If the nation’s primary care system were a patient, it would be in critical condition, researchers have found.

In delivery of primary care, including access and coordination, the U.S. trails well behind 10 other wealthy countries, according to a new report from the Commonwealth Fund.

The document, released March 15, concludes that the shortcomings in the U.S. system – from a lack of a relationship with a primary care physician to unequal access to after-hours care – “disproportionately affect Black and Latinx communities and rural areas, exacerbating disparities that have widened during the COVID-19 pandemic.”

“This report really shows that the U.S. is falling behind. We know that a strong primary care system yields better health outcomes. We have a lot to learn from other high-income countries,” coauthor Munira Z. Gunja, MPH, a senior researcher for the Commonwealth Fund’s International Program in Health Policy and Practice Innovations, told this news organization. “At baseline, we really need to make sure that everyone has health insurance in this country so they can actually use primary care services, and we need to increase the supply of those services.”

The report draws from the Commonwealth Fund’s 2019 and 2020 International Health Policy Surveys and the 2020 International Profiles of Health Care Systems. Among the main points:

• U.S. adults are the least likely to have a regular physician or place of care or a long-standing relationship with a primary care provider: 43% of American adults have a long-term relationship with a primary care doctor, compared with highs of 71% in Germany and the Netherlands.
• Access to home visits or after-hours care – excluding emergency department visits – is lowest in the United States (45%). In the Netherlands, Norway, New Zealand, and Germany, the rate is 90% to 96%.
• Half of primary care providers in the United States report adequate coordination with specialists and hospitals – around the average for the 11 countries studied.

‘Dismal mess’

Experts reacted to the report with a mix of concern and frustration – but not surprise.

“The results in this report are not surprising, and we have known them all for a number of years now,” Timothy Hoff, PhD, a health policy expert at Northeastern University, Boston, said. “Primary care doctors remain the backbone of our primary care system. But there are too few of them in the United States, and there likely will remain too few of them in the future. This opens the door to other and more diverse forms of innovation that will be required to help complement the work they do.”

Dr. Hoff, author of Searching for the Family Doctor: Primary Care on the Brink, added that comparing the United States to smaller countries like Norway or the United Kingdom is “somewhat problematic.”

“Our system has to take care of several hundred million people, trapped in a fragmented and market-based delivery system focused on specialty care, each of whom may have a different insurance plan,” he said. “Doing some of the things very small countries with government-funded insurance and a history of strong primary care delivery do in taking care of far fewer citizens is not realistic.”

Jeffrey Borkan, MD, PhD, chair and professor in the department of family medicine at the Alpert Medical School of Brown University, Providence, R.I., said the most shocking finding in the report is that despite spending far more on health care than any other country, “we cannot manage to provide one of the least expensive and most efficacious services: a relationship with a primary care doctor.”

Arthur Caplan, PhD, director of the Division of Medical Ethics at New York University Langone Medical Center, called primary care in this country “a dismal mess. It has been for many years. This is especially so in mental health. Access in many counties is nonexistent, and many primary care physicians are opting into boutique care.”

R. Shawn Martin, CEO of the 133,000-member American Academy of Family Physicians, said, “None of this surprises me. I think these are trendlines; we have been following this for many, many years here at the Academy.”

Mr. Martin added that he was disappointed that the recent, large investments in sharing and digitizing information have not closed the gaps that hinder the efficient and widespread delivery of primary care.

The findings in the report weren’t all bad. More primary care providers in the United States (30%) screen their patients for social needs such as housing, food security, and transportation – the highest among all 11 nations studied.

Also, Commonwealth Fund said the proportion of patients who said they received information on meeting their social needs and screening for domestic violence or social isolation was low everywhere. However, the percentage in the United States, Canada, and Norway was the highest, at 9%. Sweden had the lowest rate for such screenings, at 1%.

The researchers noted that social determinants of health account for as much as 55% of health outcomes. “In some countries, like the United States, the higher rates of receiving such information may be a response to the higher rates of material hardship, along with a weaker safety net,” the report states.

Ms. Gunja and her colleagues suggested several options for changes in policies, including narrowing the wage gap between primary care providers and higher-paid specialists; subsidizing medical school tuition to give students incentives to enter primary care; investing in telehealth to make primary care more accessible; and rewarding and holding providers accountable for continuity of care.

“The U.S. had the largest wage gap and highest tuition fees among the countries we studied,” Ms. Gunja told this news organization..

Researchers noted that U.S. patients could benefit from the introduction of incentives such as those paid in New Zealand to primary health organizations, which receive additional funding per capita to promote health and coordinate care.

But Dr. Caplan was skeptical that those measures would do much to correct the problems.

“We have no will to fix this ongoing, scandalous situation,” he said. “Specialist care still pays inordinately large salaries. Nurses and physician extenders are underused. Academic prestige does little to reward primary care. Plus, patients are not pressing for better access. Sorry, but I see no solutions pending in the current climate. Obamacare barely survived.”

The authors have disclosed no relevant financial relationships.

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

If the nation’s primary care system were a patient, it would be in critical condition, researchers have found.

In delivery of primary care, including access and coordination, the U.S. trails well behind 10 other wealthy countries, according to a new report from the Commonwealth Fund.

The document, released March 15, concludes that the shortcomings in the U.S. system – from a lack of a relationship with a primary care physician to unequal access to after-hours care – “disproportionately affect Black and Latinx communities and rural areas, exacerbating disparities that have widened during the COVID-19 pandemic.”

“This report really shows that the U.S. is falling behind. We know that a strong primary care system yields better health outcomes. We have a lot to learn from other high-income countries,” coauthor Munira Z. Gunja, MPH, a senior researcher for the Commonwealth Fund’s International Program in Health Policy and Practice Innovations, told this news organization. “At baseline, we really need to make sure that everyone has health insurance in this country so they can actually use primary care services, and we need to increase the supply of those services.”

The report draws from the Commonwealth Fund’s 2019 and 2020 International Health Policy Surveys and the 2020 International Profiles of Health Care Systems. Among the main points:

• U.S. adults are the least likely to have a regular physician or place of care or a long-standing relationship with a primary care provider: 43% of American adults have a long-term relationship with a primary care doctor, compared with highs of 71% in Germany and the Netherlands.
• Access to home visits or after-hours care – excluding emergency department visits – is lowest in the United States (45%). In the Netherlands, Norway, New Zealand, and Germany, the rate is 90% to 96%.
• Half of primary care providers in the United States report adequate coordination with specialists and hospitals – around the average for the 11 countries studied.

‘Dismal mess’

Experts reacted to the report with a mix of concern and frustration – but not surprise.

“The results in this report are not surprising, and we have known them all for a number of years now,” Timothy Hoff, PhD, a health policy expert at Northeastern University, Boston, said. “Primary care doctors remain the backbone of our primary care system. But there are too few of them in the United States, and there likely will remain too few of them in the future. This opens the door to other and more diverse forms of innovation that will be required to help complement the work they do.”

Dr. Hoff, author of Searching for the Family Doctor: Primary Care on the Brink, added that comparing the United States to smaller countries like Norway or the United Kingdom is “somewhat problematic.”

“Our system has to take care of several hundred million people, trapped in a fragmented and market-based delivery system focused on specialty care, each of whom may have a different insurance plan,” he said. “Doing some of the things very small countries with government-funded insurance and a history of strong primary care delivery do in taking care of far fewer citizens is not realistic.”

Jeffrey Borkan, MD, PhD, chair and professor in the department of family medicine at the Alpert Medical School of Brown University, Providence, R.I., said the most shocking finding in the report is that despite spending far more on health care than any other country, “we cannot manage to provide one of the least expensive and most efficacious services: a relationship with a primary care doctor.”

Arthur Caplan, PhD, director of the Division of Medical Ethics at New York University Langone Medical Center, called primary care in this country “a dismal mess. It has been for many years. This is especially so in mental health. Access in many counties is nonexistent, and many primary care physicians are opting into boutique care.”

R. Shawn Martin, CEO of the 133,000-member American Academy of Family Physicians, said, “None of this surprises me. I think these are trendlines; we have been following this for many, many years here at the Academy.”

Mr. Martin added that he was disappointed that the recent, large investments in sharing and digitizing information have not closed the gaps that hinder the efficient and widespread delivery of primary care.

The findings in the report weren’t all bad. More primary care providers in the United States (30%) screen their patients for social needs such as housing, food security, and transportation – the highest among all 11 nations studied.

Also, Commonwealth Fund said the proportion of patients who said they received information on meeting their social needs and screening for domestic violence or social isolation was low everywhere. However, the percentage in the United States, Canada, and Norway was the highest, at 9%. Sweden had the lowest rate for such screenings, at 1%.

The researchers noted that social determinants of health account for as much as 55% of health outcomes. “In some countries, like the United States, the higher rates of receiving such information may be a response to the higher rates of material hardship, along with a weaker safety net,” the report states.

Ms. Gunja and her colleagues suggested several options for changes in policies, including narrowing the wage gap between primary care providers and higher-paid specialists; subsidizing medical school tuition to give students incentives to enter primary care; investing in telehealth to make primary care more accessible; and rewarding and holding providers accountable for continuity of care.

“The U.S. had the largest wage gap and highest tuition fees among the countries we studied,” Ms. Gunja told this news organization..

Researchers noted that U.S. patients could benefit from the introduction of incentives such as those paid in New Zealand to primary health organizations, which receive additional funding per capita to promote health and coordinate care.

But Dr. Caplan was skeptical that those measures would do much to correct the problems.

“We have no will to fix this ongoing, scandalous situation,” he said. “Specialist care still pays inordinately large salaries. Nurses and physician extenders are underused. Academic prestige does little to reward primary care. Plus, patients are not pressing for better access. Sorry, but I see no solutions pending in the current climate. Obamacare barely survived.”

The authors have disclosed no relevant financial relationships.

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

If the nation’s primary care system were a patient, it would be in critical condition, researchers have found.

In delivery of primary care, including access and coordination, the U.S. trails well behind 10 other wealthy countries, according to a new report from the Commonwealth Fund.

The document, released March 15, concludes that the shortcomings in the U.S. system – from a lack of a relationship with a primary care physician to unequal access to after-hours care – “disproportionately affect Black and Latinx communities and rural areas, exacerbating disparities that have widened during the COVID-19 pandemic.”

“This report really shows that the U.S. is falling behind. We know that a strong primary care system yields better health outcomes. We have a lot to learn from other high-income countries,” coauthor Munira Z. Gunja, MPH, a senior researcher for the Commonwealth Fund’s International Program in Health Policy and Practice Innovations, told this news organization. “At baseline, we really need to make sure that everyone has health insurance in this country so they can actually use primary care services, and we need to increase the supply of those services.”

The report draws from the Commonwealth Fund’s 2019 and 2020 International Health Policy Surveys and the 2020 International Profiles of Health Care Systems. Among the main points:

• U.S. adults are the least likely to have a regular physician or place of care or a long-standing relationship with a primary care provider: 43% of American adults have a long-term relationship with a primary care doctor, compared with highs of 71% in Germany and the Netherlands.
• Access to home visits or after-hours care – excluding emergency department visits – is lowest in the United States (45%). In the Netherlands, Norway, New Zealand, and Germany, the rate is 90% to 96%.
• Half of primary care providers in the United States report adequate coordination with specialists and hospitals – around the average for the 11 countries studied.

‘Dismal mess’

Experts reacted to the report with a mix of concern and frustration – but not surprise.

“The results in this report are not surprising, and we have known them all for a number of years now,” Timothy Hoff, PhD, a health policy expert at Northeastern University, Boston, said. “Primary care doctors remain the backbone of our primary care system. But there are too few of them in the United States, and there likely will remain too few of them in the future. This opens the door to other and more diverse forms of innovation that will be required to help complement the work they do.”

Dr. Hoff, author of Searching for the Family Doctor: Primary Care on the Brink, added that comparing the United States to smaller countries like Norway or the United Kingdom is “somewhat problematic.”

“Our system has to take care of several hundred million people, trapped in a fragmented and market-based delivery system focused on specialty care, each of whom may have a different insurance plan,” he said. “Doing some of the things very small countries with government-funded insurance and a history of strong primary care delivery do in taking care of far fewer citizens is not realistic.”

Jeffrey Borkan, MD, PhD, chair and professor in the department of family medicine at the Alpert Medical School of Brown University, Providence, R.I., said the most shocking finding in the report is that despite spending far more on health care than any other country, “we cannot manage to provide one of the least expensive and most efficacious services: a relationship with a primary care doctor.”

Arthur Caplan, PhD, director of the Division of Medical Ethics at New York University Langone Medical Center, called primary care in this country “a dismal mess. It has been for many years. This is especially so in mental health. Access in many counties is nonexistent, and many primary care physicians are opting into boutique care.”

R. Shawn Martin, CEO of the 133,000-member American Academy of Family Physicians, said, “None of this surprises me. I think these are trendlines; we have been following this for many, many years here at the Academy.”

Mr. Martin added that he was disappointed that the recent, large investments in sharing and digitizing information have not closed the gaps that hinder the efficient and widespread delivery of primary care.

The findings in the report weren’t all bad. More primary care providers in the United States (30%) screen their patients for social needs such as housing, food security, and transportation – the highest among all 11 nations studied.

Also, Commonwealth Fund said the proportion of patients who said they received information on meeting their social needs and screening for domestic violence or social isolation was low everywhere. However, the percentage in the United States, Canada, and Norway was the highest, at 9%. Sweden had the lowest rate for such screenings, at 1%.

The researchers noted that social determinants of health account for as much as 55% of health outcomes. “In some countries, like the United States, the higher rates of receiving such information may be a response to the higher rates of material hardship, along with a weaker safety net,” the report states.

Ms. Gunja and her colleagues suggested several options for changes in policies, including narrowing the wage gap between primary care providers and higher-paid specialists; subsidizing medical school tuition to give students incentives to enter primary care; investing in telehealth to make primary care more accessible; and rewarding and holding providers accountable for continuity of care.

“The U.S. had the largest wage gap and highest tuition fees among the countries we studied,” Ms. Gunja told this news organization..

Researchers noted that U.S. patients could benefit from the introduction of incentives such as those paid in New Zealand to primary health organizations, which receive additional funding per capita to promote health and coordinate care.

But Dr. Caplan was skeptical that those measures would do much to correct the problems.

“We have no will to fix this ongoing, scandalous situation,” he said. “Specialist care still pays inordinately large salaries. Nurses and physician extenders are underused. Academic prestige does little to reward primary care. Plus, patients are not pressing for better access. Sorry, but I see no solutions pending in the current climate. Obamacare barely survived.”

The authors have disclosed no relevant financial relationships.

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

Researchers running the EMPA-KIDNEY trial that’s been testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in about 6,600 patients with chronic kidney disease (CKD) announced on March 16 that they had stopped the trial early because of positive efficacy that met the study’s prespecified threshold for early termination.

EMPA-KIDNEY is the third major trial of an agent from the sodium-glucose cotransport 2 (SGLT2) inhibitor class tested in patients with CKD to be stopped early because of positive results that met a prespecified termination rule.

HYWARDS/Getty Images

EMPA-KIDNEY enrolled a wider range of patients

EMPA-KIDNEY expands the scope of types of patients with CKD now shown to benefit from treatment with an SGLT2 inhibitor. CREDENCE tested canagliflozin only in patients with type 2 diabetes and diabetic nephropathy, and in DAPA-CKD, two-thirds of enrolled patients had type 2 diabetes, and all had CKD. In EMPA-KIDNEY, 46% of the 6,609 enrolled patients had diabetes (including a very small number with type 1 diabetes).

Another departure from prior studies of an SGLT2 inhibitor for patients selected primarily for having CKD was that in EMPA-KIDNEY, 20% of patients did not have albuminuria, and for 34%, eGFR at entry was less than 30 mL/min/1.73 m², with all enrolled patients required to have an eGFR at entry of greater than or equal to 20 mL/min/1.73 m². Average eGFR in EMPA-KIDNEY was about 38 mL/min/1.73 m². To be included in the trial, patients were not required to have albuminuria, except those whose eGFR was greater than or equal to 45 mL/min/1.73 m².

In DAPA-CKD, the minimum eGFR at entry had to be greater than or equal to 25 mL/min/1.73 m², and roughly 14% of enrolled patients had an eGFR of less than 30 mL/min/1.73 m². The average eGFR in DAPA-CKD was about 43 mL/min/1.73 m². In addition, all patients had at least microalbuminuria, with a minimum urinary albumin-to-creatinine ratio of 200. In CREDENCE, the minimum eGFR for enrollment was 30 mL/min/1.73 m², and the average eGFR was about 56 mL/min/1.73 m². All patients in CREDENCE had to have macroalbuminuria, with a urinary albumin-to-creatinine ratio of more than 300.

According to the researchers who designed EMPA-KIDNEY, the trial enrollment criteria aimed to include adults with CKD “who are frequently seen in practice but were under-represented in previous SGLT2 inhibitor trials.”

Indications for empagliflozin are expanding

The success of empagliflozin in EMPA-KIDNEY follows its positive results in both the EMPEROR-Reduced and EMPEROR-Preserved trials, which collectively proved the efficacy of the agent for patients with heart failure regardless of their left ventricular ejection fraction and regardless of whether they also had diabetes.

These results led the U.S. Food and Drug Administration to recently expand the labeled indication for empagliflozin to all patients with heart failure. Empagliflozin also has labeled indications for glycemic control in patients with type 2 diabetes and to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.

As of today, empagliflozin has no labeled indication for treating patients with CKD. Dapagliflozin received that indication in April 2021, and canagliflozin received an indication for treating patients with type 2 diabetes, diabetic nephropathy, and albuminuria in September 2019.

EMPA-KIDNEY is sponsored by Boehringer Ingelheim and Lilly, the two companies that jointly market empagliflozin (Jardiance).

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

Researchers running the EMPA-KIDNEY trial that’s been testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in about 6,600 patients with chronic kidney disease (CKD) announced on March 16 that they had stopped the trial early because of positive efficacy that met the study’s prespecified threshold for early termination.

EMPA-KIDNEY is the third major trial of an agent from the sodium-glucose cotransport 2 (SGLT2) inhibitor class tested in patients with CKD to be stopped early because of positive results that met a prespecified termination rule.

