The cumulative burden of histologic inflammation is a strong predictor of colorectal neoplasia risk in ulcerative colitis, according to a recent case-control study.

David T. Rubin, MD, was the senior author of the study, which provided independent validation of a metric for cumulative burden of inflammation as a risk stratification tool in ulcerative colitis and presented these findings at the Gastroenterology Updates, IBD, Liver Disease Conference. The metric was developed at St. Mark’s Hospital, London, which he called “a leader in the field.”

“The implication of demonstrating this is that, if you control inflammation and keep it controlled over time, it would imply that you can reduce the overall risk for cancer and dysplasia,” explained Dr. Rubin, professor of medicine and chief of the section of gastroenterology, hepatology, and nutrition at the University of Chicago.

The original retrospective St. Mark’s study included 987 patients with extensive ulcerative colitis followed with colonoscopic surveillance for a median of 13 years. Each colonoscopy was scored for severity of microscopic inflammation on a 0-3 scale. The investigators calculated a patient’s cumulative inflammatory burden by adding each histologic inflammatory activity score and multiplying that figure by the surveillance interval in years.

In a multivariate analysis, the London investigators demonstrated that the risk of colorectal neoplasia jumped by 2.1-fold for each 10-unit increase in cumulative inflammatory burden, defined as the equivalent of either 10 years of continuous mild active histologic inflammation, 5 years of continuous moderate inflammation, or 3.3 years of continuous severe inflammation.

The University of Chicago retrospective external validation study included 26 ulcerative colitis patients with colorectal neoplasia and 36 others without cancer. The mean cumulative histologic inflammatory activity score in the group with colorectal neoplasia was 12.63, compared with 7.98 in controls. For each 1-unit increase in cumulative inflammatory burden the risk of developing colorectal neoplasia increased by 8%, consistent with the magnitude of the hazard previously reported at St. Mark’s.

“The way you could take this back to your practice is by thinking carefully about what is the degree of inflammation each time you’ve done a colonoscopy and considering whether the patient who is in deep remission and doing well might deserve a longer interval between their next exam and the one you just completed,” according to the gastroenterologist.

“The most interval I give a patient is 3 years – for somebody in deep remission with no inflammation on the last exam. And when they’ve had prior inflammation but are now doing well, I keep in mind what that prior inflammation was. We’re now working on using that cumulative histologic inflammation score to guide intervals, but we don’t have prospective data to validate this approach. So when you’re not sure, the conservative approach is surveillance colonoscopy every 1-2 years after you’ve had 10 years of disease. That’s probably overutilization of our resources, but we don’t have a better way to do it yet,” Dr. Rubin said.

The novel metric for calculating cumulative histologic inflammation burden as a means of predicting colorectal cancer in ulcerative colitis dovetails with the current emphasis upon individualized risk assessment as recommended in the latest American College of Gastroenterology practice guidelines, for which Dr. Rubin was first author.

“Like we individualize our treatments, we should individualize our colorectal cancer screening and prevention strategies,” he emphasized.

Risk factors for colorectal cancer and dysplasia in patients with ulcerative colitis can be grouped as either potentially modifiable or immutable. Potentially modifiable risk factors include backwash ileitis, pseudopolyps, prior dysplasia, and mass or stricture, as well as the degree of histologic inflammation. Immutable risk factors include younger age at diagnosis, male gender, duration and extent of disease, family history of colorectal cancer, and primary sclerosing cholangitis, Dr. Rubin noted.

He reported receiving grant support from and/or serving as a consultant to more than two dozen medical companies.

[email protected]

The cumulative burden of histologic inflammation is a strong predictor of colorectal neoplasia risk in ulcerative colitis, according to a recent case-control study.

David T. Rubin, MD, was the senior author of the study, which provided independent validation of a metric for cumulative burden of inflammation as a risk stratification tool in ulcerative colitis and presented these findings at the Gastroenterology Updates, IBD, Liver Disease Conference. The metric was developed at St. Mark’s Hospital, London, which he called “a leader in the field.”

“The implication of demonstrating this is that, if you control inflammation and keep it controlled over time, it would imply that you can reduce the overall risk for cancer and dysplasia,” explained Dr. Rubin, professor of medicine and chief of the section of gastroenterology, hepatology, and nutrition at the University of Chicago.

The original retrospective St. Mark’s study included 987 patients with extensive ulcerative colitis followed with colonoscopic surveillance for a median of 13 years. Each colonoscopy was scored for severity of microscopic inflammation on a 0-3 scale. The investigators calculated a patient’s cumulative inflammatory burden by adding each histologic inflammatory activity score and multiplying that figure by the surveillance interval in years.

In a multivariate analysis, the London investigators demonstrated that the risk of colorectal neoplasia jumped by 2.1-fold for each 10-unit increase in cumulative inflammatory burden, defined as the equivalent of either 10 years of continuous mild active histologic inflammation, 5 years of continuous moderate inflammation, or 3.3 years of continuous severe inflammation.

The University of Chicago retrospective external validation study included 26 ulcerative colitis patients with colorectal neoplasia and 36 others without cancer. The mean cumulative histologic inflammatory activity score in the group with colorectal neoplasia was 12.63, compared with 7.98 in controls. For each 1-unit increase in cumulative inflammatory burden the risk of developing colorectal neoplasia increased by 8%, consistent with the magnitude of the hazard previously reported at St. Mark’s.

“The way you could take this back to your practice is by thinking carefully about what is the degree of inflammation each time you’ve done a colonoscopy and considering whether the patient who is in deep remission and doing well might deserve a longer interval between their next exam and the one you just completed,” according to the gastroenterologist.

