like rivers, lakes, and soil. About 20% of calves and 70% of piglets are colonized with C. diff. It has a high prevalence in meat products in the United States, but lower in the Europe, possibly because of different slaughtering practices.

The authors suggest that zoonotic C. diff spread is unlikely to be confined to any geographic region or population, and that widespread C. diff contamination is occurring through food or the environment. This could be occurring because spores can withstand cooking temperatures and disseminate through the air, and even through manure from food animals made into compost or fertilizer.

Veterinary efforts mimicking hospital measures have reduced animal CDI, but there are no rapid diagnostic tests for CDI in animals, making it challenging to control its spread in this context.

The authors call for enhanced antimicrobial stewardship in both human and animal settings, including banning of antimicrobial agents as growth promoters. This has been done in the United States and Europe, but not in Brazil, China, Canada, India, and Australia. They also call for research on inactivation of C. diff spores during waste treatment.

Even better, the authors suggest that vaccines should be developed and employed in both animals and humans. No such vaccine exists in animals, but Pfizer has one for humans in a phase 3 clinical trial, but it does not prevent colonization. Others are in development.

The epidemiology of CDI is an ongoing challenge, with emerging new strains and changing social and environmental conditions. “However, it is with the collaborative efforts of industry partners, policymakers, veterinarians, clinicians, and researchers that CDI needs to be approached, a perfect example of One Health. Opening an interdisciplinary dialogue to address CDI and One Health issues has to be the focus of future studies,” the authors concluded.

SOURCE: SC Lim et al. Clinical Microbiology and Infection. 2020;26:85-863.

Clostridioides difficile (C. diff) infection (CDI) is a pathogen of both humans and animals, and to control it will require an integrated approach that encompasses human health care, veterinary health care, environmental regulation, and public policy. That is the conclusion of a group led by Su-Chen Lim, MD, and Tom Riley, MD, of Edith Cowan University in Australia, who published a review in Clinical Microbiology and Infection.

CDI was generally considered a nuisance infection until the early 21st century, when a hypervirulent fluoroquinolone-resistant strain emerged in North America. The strain is now documented In the United States, Canada, and most countries in Europe.

Another new feature of CDI is increased evidence of community transmission, which was previously rare. This is defined as cases where the patient experienced symptom onset outside the hospital, and had no history of hospitalization in the previous 12 weeks or symptom onset within 48 hours of hospital admission. Community-associated CDI now accounts for 41% of U.S. cases, nearly 30% of Australian cases, and about 14% in Europe, according to recent studies.

Several features of CDI suggest a need for an integrated management plan. The preferred habitat of C. diff is the gastrointestinal track of mammals, and likely colonizes all mammalian neonates. Over time, colonization by other microbes likely crowd it out and prevent overgrowth. But widespread use of antimicrobials in animal production can lead to the creation of an environment resembling that of the neonate, allowing C. diff to expand. That has led to food animals becoming a major C. diff reservoir, and whole-genome studies showed that strains found in humans, food, animals, and the environment are closely related and sometimes genetically indistinguishable, suggesting transmission between humans and animals that may be attributable to contaminated food and environments.

The authors suggest that C. diff infection control should be guided by the One Health initiative, which seeks cooperation between physicians, osteopathic physicians, veterinarians, dentists, nurses, and other scientific and environmental disciplines. The goal is to enhance surveillance and interdisciplinary communication, as well as integrated policies. The authors note that C. diff is often thought of by physicians as primarily a hospital problem, who may be unaware of the increased prevalence of community-acquired disease. It is also a significant problem in agriculture, since as many as 50% of piglets succumb to the disease. Other studies have recently shown that asymptomatic carriers of toxigenic strains are likely to transmit the bacteria to C. diff-negative patients. Asymptomatic carriers cluster with symptomatic patients. In one Cleveland hospital, more than 25% of hospital-associated CDI cases were found to have been colonized prior to admission, suggesting that these were not true hospital-associated cases.

C. diff has been isolated from a wide range of sources, including food animals, meat, seafood, vegetables, household environments, and natural environments like rivers, lakes, and soil. About 20% of calves and 70% of piglets are colonized with C. diff. It has a high prevalence in meat products in the United States, but lower in the Europe, possibly because of different slaughtering practices.

The authors suggest that zoonotic C. diff spread is unlikely to be confined to any geographic region or population, and that widespread C. diff contamination is occurring through food or the environment. This could be occurring because spores can withstand cooking temperatures and disseminate through the air, and even through manure from food animals made into compost or fertilizer.

Veterinary efforts mimicking hospital measures have reduced animal CDI, but there are no rapid diagnostic tests for CDI in animals, making it challenging to control its spread in this context.

The authors call for enhanced antimicrobial stewardship in both human and animal settings, including banning of antimicrobial agents as growth promoters. This has been done in the United States and Europe, but not in Brazil, China, Canada, India, and Australia. They also call for research on inactivation of C. diff spores during waste treatment.

Even better, the authors suggest that vaccines should be developed and employed in both animals and humans. No such vaccine exists in animals, but Pfizer has one for humans in a phase 3 clinical trial, but it does not prevent colonization. Others are in development.

The epidemiology of CDI is an ongoing challenge, with emerging new strains and changing social and environmental conditions. “However, it is with the collaborative efforts of industry partners, policymakers, veterinarians, clinicians, and researchers that CDI needs to be approached, a perfect example of One Health. Opening an interdisciplinary dialogue to address CDI and One Health issues has to be the focus of future studies,” the authors concluded.

SOURCE: SC Lim et al. Clinical Microbiology and Infection. 2020;26:85-863.