HYWARDS/Getty Images

EMPA-KIDNEY enrolled a wider range of patients

EMPA-KIDNEY expands the scope of types of patients with CKD now shown to benefit from treatment with an SGLT2 inhibitor. CREDENCE tested canagliflozin only in patients with type 2 diabetes and diabetic nephropathy, and in DAPA-CKD, two-thirds of enrolled patients had type 2 diabetes, and all had CKD. In EMPA-KIDNEY, 46% of the 6,609 enrolled patients had diabetes (including a very small number with type 1 diabetes).

Another departure from prior studies of an SGLT2 inhibitor for patients selected primarily for having CKD was that in EMPA-KIDNEY, 20% of patients did not have albuminuria, and for 34%, eGFR at entry was less than 30 mL/min/1.73 m², with all enrolled patients required to have an eGFR at entry of greater than or equal to 20 mL/min/1.73 m². Average eGFR in EMPA-KIDNEY was about 38 mL/min/1.73 m². To be included in the trial, patients were not required to have albuminuria, except those whose eGFR was greater than or equal to 45 mL/min/1.73 m².

In DAPA-CKD, the minimum eGFR at entry had to be greater than or equal to 25 mL/min/1.73 m², and roughly 14% of enrolled patients had an eGFR of less than 30 mL/min/1.73 m². The average eGFR in DAPA-CKD was about 43 mL/min/1.73 m². In addition, all patients had at least microalbuminuria, with a minimum urinary albumin-to-creatinine ratio of 200. In CREDENCE, the minimum eGFR for enrollment was 30 mL/min/1.73 m², and the average eGFR was about 56 mL/min/1.73 m². All patients in CREDENCE had to have macroalbuminuria, with a urinary albumin-to-creatinine ratio of more than 300.

According to the researchers who designed EMPA-KIDNEY, the trial enrollment criteria aimed to include adults with CKD “who are frequently seen in practice but were under-represented in previous SGLT2 inhibitor trials.”

Indications for empagliflozin are expanding

The success of empagliflozin in EMPA-KIDNEY follows its positive results in both the EMPEROR-Reduced and EMPEROR-Preserved trials, which collectively proved the efficacy of the agent for patients with heart failure regardless of their left ventricular ejection fraction and regardless of whether they also had diabetes.

These results led the U.S. Food and Drug Administration to recently expand the labeled indication for empagliflozin to all patients with heart failure. Empagliflozin also has labeled indications for glycemic control in patients with type 2 diabetes and to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.

As of today, empagliflozin has no labeled indication for treating patients with CKD. Dapagliflozin received that indication in April 2021, and canagliflozin received an indication for treating patients with type 2 diabetes, diabetic nephropathy, and albuminuria in September 2019.

EMPA-KIDNEY is sponsored by Boehringer Ingelheim and Lilly, the two companies that jointly market empagliflozin (Jardiance).

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

Researchers running the EMPA-KIDNEY trial that’s been testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in about 6,600 patients with chronic kidney disease (CKD) announced on March 16 that they had stopped the trial early because of positive efficacy that met the study’s prespecified threshold for early termination.

EMPA-KIDNEY is the third major trial of an agent from the sodium-glucose cotransport 2 (SGLT2) inhibitor class tested in patients with CKD to be stopped early because of positive results that met a prespecified termination rule.

HYWARDS/Getty Images

EMPA-KIDNEY enrolled a wider range of patients

EMPA-KIDNEY expands the scope of types of patients with CKD now shown to benefit from treatment with an SGLT2 inhibitor. CREDENCE tested canagliflozin only in patients with type 2 diabetes and diabetic nephropathy, and in DAPA-CKD, two-thirds of enrolled patients had type 2 diabetes, and all had CKD. In EMPA-KIDNEY, 46% of the 6,609 enrolled patients had diabetes (including a very small number with type 1 diabetes).

Another departure from prior studies of an SGLT2 inhibitor for patients selected primarily for having CKD was that in EMPA-KIDNEY, 20% of patients did not have albuminuria, and for 34%, eGFR at entry was less than 30 mL/min/1.73 m², with all enrolled patients required to have an eGFR at entry of greater than or equal to 20 mL/min/1.73 m². Average eGFR in EMPA-KIDNEY was about 38 mL/min/1.73 m². To be included in the trial, patients were not required to have albuminuria, except those whose eGFR was greater than or equal to 45 mL/min/1.73 m².

In DAPA-CKD, the minimum eGFR at entry had to be greater than or equal to 25 mL/min/1.73 m², and roughly 14% of enrolled patients had an eGFR of less than 30 mL/min/1.73 m². The average eGFR in DAPA-CKD was about 43 mL/min/1.73 m². In addition, all patients had at least microalbuminuria, with a minimum urinary albumin-to-creatinine ratio of 200. In CREDENCE, the minimum eGFR for enrollment was 30 mL/min/1.73 m², and the average eGFR was about 56 mL/min/1.73 m². All patients in CREDENCE had to have macroalbuminuria, with a urinary albumin-to-creatinine ratio of more than 300.

According to the researchers who designed EMPA-KIDNEY, the trial enrollment criteria aimed to include adults with CKD “who are frequently seen in practice but were under-represented in previous SGLT2 inhibitor trials.”

Indications for empagliflozin are expanding

The success of empagliflozin in EMPA-KIDNEY follows its positive results in both the EMPEROR-Reduced and EMPEROR-Preserved trials, which collectively proved the efficacy of the agent for patients with heart failure regardless of their left ventricular ejection fraction and regardless of whether they also had diabetes.

These results led the U.S. Food and Drug Administration to recently expand the labeled indication for empagliflozin to all patients with heart failure. Empagliflozin also has labeled indications for glycemic control in patients with type 2 diabetes and to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.

As of today, empagliflozin has no labeled indication for treating patients with CKD. Dapagliflozin received that indication in April 2021, and canagliflozin received an indication for treating patients with type 2 diabetes, diabetic nephropathy, and albuminuria in September 2019.

EMPA-KIDNEY is sponsored by Boehringer Ingelheim and Lilly, the two companies that jointly market empagliflozin (Jardiance).

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

A new systematic literature review suggests that there may be – at most – a weak link between COVID-19 and alopecia areata.

If there is a connection, it’s likely not a strong one, said study author Rachel E. Christensen, a graduate student at Rutgers Robert Wood Johnson Medical School, in an interview. “Based on the reported number of cases following COVID-19, alopecia areata appears to be low on the list of common skin manifestations of COVID-19,” she said. Of 402 articles screened from three databases in the review, only 11 were identified as related to alopecia areata (AA) and COVID-19, and only 9 of those met the study inclusion criteria. “This number alone highlights the very low number of published articles investigating this connection.”

The review was published in JAAD International.

While COVID-19 has been linked to a variety of skin conditions, a 2021 South Korean study of 7,958 cases and 218,779 controls found no connection between infection and AA even after covariates such as age, gender, and income level were taken into account. In a letter to the editor published in 2020, dermatologists in Turkey reported that the percentage of patients with AA at the dermatology outpatient clinic jumped from 0.97% in May 2019 to 1.48% in May 2020. The number of patients in each group wasn’t reported.

Systematic review

The investigators launched the systematic review to gain a wider perspective, although there are still limitations. On the one hand, Ms. Christensen said, “we do know that COVID-19, like other viruses, has been linked to various dermatological disorders.”

However, “it is difficult to tease apart whether any worsening of alopecia areata we see following COVID-19 is due to the virus itself or the increased psychological burden related to the infection or to the pandemic in general,” she said. Indeed, the authors of the report in Turkey attributed the rise in cases to stress.

For the review, the researchers analyzed studies from Italy (four), Turkey (two), Brazil (one), the United States (one), and Poland (one).

Six of the studies reported cases of new-onset AA following COVID-19 infection (seven cases; average age, 37 years; females, three). Another study was a retrospective review of 32 patients with preexisting AA who developed COVID-19; none experienced significant worsening of AA within 6 months.

The review also included a study based on a survey of 389 patients with AA. The investigators found that, at a median 2.14 months after infection, 44% of those who had COVID-19 vs. 12% of those who were COVID negative had a relapse. Finally, a case report noted a patient with preexisting AA whose condition worsened following COVID infection.

The findings suggest that AA “could be a dermatological manifestation of COVID-19, with cases most often appearing 1-2 months following infection,” the authors wrote. “However, the heterogeneity of study designs and high proportion of case reports make it challenging to draw any conclusion.”

In an interview, dermatologist Brett King, MD, PhD, of the department of dermatology, Yale University, New Haven, Conn., said the review findings suggest that “there is little concern of alopecia areata following COVID infection.

Does new-onset AA happen, and are there exacerbations of preexisting disease related to COVID infection? Probably yes, but rarely.”

However, he noted that another form of alopecia, telogen effluvium (TE), is more common after COVID-19 infection. According to Dr. King, who was not involved with the systematic review, TE is typically time-limited, compared with AA’s more common chronic waxing-and-waning course.

“Distinguishing TE and AA is usually straightforward because AA typically presents with well-circumscribed patches of hair loss,” such as circular patches, “while TE manifests as diffuse hair loss,” he explained. “Rarely, however, AA does manifest diffuse hair loss without patches, similar to TE. In those cases, it may be difficult to distinguish them. A biopsy may be helpful if there is a question of the diagnosis.”

No study funding is reported. The review authors and Dr. King report no relevant disclosures.

A new systematic literature review suggests that there may be – at most – a weak link between COVID-19 and alopecia areata.

If there is a connection, it’s likely not a strong one, said study author Rachel E. Christensen, a graduate student at Rutgers Robert Wood Johnson Medical School, in an interview. “Based on the reported number of cases following COVID-19, alopecia areata appears to be low on the list of common skin manifestations of COVID-19,” she said. Of 402 articles screened from three databases in the review, only 11 were identified as related to alopecia areata (AA) and COVID-19, and only 9 of those met the study inclusion criteria. “This number alone highlights the very low number of published articles investigating this connection.”

The review was published in JAAD International.

While COVID-19 has been linked to a variety of skin conditions, a 2021 South Korean study of 7,958 cases and 218,779 controls found no connection between infection and AA even after covariates such as age, gender, and income level were taken into account. In a letter to the editor published in 2020, dermatologists in Turkey reported that the percentage of patients with AA at the dermatology outpatient clinic jumped from 0.97% in May 2019 to 1.48% in May 2020. The number of patients in each group wasn’t reported.

Systematic review

The investigators launched the systematic review to gain a wider perspective, although there are still limitations. On the one hand, Ms. Christensen said, “we do know that COVID-19, like other viruses, has been linked to various dermatological disorders.”

However, “it is difficult to tease apart whether any worsening of alopecia areata we see following COVID-19 is due to the virus itself or the increased psychological burden related to the infection or to the pandemic in general,” she said. Indeed, the authors of the report in Turkey attributed the rise in cases to stress.

For the review, the researchers analyzed studies from Italy (four), Turkey (two), Brazil (one), the United States (one), and Poland (one).

Six of the studies reported cases of new-onset AA following COVID-19 infection (seven cases; average age, 37 years; females, three). Another study was a retrospective review of 32 patients with preexisting AA who developed COVID-19; none experienced significant worsening of AA within 6 months.

The review also included a study based on a survey of 389 patients with AA. The investigators found that, at a median 2.14 months after infection, 44% of those who had COVID-19 vs. 12% of those who were COVID negative had a relapse. Finally, a case report noted a patient with preexisting AA whose condition worsened following COVID infection.

The findings suggest that AA “could be a dermatological manifestation of COVID-19, with cases most often appearing 1-2 months following infection,” the authors wrote. “However, the heterogeneity of study designs and high proportion of case reports make it challenging to draw any conclusion.”

In an interview, dermatologist Brett King, MD, PhD, of the department of dermatology, Yale University, New Haven, Conn., said the review findings suggest that “there is little concern of alopecia areata following COVID infection.

Does new-onset AA happen, and are there exacerbations of preexisting disease related to COVID infection? Probably yes, but rarely.”

However, he noted that another form of alopecia, telogen effluvium (TE), is more common after COVID-19 infection. According to Dr. King, who was not involved with the systematic review, TE is typically time-limited, compared with AA’s more common chronic waxing-and-waning course.

“Distinguishing TE and AA is usually straightforward because AA typically presents with well-circumscribed patches of hair loss,” such as circular patches, “while TE manifests as diffuse hair loss,” he explained. “Rarely, however, AA does manifest diffuse hair loss without patches, similar to TE. In those cases, it may be difficult to distinguish them. A biopsy may be helpful if there is a question of the diagnosis.”

No study funding is reported. The review authors and Dr. King report no relevant disclosures.

A new systematic literature review suggests that there may be – at most – a weak link between COVID-19 and alopecia areata.

If there is a connection, it’s likely not a strong one, said study author Rachel E. Christensen, a graduate student at Rutgers Robert Wood Johnson Medical School, in an interview. “Based on the reported number of cases following COVID-19, alopecia areata appears to be low on the list of common skin manifestations of COVID-19,” she said. Of 402 articles screened from three databases in the review, only 11 were identified as related to alopecia areata (AA) and COVID-19, and only 9 of those met the study inclusion criteria. “This number alone highlights the very low number of published articles investigating this connection.”

The review was published in JAAD International.

While COVID-19 has been linked to a variety of skin conditions, a 2021 South Korean study of 7,958 cases and 218,779 controls found no connection between infection and AA even after covariates such as age, gender, and income level were taken into account. In a letter to the editor published in 2020, dermatologists in Turkey reported that the percentage of patients with AA at the dermatology outpatient clinic jumped from 0.97% in May 2019 to 1.48% in May 2020. The number of patients in each group wasn’t reported.

Systematic review

The investigators launched the systematic review to gain a wider perspective, although there are still limitations. On the one hand, Ms. Christensen said, “we do know that COVID-19, like other viruses, has been linked to various dermatological disorders.”

However, “it is difficult to tease apart whether any worsening of alopecia areata we see following COVID-19 is due to the virus itself or the increased psychological burden related to the infection or to the pandemic in general,” she said. Indeed, the authors of the report in Turkey attributed the rise in cases to stress.

For the review, the researchers analyzed studies from Italy (four), Turkey (two), Brazil (one), the United States (one), and Poland (one).

Six of the studies reported cases of new-onset AA following COVID-19 infection (seven cases; average age, 37 years; females, three). Another study was a retrospective review of 32 patients with preexisting AA who developed COVID-19; none experienced significant worsening of AA within 6 months.

The review also included a study based on a survey of 389 patients with AA. The investigators found that, at a median 2.14 months after infection, 44% of those who had COVID-19 vs. 12% of those who were COVID negative had a relapse. Finally, a case report noted a patient with preexisting AA whose condition worsened following COVID infection.

The findings suggest that AA “could be a dermatological manifestation of COVID-19, with cases most often appearing 1-2 months following infection,” the authors wrote. “However, the heterogeneity of study designs and high proportion of case reports make it challenging to draw any conclusion.”

In an interview, dermatologist Brett King, MD, PhD, of the department of dermatology, Yale University, New Haven, Conn., said the review findings suggest that “there is little concern of alopecia areata following COVID infection.

Does new-onset AA happen, and are there exacerbations of preexisting disease related to COVID infection? Probably yes, but rarely.”

However, he noted that another form of alopecia, telogen effluvium (TE), is more common after COVID-19 infection. According to Dr. King, who was not involved with the systematic review, TE is typically time-limited, compared with AA’s more common chronic waxing-and-waning course.

“Distinguishing TE and AA is usually straightforward because AA typically presents with well-circumscribed patches of hair loss,” such as circular patches, “while TE manifests as diffuse hair loss,” he explained. “Rarely, however, AA does manifest diffuse hair loss without patches, similar to TE. In those cases, it may be difficult to distinguish them. A biopsy may be helpful if there is a question of the diagnosis.”

No study funding is reported. The review authors and Dr. King report no relevant disclosures.

Over 2.5 million people have fled the ghastly war in Ukraine for safety. But, not everyone is trying to leave. Shockingly, hundreds of thousands are actually flocking toward the danger in Ukraine right now. Many of them are women. 

I was commuting to work when I first heard this story on a podcast. In astonishing numbers, women have chosen to return to or stay in Ukraine because they’re needed to fight and to protect their families. My reaction, like yours, was to be inspired. What amazing courage! Twitter and Instagram will swell with images of their balaclava masked faces standing in the breach once more. Like the women in medicine who armed themselves with surgical masks and face shields and babies on their backs to join the fight against COVID-19. They will be poster girls, blue sleeves rolled up and red polka dotted bandanas covering their hair. 

But that’s not what they want. “We don’t want to be an inspiration,” said one fearless Ukrainian fighter in the story, “we want to be alive.”

At the time of this writing as we celebrate the brilliant accomplishments of women on March 8, International Women’s Day, I wonder if we don’t have it slightly wrong.

Although acknowledgment is appreciated, the women I work alongside don’t need me to be inspired by them. They need me to stand with them, to help them. There has been extensive reporting on the disproportionate burden that women have borne though the pandemic: lost income, lost status, lost jobs. The “she-session” it’s been called, refers to the million women who have not rejoined the workforce since COVID-19. This is especially acute for us in medicine where women are significantly more likely than are men to report not working full time, or not working at all.

The truth is that even in 2022, the burdens of family life are still not borne equally. Bias against mothers in particular can be insidious. Take academia, where there is little sympathy for not publishing on schedule. Perhaps there are unexplained gaps, but where exactly on a CV does one put “recurrent pregnancy loss?” Do you know how many clinics or ORs a woman must cancel to attempt maddeningly unpredictable egg retrievals and embryo transfers? A lot. Not to mention the financial burden of doing so. 

During the pandemic, female physicians were more likely to manage child care, schooling, and household duties, compared to male physicians.

And yet (perhaps even because of that?) women in medicine make less money. How much? About $80,000 less on average in dermatology. Inspired? Indeed. No thanks. Let’s #BreakTheBias rather. 