“The most interval I give a patient is 3 years – for somebody in deep remission with no inflammation on the last exam. And when they’ve had prior inflammation but are now doing well, I keep in mind what that prior inflammation was. We’re now working on using that cumulative histologic inflammation score to guide intervals, but we don’t have prospective data to validate this approach. So when you’re not sure, the conservative approach is surveillance colonoscopy every 1-2 years after you’ve had 10 years of disease. That’s probably overutilization of our resources, but we don’t have a better way to do it yet,” Dr. Rubin said.

The novel metric for calculating cumulative histologic inflammation burden as a means of predicting colorectal cancer in ulcerative colitis dovetails with the current emphasis upon individualized risk assessment as recommended in the latest American College of Gastroenterology practice guidelines, for which Dr. Rubin was first author.

“Like we individualize our treatments, we should individualize our colorectal cancer screening and prevention strategies,” he emphasized.

Risk factors for colorectal cancer and dysplasia in patients with ulcerative colitis can be grouped as either potentially modifiable or immutable. Potentially modifiable risk factors include backwash ileitis, pseudopolyps, prior dysplasia, and mass or stricture, as well as the degree of histologic inflammation. Immutable risk factors include younger age at diagnosis, male gender, duration and extent of disease, family history of colorectal cancer, and primary sclerosing cholangitis, Dr. Rubin noted.

He reported receiving grant support from and/or serving as a consultant to more than two dozen medical companies.

[email protected]

The cumulative burden of histologic inflammation is a strong predictor of colorectal neoplasia risk in ulcerative colitis, according to a recent case-control study.

David T. Rubin, MD, was the senior author of the study, which provided independent validation of a metric for cumulative burden of inflammation as a risk stratification tool in ulcerative colitis and presented these findings at the Gastroenterology Updates, IBD, Liver Disease Conference. The metric was developed at St. Mark’s Hospital, London, which he called “a leader in the field.”

“The implication of demonstrating this is that, if you control inflammation and keep it controlled over time, it would imply that you can reduce the overall risk for cancer and dysplasia,” explained Dr. Rubin, professor of medicine and chief of the section of gastroenterology, hepatology, and nutrition at the University of Chicago.

The original retrospective St. Mark’s study included 987 patients with extensive ulcerative colitis followed with colonoscopic surveillance for a median of 13 years. Each colonoscopy was scored for severity of microscopic inflammation on a 0-3 scale. The investigators calculated a patient’s cumulative inflammatory burden by adding each histologic inflammatory activity score and multiplying that figure by the surveillance interval in years.

In a multivariate analysis, the London investigators demonstrated that the risk of colorectal neoplasia jumped by 2.1-fold for each 10-unit increase in cumulative inflammatory burden, defined as the equivalent of either 10 years of continuous mild active histologic inflammation, 5 years of continuous moderate inflammation, or 3.3 years of continuous severe inflammation.

The University of Chicago retrospective external validation study included 26 ulcerative colitis patients with colorectal neoplasia and 36 others without cancer. The mean cumulative histologic inflammatory activity score in the group with colorectal neoplasia was 12.63, compared with 7.98 in controls. For each 1-unit increase in cumulative inflammatory burden the risk of developing colorectal neoplasia increased by 8%, consistent with the magnitude of the hazard previously reported at St. Mark’s.

“The way you could take this back to your practice is by thinking carefully about what is the degree of inflammation each time you’ve done a colonoscopy and considering whether the patient who is in deep remission and doing well might deserve a longer interval between their next exam and the one you just completed,” according to the gastroenterologist.

“The most interval I give a patient is 3 years – for somebody in deep remission with no inflammation on the last exam. And when they’ve had prior inflammation but are now doing well, I keep in mind what that prior inflammation was. We’re now working on using that cumulative histologic inflammation score to guide intervals, but we don’t have prospective data to validate this approach. So when you’re not sure, the conservative approach is surveillance colonoscopy every 1-2 years after you’ve had 10 years of disease. That’s probably overutilization of our resources, but we don’t have a better way to do it yet,” Dr. Rubin said.

The novel metric for calculating cumulative histologic inflammation burden as a means of predicting colorectal cancer in ulcerative colitis dovetails with the current emphasis upon individualized risk assessment as recommended in the latest American College of Gastroenterology practice guidelines, for which Dr. Rubin was first author.

“Like we individualize our treatments, we should individualize our colorectal cancer screening and prevention strategies,” he emphasized.

Risk factors for colorectal cancer and dysplasia in patients with ulcerative colitis can be grouped as either potentially modifiable or immutable. Potentially modifiable risk factors include backwash ileitis, pseudopolyps, prior dysplasia, and mass or stricture, as well as the degree of histologic inflammation. Immutable risk factors include younger age at diagnosis, male gender, duration and extent of disease, family history of colorectal cancer, and primary sclerosing cholangitis, Dr. Rubin noted.

He reported receiving grant support from and/or serving as a consultant to more than two dozen medical companies.

[email protected]

Women with gynecologic cancers can safely continue anticancer therapy, despite the threat of COVID-19, according to researchers.

The team found no significant association between recent anticancer therapy and COVID-19 hospitalization or mortality among patients with gynecologic cancers and COVID-19.

Some gynecologic cancer patients have expressed concerns that chemotherapy would weaken their immune system and increase their risk of more severe illness if they developed COVID-19, according to Olivia Lara, MD, a gynecologic oncology fellow at New York University.

Furthermore, some prior studies had shown an increased risk of health complications from COVID-19 among cancer patients. However, patients with gynecologic cancer were underrepresented in those studies.

With all this in mind, Dr. Lara and colleagues conducted a study of 193 patients with gynecologic cancers and COVID-19 who were treated at eight hospital systems in the New York City area from March 2020 through May 2020.

Dr. Lara presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10663).
 

Study results

Of the 193 patients analyzed, 106 (54.9%) required hospitalization for COVID-19, including 13 (12.3%) who required mechanical ventilation and 39 (36.8%) who required ICU admission. There were 34 patients (17.6%) who died of COVID-19-related complications, including all who required mechanical ventilation.