I’m not a policy expert nor a sociologist. I don’t know what advice might be helpful here. I’d say raising our collective consciousness of the unfairness, highlighting discrepancies, and advocating for equality are good starts. But, International Women’s Day isn’t new. It’s old. Like over a hundred years old (since 1909 to be exact). We don’t just need a better hashtag, we need to do something. Give equity in pay. Offer opportunities for leadership that accommodate the extra duty women might have outside work. Create flexibility in schedules and without the penalty of having to pump at work or leave early to pick up a child. Not to mention all the opportunities we men have to do more of the household work that women currently do. 

The gallant women of Ukraine don’t need our approbation. They need our aid and our prayers. Like the women in my department, at my medical center, in my community, they aren’t posing to be made into posters. There’s work to be done and they are flocking toward it right now. 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Over 2.5 million people have fled the ghastly war in Ukraine for safety. But, not everyone is trying to leave. Shockingly, hundreds of thousands are actually flocking toward the danger in Ukraine right now. Many of them are women. 

I was commuting to work when I first heard this story on a podcast. In astonishing numbers, women have chosen to return to or stay in Ukraine because they’re needed to fight and to protect their families. My reaction, like yours, was to be inspired. What amazing courage! Twitter and Instagram will swell with images of their balaclava masked faces standing in the breach once more. Like the women in medicine who armed themselves with surgical masks and face shields and babies on their backs to join the fight against COVID-19. They will be poster girls, blue sleeves rolled up and red polka dotted bandanas covering their hair. 

But that’s not what they want. “We don’t want to be an inspiration,” said one fearless Ukrainian fighter in the story, “we want to be alive.”

At the time of this writing as we celebrate the brilliant accomplishments of women on March 8, International Women’s Day, I wonder if we don’t have it slightly wrong.

Although acknowledgment is appreciated, the women I work alongside don’t need me to be inspired by them. They need me to stand with them, to help them. There has been extensive reporting on the disproportionate burden that women have borne though the pandemic: lost income, lost status, lost jobs. The “she-session” it’s been called, refers to the million women who have not rejoined the workforce since COVID-19. This is especially acute for us in medicine where women are significantly more likely than are men to report not working full time, or not working at all.

The truth is that even in 2022, the burdens of family life are still not borne equally. Bias against mothers in particular can be insidious. Take academia, where there is little sympathy for not publishing on schedule. Perhaps there are unexplained gaps, but where exactly on a CV does one put “recurrent pregnancy loss?” Do you know how many clinics or ORs a woman must cancel to attempt maddeningly unpredictable egg retrievals and embryo transfers? A lot. Not to mention the financial burden of doing so. 

During the pandemic, female physicians were more likely to manage child care, schooling, and household duties, compared to male physicians.

And yet (perhaps even because of that?) women in medicine make less money. How much? About $80,000 less on average in dermatology. Inspired? Indeed. No thanks. Let’s #BreakTheBias rather. 

I’m not a policy expert nor a sociologist. I don’t know what advice might be helpful here. I’d say raising our collective consciousness of the unfairness, highlighting discrepancies, and advocating for equality are good starts. But, International Women’s Day isn’t new. It’s old. Like over a hundred years old (since 1909 to be exact). We don’t just need a better hashtag, we need to do something. Give equity in pay. Offer opportunities for leadership that accommodate the extra duty women might have outside work. Create flexibility in schedules and without the penalty of having to pump at work or leave early to pick up a child. Not to mention all the opportunities we men have to do more of the household work that women currently do. 

The gallant women of Ukraine don’t need our approbation. They need our aid and our prayers. Like the women in my department, at my medical center, in my community, they aren’t posing to be made into posters. There’s work to be done and they are flocking toward it right now. 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Over 2.5 million people have fled the ghastly war in Ukraine for safety. But, not everyone is trying to leave. Shockingly, hundreds of thousands are actually flocking toward the danger in Ukraine right now. Many of them are women. 

I was commuting to work when I first heard this story on a podcast. In astonishing numbers, women have chosen to return to or stay in Ukraine because they’re needed to fight and to protect their families. My reaction, like yours, was to be inspired. What amazing courage! Twitter and Instagram will swell with images of their balaclava masked faces standing in the breach once more. Like the women in medicine who armed themselves with surgical masks and face shields and babies on their backs to join the fight against COVID-19. They will be poster girls, blue sleeves rolled up and red polka dotted bandanas covering their hair. 

But that’s not what they want. “We don’t want to be an inspiration,” said one fearless Ukrainian fighter in the story, “we want to be alive.”

At the time of this writing as we celebrate the brilliant accomplishments of women on March 8, International Women’s Day, I wonder if we don’t have it slightly wrong.

Although acknowledgment is appreciated, the women I work alongside don’t need me to be inspired by them. They need me to stand with them, to help them. There has been extensive reporting on the disproportionate burden that women have borne though the pandemic: lost income, lost status, lost jobs. The “she-session” it’s been called, refers to the million women who have not rejoined the workforce since COVID-19. This is especially acute for us in medicine where women are significantly more likely than are men to report not working full time, or not working at all.

The truth is that even in 2022, the burdens of family life are still not borne equally. Bias against mothers in particular can be insidious. Take academia, where there is little sympathy for not publishing on schedule. Perhaps there are unexplained gaps, but where exactly on a CV does one put “recurrent pregnancy loss?” Do you know how many clinics or ORs a woman must cancel to attempt maddeningly unpredictable egg retrievals and embryo transfers? A lot. Not to mention the financial burden of doing so. 

During the pandemic, female physicians were more likely to manage child care, schooling, and household duties, compared to male physicians.

And yet (perhaps even because of that?) women in medicine make less money. How much? About $80,000 less on average in dermatology. Inspired? Indeed. No thanks. Let’s #BreakTheBias rather. 

I’m not a policy expert nor a sociologist. I don’t know what advice might be helpful here. I’d say raising our collective consciousness of the unfairness, highlighting discrepancies, and advocating for equality are good starts. But, International Women’s Day isn’t new. It’s old. Like over a hundred years old (since 1909 to be exact). We don’t just need a better hashtag, we need to do something. Give equity in pay. Offer opportunities for leadership that accommodate the extra duty women might have outside work. Create flexibility in schedules and without the penalty of having to pump at work or leave early to pick up a child. Not to mention all the opportunities we men have to do more of the household work that women currently do. 

The gallant women of Ukraine don’t need our approbation. They need our aid and our prayers. Like the women in my department, at my medical center, in my community, they aren’t posing to be made into posters. There’s work to be done and they are flocking toward it right now. 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Bleeding risk after cold snare polypectomy is reduced when direct-acting oral anticoagulants (DOACs) are withheld only on the day of the procedure rather than continuing use of these agents, data from a new study suggest.

Findings of the study, led by Atsushi Morita, MD, of the Digestive Disease Center, Showa Inan General Hospital in Komagane, Japan, were published in Gastrointestinal Endoscopy.
 

This prospective, observational single-center study enrolled two consecutive groups of patients receiving antithrombotic medications who were undergoing cold snare polypectomy of colorectal polyps of 10 mm or less.

All colonoscopies were performed by endoscopists who each perform more than 500 endoscopies a year.

During period 1 of the study (2017 and 2018), DOACs were continued, even on the day of polypectomy (DOAC continued group); during period 2 (2019 and 2020), DOACs were withheld only on the day of the procedure (DOAC withheld group).

© pavlen/iStockphoto

The primary outcome was the frequency of delayed bleeding requiring endoscopic treatment within 2 weeks after cold snare polypectomy. Among the secondary outcomes were immediate bleeding and the number of hemostatic clips used.

Clinical features were similar between the two groups. The first group included 204 patients, 34% of whom were female (average age, 75 years); the second group included 264 patients, 34% of whom were female (average age, 74 years). The number of cold snare polypectomies was similar between the groups (47 vs. 66, P = .55), as was the average number of polyps per patient (0.72 vs. 0.70, P = .76).

Delayed bleeding after cold snare polypectomy occurred in 4 out of 47 (8.5%) participants in the continued DOAC group versus 0 out of 66 (0%) participants in the DOAC-withheld group (P < .001). There was similar improvement in immediate postpolypectomy bleeding (secondary outcome) between the two groups.

Immediate bleeding after endoscopy lasting more than 30 seconds occurred about four times as often in continued DOAC group versus the DOAC withheld group (12 out of 47 [25.5%] participants vs. 4 out of 66 [6.1%] participants; P < .008).

Polyps measuring up to 10 mm (excluding tiny hyperplastic polyps in the rectum and distal sigmoid colon), were removed using dedicated cold snares measuring 0.30 mm in diameter.

“This result is consistent with the best practice recommendation of short interruptions of DOACs based on the patient’s creatinine clearance before all polypectomy techniques, including cold snare polypectomy,” the authors wrote.
 

Countries’ guidelines differ

Guidelines from American Society for Gastrointestinal Endoscopy, the authors noted, currently recommend stopping DOACs before polypectomy, including cold snare procedures, and restarting them only after hemostasis has been achieved. Moreover, since there is no way for a clinician to predict polyp size, the U.S. guidelines further recommend holding warfarin for 5 days and DOACs for 2-3 days before colonoscopy.

In contrast to the U.S. guidelines, the Japanese Gastroenterological Endoscopy Society guidelines suggest clinicians withhold DOACs only on the day of the procedure.

“This policy of withholding DOACs only on the day of colonoscopy should be considered for routine clinical practice,” the authors wrote.

Rajesh N. Keswani, MD, associate professor of medicine in gastroenterology and hepatology at Northwestern University, Chicago, said in an interview it is difficult to draw firm conclusions from this paper because of its study design but added the authors “appear to have delineated a preferred method for managing DOACs prior to colonoscopy.”

He further noted that most polyps encountered during colonoscopy are less than 10 mm and can be safely managed with cold snare polypectomy.

“The management of DOACs prior to colonoscopy is variable,” Dr. Keswani said, “but ranges from cessation of DOACs multiple days prior to colonoscopy versus uninterrupted use of DOACs throughout the colonoscopy period.”

“The authors suggest that holding DOACs on the day of colonoscopy is the optimal balance between minimizing thromboembolic risk and postpolypectomy bleeding. While this data will need to be validated in larger samples, this provides some guidance to colonoscopists tasked with managing DOACs prior to colonoscopy,” Dr. Keswani said.

Limitations of the study included the small number of patients who received DOACs, conduction of the study at a single hospital in Japan, and the definition of immediate bleeding, which differs based on study design.

No commercial funding or conflicts of interest were reported. Dr. Keswani is a consultant for Boston Scientific and Neptune Medical and receives research support from Virgo.

This article was updated March 24, 2022.

Bleeding risk after cold snare polypectomy is reduced when direct-acting oral anticoagulants (DOACs) are withheld only on the day of the procedure rather than continuing use of these agents, data from a new study suggest.

Findings of the study, led by Atsushi Morita, MD, of the Digestive Disease Center, Showa Inan General Hospital in Komagane, Japan, were published in Gastrointestinal Endoscopy.
 

This prospective, observational single-center study enrolled two consecutive groups of patients receiving antithrombotic medications who were undergoing cold snare polypectomy of colorectal polyps of 10 mm or less.

All colonoscopies were performed by endoscopists who each perform more than 500 endoscopies a year.

During period 1 of the study (2017 and 2018), DOACs were continued, even on the day of polypectomy (DOAC continued group); during period 2 (2019 and 2020), DOACs were withheld only on the day of the procedure (DOAC withheld group).

© pavlen/iStockphoto

The primary outcome was the frequency of delayed bleeding requiring endoscopic treatment within 2 weeks after cold snare polypectomy. Among the secondary outcomes were immediate bleeding and the number of hemostatic clips used.

Clinical features were similar between the two groups. The first group included 204 patients, 34% of whom were female (average age, 75 years); the second group included 264 patients, 34% of whom were female (average age, 74 years). The number of cold snare polypectomies was similar between the groups (47 vs. 66, P = .55), as was the average number of polyps per patient (0.72 vs. 0.70, P = .76).

Delayed bleeding after cold snare polypectomy occurred in 4 out of 47 (8.5%) participants in the continued DOAC group versus 0 out of 66 (0%) participants in the DOAC-withheld group (P < .001). There was similar improvement in immediate postpolypectomy bleeding (secondary outcome) between the two groups.

Immediate bleeding after endoscopy lasting more than 30 seconds occurred about four times as often in continued DOAC group versus the DOAC withheld group (12 out of 47 [25.5%] participants vs. 4 out of 66 [6.1%] participants; P < .008).

Polyps measuring up to 10 mm (excluding tiny hyperplastic polyps in the rectum and distal sigmoid colon), were removed using dedicated cold snares measuring 0.30 mm in diameter.

“This result is consistent with the best practice recommendation of short interruptions of DOACs based on the patient’s creatinine clearance before all polypectomy techniques, including cold snare polypectomy,” the authors wrote.
 

Countries’ guidelines differ

Guidelines from American Society for Gastrointestinal Endoscopy, the authors noted, currently recommend stopping DOACs before polypectomy, including cold snare procedures, and restarting them only after hemostasis has been achieved. Moreover, since there is no way for a clinician to predict polyp size, the U.S. guidelines further recommend holding warfarin for 5 days and DOACs for 2-3 days before colonoscopy.

In contrast to the U.S. guidelines, the Japanese Gastroenterological Endoscopy Society guidelines suggest clinicians withhold DOACs only on the day of the procedure.

“This policy of withholding DOACs only on the day of colonoscopy should be considered for routine clinical practice,” the authors wrote.

Rajesh N. Keswani, MD, associate professor of medicine in gastroenterology and hepatology at Northwestern University, Chicago, said in an interview it is difficult to draw firm conclusions from this paper because of its study design but added the authors “appear to have delineated a preferred method for managing DOACs prior to colonoscopy.”

He further noted that most polyps encountered during colonoscopy are less than 10 mm and can be safely managed with cold snare polypectomy.

“The management of DOACs prior to colonoscopy is variable,” Dr. Keswani said, “but ranges from cessation of DOACs multiple days prior to colonoscopy versus uninterrupted use of DOACs throughout the colonoscopy period.”

“The authors suggest that holding DOACs on the day of colonoscopy is the optimal balance between minimizing thromboembolic risk and postpolypectomy bleeding. While this data will need to be validated in larger samples, this provides some guidance to colonoscopists tasked with managing DOACs prior to colonoscopy,” Dr. Keswani said.

Limitations of the study included the small number of patients who received DOACs, conduction of the study at a single hospital in Japan, and the definition of immediate bleeding, which differs based on study design.

No commercial funding or conflicts of interest were reported. Dr. Keswani is a consultant for Boston Scientific and Neptune Medical and receives research support from Virgo.

This article was updated March 24, 2022.

Bleeding risk after cold snare polypectomy is reduced when direct-acting oral anticoagulants (DOACs) are withheld only on the day of the procedure rather than continuing use of these agents, data from a new study suggest.

Findings of the study, led by Atsushi Morita, MD, of the Digestive Disease Center, Showa Inan General Hospital in Komagane, Japan, were published in Gastrointestinal Endoscopy.
 

This prospective, observational single-center study enrolled two consecutive groups of patients receiving antithrombotic medications who were undergoing cold snare polypectomy of colorectal polyps of 10 mm or less.

All colonoscopies were performed by endoscopists who each perform more than 500 endoscopies a year.

During period 1 of the study (2017 and 2018), DOACs were continued, even on the day of polypectomy (DOAC continued group); during period 2 (2019 and 2020), DOACs were withheld only on the day of the procedure (DOAC withheld group).

© pavlen/iStockphoto

The primary outcome was the frequency of delayed bleeding requiring endoscopic treatment within 2 weeks after cold snare polypectomy. Among the secondary outcomes were immediate bleeding and the number of hemostatic clips used.

Clinical features were similar between the two groups. The first group included 204 patients, 34% of whom were female (average age, 75 years); the second group included 264 patients, 34% of whom were female (average age, 74 years). The number of cold snare polypectomies was similar between the groups (47 vs. 66, P = .55), as was the average number of polyps per patient (0.72 vs. 0.70, P = .76).

Delayed bleeding after cold snare polypectomy occurred in 4 out of 47 (8.5%) participants in the continued DOAC group versus 0 out of 66 (0%) participants in the DOAC-withheld group (P < .001). There was similar improvement in immediate postpolypectomy bleeding (secondary outcome) between the two groups.

Immediate bleeding after endoscopy lasting more than 30 seconds occurred about four times as often in continued DOAC group versus the DOAC withheld group (12 out of 47 [25.5%] participants vs. 4 out of 66 [6.1%] participants; P < .008).

Polyps measuring up to 10 mm (excluding tiny hyperplastic polyps in the rectum and distal sigmoid colon), were removed using dedicated cold snares measuring 0.30 mm in diameter.

“This result is consistent with the best practice recommendation of short interruptions of DOACs based on the patient’s creatinine clearance before all polypectomy techniques, including cold snare polypectomy,” the authors wrote.
 

Countries’ guidelines differ

Guidelines from American Society for Gastrointestinal Endoscopy, the authors noted, currently recommend stopping DOACs before polypectomy, including cold snare procedures, and restarting them only after hemostasis has been achieved. Moreover, since there is no way for a clinician to predict polyp size, the U.S. guidelines further recommend holding warfarin for 5 days and DOACs for 2-3 days before colonoscopy.

In contrast to the U.S. guidelines, the Japanese Gastroenterological Endoscopy Society guidelines suggest clinicians withhold DOACs only on the day of the procedure.

“This policy of withholding DOACs only on the day of colonoscopy should be considered for routine clinical practice,” the authors wrote.

Rajesh N. Keswani, MD, associate professor of medicine in gastroenterology and hepatology at Northwestern University, Chicago, said in an interview it is difficult to draw firm conclusions from this paper because of its study design but added the authors “appear to have delineated a preferred method for managing DOACs prior to colonoscopy.”

He further noted that most polyps encountered during colonoscopy are less than 10 mm and can be safely managed with cold snare polypectomy.

“The management of DOACs prior to colonoscopy is variable,” Dr. Keswani said, “but ranges from cessation of DOACs multiple days prior to colonoscopy versus uninterrupted use of DOACs throughout the colonoscopy period.”

“The authors suggest that holding DOACs on the day of colonoscopy is the optimal balance between minimizing thromboembolic risk and postpolypectomy bleeding. While this data will need to be validated in larger samples, this provides some guidance to colonoscopists tasked with managing DOACs prior to colonoscopy,” Dr. Keswani said.

Limitations of the study included the small number of patients who received DOACs, conduction of the study at a single hospital in Japan, and the definition of immediate bleeding, which differs based on study design.

No commercial funding or conflicts of interest were reported. Dr. Keswani is a consultant for Boston Scientific and Neptune Medical and receives research support from Virgo.

This article was updated March 24, 2022.

A large global report shows a decline in mental health worldwide, with the poorest outcomes reported in young adults.

The Mental Health Million project of Sapien Labs issued its second report, published online March 15, encompassing 34 countries and over 220,000 Internet-enabled adults. It found a continued decline in mental health in all age groups and genders, with English-speaking countries having the lowest mental well-being.

The decline was significantly correlated with the stringency of COVID-19 lockdown measures in each country and was directionally correlated to the cases and deaths per million.

The youngest age group (18-24 years) reported the poorest mental well-being, with better mental health scores rising in every successively older age group.

“Some of our findings, especially regarding mental health in young adults, are alarming,” Tara Thiagarajan, PhD, Sapien Labs founder and chief scientist, told this news organization.

“Our data, which are continually updated in real time, are freely available for nonprofit, noncommercial use and research, and we hope that researchers will get involved in an interdisciplinary way that spans sociology, economics, psychiatry, and other fields,” she said.
 

Pioneering research

Dr. Thiagarajan and her team pioneered the Mental Health Million project, an ongoing research initiative utilizing a “free and anonymous assessment tool,” the Mental Health Quotient (MHQ), which “encompasses a comprehensive view of our emotional, social, and cognitive function and capability.”

The MHQ consists of 47 “elements of mental well-being,” with scores ranging from –100 to +200. (Negative scores indicate poorer mental well-being.) The MHQ categorizes respondents as “clinical, at-risk, enduring, managing, succeeding, and thriving” and computes scores on the basis of six broad dimensions of mental health: core cognition, complex cognition, mood and outlook, drive and motivation, social self, and mind-body connection.

As reported by this news organization, Sapien Lab’s first Mental Health State of the World report (n = 49,000 adults) was conducted in eight English-speaking countries in 2020. Participants were compared to a smaller sample of people from the same countries polled in 2019.

In this year’s report, “we expanded quite substantially,” Dr. Thiagarajan said. The project added Spanish, French, and Arabic and recruited participants from 34 countries on six continents (n = 223,087) via advertising on Google and Facebook.

Economic prosperity not protective

Across the eight English-speaking countries, there was a decline in mental well-being of 3% from 2020 to 2021, which was smaller than the 8% decline from 2019 to 2020. The percentage of people who were “distressed or struggling” increased from 26% to 30% in 2021.

“Now that a lot of pandemic issue seems to be easing up, I hope we’ll see mental well-being coming back up, but at least it’s a smaller decline than we saw between 2019 and 2020,” said Dr. Thiagarajan.

The decline across countries from 2019 to 2021 was significantly correlated with the stringency of governmental COVID-19-related measures (based on the Oxford COVID-19 Government Response Tracker, 2022; r = .54) and directionally correlated to the cases and deaths per million.

In total, 30% of respondents in English-speaking countries had mental well-being scores in the “distressed” or “struggling” range – higher than the Middle Eastern countries, North Africa, Latin America, and Europe (23%, 23%, 24%, and 18%, respectively).

Only 36% of participants in the English-speaking countries, the Middle East, and North Africa reported “thriving or succeeding,” vs. 45% and 46% in Latin America and Europe, respectively. Venezuela topped the list with an average MHQ of 91, while the United Kingdom and South Africa had the lowest scores, at 46 each.

Mental well-being was slightly higher in males than in females but was dramatically lower in nonbinary/third-gender respondents. In fact, those identifying as nonbinary/third gender had the lowest mental well-being of any group.

Across all countries and languages, higher education was associated with better mental well-being. Employment was also associated with superior mental well-being, compared with being unemployed – particularly in core English-speaking countries.

However, “country indicators of economic prosperity were negatively correlated with mental well-being, particularly for young adults and males, belying the commonly held belief that national economic prosperity translates into greater mental well-being,” said Dr. Thiagarajan.
 

‘Stark’ contrast

The most dramatic finding was the difference in mental well-being between younger and older adults, which was two- to threefold larger than differences in other dimensions (for example, age, gender, employment). Even the maximum difference between countries overall (15%) was still smaller than the generational gap within any region.

While only 7% (6%- 9%) of participants aged ≥65 years were “distressed and struggling” with their mental well-being to a “clinical” extent, 44% (38%-50%) of those aged 18-24 years reported mental well-being scores in the “distressed or struggling” range – representing a “growing gap between generations that, while present prior to the COVID-19 pandemic, has since been exacerbated,” the authors state.

With every successive decrement in age group, mental well-being “plummeted,” Dr. Thiagarajan said. She noted that research conducted prior to 2010 in several regions of the world showed that young adults typically had the highest well-being. “Our findings stand in stark contrast to these previous patterns.”

The relationship between lockdown stringency and poorer mental health could play a role. “The impact of social isolation may be most strongly felt in younger people,” she said.
 

Internet a culprit?

“Within almost every region, scores for cognition and drive and motivation were highest while mood and outlook and social self were the lowest,” the authors report.

The aggregate percentage of respondents who reported being “distressed or struggling” in the various MHQ dimensions is shown in the following table.

Sedentary time

Commenting for this news organization, Bernardo Ng, MD, a member of the American Psychiatric Association’s Council on International Psychiatry and Global Health and medical director of Sun Valley Research Center, Imperial, Calif., called the report “interesting, with an impressive sample size” and an “impressive geographic distribution.”

Courtesy Sun Valley Research Center

Dr. Ng, who was not involved in the report, said, “I did not think the impact of Internet use on mental health was as dramatic before looking at this report.

“On the other hand, I have personally been interested in the impact of sedentarism in mental health – not only emotionally but also biologically. Sedentarism, which is directly related to screen use time, produces inflammation that worsens brain function.”

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

A large global report shows a decline in mental health worldwide, with the poorest outcomes reported in young adults.

The Mental Health Million project of Sapien Labs issued its second report, published online March 15, encompassing 34 countries and over 220,000 Internet-enabled adults. It found a continued decline in mental health in all age groups and genders, with English-speaking countries having the lowest mental well-being.

The decline was significantly correlated with the stringency of COVID-19 lockdown measures in each country and was directionally correlated to the cases and deaths per million.

The youngest age group (18-24 years) reported the poorest mental well-being, with better mental health scores rising in every successively older age group.

“Some of our findings, especially regarding mental health in young adults, are alarming,” Tara Thiagarajan, PhD, Sapien Labs founder and chief scientist, told this news organization.

“Our data, which are continually updated in real time, are freely available for nonprofit, noncommercial use and research, and we hope that researchers will get involved in an interdisciplinary way that spans sociology, economics, psychiatry, and other fields,” she said.
 

Pioneering research

Dr. Thiagarajan and her team pioneered the Mental Health Million project, an ongoing research initiative utilizing a “free and anonymous assessment tool,” the Mental Health Quotient (MHQ), which “encompasses a comprehensive view of our emotional, social, and cognitive function and capability.”

The MHQ consists of 47 “elements of mental well-being,” with scores ranging from –100 to +200. (Negative scores indicate poorer mental well-being.) The MHQ categorizes respondents as “clinical, at-risk, enduring, managing, succeeding, and thriving” and computes scores on the basis of six broad dimensions of mental health: core cognition, complex cognition, mood and outlook, drive and motivation, social self, and mind-body connection.

As reported by this news organization, Sapien Lab’s first Mental Health State of the World report (n = 49,000 adults) was conducted in eight English-speaking countries in 2020. Participants were compared to a smaller sample of people from the same countries polled in 2019.

In this year’s report, “we expanded quite substantially,” Dr. Thiagarajan said. The project added Spanish, French, and Arabic and recruited participants from 34 countries on six continents (n = 223,087) via advertising on Google and Facebook.

Economic prosperity not protective

Across the eight English-speaking countries, there was a decline in mental well-being of 3% from 2020 to 2021, which was smaller than the 8% decline from 2019 to 2020. The percentage of people who were “distressed or struggling” increased from 26% to 30% in 2021.

“Now that a lot of pandemic issue seems to be easing up, I hope we’ll see mental well-being coming back up, but at least it’s a smaller decline than we saw between 2019 and 2020,” said Dr. Thiagarajan.

The decline across countries from 2019 to 2021 was significantly correlated with the stringency of governmental COVID-19-related measures (based on the Oxford COVID-19 Government Response Tracker, 2022; r = .54) and directionally correlated to the cases and deaths per million.

In total, 30% of respondents in English-speaking countries had mental well-being scores in the “distressed” or “struggling” range – higher than the Middle Eastern countries, North Africa, Latin America, and Europe (23%, 23%, 24%, and 18%, respectively).

Only 36% of participants in the English-speaking countries, the Middle East, and North Africa reported “thriving or succeeding,” vs. 45% and 46% in Latin America and Europe, respectively. Venezuela topped the list with an average MHQ of 91, while the United Kingdom and South Africa had the lowest scores, at 46 each.

Mental well-being was slightly higher in males than in females but was dramatically lower in nonbinary/third-gender respondents. In fact, those identifying as nonbinary/third gender had the lowest mental well-being of any group.

Across all countries and languages, higher education was associated with better mental well-being. Employment was also associated with superior mental well-being, compared with being unemployed – particularly in core English-speaking countries.

However, “country indicators of economic prosperity were negatively correlated with mental well-being, particularly for young adults and males, belying the commonly held belief that national economic prosperity translates into greater mental well-being,” said Dr. Thiagarajan.
 

‘Stark’ contrast

The most dramatic finding was the difference in mental well-being between younger and older adults, which was two- to threefold larger than differences in other dimensions (for example, age, gender, employment). Even the maximum difference between countries overall (15%) was still smaller than the generational gap within any region.

While only 7% (6%- 9%) of participants aged ≥65 years were “distressed and struggling” with their mental well-being to a “clinical” extent, 44% (38%-50%) of those aged 18-24 years reported mental well-being scores in the “distressed or struggling” range – representing a “growing gap between generations that, while present prior to the COVID-19 pandemic, has since been exacerbated,” the authors state.

With every successive decrement in age group, mental well-being “plummeted,” Dr. Thiagarajan said. She noted that research conducted prior to 2010 in several regions of the world showed that young adults typically had the highest well-being. “Our findings stand in stark contrast to these previous patterns.”

The relationship between lockdown stringency and poorer mental health could play a role. “The impact of social isolation may be most strongly felt in younger people,” she said.
 

Internet a culprit?

“Within almost every region, scores for cognition and drive and motivation were highest while mood and outlook and social self were the lowest,” the authors report.

The aggregate percentage of respondents who reported being “distressed or struggling” in the various MHQ dimensions is shown in the following table.

Sedentary time

Commenting for this news organization, Bernardo Ng, MD, a member of the American Psychiatric Association’s Council on International Psychiatry and Global Health and medical director of Sun Valley Research Center, Imperial, Calif., called the report “interesting, with an impressive sample size” and an “impressive geographic distribution.”

Courtesy Sun Valley Research Center

Dr. Ng, who was not involved in the report, said, “I did not think the impact of Internet use on mental health was as dramatic before looking at this report.

“On the other hand, I have personally been interested in the impact of sedentarism in mental health – not only emotionally but also biologically. Sedentarism, which is directly related to screen use time, produces inflammation that worsens brain function.”

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

A large global report shows a decline in mental health worldwide, with the poorest outcomes reported in young adults.

The Mental Health Million project of Sapien Labs issued its second report, published online March 15, encompassing 34 countries and over 220,000 Internet-enabled adults. It found a continued decline in mental health in all age groups and genders, with English-speaking countries having the lowest mental well-being.

The decline was significantly correlated with the stringency of COVID-19 lockdown measures in each country and was directionally correlated to the cases and deaths per million.

The youngest age group (18-24 years) reported the poorest mental well-being, with better mental health scores rising in every successively older age group.

“Some of our findings, especially regarding mental health in young adults, are alarming,” Tara Thiagarajan, PhD, Sapien Labs founder and chief scientist, told this news organization.

“Our data, which are continually updated in real time, are freely available for nonprofit, noncommercial use and research, and we hope that researchers will get involved in an interdisciplinary way that spans sociology, economics, psychiatry, and other fields,” she said.
 

Pioneering research

Dr. Thiagarajan and her team pioneered the Mental Health Million project, an ongoing research initiative utilizing a “free and anonymous assessment tool,” the Mental Health Quotient (MHQ), which “encompasses a comprehensive view of our emotional, social, and cognitive function and capability.”

The MHQ consists of 47 “elements of mental well-being,” with scores ranging from –100 to +200. (Negative scores indicate poorer mental well-being.) The MHQ categorizes respondents as “clinical, at-risk, enduring, managing, succeeding, and thriving” and computes scores on the basis of six broad dimensions of mental health: core cognition, complex cognition, mood and outlook, drive and motivation, social self, and mind-body connection.

As reported by this news organization, Sapien Lab’s first Mental Health State of the World report (n = 49,000 adults) was conducted in eight English-speaking countries in 2020. Participants were compared to a smaller sample of people from the same countries polled in 2019.

In this year’s report, “we expanded quite substantially,” Dr. Thiagarajan said. The project added Spanish, French, and Arabic and recruited participants from 34 countries on six continents (n = 223,087) via advertising on Google and Facebook.

Economic prosperity not protective

Across the eight English-speaking countries, there was a decline in mental well-being of 3% from 2020 to 2021, which was smaller than the 8% decline from 2019 to 2020. The percentage of people who were “distressed or struggling” increased from 26% to 30% in 2021.

“Now that a lot of pandemic issue seems to be easing up, I hope we’ll see mental well-being coming back up, but at least it’s a smaller decline than we saw between 2019 and 2020,” said Dr. Thiagarajan.

The decline across countries from 2019 to 2021 was significantly correlated with the stringency of governmental COVID-19-related measures (based on the Oxford COVID-19 Government Response Tracker, 2022; r = .54) and directionally correlated to the cases and deaths per million.

In total, 30% of respondents in English-speaking countries had mental well-being scores in the “distressed” or “struggling” range – higher than the Middle Eastern countries, North Africa, Latin America, and Europe (23%, 23%, 24%, and 18%, respectively).

Only 36% of participants in the English-speaking countries, the Middle East, and North Africa reported “thriving or succeeding,” vs. 45% and 46% in Latin America and Europe, respectively. Venezuela topped the list with an average MHQ of 91, while the United Kingdom and South Africa had the lowest scores, at 46 each.

Mental well-being was slightly higher in males than in females but was dramatically lower in nonbinary/third-gender respondents. In fact, those identifying as nonbinary/third gender had the lowest mental well-being of any group.

Across all countries and languages, higher education was associated with better mental well-being. Employment was also associated with superior mental well-being, compared with being unemployed – particularly in core English-speaking countries.

However, “country indicators of economic prosperity were negatively correlated with mental well-being, particularly for young adults and males, belying the commonly held belief that national economic prosperity translates into greater mental well-being,” said Dr. Thiagarajan.
 

‘Stark’ contrast

The most dramatic finding was the difference in mental well-being between younger and older adults, which was two- to threefold larger than differences in other dimensions (for example, age, gender, employment). Even the maximum difference between countries overall (15%) was still smaller than the generational gap within any region.

While only 7% (6%- 9%) of participants aged ≥65 years were “distressed and struggling” with their mental well-being to a “clinical” extent, 44% (38%-50%) of those aged 18-24 years reported mental well-being scores in the “distressed or struggling” range – representing a “growing gap between generations that, while present prior to the COVID-19 pandemic, has since been exacerbated,” the authors state.

With every successive decrement in age group, mental well-being “plummeted,” Dr. Thiagarajan said. She noted that research conducted prior to 2010 in several regions of the world showed that young adults typically had the highest well-being. “Our findings stand in stark contrast to these previous patterns.”

The relationship between lockdown stringency and poorer mental health could play a role. “The impact of social isolation may be most strongly felt in younger people,” she said.
 

Internet a culprit?

“Within almost every region, scores for cognition and drive and motivation were highest while mood and outlook and social self were the lowest,” the authors report.

The aggregate percentage of respondents who reported being “distressed or struggling” in the various MHQ dimensions is shown in the following table.

Sedentary time

Commenting for this news organization, Bernardo Ng, MD, a member of the American Psychiatric Association’s Council on International Psychiatry and Global Health and medical director of Sun Valley Research Center, Imperial, Calif., called the report “interesting, with an impressive sample size” and an “impressive geographic distribution.”

Courtesy Sun Valley Research Center

Dr. Ng, who was not involved in the report, said, “I did not think the impact of Internet use on mental health was as dramatic before looking at this report.

“On the other hand, I have personally been interested in the impact of sedentarism in mental health – not only emotionally but also biologically. Sedentarism, which is directly related to screen use time, produces inflammation that worsens brain function.”

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

In his first State of the Union address in early March, President Joe Biden broached a tax policy question that neuroscientists and pediatricians also see as a scientific one.

President Biden urged lawmakers to extend the Child Tax Credit “so no one has to raise a family in poverty.”

Apart from the usual political and budgetary calculus, physicians and social scientists are actively examining the ramifications that such policies could have on child development and long-term health outcomes.

To do so, they have turned to brain scans and rigorous studies to better understand the effects of being raised in poverty and whether giving families more cash makes a difference.

Initial results from an ongoing study known as Baby’s First Years suggest that providing extra money to mothers may influence brain activity in infants in ways that reflect improvements in cognitive ability.

Researchers, doctors, and advocates say the findings cement the case for policies such as the expanded Child Tax Credit. Others argue that reducing child poverty is a social good on its own, regardless of what brain scans show.

The new findings were published Jan. 24 in Proceedings of the National Academy of Sciences (PNAS), as lawmakers were weighing whether to resume an expansion of the tax credit, which had temporarily provided monthly payments akin to the $333 a month looked at in the study.