Multivariable analyses showed that recent cytotoxic chemotherapy, which was used in 13 of the 34 patients who died (38.2%), and recent immunotherapy, which was used in 4 of the 34 patients (11.8%), were not predictive of COVID-19 hospitalization or mortality.

Only current or former smoking was associated with COVID-19-related death (odds ratio, 2.75).

An earlier analysis of data from 121 patients in this cohort showed an association between immunotherapy and COVID-19-related death, but this was no longer statistically significant in the updated analysis.

Factors significantly associated with hospitalization in the updated cohort were age 65 years or older (OR, 2.12), Black race (OR, 2.53), performance status of 2 or greater (OR, 3.67), and the presence of three or more comorbidities (OR, 2.00), the most common of which were hypertension, diabetes, and chronic kidney disease.
 

More research needed

The current findings show that recent chemotherapy or immunotherapy for gynecologic cancer do not raise the risk of death due to COVID-19, Dr. Lara said, adding that “[w]e can reassure women with gynecologic cancer that they can continue anticancer therapy.”

The finding of a nearly threefold increased risk of hospitalization among Black patients in this study underscores the need for “better understanding of the risks of COVID-19 in vulnerable populations,” Dr. Lara noted.

“Going forward, the impact of the COVID-19 pandemic on cancer care delivery and cancer screening must be evaluated,” she said. “Data collection is ongoing, with additional analyses and studies planned to investigate the impact COVID-19 has had on gynecologic cancer care through the SGO registry.”

The current findings are strengthened by the collaborative multicenter study design and use of multivariable analyses, said invited discussant and study coauthor Bhavana Pothuri, MD, of New York University.

However, it is unclear whether the results are generalizable to other parts of the country or world, and whether the outcomes have changed since the initial surge of COVID-19 cases.

Dr. Lara said the fatality rate in this cohort is similar to that of age-matched women with COVID-19 who did not have cancer, and she acknowledged that fatality rates may be lower now than they were early in the pandemic when the study was conducted.

This study was supported, in part, by a Cancer Center Support Grant from the National Institutes of Health/National Cancer Institute. Dr. Lara reported having no disclosures. Dr. Pothuri disclosed relationships with Tesaro/GlaxoSmithKline, AstraZeneca, Merck, Genentech/Roche, Celsion, Clovis Oncology, Toray, Mersana, Elevar, and Eisai. She is also a member of GOG Partners leadership.

[email protected]

Women with gynecologic cancers can safely continue anticancer therapy, despite the threat of COVID-19, according to researchers.

The team found no significant association between recent anticancer therapy and COVID-19 hospitalization or mortality among patients with gynecologic cancers and COVID-19.

Some gynecologic cancer patients have expressed concerns that chemotherapy would weaken their immune system and increase their risk of more severe illness if they developed COVID-19, according to Olivia Lara, MD, a gynecologic oncology fellow at New York University.

Furthermore, some prior studies had shown an increased risk of health complications from COVID-19 among cancer patients. However, patients with gynecologic cancer were underrepresented in those studies.

With all this in mind, Dr. Lara and colleagues conducted a study of 193 patients with gynecologic cancers and COVID-19 who were treated at eight hospital systems in the New York City area from March 2020 through May 2020.

Dr. Lara presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10663).
 

Study results

Of the 193 patients analyzed, 106 (54.9%) required hospitalization for COVID-19, including 13 (12.3%) who required mechanical ventilation and 39 (36.8%) who required ICU admission. There were 34 patients (17.6%) who died of COVID-19-related complications, including all who required mechanical ventilation.

Multivariable analyses showed that recent cytotoxic chemotherapy, which was used in 13 of the 34 patients who died (38.2%), and recent immunotherapy, which was used in 4 of the 34 patients (11.8%), were not predictive of COVID-19 hospitalization or mortality.

Only current or former smoking was associated with COVID-19-related death (odds ratio, 2.75).

An earlier analysis of data from 121 patients in this cohort showed an association between immunotherapy and COVID-19-related death, but this was no longer statistically significant in the updated analysis.

Factors significantly associated with hospitalization in the updated cohort were age 65 years or older (OR, 2.12), Black race (OR, 2.53), performance status of 2 or greater (OR, 3.67), and the presence of three or more comorbidities (OR, 2.00), the most common of which were hypertension, diabetes, and chronic kidney disease.
 

More research needed

The current findings show that recent chemotherapy or immunotherapy for gynecologic cancer do not raise the risk of death due to COVID-19, Dr. Lara said, adding that “[w]e can reassure women with gynecologic cancer that they can continue anticancer therapy.”

The finding of a nearly threefold increased risk of hospitalization among Black patients in this study underscores the need for “better understanding of the risks of COVID-19 in vulnerable populations,” Dr. Lara noted.

“Going forward, the impact of the COVID-19 pandemic on cancer care delivery and cancer screening must be evaluated,” she said. “Data collection is ongoing, with additional analyses and studies planned to investigate the impact COVID-19 has had on gynecologic cancer care through the SGO registry.”

The current findings are strengthened by the collaborative multicenter study design and use of multivariable analyses, said invited discussant and study coauthor Bhavana Pothuri, MD, of New York University.

However, it is unclear whether the results are generalizable to other parts of the country or world, and whether the outcomes have changed since the initial surge of COVID-19 cases.

Dr. Lara said the fatality rate in this cohort is similar to that of age-matched women with COVID-19 who did not have cancer, and she acknowledged that fatality rates may be lower now than they were early in the pandemic when the study was conducted.

This study was supported, in part, by a Cancer Center Support Grant from the National Institutes of Health/National Cancer Institute. Dr. Lara reported having no disclosures. Dr. Pothuri disclosed relationships with Tesaro/GlaxoSmithKline, AstraZeneca, Merck, Genentech/Roche, Celsion, Clovis Oncology, Toray, Mersana, Elevar, and Eisai. She is also a member of GOG Partners leadership.

[email protected]

Women with gynecologic cancers can safely continue anticancer therapy, despite the threat of COVID-19, according to researchers.

The team found no significant association between recent anticancer therapy and COVID-19 hospitalization or mortality among patients with gynecologic cancers and COVID-19.

Some gynecologic cancer patients have expressed concerns that chemotherapy would weaken their immune system and increase their risk of more severe illness if they developed COVID-19, according to Olivia Lara, MD, a gynecologic oncology fellow at New York University.

Furthermore, some prior studies had shown an increased risk of health complications from COVID-19 among cancer patients. However, patients with gynecologic cancer were underrepresented in those studies.

With all this in mind, Dr. Lara and colleagues conducted a study of 193 patients with gynecologic cancers and COVID-19 who were treated at eight hospital systems in the New York City area from March 2020 through May 2020.

Dr. Lara presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10663).
 

Study results

Of the 193 patients analyzed, 106 (54.9%) required hospitalization for COVID-19, including 13 (12.3%) who required mechanical ventilation and 39 (36.8%) who required ICU admission. There were 34 patients (17.6%) who died of COVID-19-related complications, including all who required mechanical ventilation.

Multivariable analyses showed that recent cytotoxic chemotherapy, which was used in 13 of the 34 patients who died (38.2%), and recent immunotherapy, which was used in 4 of the 34 patients (11.8%), were not predictive of COVID-19 hospitalization or mortality.

Only current or former smoking was associated with COVID-19-related death (odds ratio, 2.75).

An earlier analysis of data from 121 patients in this cohort showed an association between immunotherapy and COVID-19-related death, but this was no longer statistically significant in the updated analysis.

Factors significantly associated with hospitalization in the updated cohort were age 65 years or older (OR, 2.12), Black race (OR, 2.53), performance status of 2 or greater (OR, 3.67), and the presence of three or more comorbidities (OR, 2.00), the most common of which were hypertension, diabetes, and chronic kidney disease.
 

More research needed

The current findings show that recent chemotherapy or immunotherapy for gynecologic cancer do not raise the risk of death due to COVID-19, Dr. Lara said, adding that “[w]e can reassure women with gynecologic cancer that they can continue anticancer therapy.”

The finding of a nearly threefold increased risk of hospitalization among Black patients in this study underscores the need for “better understanding of the risks of COVID-19 in vulnerable populations,” Dr. Lara noted.

“Going forward, the impact of the COVID-19 pandemic on cancer care delivery and cancer screening must be evaluated,” she said. “Data collection is ongoing, with additional analyses and studies planned to investigate the impact COVID-19 has had on gynecologic cancer care through the SGO registry.”

The current findings are strengthened by the collaborative multicenter study design and use of multivariable analyses, said invited discussant and study coauthor Bhavana Pothuri, MD, of New York University.

However, it is unclear whether the results are generalizable to other parts of the country or world, and whether the outcomes have changed since the initial surge of COVID-19 cases.

Dr. Lara said the fatality rate in this cohort is similar to that of age-matched women with COVID-19 who did not have cancer, and she acknowledged that fatality rates may be lower now than they were early in the pandemic when the study was conducted.

This study was supported, in part, by a Cancer Center Support Grant from the National Institutes of Health/National Cancer Institute. Dr. Lara reported having no disclosures. Dr. Pothuri disclosed relationships with Tesaro/GlaxoSmithKline, AstraZeneca, Merck, Genentech/Roche, Celsion, Clovis Oncology, Toray, Mersana, Elevar, and Eisai. She is also a member of GOG Partners leadership.

[email protected]

Federal regulators on March 23 said they were “concerned” that drug maker AstraZeneca included “outdated information” in its announcement the previous day that the company’s COVID-19 vaccine was effective.

The federal Data and Safety Monitoring Board shared those concerns with the company as well as with the National Institute of Allergy and Infectious Diseases, and the U.S. Biomedical Advanced Research and Development Authority, according to a statement from NIAID issued early March 23.

“We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible,” the agency said.

The NIAID statement does not say what data may have been outdated or how it may have changed the results. The company said March 22 it plans to see U.S. authorization for the vaccine in April.

The statement from NIAID comes a day after AstraZeneca said the interim results of their phase III U.S. study found it was 79% effective against symptomatic COVID-19, 80% effective in people 65 years and older, and 100% effective against severe or critical disease and hospitalization.

Company officials and clinical trial investigators on March 22 also addressed the recent concerns about blood clots, how well the vaccine will perform against variants, and provided a timeline for seeking regulatory approval.

“There are many countries in Europe and throughout the world that have already authorized this. The fact that a United States-run study has confirmed the efficacy and safety of this vaccine, I think is an important contribution to global health in general,” Anthony Fauci, MD, chief medical advisor to President Joe Biden, said during a White House press briefing March 22.

Andy Slavitt, White House senior advisor for the COVID-19 Response Team, had a more tempered reaction.

“It’s important to remind everyone we cannot and will not get ahead of the FDA,” he said. “While we would certainly call today’s news encouraging, it’s the kind of thing we like to see, we have a rigorous process that will come once an EUA is submitted and that will give us more information.”

With 30 million doses at the ready, the company plans to file for FDA emergency use authorization “within weeks,” Menelas Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said during a media briefing March 22.
 

Risk of thrombosis addressed

Regarding highly publicized reports of problems with blood clots from the AstraZeneca vaccine, the World Health Organization found the vaccine creates no greater risks, as did the European Medicines Agency

“We’ve had absolute confidence in the efficacy of the vaccine. Seeing this data now I hope gives others increased confidence that this is a very safe and effective vaccine,” Mr. Pangalos said.