The expiration of the expanded credit in December left some 3.6 million more children in poverty, bringing the total number to more than 12.5 million and pushing the child poverty rate to 17%.

Philanthropists and research teams have partnered to conduct other guaranteed income experiments around the United States, including one in New York called the Bridge Project, which is evaluating different levels of financial support for mothers with babies.

Some mothers are receiving $500 per month, others twice that amount.

Angelina Matos, 18, receives $1,000 a month, allowing her to attend college and pay for necessities like diapers, clothes, and toys for her nearly 1-year-old daughter.

As one of 600 mothers participating in the project, Ms. Matos periodically answers questions about her daughter’s progress, like whether she is eating solid foods.

Megha Agarwal, BS, executive director of the Bridge Project and its funder the Monarch Foundation, said she was thrilled to see the early results from Baby’s First Years. “We are looking for ways in which we can strengthen our future generations,” she said. “It is exciting to see that direct cash and a guaranteed income might be part of the solution.”
 

A scientific perspective

Growing up in poverty is well-known to increase the likelihood of lower academic achievement and chronic conditions such as asthma and obesity. Relative to higher income levels, poverty is associated with differences in the structure and function of the developing brain. But whether interventions to reduce poverty can influence how newborns develop is less clear.

“There would be plenty of people who would say, ‘Well, it’s not poverty. It’s all the things associated with poverty. It’s the choices you make that are actually leading to differences in outcomes,’” said Kimberly Noble, MD, PhD, a neuroscientist at Columbia University, New York, and a coauthor of the PNAS study. Regardless of ideology, she said, the best way to address that question from a scientific perspective is through a randomized controlled trial.

“You can’t, and wouldn’t want to, randomize kids to living in poverty or not, but you can take a group of families who are unfortunately living in poverty and randomize them to receive different levels of economic support,” Dr. Noble said.
 

$333 per month

Baby’s First Years has done just that. Researchers gave 1,000 low-income mothers with newborns a cash gift of $333 per month or a smaller gift of $20 per month, disbursed on debit cards, starting in 2018. Participants live in four metropolitan areas – New York City, greater New Orleans, Minneapolis-Saint Paul, and Omaha – and were recruited at the time of their child’s birth. Investigators currently have funding to continue the cash support until the children turn 4 years old.

When the infants were about 1 year old, investigators measured their resting brain activity using EEG.

The COVID-19 pandemic disrupted the ability to conduct in-person testing, so the number of children with EEG data was smaller than planned. Still, the researchers analyzed data from 251 kids in the group that received the smaller cash gift and 184 kids in the group that received the larger amount. Patterns of brain activity largely tracked those seen in earlier observational studies: more mid- and high-frequency activity (alpha-, beta-, and gamma-bands) and less low-frequency activity (theta-bands) among children in the households that received more money.

Faster brain activity is associated with better scores on measures of language, cognition, and social-emotional development. Slower activity has been linked to problems with behavior, attention, and learning.

“We predicted that our poverty reduction intervention would mitigate the neurobiological signal of poverty,” Dr. Noble said. “And that’s exactly what we report in this paper.”

The study builds on decades of work showing that poverty can harm child development, said Joan Luby, MD, with Washington University School of Medicine, St. Louis, who served as a peer reviewer for the PNAS paper.

More follow-up data and information about the babies’ cognitive function and behavior over time are needed, but the study shows a signal that cannot be ignored, Dr. Luby said.

Dr. Luby began exploring the effects of poverty on brain development in earnest while working on a study that was meant to focus on another variable altogether: early childhood depression. The investigators on that 2013 study found that poverty had a “very, very big effect in our sample, and we realized we had to learn more about it,” she said.

The American Academy of Pediatrics likewise has recognized poverty as an important determinant of health. A policy statement that the group published in 2016 and reaffirmed in 2021 outlines ways pediatricians and social programs can address poverty.

Benard Dreyer, MD, director of pediatrics at Bellevue Hospital, New York, was president of the AAP when it published this guidance.

One lingering question has been how much low income worsens educational outcomes, Dr. Dreyer said. Perhaps other issues, such as single motherhood, a lack of parental education, or living in neighborhoods with more crime may be the cause. If so, simply giving more money to parents might not overcome those barriers.

Natural experiments have hinted that money itself can influence child development. For example, families on an American Indian reservation in North Carolina started receiving a share of casino profits after a casino opened there.

The new infusion of funds arrived in the middle of a study in which researchers were examining the development of mental illness in children.

Among children who were no longer poor as a result of the casino payments, symptoms of conduct and oppositional defiant disorders decreased.
 

Guaranteeing income

How extra money affects families across different levels of income also interests researchers and policymakers.

“One of the policy debates in Washington is to what degree should it be to everyone,” Ajay Chaudry, PhD, a research scholar at New York University who is advising the Bridge Project, said.

Guaranteed income programs may need to be available to most of the population out of political necessity, even if the benefits turn out to be the most pronounced at lower income levels, added Dr. Chaudry, who served in the Obama administration as deputy assistant secretary for human services policy.

If giving moms money affects babies’ brains, Dr. Dreyer pointed to two pathways that could explain the link: more resources and less family stress.

Money helps families buy toys and books, which in turn could support a child’s cognitive development. Meanwhile, low-income mothers and fathers may experience worries about eviction, adequate food, and the loss of heat and electricity, which could detract from their ability to parent.

Of course, many ways to support a child’s development do not require money. Engaging with children in a warm and nurturing way, having conversations with them, and reading with them are all important.

If the pattern in the PNAS study holds, individual experiences and outcomes will still vary, Dr. Noble said. Many children in the group that received the smaller gift had fast-paced brain activity, whereas some babies in the group that received the larger gift showed slower brain activity. Knowing family income would not allow you to accurately predict anything about an individual child’s brain, Dr. Noble said.

“I certainly wouldn’t want the message to be that money is the only thing that matters,” Dr. Noble said. “Money is something that can be easily manipulated by policy, which is why I think this is important.”

For the 18-year-old new mom Ms. Matos, accepting assistance “makes me feel less of myself. But honestly, I feel like mothers shouldn’t be afraid to ask for help or reach out for help or apply to programs like these.”

The sources reported a variety of funders, including federal agencies and foundations and donors.

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

In his first State of the Union address in early March, President Joe Biden broached a tax policy question that neuroscientists and pediatricians also see as a scientific one.

President Biden urged lawmakers to extend the Child Tax Credit “so no one has to raise a family in poverty.”

Apart from the usual political and budgetary calculus, physicians and social scientists are actively examining the ramifications that such policies could have on child development and long-term health outcomes.

To do so, they have turned to brain scans and rigorous studies to better understand the effects of being raised in poverty and whether giving families more cash makes a difference.

Initial results from an ongoing study known as Baby’s First Years suggest that providing extra money to mothers may influence brain activity in infants in ways that reflect improvements in cognitive ability.

Researchers, doctors, and advocates say the findings cement the case for policies such as the expanded Child Tax Credit. Others argue that reducing child poverty is a social good on its own, regardless of what brain scans show.

The new findings were published Jan. 24 in Proceedings of the National Academy of Sciences (PNAS), as lawmakers were weighing whether to resume an expansion of the tax credit, which had temporarily provided monthly payments akin to the $333 a month looked at in the study.

The expiration of the expanded credit in December left some 3.6 million more children in poverty, bringing the total number to more than 12.5 million and pushing the child poverty rate to 17%.

Philanthropists and research teams have partnered to conduct other guaranteed income experiments around the United States, including one in New York called the Bridge Project, which is evaluating different levels of financial support for mothers with babies.

Some mothers are receiving $500 per month, others twice that amount.

Angelina Matos, 18, receives $1,000 a month, allowing her to attend college and pay for necessities like diapers, clothes, and toys for her nearly 1-year-old daughter.

As one of 600 mothers participating in the project, Ms. Matos periodically answers questions about her daughter’s progress, like whether she is eating solid foods.

Megha Agarwal, BS, executive director of the Bridge Project and its funder the Monarch Foundation, said she was thrilled to see the early results from Baby’s First Years. “We are looking for ways in which we can strengthen our future generations,” she said. “It is exciting to see that direct cash and a guaranteed income might be part of the solution.”
 

A scientific perspective

Growing up in poverty is well-known to increase the likelihood of lower academic achievement and chronic conditions such as asthma and obesity. Relative to higher income levels, poverty is associated with differences in the structure and function of the developing brain. But whether interventions to reduce poverty can influence how newborns develop is less clear.

“There would be plenty of people who would say, ‘Well, it’s not poverty. It’s all the things associated with poverty. It’s the choices you make that are actually leading to differences in outcomes,’” said Kimberly Noble, MD, PhD, a neuroscientist at Columbia University, New York, and a coauthor of the PNAS study. Regardless of ideology, she said, the best way to address that question from a scientific perspective is through a randomized controlled trial.

“You can’t, and wouldn’t want to, randomize kids to living in poverty or not, but you can take a group of families who are unfortunately living in poverty and randomize them to receive different levels of economic support,” Dr. Noble said.
 

$333 per month

Baby’s First Years has done just that. Researchers gave 1,000 low-income mothers with newborns a cash gift of $333 per month or a smaller gift of $20 per month, disbursed on debit cards, starting in 2018. Participants live in four metropolitan areas – New York City, greater New Orleans, Minneapolis-Saint Paul, and Omaha – and were recruited at the time of their child’s birth. Investigators currently have funding to continue the cash support until the children turn 4 years old.

When the infants were about 1 year old, investigators measured their resting brain activity using EEG.

The COVID-19 pandemic disrupted the ability to conduct in-person testing, so the number of children with EEG data was smaller than planned. Still, the researchers analyzed data from 251 kids in the group that received the smaller cash gift and 184 kids in the group that received the larger amount. Patterns of brain activity largely tracked those seen in earlier observational studies: more mid- and high-frequency activity (alpha-, beta-, and gamma-bands) and less low-frequency activity (theta-bands) among children in the households that received more money.

Faster brain activity is associated with better scores on measures of language, cognition, and social-emotional development. Slower activity has been linked to problems with behavior, attention, and learning.

“We predicted that our poverty reduction intervention would mitigate the neurobiological signal of poverty,” Dr. Noble said. “And that’s exactly what we report in this paper.”

The study builds on decades of work showing that poverty can harm child development, said Joan Luby, MD, with Washington University School of Medicine, St. Louis, who served as a peer reviewer for the PNAS paper.

More follow-up data and information about the babies’ cognitive function and behavior over time are needed, but the study shows a signal that cannot be ignored, Dr. Luby said.

Dr. Luby began exploring the effects of poverty on brain development in earnest while working on a study that was meant to focus on another variable altogether: early childhood depression. The investigators on that 2013 study found that poverty had a “very, very big effect in our sample, and we realized we had to learn more about it,” she said.

The American Academy of Pediatrics likewise has recognized poverty as an important determinant of health. A policy statement that the group published in 2016 and reaffirmed in 2021 outlines ways pediatricians and social programs can address poverty.

Benard Dreyer, MD, director of pediatrics at Bellevue Hospital, New York, was president of the AAP when it published this guidance.

One lingering question has been how much low income worsens educational outcomes, Dr. Dreyer said. Perhaps other issues, such as single motherhood, a lack of parental education, or living in neighborhoods with more crime may be the cause. If so, simply giving more money to parents might not overcome those barriers.

Natural experiments have hinted that money itself can influence child development. For example, families on an American Indian reservation in North Carolina started receiving a share of casino profits after a casino opened there.

The new infusion of funds arrived in the middle of a study in which researchers were examining the development of mental illness in children.

Among children who were no longer poor as a result of the casino payments, symptoms of conduct and oppositional defiant disorders decreased.
 

Guaranteeing income

How extra money affects families across different levels of income also interests researchers and policymakers.

“One of the policy debates in Washington is to what degree should it be to everyone,” Ajay Chaudry, PhD, a research scholar at New York University who is advising the Bridge Project, said.

Guaranteed income programs may need to be available to most of the population out of political necessity, even if the benefits turn out to be the most pronounced at lower income levels, added Dr. Chaudry, who served in the Obama administration as deputy assistant secretary for human services policy.

If giving moms money affects babies’ brains, Dr. Dreyer pointed to two pathways that could explain the link: more resources and less family stress.

Money helps families buy toys and books, which in turn could support a child’s cognitive development. Meanwhile, low-income mothers and fathers may experience worries about eviction, adequate food, and the loss of heat and electricity, which could detract from their ability to parent.

Of course, many ways to support a child’s development do not require money. Engaging with children in a warm and nurturing way, having conversations with them, and reading with them are all important.

If the pattern in the PNAS study holds, individual experiences and outcomes will still vary, Dr. Noble said. Many children in the group that received the smaller gift had fast-paced brain activity, whereas some babies in the group that received the larger gift showed slower brain activity. Knowing family income would not allow you to accurately predict anything about an individual child’s brain, Dr. Noble said.

“I certainly wouldn’t want the message to be that money is the only thing that matters,” Dr. Noble said. “Money is something that can be easily manipulated by policy, which is why I think this is important.”

For the 18-year-old new mom Ms. Matos, accepting assistance “makes me feel less of myself. But honestly, I feel like mothers shouldn’t be afraid to ask for help or reach out for help or apply to programs like these.”

The sources reported a variety of funders, including federal agencies and foundations and donors.

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

In his first State of the Union address in early March, President Joe Biden broached a tax policy question that neuroscientists and pediatricians also see as a scientific one.

President Biden urged lawmakers to extend the Child Tax Credit “so no one has to raise a family in poverty.”

Apart from the usual political and budgetary calculus, physicians and social scientists are actively examining the ramifications that such policies could have on child development and long-term health outcomes.

To do so, they have turned to brain scans and rigorous studies to better understand the effects of being raised in poverty and whether giving families more cash makes a difference.

Initial results from an ongoing study known as Baby’s First Years suggest that providing extra money to mothers may influence brain activity in infants in ways that reflect improvements in cognitive ability.

Researchers, doctors, and advocates say the findings cement the case for policies such as the expanded Child Tax Credit. Others argue that reducing child poverty is a social good on its own, regardless of what brain scans show.

The new findings were published Jan. 24 in Proceedings of the National Academy of Sciences (PNAS), as lawmakers were weighing whether to resume an expansion of the tax credit, which had temporarily provided monthly payments akin to the $333 a month looked at in the study.

The expiration of the expanded credit in December left some 3.6 million more children in poverty, bringing the total number to more than 12.5 million and pushing the child poverty rate to 17%.

Philanthropists and research teams have partnered to conduct other guaranteed income experiments around the United States, including one in New York called the Bridge Project, which is evaluating different levels of financial support for mothers with babies.

Some mothers are receiving $500 per month, others twice that amount.

Angelina Matos, 18, receives $1,000 a month, allowing her to attend college and pay for necessities like diapers, clothes, and toys for her nearly 1-year-old daughter.

As one of 600 mothers participating in the project, Ms. Matos periodically answers questions about her daughter’s progress, like whether she is eating solid foods.

Megha Agarwal, BS, executive director of the Bridge Project and its funder the Monarch Foundation, said she was thrilled to see the early results from Baby’s First Years. “We are looking for ways in which we can strengthen our future generations,” she said. “It is exciting to see that direct cash and a guaranteed income might be part of the solution.”
 

A scientific perspective

Growing up in poverty is well-known to increase the likelihood of lower academic achievement and chronic conditions such as asthma and obesity. Relative to higher income levels, poverty is associated with differences in the structure and function of the developing brain. But whether interventions to reduce poverty can influence how newborns develop is less clear.

“There would be plenty of people who would say, ‘Well, it’s not poverty. It’s all the things associated with poverty. It’s the choices you make that are actually leading to differences in outcomes,’” said Kimberly Noble, MD, PhD, a neuroscientist at Columbia University, New York, and a coauthor of the PNAS study. Regardless of ideology, she said, the best way to address that question from a scientific perspective is through a randomized controlled trial.

“You can’t, and wouldn’t want to, randomize kids to living in poverty or not, but you can take a group of families who are unfortunately living in poverty and randomize them to receive different levels of economic support,” Dr. Noble said.
 

$333 per month

Baby’s First Years has done just that. Researchers gave 1,000 low-income mothers with newborns a cash gift of $333 per month or a smaller gift of $20 per month, disbursed on debit cards, starting in 2018. Participants live in four metropolitan areas – New York City, greater New Orleans, Minneapolis-Saint Paul, and Omaha – and were recruited at the time of their child’s birth. Investigators currently have funding to continue the cash support until the children turn 4 years old.

When the infants were about 1 year old, investigators measured their resting brain activity using EEG.

The COVID-19 pandemic disrupted the ability to conduct in-person testing, so the number of children with EEG data was smaller than planned. Still, the researchers analyzed data from 251 kids in the group that received the smaller cash gift and 184 kids in the group that received the larger amount. Patterns of brain activity largely tracked those seen in earlier observational studies: more mid- and high-frequency activity (alpha-, beta-, and gamma-bands) and less low-frequency activity (theta-bands) among children in the households that received more money.

Faster brain activity is associated with better scores on measures of language, cognition, and social-emotional development. Slower activity has been linked to problems with behavior, attention, and learning.

“We predicted that our poverty reduction intervention would mitigate the neurobiological signal of poverty,” Dr. Noble said. “And that’s exactly what we report in this paper.”

The study builds on decades of work showing that poverty can harm child development, said Joan Luby, MD, with Washington University School of Medicine, St. Louis, who served as a peer reviewer for the PNAS paper.

More follow-up data and information about the babies’ cognitive function and behavior over time are needed, but the study shows a signal that cannot be ignored, Dr. Luby said.

Dr. Luby began exploring the effects of poverty on brain development in earnest while working on a study that was meant to focus on another variable altogether: early childhood depression. The investigators on that 2013 study found that poverty had a “very, very big effect in our sample, and we realized we had to learn more about it,” she said.

The American Academy of Pediatrics likewise has recognized poverty as an important determinant of health. A policy statement that the group published in 2016 and reaffirmed in 2021 outlines ways pediatricians and social programs can address poverty.

Benard Dreyer, MD, director of pediatrics at Bellevue Hospital, New York, was president of the AAP when it published this guidance.