“We’re glad this is being investigated really thoroughly,” Magda Sobieszczyk, MD, an infectious disease specialist at Columbia University In New York City, said. “It’s incredibly reassuring that the regulatory agencies have looked at the data thoroughly and there is no enhanced signal above what is seen in the population.”

“There were no concerning signals noted in the U.S. data,” she added.

Regarding the risk of blood clots, “These data are therefore timely in further addressing any safety concerns that could undermine vaccine uptake.” Andrew Garrett, PhD, executive vice president of scientific operations at ICON Clinical Research, agreed.

The vaccine was well-tolerated, the company reported, with no serious adverse events. Temporary pain and tenderness at the injection site, mild-to-moderate headaches, fatigue, chills, fever, muscle aches. and malaise were among the reported reactions.

The phase III interim results show 141 cases of symptomatic COVID-19 in the study of 32,449 adults. “We don’t have the whole breakdown yet . . . these are the high-level results we just got this week,” Mr. Pangalos said. Further information on rates of mild to moderate COVID-19 illness between groups is not yet available, for example.

The company explained that participants were randomly assigned to vaccine or placebo, with twice as many receiving the actual vaccine.

The trial is ongoing, so the FDA will receive information on more than the 141 COVID-19 symptomatic cases when the company submits a full primary analysis to the agency, Mr. Pangalos said.

In the phase III study, patients received two doses 4 weeks apart.

Beyond the U.S. study, the company has additional information, including real-world data from the United Kingdom, that it intends to submit to the FDA. Part of this evidence suggests increased efficacy when a second dose is administered at 3 months
 

‘Robust’ findings

“This is a large study, so these results can be expected to be robust. They could be expected to be even more so if there were more cases to compare between the groups, but 141 is still a substantial number of cases,” said Peter English, MD, of Horsham, United Kingdom, who is immediate past chair of the British Medical Association Public Health Medicine Committee.

Experts welcomed the 80% efficacy in people 65 and older in particular. “Importantly, the trial provides further support for efficacy in the elderly where previous clinical trial data, other than immunologic data, had been lacking,” Dr. Garrett said.

“It is clear this vaccine has very good efficacy. Remember that 60% was, prior to any trials being started, regarded as a good target,” said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. “This efficacy does not show a notable decline at older ages. This was expected and the speculation that it was ineffective or quasi-ineffective at older ages was totally unjustified.

“This is good news for the global community and one hopes that any political statements around this good news are avoided,” he added.
 

Efficacy against variants?

Regarding virus variants, Mr. Pangalos noted the study was conducted when several variants of concern were in circulation.

“What I can say is given this study was conducted much later in terms of timing, it’s very encouraging that we’ve got such high efficacy numbers when undoubtedly there are variants of concern in circulation in this study,” Mr. Pangalos said.

“It also highlights why we believe that against severe disease, our vaccine will be effective against all variants of concern,” he added.

Once the company submits its EUA to the FDA, the company is ready to immediately distribute 30 million doses of the vaccine and expects to ship 50 million total within the first month, Ruud Dobber, PhD, AstraZeneca executive vice president and president of the AZ Biopharmaceuticals Business Unit, said during the briefing.

The vaccine can be stored at 2 to 8 degrees Celsius for at least 6 months. Like other COVID-19 vaccines already authorized for emergency use, the duration of protection with the AstraZeneca product remains unknown.

This article was updated March 23, 2021.

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

Federal regulators on March 23 said they were “concerned” that drug maker AstraZeneca included “outdated information” in its announcement the previous day that the company’s COVID-19 vaccine was effective.

The federal Data and Safety Monitoring Board shared those concerns with the company as well as with the National Institute of Allergy and Infectious Diseases, and the U.S. Biomedical Advanced Research and Development Authority, according to a statement from NIAID issued early March 23.

“We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible,” the agency said.

The NIAID statement does not say what data may have been outdated or how it may have changed the results. The company said March 22 it plans to see U.S. authorization for the vaccine in April.

The statement from NIAID comes a day after AstraZeneca said the interim results of their phase III U.S. study found it was 79% effective against symptomatic COVID-19, 80% effective in people 65 years and older, and 100% effective against severe or critical disease and hospitalization.

Company officials and clinical trial investigators on March 22 also addressed the recent concerns about blood clots, how well the vaccine will perform against variants, and provided a timeline for seeking regulatory approval.

“There are many countries in Europe and throughout the world that have already authorized this. The fact that a United States-run study has confirmed the efficacy and safety of this vaccine, I think is an important contribution to global health in general,” Anthony Fauci, MD, chief medical advisor to President Joe Biden, said during a White House press briefing March 22.

Andy Slavitt, White House senior advisor for the COVID-19 Response Team, had a more tempered reaction.

“It’s important to remind everyone we cannot and will not get ahead of the FDA,” he said. “While we would certainly call today’s news encouraging, it’s the kind of thing we like to see, we have a rigorous process that will come once an EUA is submitted and that will give us more information.”

With 30 million doses at the ready, the company plans to file for FDA emergency use authorization “within weeks,” Menelas Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said during a media briefing March 22.
 

Risk of thrombosis addressed

Regarding highly publicized reports of problems with blood clots from the AstraZeneca vaccine, the World Health Organization found the vaccine creates no greater risks, as did the European Medicines Agency

“We’ve had absolute confidence in the efficacy of the vaccine. Seeing this data now I hope gives others increased confidence that this is a very safe and effective vaccine,” Mr. Pangalos said.

“We’re glad this is being investigated really thoroughly,” Magda Sobieszczyk, MD, an infectious disease specialist at Columbia University In New York City, said. “It’s incredibly reassuring that the regulatory agencies have looked at the data thoroughly and there is no enhanced signal above what is seen in the population.”

“There were no concerning signals noted in the U.S. data,” she added.

Regarding the risk of blood clots, “These data are therefore timely in further addressing any safety concerns that could undermine vaccine uptake.” Andrew Garrett, PhD, executive vice president of scientific operations at ICON Clinical Research, agreed.

The vaccine was well-tolerated, the company reported, with no serious adverse events. Temporary pain and tenderness at the injection site, mild-to-moderate headaches, fatigue, chills, fever, muscle aches. and malaise were among the reported reactions.

The phase III interim results show 141 cases of symptomatic COVID-19 in the study of 32,449 adults. “We don’t have the whole breakdown yet . . . these are the high-level results we just got this week,” Mr. Pangalos said. Further information on rates of mild to moderate COVID-19 illness between groups is not yet available, for example.

The company explained that participants were randomly assigned to vaccine or placebo, with twice as many receiving the actual vaccine.

The trial is ongoing, so the FDA will receive information on more than the 141 COVID-19 symptomatic cases when the company submits a full primary analysis to the agency, Mr. Pangalos said.

In the phase III study, patients received two doses 4 weeks apart.

Beyond the U.S. study, the company has additional information, including real-world data from the United Kingdom, that it intends to submit to the FDA. Part of this evidence suggests increased efficacy when a second dose is administered at 3 months
 

‘Robust’ findings

“This is a large study, so these results can be expected to be robust. They could be expected to be even more so if there were more cases to compare between the groups, but 141 is still a substantial number of cases,” said Peter English, MD, of Horsham, United Kingdom, who is immediate past chair of the British Medical Association Public Health Medicine Committee.

Experts welcomed the 80% efficacy in people 65 and older in particular. “Importantly, the trial provides further support for efficacy in the elderly where previous clinical trial data, other than immunologic data, had been lacking,” Dr. Garrett said.

“It is clear this vaccine has very good efficacy. Remember that 60% was, prior to any trials being started, regarded as a good target,” said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. “This efficacy does not show a notable decline at older ages. This was expected and the speculation that it was ineffective or quasi-ineffective at older ages was totally unjustified.

“This is good news for the global community and one hopes that any political statements around this good news are avoided,” he added.
 

Efficacy against variants?

Regarding virus variants, Mr. Pangalos noted the study was conducted when several variants of concern were in circulation.

“What I can say is given this study was conducted much later in terms of timing, it’s very encouraging that we’ve got such high efficacy numbers when undoubtedly there are variants of concern in circulation in this study,” Mr. Pangalos said.

“It also highlights why we believe that against severe disease, our vaccine will be effective against all variants of concern,” he added.

Once the company submits its EUA to the FDA, the company is ready to immediately distribute 30 million doses of the vaccine and expects to ship 50 million total within the first month, Ruud Dobber, PhD, AstraZeneca executive vice president and president of the AZ Biopharmaceuticals Business Unit, said during the briefing.

The vaccine can be stored at 2 to 8 degrees Celsius for at least 6 months. Like other COVID-19 vaccines already authorized for emergency use, the duration of protection with the AstraZeneca product remains unknown.

This article was updated March 23, 2021.

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

Federal regulators on March 23 said they were “concerned” that drug maker AstraZeneca included “outdated information” in its announcement the previous day that the company’s COVID-19 vaccine was effective.

The federal Data and Safety Monitoring Board shared those concerns with the company as well as with the National Institute of Allergy and Infectious Diseases, and the U.S. Biomedical Advanced Research and Development Authority, according to a statement from NIAID issued early March 23.

“We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible,” the agency said.

The NIAID statement does not say what data may have been outdated or how it may have changed the results. The company said March 22 it plans to see U.S. authorization for the vaccine in April.

The statement from NIAID comes a day after AstraZeneca said the interim results of their phase III U.S. study found it was 79% effective against symptomatic COVID-19, 80% effective in people 65 years and older, and 100% effective against severe or critical disease and hospitalization.

Company officials and clinical trial investigators on March 22 also addressed the recent concerns about blood clots, how well the vaccine will perform against variants, and provided a timeline for seeking regulatory approval.

“There are many countries in Europe and throughout the world that have already authorized this. The fact that a United States-run study has confirmed the efficacy and safety of this vaccine, I think is an important contribution to global health in general,” Anthony Fauci, MD, chief medical advisor to President Joe Biden, said during a White House press briefing March 22.

Andy Slavitt, White House senior advisor for the COVID-19 Response Team, had a more tempered reaction.

“It’s important to remind everyone we cannot and will not get ahead of the FDA,” he said. “While we would certainly call today’s news encouraging, it’s the kind of thing we like to see, we have a rigorous process that will come once an EUA is submitted and that will give us more information.”

With 30 million doses at the ready, the company plans to file for FDA emergency use authorization “within weeks,” Menelas Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said during a media briefing March 22.
 

Risk of thrombosis addressed

Regarding highly publicized reports of problems with blood clots from the AstraZeneca vaccine, the World Health Organization found the vaccine creates no greater risks, as did the European Medicines Agency

“We’ve had absolute confidence in the efficacy of the vaccine. Seeing this data now I hope gives others increased confidence that this is a very safe and effective vaccine,” Mr. Pangalos said.

“We’re glad this is being investigated really thoroughly,” Magda Sobieszczyk, MD, an infectious disease specialist at Columbia University In New York City, said. “It’s incredibly reassuring that the regulatory agencies have looked at the data thoroughly and there is no enhanced signal above what is seen in the population.”

“There were no concerning signals noted in the U.S. data,” she added.

Regarding the risk of blood clots, “These data are therefore timely in further addressing any safety concerns that could undermine vaccine uptake.” Andrew Garrett, PhD, executive vice president of scientific operations at ICON Clinical Research, agreed.

The vaccine was well-tolerated, the company reported, with no serious adverse events. Temporary pain and tenderness at the injection site, mild-to-moderate headaches, fatigue, chills, fever, muscle aches. and malaise were among the reported reactions.