One lingering question has been how much low income worsens educational outcomes, Dr. Dreyer said. Perhaps other issues, such as single motherhood, a lack of parental education, or living in neighborhoods with more crime may be the cause. If so, simply giving more money to parents might not overcome those barriers.

Natural experiments have hinted that money itself can influence child development. For example, families on an American Indian reservation in North Carolina started receiving a share of casino profits after a casino opened there.

The new infusion of funds arrived in the middle of a study in which researchers were examining the development of mental illness in children.

Among children who were no longer poor as a result of the casino payments, symptoms of conduct and oppositional defiant disorders decreased.
 

Guaranteeing income

How extra money affects families across different levels of income also interests researchers and policymakers.

“One of the policy debates in Washington is to what degree should it be to everyone,” Ajay Chaudry, PhD, a research scholar at New York University who is advising the Bridge Project, said.

Guaranteed income programs may need to be available to most of the population out of political necessity, even if the benefits turn out to be the most pronounced at lower income levels, added Dr. Chaudry, who served in the Obama administration as deputy assistant secretary for human services policy.

If giving moms money affects babies’ brains, Dr. Dreyer pointed to two pathways that could explain the link: more resources and less family stress.

Money helps families buy toys and books, which in turn could support a child’s cognitive development. Meanwhile, low-income mothers and fathers may experience worries about eviction, adequate food, and the loss of heat and electricity, which could detract from their ability to parent.

Of course, many ways to support a child’s development do not require money. Engaging with children in a warm and nurturing way, having conversations with them, and reading with them are all important.

If the pattern in the PNAS study holds, individual experiences and outcomes will still vary, Dr. Noble said. Many children in the group that received the smaller gift had fast-paced brain activity, whereas some babies in the group that received the larger gift showed slower brain activity. Knowing family income would not allow you to accurately predict anything about an individual child’s brain, Dr. Noble said.

“I certainly wouldn’t want the message to be that money is the only thing that matters,” Dr. Noble said. “Money is something that can be easily manipulated by policy, which is why I think this is important.”

For the 18-year-old new mom Ms. Matos, accepting assistance “makes me feel less of myself. But honestly, I feel like mothers shouldn’t be afraid to ask for help or reach out for help or apply to programs like these.”

The sources reported a variety of funders, including federal agencies and foundations and donors.

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

WASHINGTON – Research on standardized microbiome-based therapies designed to prevent the recurrence of Clostridioides difficile infection (CDI) is moving “with a lot of momentum,” according to one expert, and modulation of the gut microbiome may even enhance responses to immunotherapy and/or abrogate toxicity, according to another.

Several products for prevention of CDI recurrence are poised for either phase 3 trials or upcoming Food and Drug Administration approval, Sahil Khanna, MBBS, MS, professor of medicine, gastroenterology, and hepatology at the Mayo Clinic in Rochester, Minn., reported at the annual Gut Microbiota for Health World Summit.

Jennifer A. Wargo, MD, MMSc, of the University of Texas MD Anderson Cancer Center, Houston, described her investigations of microbiome modulation’s role in cancer treatment. “I used to say yes [we can do this] somewhat enthusiastically without data, but now we have data to support this,” she said at the meeting, sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility. “The answer now is totally yes.”
 

New approaches for CDI

“Based on how the field is moving, we might be able to [offer our patients] earlier microbiome restoration” than is currently afforded with fecal microbiota transplantation (FMT), he said. “Right now the [Food and Drug Administration] and our clinical guidelines say we should do FMT after three or more episodes [of CDI] – that’s heartbreaking for patients.”

Several of the microbiome-based therapies under investigation – including two poised for phase 3 trials – have shown efficacy after a second episode of CDI, and one of these two has also had positive results after one episode of CDI in patients 65 at older, a group at particularly high risk of recurrence, said Dr. Khanna.

The value of standardized, mostly pill-form microbiome therapies has been heightened during the pandemic. “We’ve been doing conventional FMT for recurrent C. difficile for over a decade now, and it’s probably the most effective treatment we have,” said Colleen R. Kelly, MD, associate professor of medicine at Brown University, Providence, R.I., and moderator of the session on microbiota-based therapies.

Prepandemic “it got really hard, with issues of identifying donors, and quality control and safety ... And then when COVID hit the stool banks shut down,” she said in an interview after the meeting. With stool testing for SARS-CoV-2 now in place, some stool is again available, “but it made me realize how fragile our current system is,” Dr. Kelly said. “The fact that companies are putting these products through the FDA pipeline and investigating them in rigorous, scientific randomized controlled trials is really good for the field.”

The products vary in composition; some are live multi-strain biotherapeutics derived from donor stool, for instance, while others are defined live bacterial consortia not from stool. Most are oral formulations, given one or multiple times, that do not require any bowel preparation.

One of the products most advanced in the pipeline, RBX2660 (Rebiotix, Ferring Pharmaceuticals) is stool derived and rectally administered. In phase 3 research, 70.5% of patients who received one active enema after having had two or more CDI recurrences and standard-of-care antibiotic treatment had no additional recurrence at 8 weeks compared to 58.1% in the placebo group, Dr. Khanna said.

The other product with positive phase 3 results, SER-109 (Seres Therapeutics), is a donor stool-derived oral formulation of purified Firmicutes spores that is administered after bowel prep. In results published earlier this year, the percentage of patients with recurrence of CDI up to 8 weeks after standard antibiotic treatment was 12% in the SER-109 group and 40% in the placebo group.

Patients in this trial were required to have had three episodes of CDI, and interestingly, Dr. Khanna said, the diagnosis of CDI was made only by toxin enzyme immunoassay (EIA). Earlier phase 2 research, which allowed either toxin EIA or polymerase chain reaction testing for the diagnosis of CDI (as other trials have done), produced negative results, leading investigators to surmise that some of the included patients had been colonized with C. difficile rather than being actively infected, Dr. Khanna said.

Researchers of these trials are documenting not only resolution of CDI but what they believe are positive shifts in the gut microbiota after microbiome-based therapy, he said. For instance, a phase 1 trial he led of the product RBX7455 (Rebiotix, Ferring Pharmaceuticals) – an oral capsule of lyophilized stool-based bacteria that can be kept for several days at room temperature – showed increases in Bacteroidia and Clostridia.

And other trials’ analyses of microbiome engraftment have demonstrated that “you can restore [species] even when these bacteria aren’t [included in the therapy],” he noted. “As the milieu of the gut improves, species that were not detected start coming back up.”

Asked about rates of efficacy in the trials’ placebo arms, Dr. Khanna said that “we’ve become smarter with our antibiotic regimens ... the placebo response rate is the response to newer guideline-based therapies.”

In addition to CDI, microbiome-based therapies are being studied, mostly in phase 1 research, for indications such as Crohn’s disease, ulcerative colitis, autism spectrum disorder, hepatitis B, and hepatic encephalopathy, Dr. Khanna noted.

Dr. Kelly, whose own research has focused on FMT for CDI, said she anticipates an expansion of research into other indications once products to prevent CDI recurrence are on the market. “There have been a couple of promising ulcerative colitis trials that haven’t gone anywhere clinically yet,” she said in the interview. “But will we now identify patients with UC who may be more sensitive to microbial manipulation, for whom we can use these microbial therapies along with a biologic?”

Some of her patients with IBD and CDI who are treated with FMT have not only had their CDI eradicated but have subsequently seen improvements in their IBD, she noted.

The role of traditional FMT and of stool banks will likely change in the future with new standardized oral microbiome-based therapies that can be approved and regulated by the FDA, she said. However, “we think the stool banks will still have some value,” she said, certainly for clinical research and probably for some treatment purposes as well. Regarding new therapies, “I just really hope they’re affordable,” she said.
 

Gut microbiome manipulation for cancer

Dr. Wargo’s research at MD Anderson has focused on metastatic breast cancer and immunotherapeutic checkpoint blockade. By sequencing microbiota samples and performing immune profiling in hundreds of patients, her team found that responders to PD-1 blockage have a greater diversity of gut bacteria and that “favorable signatures in the gut microbiome” are associated with enhanced immune responses in the tumor microenvironment.

Studies published last year in Science from investigators in Israel (2021 Feb 5;371[6529]:602-9) and Pittsburgh (2021 Feb 5;371[6529]:595-602), demonstrated that FMT promotes response in immunotherapy-refractory melanoma patients. In one study, FMT provided clinical benefit in 6 of 15 patients whose cancer had progressed on prior anti-PD-1 therapy, “which is pretty remarkable,” Dr. Wargo said.

Both research groups, she noted, saw favorable changes in the gut microbiome and immune cell infiltrates both at the level of the colon and the tumor.

Current research on FMT and other microbiome modulation strategies for cancer is guided in part by knowledge that tumors have microbial signatures – these signatures are now being identified across all tumor types – and by findings of “cross talk” between the gut and tumor microbiomes, she explained.

“Researchers are working hard to identify optimal consortia to enhance immune responses in the cancer setting, with promising work in preclinical models,” she said, and clinical trials are in progress. The role of diet in modulating the microbiome and enhancing anti-tumor immunity, with a focus on high dietary fiber intake, is also being investigated, she said.

Dr. Wargo reported that she serves on the advisory boards and is a paid speaker of numerous pharmaceutical and biotechnology companies, and is the coinventor of a patent submitted by the Texas MD Anderson Cancer Center on modulating the microbiome to enhance response to checkpoint blockade, and another related patent. Dr. Khanna reported that he is involved in research with Ferring/Rebiotix, Finch, Seres, Pfizer and Vendata, and does consulting for Immuron and several other companies. Dr. Kelly said she serves as an unpaid adviser for OpenBiome, a nonprofit stool bank, and that her site has enrolled patients in two of the trials testing products for CDI.

WASHINGTON – Research on standardized microbiome-based therapies designed to prevent the recurrence of Clostridioides difficile infection (CDI) is moving “with a lot of momentum,” according to one expert, and modulation of the gut microbiome may even enhance responses to immunotherapy and/or abrogate toxicity, according to another.

Several products for prevention of CDI recurrence are poised for either phase 3 trials or upcoming Food and Drug Administration approval, Sahil Khanna, MBBS, MS, professor of medicine, gastroenterology, and hepatology at the Mayo Clinic in Rochester, Minn., reported at the annual Gut Microbiota for Health World Summit.

Jennifer A. Wargo, MD, MMSc, of the University of Texas MD Anderson Cancer Center, Houston, described her investigations of microbiome modulation’s role in cancer treatment. “I used to say yes [we can do this] somewhat enthusiastically without data, but now we have data to support this,” she said at the meeting, sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility. “The answer now is totally yes.”
 

New approaches for CDI

“Based on how the field is moving, we might be able to [offer our patients] earlier microbiome restoration” than is currently afforded with fecal microbiota transplantation (FMT), he said. “Right now the [Food and Drug Administration] and our clinical guidelines say we should do FMT after three or more episodes [of CDI] – that’s heartbreaking for patients.”

Several of the microbiome-based therapies under investigation – including two poised for phase 3 trials – have shown efficacy after a second episode of CDI, and one of these two has also had positive results after one episode of CDI in patients 65 at older, a group at particularly high risk of recurrence, said Dr. Khanna.

The value of standardized, mostly pill-form microbiome therapies has been heightened during the pandemic. “We’ve been doing conventional FMT for recurrent C. difficile for over a decade now, and it’s probably the most effective treatment we have,” said Colleen R. Kelly, MD, associate professor of medicine at Brown University, Providence, R.I., and moderator of the session on microbiota-based therapies.

Prepandemic “it got really hard, with issues of identifying donors, and quality control and safety ... And then when COVID hit the stool banks shut down,” she said in an interview after the meeting. With stool testing for SARS-CoV-2 now in place, some stool is again available, “but it made me realize how fragile our current system is,” Dr. Kelly said. “The fact that companies are putting these products through the FDA pipeline and investigating them in rigorous, scientific randomized controlled trials is really good for the field.”

The products vary in composition; some are live multi-strain biotherapeutics derived from donor stool, for instance, while others are defined live bacterial consortia not from stool. Most are oral formulations, given one or multiple times, that do not require any bowel preparation.

One of the products most advanced in the pipeline, RBX2660 (Rebiotix, Ferring Pharmaceuticals) is stool derived and rectally administered. In phase 3 research, 70.5% of patients who received one active enema after having had two or more CDI recurrences and standard-of-care antibiotic treatment had no additional recurrence at 8 weeks compared to 58.1% in the placebo group, Dr. Khanna said.

The other product with positive phase 3 results, SER-109 (Seres Therapeutics), is a donor stool-derived oral formulation of purified Firmicutes spores that is administered after bowel prep. In results published earlier this year, the percentage of patients with recurrence of CDI up to 8 weeks after standard antibiotic treatment was 12% in the SER-109 group and 40% in the placebo group.

Patients in this trial were required to have had three episodes of CDI, and interestingly, Dr. Khanna said, the diagnosis of CDI was made only by toxin enzyme immunoassay (EIA). Earlier phase 2 research, which allowed either toxin EIA or polymerase chain reaction testing for the diagnosis of CDI (as other trials have done), produced negative results, leading investigators to surmise that some of the included patients had been colonized with C. difficile rather than being actively infected, Dr. Khanna said.

Researchers of these trials are documenting not only resolution of CDI but what they believe are positive shifts in the gut microbiota after microbiome-based therapy, he said. For instance, a phase 1 trial he led of the product RBX7455 (Rebiotix, Ferring Pharmaceuticals) – an oral capsule of lyophilized stool-based bacteria that can be kept for several days at room temperature – showed increases in Bacteroidia and Clostridia.

And other trials’ analyses of microbiome engraftment have demonstrated that “you can restore [species] even when these bacteria aren’t [included in the therapy],” he noted. “As the milieu of the gut improves, species that were not detected start coming back up.”

Asked about rates of efficacy in the trials’ placebo arms, Dr. Khanna said that “we’ve become smarter with our antibiotic regimens ... the placebo response rate is the response to newer guideline-based therapies.”

In addition to CDI, microbiome-based therapies are being studied, mostly in phase 1 research, for indications such as Crohn’s disease, ulcerative colitis, autism spectrum disorder, hepatitis B, and hepatic encephalopathy, Dr. Khanna noted.

Dr. Kelly, whose own research has focused on FMT for CDI, said she anticipates an expansion of research into other indications once products to prevent CDI recurrence are on the market. “There have been a couple of promising ulcerative colitis trials that haven’t gone anywhere clinically yet,” she said in the interview. “But will we now identify patients with UC who may be more sensitive to microbial manipulation, for whom we can use these microbial therapies along with a biologic?”

Some of her patients with IBD and CDI who are treated with FMT have not only had their CDI eradicated but have subsequently seen improvements in their IBD, she noted.

The role of traditional FMT and of stool banks will likely change in the future with new standardized oral microbiome-based therapies that can be approved and regulated by the FDA, she said. However, “we think the stool banks will still have some value,” she said, certainly for clinical research and probably for some treatment purposes as well. Regarding new therapies, “I just really hope they’re affordable,” she said.
 

Gut microbiome manipulation for cancer

Dr. Wargo’s research at MD Anderson has focused on metastatic breast cancer and immunotherapeutic checkpoint blockade. By sequencing microbiota samples and performing immune profiling in hundreds of patients, her team found that responders to PD-1 blockage have a greater diversity of gut bacteria and that “favorable signatures in the gut microbiome” are associated with enhanced immune responses in the tumor microenvironment.

Studies published last year in Science from investigators in Israel (2021 Feb 5;371[6529]:602-9) and Pittsburgh (2021 Feb 5;371[6529]:595-602), demonstrated that FMT promotes response in immunotherapy-refractory melanoma patients. In one study, FMT provided clinical benefit in 6 of 15 patients whose cancer had progressed on prior anti-PD-1 therapy, “which is pretty remarkable,” Dr. Wargo said.

Both research groups, she noted, saw favorable changes in the gut microbiome and immune cell infiltrates both at the level of the colon and the tumor.

Current research on FMT and other microbiome modulation strategies for cancer is guided in part by knowledge that tumors have microbial signatures – these signatures are now being identified across all tumor types – and by findings of “cross talk” between the gut and tumor microbiomes, she explained.

“Researchers are working hard to identify optimal consortia to enhance immune responses in the cancer setting, with promising work in preclinical models,” she said, and clinical trials are in progress. The role of diet in modulating the microbiome and enhancing anti-tumor immunity, with a focus on high dietary fiber intake, is also being investigated, she said.

Dr. Wargo reported that she serves on the advisory boards and is a paid speaker of numerous pharmaceutical and biotechnology companies, and is the coinventor of a patent submitted by the Texas MD Anderson Cancer Center on modulating the microbiome to enhance response to checkpoint blockade, and another related patent. Dr. Khanna reported that he is involved in research with Ferring/Rebiotix, Finch, Seres, Pfizer and Vendata, and does consulting for Immuron and several other companies. Dr. Kelly said she serves as an unpaid adviser for OpenBiome, a nonprofit stool bank, and that her site has enrolled patients in two of the trials testing products for CDI.

WASHINGTON – Research on standardized microbiome-based therapies designed to prevent the recurrence of Clostridioides difficile infection (CDI) is moving “with a lot of momentum,” according to one expert, and modulation of the gut microbiome may even enhance responses to immunotherapy and/or abrogate toxicity, according to another.

Several products for prevention of CDI recurrence are poised for either phase 3 trials or upcoming Food and Drug Administration approval, Sahil Khanna, MBBS, MS, professor of medicine, gastroenterology, and hepatology at the Mayo Clinic in Rochester, Minn., reported at the annual Gut Microbiota for Health World Summit.

Jennifer A. Wargo, MD, MMSc, of the University of Texas MD Anderson Cancer Center, Houston, described her investigations of microbiome modulation’s role in cancer treatment. “I used to say yes [we can do this] somewhat enthusiastically without data, but now we have data to support this,” she said at the meeting, sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility. “The answer now is totally yes.”
 

New approaches for CDI

“Based on how the field is moving, we might be able to [offer our patients] earlier microbiome restoration” than is currently afforded with fecal microbiota transplantation (FMT), he said. “Right now the [Food and Drug Administration] and our clinical guidelines say we should do FMT after three or more episodes [of CDI] – that’s heartbreaking for patients.”