The phase III interim results show 141 cases of symptomatic COVID-19 in the study of 32,449 adults. “We don’t have the whole breakdown yet . . . these are the high-level results we just got this week,” Mr. Pangalos said. Further information on rates of mild to moderate COVID-19 illness between groups is not yet available, for example.

The company explained that participants were randomly assigned to vaccine or placebo, with twice as many receiving the actual vaccine.

The trial is ongoing, so the FDA will receive information on more than the 141 COVID-19 symptomatic cases when the company submits a full primary analysis to the agency, Mr. Pangalos said.

In the phase III study, patients received two doses 4 weeks apart.

Beyond the U.S. study, the company has additional information, including real-world data from the United Kingdom, that it intends to submit to the FDA. Part of this evidence suggests increased efficacy when a second dose is administered at 3 months
 

‘Robust’ findings

“This is a large study, so these results can be expected to be robust. They could be expected to be even more so if there were more cases to compare between the groups, but 141 is still a substantial number of cases,” said Peter English, MD, of Horsham, United Kingdom, who is immediate past chair of the British Medical Association Public Health Medicine Committee.

Experts welcomed the 80% efficacy in people 65 and older in particular. “Importantly, the trial provides further support for efficacy in the elderly where previous clinical trial data, other than immunologic data, had been lacking,” Dr. Garrett said.

“It is clear this vaccine has very good efficacy. Remember that 60% was, prior to any trials being started, regarded as a good target,” said Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. “This efficacy does not show a notable decline at older ages. This was expected and the speculation that it was ineffective or quasi-ineffective at older ages was totally unjustified.

“This is good news for the global community and one hopes that any political statements around this good news are avoided,” he added.
 

Efficacy against variants?

Regarding virus variants, Mr. Pangalos noted the study was conducted when several variants of concern were in circulation.

“What I can say is given this study was conducted much later in terms of timing, it’s very encouraging that we’ve got such high efficacy numbers when undoubtedly there are variants of concern in circulation in this study,” Mr. Pangalos said.

“It also highlights why we believe that against severe disease, our vaccine will be effective against all variants of concern,” he added.

Once the company submits its EUA to the FDA, the company is ready to immediately distribute 30 million doses of the vaccine and expects to ship 50 million total within the first month, Ruud Dobber, PhD, AstraZeneca executive vice president and president of the AZ Biopharmaceuticals Business Unit, said during the briefing.

The vaccine can be stored at 2 to 8 degrees Celsius for at least 6 months. Like other COVID-19 vaccines already authorized for emergency use, the duration of protection with the AstraZeneca product remains unknown.

This article was updated March 23, 2021.

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

From my residency training graduation date, June 1978, many changes to the family medicine specialty have occurred. These are not due to certification requirements but to the dilution of physician control in health care.

The need to provide more affordable health care by insurance companies while maintaining quality prompted more changes. Additionally, employer-based decisions to change insurance plans, since they were the payer for employer-based health insurance, sometimes yearly, prompted mandatory changes in health insurance.

To achieve hospital-based goals and cost containment the advent and use of hospitalists and the expanded use of physician extenders emerged. While I have some support for these changes, they have redefined elements of the Folsom report^, which concluded that every American should have a personal physician to care for them and help integrate them into the health care system.

Changes in the health care delivery system and insurance companies’ need to contain costs, while expanding preventative medicine, coupled with a decreasing number of trained family medicine physicians, represents the background of some of the changes in family medicine over the past 50 years. Managed health care, I believe, was certainly part of the answer to implementing the following recommendation of the Folsom report: every American should have a physician-manager for their health care.

Despite the continual output of new family physicians, a shortage of physicians trained in this specialty remained. Advances in health care, which lengthened life expectancy and the fact that most health insurance companies required its members to name a primary care physician expanded the population requiring primary health care services. This only exacerbated the shortage of family physicians and lowered earning power for doctors practicing family medicine, and it created greater professional demands on family physicians, compared with those in other, more limited-scope specialties. The primary care physician shortage needed to be addressed, prompting a redefinition in the traditional nurse practitioner role.
 

The expansion of nurse practitioners and physician assistants’ roles

The nursing profession began training advanced-placement nurses and instituted a Doctor of Nurse Practitioner degree. At the same time physician assistants, a program that began while I was a resident, had a further role expansion, including training confined to a single specialty area of medicine. These roles were expanded by state legislators who added them to the list of primary care providers, in some locations, permitting independent practice and placing the physician assistant under the state medical boards and the nurse practitioner and Doctor of Nurse Practitioners under the nursing boards, for expanded regulations and the implementation of the new provider requirements for licensure.
 

The effects of insurance companies on primary care physicians and patients

When I started practicing medicine the physician was truly the manager of a person’s health care. With the advent of managed health care, that has changed. Physicians are no longer the managers; an uninvited marriage between physician, physician extender, insurance company, employer, and patient jointly controls health care.

Patients are opting for less care at the cheapest price based on incentives driven by cost and abetted by insurance companies and employers. The cost of medications has increased and provider services, coupled with medication and specialty costs have nearly priced many beyond their economic limits to pay. As a result, the patient is not always as committed as their provider to meeting the metrics of their insurance company, especially if that is increasing their out-of-pocket cost.

In addition to usual services, the primary care physician is required to demonstrate the adequacy of services provided through meeting certain practice quality metrics for nearly all insurance carriers, including Medicare and Medicaid. Because meeting these metrics carries a significant economic incentive many practices are retaining fewer noncompliant patients and have opted to bolster their bottom line with the more complaint. This adversely impacts the delivery of primary care to a significant portion of the population.

Patients that reside in poorer neighborhoods, rural areas, as well the marginalized compose a significant portion of many primary care provider’s practices and make up a significant percentage of noncompliant patients. Recognizing that the primary care physician’s overhead is high, coupled with the amount of financial and personal resources put into place to meet metrics, it costs much more to care for the marginalized, poor, and rural populations than easier-to-care for patient groups. This creates a disparity in health care.