Several of the microbiome-based therapies under investigation – including two poised for phase 3 trials – have shown efficacy after a second episode of CDI, and one of these two has also had positive results after one episode of CDI in patients 65 at older, a group at particularly high risk of recurrence, said Dr. Khanna.

The value of standardized, mostly pill-form microbiome therapies has been heightened during the pandemic. “We’ve been doing conventional FMT for recurrent C. difficile for over a decade now, and it’s probably the most effective treatment we have,” said Colleen R. Kelly, MD, associate professor of medicine at Brown University, Providence, R.I., and moderator of the session on microbiota-based therapies.

Prepandemic “it got really hard, with issues of identifying donors, and quality control and safety ... And then when COVID hit the stool banks shut down,” she said in an interview after the meeting. With stool testing for SARS-CoV-2 now in place, some stool is again available, “but it made me realize how fragile our current system is,” Dr. Kelly said. “The fact that companies are putting these products through the FDA pipeline and investigating them in rigorous, scientific randomized controlled trials is really good for the field.”

The products vary in composition; some are live multi-strain biotherapeutics derived from donor stool, for instance, while others are defined live bacterial consortia not from stool. Most are oral formulations, given one or multiple times, that do not require any bowel preparation.

One of the products most advanced in the pipeline, RBX2660 (Rebiotix, Ferring Pharmaceuticals) is stool derived and rectally administered. In phase 3 research, 70.5% of patients who received one active enema after having had two or more CDI recurrences and standard-of-care antibiotic treatment had no additional recurrence at 8 weeks compared to 58.1% in the placebo group, Dr. Khanna said.

The other product with positive phase 3 results, SER-109 (Seres Therapeutics), is a donor stool-derived oral formulation of purified Firmicutes spores that is administered after bowel prep. In results published earlier this year, the percentage of patients with recurrence of CDI up to 8 weeks after standard antibiotic treatment was 12% in the SER-109 group and 40% in the placebo group.

Patients in this trial were required to have had three episodes of CDI, and interestingly, Dr. Khanna said, the diagnosis of CDI was made only by toxin enzyme immunoassay (EIA). Earlier phase 2 research, which allowed either toxin EIA or polymerase chain reaction testing for the diagnosis of CDI (as other trials have done), produced negative results, leading investigators to surmise that some of the included patients had been colonized with C. difficile rather than being actively infected, Dr. Khanna said.

Researchers of these trials are documenting not only resolution of CDI but what they believe are positive shifts in the gut microbiota after microbiome-based therapy, he said. For instance, a phase 1 trial he led of the product RBX7455 (Rebiotix, Ferring Pharmaceuticals) – an oral capsule of lyophilized stool-based bacteria that can be kept for several days at room temperature – showed increases in Bacteroidia and Clostridia.

And other trials’ analyses of microbiome engraftment have demonstrated that “you can restore [species] even when these bacteria aren’t [included in the therapy],” he noted. “As the milieu of the gut improves, species that were not detected start coming back up.”

Asked about rates of efficacy in the trials’ placebo arms, Dr. Khanna said that “we’ve become smarter with our antibiotic regimens ... the placebo response rate is the response to newer guideline-based therapies.”

In addition to CDI, microbiome-based therapies are being studied, mostly in phase 1 research, for indications such as Crohn’s disease, ulcerative colitis, autism spectrum disorder, hepatitis B, and hepatic encephalopathy, Dr. Khanna noted.

Dr. Kelly, whose own research has focused on FMT for CDI, said she anticipates an expansion of research into other indications once products to prevent CDI recurrence are on the market. “There have been a couple of promising ulcerative colitis trials that haven’t gone anywhere clinically yet,” she said in the interview. “But will we now identify patients with UC who may be more sensitive to microbial manipulation, for whom we can use these microbial therapies along with a biologic?”

Some of her patients with IBD and CDI who are treated with FMT have not only had their CDI eradicated but have subsequently seen improvements in their IBD, she noted.

The role of traditional FMT and of stool banks will likely change in the future with new standardized oral microbiome-based therapies that can be approved and regulated by the FDA, she said. However, “we think the stool banks will still have some value,” she said, certainly for clinical research and probably for some treatment purposes as well. Regarding new therapies, “I just really hope they’re affordable,” she said.
 

Gut microbiome manipulation for cancer

Dr. Wargo’s research at MD Anderson has focused on metastatic breast cancer and immunotherapeutic checkpoint blockade. By sequencing microbiota samples and performing immune profiling in hundreds of patients, her team found that responders to PD-1 blockage have a greater diversity of gut bacteria and that “favorable signatures in the gut microbiome” are associated with enhanced immune responses in the tumor microenvironment.

Studies published last year in Science from investigators in Israel (2021 Feb 5;371[6529]:602-9) and Pittsburgh (2021 Feb 5;371[6529]:595-602), demonstrated that FMT promotes response in immunotherapy-refractory melanoma patients. In one study, FMT provided clinical benefit in 6 of 15 patients whose cancer had progressed on prior anti-PD-1 therapy, “which is pretty remarkable,” Dr. Wargo said.

Both research groups, she noted, saw favorable changes in the gut microbiome and immune cell infiltrates both at the level of the colon and the tumor.

Current research on FMT and other microbiome modulation strategies for cancer is guided in part by knowledge that tumors have microbial signatures – these signatures are now being identified across all tumor types – and by findings of “cross talk” between the gut and tumor microbiomes, she explained.

“Researchers are working hard to identify optimal consortia to enhance immune responses in the cancer setting, with promising work in preclinical models,” she said, and clinical trials are in progress. The role of diet in modulating the microbiome and enhancing anti-tumor immunity, with a focus on high dietary fiber intake, is also being investigated, she said.

Dr. Wargo reported that she serves on the advisory boards and is a paid speaker of numerous pharmaceutical and biotechnology companies, and is the coinventor of a patent submitted by the Texas MD Anderson Cancer Center on modulating the microbiome to enhance response to checkpoint blockade, and another related patent. Dr. Khanna reported that he is involved in research with Ferring/Rebiotix, Finch, Seres, Pfizer and Vendata, and does consulting for Immuron and several other companies. Dr. Kelly said she serves as an unpaid adviser for OpenBiome, a nonprofit stool bank, and that her site has enrolled patients in two of the trials testing products for CDI.

Patients with cirrhosis and larger spontaneous shunt diameters showed a significantly greater increase in hepatic venous pressure gradient (HVPG) following balloon-occluded retrograde transvenous obliteration compared to patients with smaller shunt diameters, based on data from 34 adults.

Portal hypertension remains a key source of complications that greatly impact quality of life in patients with cirrhosis, wrote Akihisa Tatsumi, MD, of the University of Yamanashi, Japan, and colleagues. These patients sometimes develop spontaneous portosystemic shunts (SPSS) to lower portal pressure, but these natural shunts are an incomplete solution – one that may contribute to liver dysfunction by reducing hepatic portal blood flow. However, the association of SPSS with liver functional reserve remains unclear, the researchers said.

Copyright Sebastian Kaulitzki/Thinkstock

Balloon-occluded retrograde transvenous obliteration (BRTO) is gaining popularity as a treatment for SPSS in patients with cirrhosis but determining the patients who will benefit from this procedure remains a challenge, the researchers wrote. “Apart from BRTO, some recent studies have reported the impact of the SPSS diameter on the future pathological state of the liver,” which prompted the question of whether SPSS diameter plays a role in predicting portal hypertension–related liver function at baseline and after BRTO, the researchers explained.

In their study, published in JGH Open, the researchers identified 34 cirrhotic patients with SPSS who underwent BRTO at a single center in Japan between 2006 and 2018; all of the patients were available for follow-up at least 6 months after the procedure.

The reasons for BRTO were intractable gastric varices in 18 patients and refractory hepatic encephalopathy with shunt in 16 patients; the mean observation period was 1,182 days (3.24 years). The median age of the patients was 66.5 years, and 53% were male. A majority (76%) of the patients had decompensated cirrhosis with Child-Pugh (CP) scores of B or C, and the maximum diameter of SPSS increased significantly with increased in CP scores (P < .001), the researchers noted.

Overall, at 6 months after BRTO, patients showed significant improvements in liver function from baseline. However, the improvement rate was lower in patients whose shunt diameter was 10 mm or less, and improvement was greatest when the shunt diameter was between 10 mm and 20 mm. “Because the CP score is a significant cofounding factor of the SPSS diameter, we next evaluated the changes in liver function classified by CP scores,” the researchers wrote. In this analysis, the post-BRTO changes in liver function in patients with CP scores of A or B still showed an association between improvement in liver function and larger shunt diameter, but this relationship did not extend to patients with CP scores of C, the researchers said.

A larger shunt diameter also was significantly associated with a greater increase in HVPG after balloon occlusion (P = .005).

“Considering that patients with large SPSS diameters might gain higher portal flow following elevation of HVPG after BRTO, it is natural that the larger the SPSS diameter, the greater the improvements in liver function,” the researchers wrote in their discussion of the findings. “However, such a clear correlation was evident only when the baseline CP scores were within A or B, and not in C, indicating that the improvement of liver function might not parallel HVPG increase in some CP C patients,” they noted.

The study was limited by several factors including the retrospective design from a single center and its small sample size, the researchers noted. Other limitations included selecting and measuring only the largest SPSS of each patient and lack of data on the impact of SPSS diameter on overall survival, they said.

However, the results suggest that SPSS diameter may serve not only as an indicator of portal hypertension involvement at baseline, but also as a useful clinical predictor of liver function after BRTO, they concluded.
 

Study supports potential benefits of BRTO

“While the association between SPSS and complications of portal hypertension such as variceal bleeding and hepatic encephalopathy have been known, data are lacking in regard to characteristics of SPSS that are most dysfunctional, and whether certain patients may benefit from BRTO to occlude these shunts,” Khashayar Farsad, MD, of Oregon Health & Science University, Portland, said in an interview.

“The results are in many ways expected based on anticipated impact of larger versus smaller SPSS in overall liver function,” Dr. Farsad noted. “The study, however, does show a nice correlation between several factors involved in liver function and their changes depending on shunt diameter, correlated with changes in the relative venous pressure gradient across the liver,” he said. “Furthermore, the finding that changes were most evident in those with relatively preserved liver function [Child-Turcotte-Pugh grades A and B] suggests less of a relationship between SPSS and liver function in those with more decompensated liver disease,” he added.

“The impact of the study is significantly limited by its retrospective design, small numbers with potential patient heterogeneity, and lack of a control cohort,” said Dr. Farsad. However, “The major take-home message for clinicians is a potential signal that the size of the SPSS at baseline may predict the impact of the SPSS on liver function, and therefore, the potential benefit of a procedure such as BRTO to positively influence this,” he said. “Additional research with larger cohorts and a prospective study design would be warranted, however, before this information would be meaningful in daily clinical decision making,” he emphasized.

The study was supported by the Research Program on Hepatitis of the Japanese Agency for Medical Research and Development. The researchers had no financial conflicts to disclose. Dr. Farsad disclosed research support from W.L. Gore & Associates, Guerbet LLC, Boston Scientific, and Exelixis; serving as a consultant for NeuWave Medical, Cook Medical, Guerbet LLC, and Eisai, and holding equity in Auxetics Inc.

Patients with cirrhosis and larger spontaneous shunt diameters showed a significantly greater increase in hepatic venous pressure gradient (HVPG) following balloon-occluded retrograde transvenous obliteration compared to patients with smaller shunt diameters, based on data from 34 adults.

Portal hypertension remains a key source of complications that greatly impact quality of life in patients with cirrhosis, wrote Akihisa Tatsumi, MD, of the University of Yamanashi, Japan, and colleagues. These patients sometimes develop spontaneous portosystemic shunts (SPSS) to lower portal pressure, but these natural shunts are an incomplete solution – one that may contribute to liver dysfunction by reducing hepatic portal blood flow. However, the association of SPSS with liver functional reserve remains unclear, the researchers said.

Copyright Sebastian Kaulitzki/Thinkstock

Balloon-occluded retrograde transvenous obliteration (BRTO) is gaining popularity as a treatment for SPSS in patients with cirrhosis but determining the patients who will benefit from this procedure remains a challenge, the researchers wrote. “Apart from BRTO, some recent studies have reported the impact of the SPSS diameter on the future pathological state of the liver,” which prompted the question of whether SPSS diameter plays a role in predicting portal hypertension–related liver function at baseline and after BRTO, the researchers explained.

In their study, published in JGH Open, the researchers identified 34 cirrhotic patients with SPSS who underwent BRTO at a single center in Japan between 2006 and 2018; all of the patients were available for follow-up at least 6 months after the procedure.

The reasons for BRTO were intractable gastric varices in 18 patients and refractory hepatic encephalopathy with shunt in 16 patients; the mean observation period was 1,182 days (3.24 years). The median age of the patients was 66.5 years, and 53% were male. A majority (76%) of the patients had decompensated cirrhosis with Child-Pugh (CP) scores of B or C, and the maximum diameter of SPSS increased significantly with increased in CP scores (P < .001), the researchers noted.

Overall, at 6 months after BRTO, patients showed significant improvements in liver function from baseline. However, the improvement rate was lower in patients whose shunt diameter was 10 mm or less, and improvement was greatest when the shunt diameter was between 10 mm and 20 mm. “Because the CP score is a significant cofounding factor of the SPSS diameter, we next evaluated the changes in liver function classified by CP scores,” the researchers wrote. In this analysis, the post-BRTO changes in liver function in patients with CP scores of A or B still showed an association between improvement in liver function and larger shunt diameter, but this relationship did not extend to patients with CP scores of C, the researchers said.

A larger shunt diameter also was significantly associated with a greater increase in HVPG after balloon occlusion (P = .005).

“Considering that patients with large SPSS diameters might gain higher portal flow following elevation of HVPG after BRTO, it is natural that the larger the SPSS diameter, the greater the improvements in liver function,” the researchers wrote in their discussion of the findings. “However, such a clear correlation was evident only when the baseline CP scores were within A or B, and not in C, indicating that the improvement of liver function might not parallel HVPG increase in some CP C patients,” they noted.

The study was limited by several factors including the retrospective design from a single center and its small sample size, the researchers noted. Other limitations included selecting and measuring only the largest SPSS of each patient and lack of data on the impact of SPSS diameter on overall survival, they said.

However, the results suggest that SPSS diameter may serve not only as an indicator of portal hypertension involvement at baseline, but also as a useful clinical predictor of liver function after BRTO, they concluded.
 

Study supports potential benefits of BRTO

“While the association between SPSS and complications of portal hypertension such as variceal bleeding and hepatic encephalopathy have been known, data are lacking in regard to characteristics of SPSS that are most dysfunctional, and whether certain patients may benefit from BRTO to occlude these shunts,” Khashayar Farsad, MD, of Oregon Health & Science University, Portland, said in an interview.

“The results are in many ways expected based on anticipated impact of larger versus smaller SPSS in overall liver function,” Dr. Farsad noted. “The study, however, does show a nice correlation between several factors involved in liver function and their changes depending on shunt diameter, correlated with changes in the relative venous pressure gradient across the liver,” he said. “Furthermore, the finding that changes were most evident in those with relatively preserved liver function [Child-Turcotte-Pugh grades A and B] suggests less of a relationship between SPSS and liver function in those with more decompensated liver disease,” he added.

“The impact of the study is significantly limited by its retrospective design, small numbers with potential patient heterogeneity, and lack of a control cohort,” said Dr. Farsad. However, “The major take-home message for clinicians is a potential signal that the size of the SPSS at baseline may predict the impact of the SPSS on liver function, and therefore, the potential benefit of a procedure such as BRTO to positively influence this,” he said. “Additional research with larger cohorts and a prospective study design would be warranted, however, before this information would be meaningful in daily clinical decision making,” he emphasized.

The study was supported by the Research Program on Hepatitis of the Japanese Agency for Medical Research and Development. The researchers had no financial conflicts to disclose. Dr. Farsad disclosed research support from W.L. Gore & Associates, Guerbet LLC, Boston Scientific, and Exelixis; serving as a consultant for NeuWave Medical, Cook Medical, Guerbet LLC, and Eisai, and holding equity in Auxetics Inc.

Patients with cirrhosis and larger spontaneous shunt diameters showed a significantly greater increase in hepatic venous pressure gradient (HVPG) following balloon-occluded retrograde transvenous obliteration compared to patients with smaller shunt diameters, based on data from 34 adults.

Portal hypertension remains a key source of complications that greatly impact quality of life in patients with cirrhosis, wrote Akihisa Tatsumi, MD, of the University of Yamanashi, Japan, and colleagues. These patients sometimes develop spontaneous portosystemic shunts (SPSS) to lower portal pressure, but these natural shunts are an incomplete solution – one that may contribute to liver dysfunction by reducing hepatic portal blood flow. However, the association of SPSS with liver functional reserve remains unclear, the researchers said.

Copyright Sebastian Kaulitzki/Thinkstock

Balloon-occluded retrograde transvenous obliteration (BRTO) is gaining popularity as a treatment for SPSS in patients with cirrhosis but determining the patients who will benefit from this procedure remains a challenge, the researchers wrote. “Apart from BRTO, some recent studies have reported the impact of the SPSS diameter on the future pathological state of the liver,” which prompted the question of whether SPSS diameter plays a role in predicting portal hypertension–related liver function at baseline and after BRTO, the researchers explained.

In their study, published in JGH Open, the researchers identified 34 cirrhotic patients with SPSS who underwent BRTO at a single center in Japan between 2006 and 2018; all of the patients were available for follow-up at least 6 months after the procedure.

The reasons for BRTO were intractable gastric varices in 18 patients and refractory hepatic encephalopathy with shunt in 16 patients; the mean observation period was 1,182 days (3.24 years). The median age of the patients was 66.5 years, and 53% were male. A majority (76%) of the patients had decompensated cirrhosis with Child-Pugh (CP) scores of B or C, and the maximum diameter of SPSS increased significantly with increased in CP scores (P < .001), the researchers noted.

Overall, at 6 months after BRTO, patients showed significant improvements in liver function from baseline. However, the improvement rate was lower in patients whose shunt diameter was 10 mm or less, and improvement was greatest when the shunt diameter was between 10 mm and 20 mm. “Because the CP score is a significant cofounding factor of the SPSS diameter, we next evaluated the changes in liver function classified by CP scores,” the researchers wrote. In this analysis, the post-BRTO changes in liver function in patients with CP scores of A or B still showed an association between improvement in liver function and larger shunt diameter, but this relationship did not extend to patients with CP scores of C, the researchers said.

A larger shunt diameter also was significantly associated with a greater increase in HVPG after balloon occlusion (P = .005).

“Considering that patients with large SPSS diameters might gain higher portal flow following elevation of HVPG after BRTO, it is natural that the larger the SPSS diameter, the greater the improvements in liver function,” the researchers wrote in their discussion of the findings. “However, such a clear correlation was evident only when the baseline CP scores were within A or B, and not in C, indicating that the improvement of liver function might not parallel HVPG increase in some CP C patients,” they noted.

The study was limited by several factors including the retrospective design from a single center and its small sample size, the researchers noted. Other limitations included selecting and measuring only the largest SPSS of each patient and lack of data on the impact of SPSS diameter on overall survival, they said.

However, the results suggest that SPSS diameter may serve not only as an indicator of portal hypertension involvement at baseline, but also as a useful clinical predictor of liver function after BRTO, they concluded.
 

Study supports potential benefits of BRTO

“While the association between SPSS and complications of portal hypertension such as variceal bleeding and hepatic encephalopathy have been known, data are lacking in regard to characteristics of SPSS that are most dysfunctional, and whether certain patients may benefit from BRTO to occlude these shunts,” Khashayar Farsad, MD, of Oregon Health & Science University, Portland, said in an interview.

“The results are in many ways expected based on anticipated impact of larger versus smaller SPSS in overall liver function,” Dr. Farsad noted. “The study, however, does show a nice correlation between several factors involved in liver function and their changes depending on shunt diameter, correlated with changes in the relative venous pressure gradient across the liver,” he said. “Furthermore, the finding that changes were most evident in those with relatively preserved liver function [Child-Turcotte-Pugh grades A and B] suggests less of a relationship between SPSS and liver function in those with more decompensated liver disease,” he added.

“The impact of the study is significantly limited by its retrospective design, small numbers with potential patient heterogeneity, and lack of a control cohort,” said Dr. Farsad. However, “The major take-home message for clinicians is a potential signal that the size of the SPSS at baseline may predict the impact of the SPSS on liver function, and therefore, the potential benefit of a procedure such as BRTO to positively influence this,” he said. “Additional research with larger cohorts and a prospective study design would be warranted, however, before this information would be meaningful in daily clinical decision making,” he emphasized.

The study was supported by the Research Program on Hepatitis of the Japanese Agency for Medical Research and Development. The researchers had no financial conflicts to disclose. Dr. Farsad disclosed research support from W.L. Gore & Associates, Guerbet LLC, Boston Scientific, and Exelixis; serving as a consultant for NeuWave Medical, Cook Medical, Guerbet LLC, and Eisai, and holding equity in Auxetics Inc.

All Kawasaki disease (KD) patients should be treated first with intravenous immunoglobulin, according to an updated guideline issued jointly by the American College of Rheumatology and the Vasculitis Foundation.

KD has low mortality when treated appropriately, guideline first author Mark Gorelik, MD, assistant professor of pediatrics at Columbia University, New York, and colleagues wrote.

The update is important at this time because new evidence continues to emerge in the clinical management of KD, Dr. Gorelik said in an interview.

“In addition, this guideline approaches Kawasaki disease from a perspective of acting as an adjunct to the already existing and excellent American Heart Association guidelines by adding information in areas that rheumatologists may play a role,” Dr. Gorelik said. “This is specifically regarding patients who may require additional therapy beyond standard IVIg, such as patients who may be at higher risk of morbidity from disease and patients who have refractory disease,” he explained.

The guideline, published in Arthritis & Rheumatology, includes 11 recommendations, 1 good practice statement, and 1 ungraded position statement. The good practice statement emphasizes that all patients with KD should be initially treated with IVIg.

The position statement advises that either nonglucocorticoid immunosuppressive therapy or glucocorticoids may be used for patients with acute KD whose fever persists despite repeated IVIg treatment. No clinical evidence currently supports the superiority of either nonglucocorticoid immunosuppressive therapy or glucocorticoids; therefore, the authors support the use of either based on what is appropriate in any given clinical situation. Although optimal dosage and duration of glucocorticoids have yet to be determined in a U.S. population, the authors described a typical glucocorticoid dosage as starting prednisone at 2 mg/kg per day, with a maximum of 60 mg/day, and dose tapering over 15 days.

The 11 recommendations consist of 7 strong and 4 conditional recommendations. The strong recommendations focus on prompt treatment of incomplete KD, treatment with aspirin, and obtaining an echocardiogram in patients with unexplained macrophage activation syndrome or shock. The conditional recommendations support using established therapy promptly at disease onset, then identifying cases in which additional therapy is needed.

Dr. Gorelik highlighted four clinical takeaways from the guideline. First, “patients with higher risk for complications do exist in Kawasaki disease, and that these patients can be treated more aggressively,” he said. “Specifically, patients with aneurysms seen at first ultrasound, and patients who are under 6 months, are more likely to have progressive and/or refractory disease; these patients can be treated with an adjunctive short course of corticosteroids.”

Second, “the use of high-dose aspirin for patients with Kawasaki disease does not have strong basis in evidence. While aspirin itself of some dose is necessary for patients with Kawasaki disease, use of either high- or low-dose aspirin has the same outcome for patients, and a physician may choose either of these in practice,” he said.

Third, “we continue to recommend that refractory patients with Kawasaki disease be treated with a second dose of IVIg; however, there are many scenarios in which a physician may choose either corticosteroids [either a single high dose of >10 mg/kg, or a short moderate-dose course of 2 mg/kg per day for 5-7 days] or a biologic agent such as infliximab. ... These are valid choices for therapy in patients with refractory Kawasaki disease,” he emphasized.

Fourth, “physicians should discard the idea of treating before [and conversely, not treating after] 10 days of fever,” Dr. Gorelik said. “Patients with Kawasaki disease should be treated as soon as the diagnosis is made, regardless of whether this patient is on day 5, day 12, or day 20 of symptoms.”

Update incorporates emerging evidence

Potential barriers to implementing the guideline in practice include the challenge of weaning doctors from practices that are habitual in medicine, Dr. Gorelik said. “One of these is the use of high-dose aspirin for Kawasaki disease; a number of studies have shown over the past decade or more that high-dose aspirin has no greater effect than lower-dose aspirin for Kawasaki disease. Despite all of these studies, the use of high-dose aspirin continued. High-dose aspirin for Kawasaki disease was used in the era prior to use of IVIg as an anti-inflammatory agent. However, it has poor efficacy in this regard, and the true benefit for aspirin is for anticoagulation for patients at risk of a clot, and this is just as effective in lower doses. Expressing this in a guideline could help to change practices by helping physicians understand not only what they are guided to do, but why.”

Additional research is needed to better identify high-risk patients in non-Japanese populations, he noted. “While studies from Japan suggest that higher-risk patients can be identified based on various parameters, these have not been well replicated in non-Japanese populations. Good research that identifies which patients may be more at risk in other populations would be helpful to more precisely target high-risk therapy.”

Other research needs include a clearer understanding of the best therapies for refractory patients, Dr. Gorelik said. “One area of the most difficulty was determining whether patients with refractory disease should have repeated IVIg or a switch to glucocorticoids and biologic agents. Some of this research is underway, and some was published just as these guidelines were being drawn, and this particular area is one that is likely to change significantly. While currently we recommend a repeated dose of IVIg, it is likely that over the very near term, the use of repeated IVIg in KD will be curtailed” because of concerns such as the relatively high rate of hemolysis. Research to identify which therapy has a noninferior effect with a superior risk profile is needed; such research “will likely result in a future iteration of these guidelines specifically related to this question,” he concluded.

The KD guideline is the final companion to three additional ACR/VF vasculitis guidelines that were released in July 2021. The guideline research received no outside funding. The researchers had no financial conflicts to disclose.

All Kawasaki disease (KD) patients should be treated first with intravenous immunoglobulin, according to an updated guideline issued jointly by the American College of Rheumatology and the Vasculitis Foundation.

KD has low mortality when treated appropriately, guideline first author Mark Gorelik, MD, assistant professor of pediatrics at Columbia University, New York, and colleagues wrote.

The update is important at this time because new evidence continues to emerge in the clinical management of KD, Dr. Gorelik said in an interview.

“In addition, this guideline approaches Kawasaki disease from a perspective of acting as an adjunct to the already existing and excellent American Heart Association guidelines by adding information in areas that rheumatologists may play a role,” Dr. Gorelik said. “This is specifically regarding patients who may require additional therapy beyond standard IVIg, such as patients who may be at higher risk of morbidity from disease and patients who have refractory disease,” he explained.

The guideline, published in Arthritis & Rheumatology, includes 11 recommendations, 1 good practice statement, and 1 ungraded position statement. The good practice statement emphasizes that all patients with KD should be initially treated with IVIg.

The position statement advises that either nonglucocorticoid immunosuppressive therapy or glucocorticoids may be used for patients with acute KD whose fever persists despite repeated IVIg treatment. No clinical evidence currently supports the superiority of either nonglucocorticoid immunosuppressive therapy or glucocorticoids; therefore, the authors support the use of either based on what is appropriate in any given clinical situation. Although optimal dosage and duration of glucocorticoids have yet to be determined in a U.S. population, the authors described a typical glucocorticoid dosage as starting prednisone at 2 mg/kg per day, with a maximum of 60 mg/day, and dose tapering over 15 days.

The 11 recommendations consist of 7 strong and 4 conditional recommendations. The strong recommendations focus on prompt treatment of incomplete KD, treatment with aspirin, and obtaining an echocardiogram in patients with unexplained macrophage activation syndrome or shock. The conditional recommendations support using established therapy promptly at disease onset, then identifying cases in which additional therapy is needed.

Dr. Gorelik highlighted four clinical takeaways from the guideline. First, “patients with higher risk for complications do exist in Kawasaki disease, and that these patients can be treated more aggressively,” he said. “Specifically, patients with aneurysms seen at first ultrasound, and patients who are under 6 months, are more likely to have progressive and/or refractory disease; these patients can be treated with an adjunctive short course of corticosteroids.”

Second, “the use of high-dose aspirin for patients with Kawasaki disease does not have strong basis in evidence. While aspirin itself of some dose is necessary for patients with Kawasaki disease, use of either high- or low-dose aspirin has the same outcome for patients, and a physician may choose either of these in practice,” he said.

Third, “we continue to recommend that refractory patients with Kawasaki disease be treated with a second dose of IVIg; however, there are many scenarios in which a physician may choose either corticosteroids [either a single high dose of >10 mg/kg, or a short moderate-dose course of 2 mg/kg per day for 5-7 days] or a biologic agent such as infliximab. ... These are valid choices for therapy in patients with refractory Kawasaki disease,” he emphasized.

Fourth, “physicians should discard the idea of treating before [and conversely, not treating after] 10 days of fever,” Dr. Gorelik said. “Patients with Kawasaki disease should be treated as soon as the diagnosis is made, regardless of whether this patient is on day 5, day 12, or day 20 of symptoms.”

Update incorporates emerging evidence

Potential barriers to implementing the guideline in practice include the challenge of weaning doctors from practices that are habitual in medicine, Dr. Gorelik said. “One of these is the use of high-dose aspirin for Kawasaki disease; a number of studies have shown over the past decade or more that high-dose aspirin has no greater effect than lower-dose aspirin for Kawasaki disease. Despite all of these studies, the use of high-dose aspirin continued. High-dose aspirin for Kawasaki disease was used in the era prior to use of IVIg as an anti-inflammatory agent. However, it has poor efficacy in this regard, and the true benefit for aspirin is for anticoagulation for patients at risk of a clot, and this is just as effective in lower doses. Expressing this in a guideline could help to change practices by helping physicians understand not only what they are guided to do, but why.”

Additional research is needed to better identify high-risk patients in non-Japanese populations, he noted. “While studies from Japan suggest that higher-risk patients can be identified based on various parameters, these have not been well replicated in non-Japanese populations. Good research that identifies which patients may be more at risk in other populations would be helpful to more precisely target high-risk therapy.”

Other research needs include a clearer understanding of the best therapies for refractory patients, Dr. Gorelik said. “One area of the most difficulty was determining whether patients with refractory disease should have repeated IVIg or a switch to glucocorticoids and biologic agents. Some of this research is underway, and some was published just as these guidelines were being drawn, and this particular area is one that is likely to change significantly. While currently we recommend a repeated dose of IVIg, it is likely that over the very near term, the use of repeated IVIg in KD will be curtailed” because of concerns such as the relatively high rate of hemolysis. Research to identify which therapy has a noninferior effect with a superior risk profile is needed; such research “will likely result in a future iteration of these guidelines specifically related to this question,” he concluded.

The KD guideline is the final companion to three additional ACR/VF vasculitis guidelines that were released in July 2021. The guideline research received no outside funding. The researchers had no financial conflicts to disclose.

All Kawasaki disease (KD) patients should be treated first with intravenous immunoglobulin, according to an updated guideline issued jointly by the American College of Rheumatology and the Vasculitis Foundation.

KD has low mortality when treated appropriately, guideline first author Mark Gorelik, MD, assistant professor of pediatrics at Columbia University, New York, and colleagues wrote.

The update is important at this time because new evidence continues to emerge in the clinical management of KD, Dr. Gorelik said in an interview.

“In addition, this guideline approaches Kawasaki disease from a perspective of acting as an adjunct to the already existing and excellent American Heart Association guidelines by adding information in areas that rheumatologists may play a role,” Dr. Gorelik said. “This is specifically regarding patients who may require additional therapy beyond standard IVIg, such as patients who may be at higher risk of morbidity from disease and patients who have refractory disease,” he explained.

The guideline, published in Arthritis & Rheumatology, includes 11 recommendations, 1 good practice statement, and 1 ungraded position statement. The good practice statement emphasizes that all patients with KD should be initially treated with IVIg.

The position statement advises that either nonglucocorticoid immunosuppressive therapy or glucocorticoids may be used for patients with acute KD whose fever persists despite repeated IVIg treatment. No clinical evidence currently supports the superiority of either nonglucocorticoid immunosuppressive therapy or glucocorticoids; therefore, the authors support the use of either based on what is appropriate in any given clinical situation. Although optimal dosage and duration of glucocorticoids have yet to be determined in a U.S. population, the authors described a typical glucocorticoid dosage as starting prednisone at 2 mg/kg per day, with a maximum of 60 mg/day, and dose tapering over 15 days.

The 11 recommendations consist of 7 strong and 4 conditional recommendations. The strong recommendations focus on prompt treatment of incomplete KD, treatment with aspirin, and obtaining an echocardiogram in patients with unexplained macrophage activation syndrome or shock. The conditional recommendations support using established therapy promptly at disease onset, then identifying cases in which additional therapy is needed.

Dr. Gorelik highlighted four clinical takeaways from the guideline. First, “patients with higher risk for complications do exist in Kawasaki disease, and that these patients can be treated more aggressively,” he said. “Specifically, patients with aneurysms seen at first ultrasound, and patients who are under 6 months, are more likely to have progressive and/or refractory disease; these patients can be treated with an adjunctive short course of corticosteroids.”

Second, “the use of high-dose aspirin for patients with Kawasaki disease does not have strong basis in evidence. While aspirin itself of some dose is necessary for patients with Kawasaki disease, use of either high- or low-dose aspirin has the same outcome for patients, and a physician may choose either of these in practice,” he said.

Third, “we continue to recommend that refractory patients with Kawasaki disease be treated with a second dose of IVIg; however, there are many scenarios in which a physician may choose either corticosteroids [either a single high dose of >10 mg/kg, or a short moderate-dose course of 2 mg/kg per day for 5-7 days] or a biologic agent such as infliximab. ... These are valid choices for therapy in patients with refractory Kawasaki disease,” he emphasized.

Fourth, “physicians should discard the idea of treating before [and conversely, not treating after] 10 days of fever,” Dr. Gorelik said. “Patients with Kawasaki disease should be treated as soon as the diagnosis is made, regardless of whether this patient is on day 5, day 12, or day 20 of symptoms.”

Update incorporates emerging evidence

Potential barriers to implementing the guideline in practice include the challenge of weaning doctors from practices that are habitual in medicine, Dr. Gorelik said. “One of these is the use of high-dose aspirin for Kawasaki disease; a number of studies have shown over the past decade or more that high-dose aspirin has no greater effect than lower-dose aspirin for Kawasaki disease. Despite all of these studies, the use of high-dose aspirin continued. High-dose aspirin for Kawasaki disease was used in the era prior to use of IVIg as an anti-inflammatory agent. However, it has poor efficacy in this regard, and the true benefit for aspirin is for anticoagulation for patients at risk of a clot, and this is just as effective in lower doses. Expressing this in a guideline could help to change practices by helping physicians understand not only what they are guided to do, but why.”

Additional research is needed to better identify high-risk patients in non-Japanese populations, he noted. “While studies from Japan suggest that higher-risk patients can be identified based on various parameters, these have not been well replicated in non-Japanese populations. Good research that identifies which patients may be more at risk in other populations would be helpful to more precisely target high-risk therapy.”

Other research needs include a clearer understanding of the best therapies for refractory patients, Dr. Gorelik said. “One area of the most difficulty was determining whether patients with refractory disease should have repeated IVIg or a switch to glucocorticoids and biologic agents. Some of this research is underway, and some was published just as these guidelines were being drawn, and this particular area is one that is likely to change significantly. While currently we recommend a repeated dose of IVIg, it is likely that over the very near term, the use of repeated IVIg in KD will be curtailed” because of concerns such as the relatively high rate of hemolysis. Research to identify which therapy has a noninferior effect with a superior risk profile is needed; such research “will likely result in a future iteration of these guidelines specifically related to this question,” he concluded.

The KD guideline is the final companion to three additional ACR/VF vasculitis guidelines that were released in July 2021. The guideline research received no outside funding. The researchers had no financial conflicts to disclose.