A study that revisited the Folsom report concluded that “the 21st century primary care physician must be a true public health professional, forming partnerships and assisting data sharing with community organizations to facilitate healthy changes.” These observations have redefined primary care. This type of medicine is no longer tied to a physician; it is tied to a fairly expensive team of providers, which includes a nurse manager, physician, physician extender, social worker, and in some cases, a pharmacist. The days of mostly solo practitioners are waning and the days of the traditional family medicine residency training requires continuous nuancing, to accommodate the expanded list of practice-related responsibilities assigned to the family doctor.
 

Low reimbursements rates and high office overhead

The last change I have observed in the practice of family medicine over the past 50 years is a decline in the ratio of reimbursement rate for services to practice expenses. Many practitioners opt out of Medicaid or have certainly curtailed the number of Medicaid recipients on their panel because of its unacceptably low reimbursement rates combined with their high office overhead. The requirements for organizing community resources, including nursing agencies and church and community groups, carry no reimbursement for time invested. The primary care provider is responsible and evaluated on patient outcomes despite the noncompliant behavior of the patient.

What is the future of the primary care physician or provider?

The factors that determine this answer lie in what will be required of the provider and the role of the insurance company in assisting the provider of services. Insurance companies have a responsibility because they receive money to pay for metrics while remaining profitable. They must be brought into the success formula and assist the provider in order for the latter to survive. Currently the primary care provider, in an abundance of caution, is required to seek more specialty services, which drives up the cost of health care. Instead, the insurance company should allow the primary care provider to direct the health care and stop being the manager, approving or disapproving services. In summary, much has happened in family medicine over the past 50 years. The ongoing personal doctor-patient relationship has turned into a doctor-patient-insurance company relationship. The introduction of the third party has created an economic incentive for the physician to meet practice metrics, which sometimes, from the patient’s economic perspective, creates economic hardship.

Some patients enlist a primary care physician in name only but continue to drive their health care by the older model, thanks to the advent of the urgent care centers. These patients see participating in the crisis-care model as resulting in lower out-of-pocket costs. Insurance companies should enlist patient support by expanding their patient education to include the benefits of health, the benefits of meeting quality metrics by their physician, and the necessity of maintaining a compliant doctor-patient relationship. Just as they offer incentives to the primary care practitioner for meeting quality metrics incentives should be offered to those patients that meet quality metrics as well.

In the 21st century, a new model of health care emerged, which includes a primary care practitioner, nurse manager-educator, social worker, and a pharmacist. To deliver quality health care one person can’t be responsible for this burden and do it effectively. Many family practice residencies already use this model and most likely advise their graduates to seek employment where this model exists. Additionally, I am sure that family practice residencies are continually nuanced to achieve the teaching mantra required for successful postgraduate employment and good patient outcomes.
 

What is the future of family medicine?

The family medicine specialty is represented by a practice that looks at outcome metrics primarily without an incentive for helping the marginalized, poor, homeless, and displaced members of our society.

Urban family medicine, much like what I have practiced in this my 43rd year, is different. My practice community includes every segment of society and my approach lies in the improvement of outcomes from all that I serve. It is my impression that the future of family medicine education must include all members of our society and train residents to effectively care for all, irrespective of economic status, and evolve ways to improve the health outcomes for all.

The federal government, through reimbursement and incentive programs, needs to include such efforts in the model of care for these individuals to reduce the expense burden on the practitioner achieving better practice success and less burnout.

Dr. Betton practices family medicine in Little Rock, Ark. He also serves on the editorial advisory board of Family Practice News.

From my residency training graduation date, June 1978, many changes to the family medicine specialty have occurred. These are not due to certification requirements but to the dilution of physician control in health care.

The need to provide more affordable health care by insurance companies while maintaining quality prompted more changes. Additionally, employer-based decisions to change insurance plans, since they were the payer for employer-based health insurance, sometimes yearly, prompted mandatory changes in health insurance.

To achieve hospital-based goals and cost containment the advent and use of hospitalists and the expanded use of physician extenders emerged. While I have some support for these changes, they have redefined elements of the Folsom report^, which concluded that every American should have a personal physician to care for them and help integrate them into the health care system.

Changes in the health care delivery system and insurance companies’ need to contain costs, while expanding preventative medicine, coupled with a decreasing number of trained family medicine physicians, represents the background of some of the changes in family medicine over the past 50 years. Managed health care, I believe, was certainly part of the answer to implementing the following recommendation of the Folsom report: every American should have a physician-manager for their health care.

Despite the continual output of new family physicians, a shortage of physicians trained in this specialty remained. Advances in health care, which lengthened life expectancy and the fact that most health insurance companies required its members to name a primary care physician expanded the population requiring primary health care services. This only exacerbated the shortage of family physicians and lowered earning power for doctors practicing family medicine, and it created greater professional demands on family physicians, compared with those in other, more limited-scope specialties. The primary care physician shortage needed to be addressed, prompting a redefinition in the traditional nurse practitioner role.
 

The expansion of nurse practitioners and physician assistants’ roles

The nursing profession began training advanced-placement nurses and instituted a Doctor of Nurse Practitioner degree. At the same time physician assistants, a program that began while I was a resident, had a further role expansion, including training confined to a single specialty area of medicine. These roles were expanded by state legislators who added them to the list of primary care providers, in some locations, permitting independent practice and placing the physician assistant under the state medical boards and the nurse practitioner and Doctor of Nurse Practitioners under the nursing boards, for expanded regulations and the implementation of the new provider requirements for licensure.
 

The effects of insurance companies on primary care physicians and patients

When I started practicing medicine the physician was truly the manager of a person’s health care. With the advent of managed health care, that has changed. Physicians are no longer the managers; an uninvited marriage between physician, physician extender, insurance company, employer, and patient jointly controls health care.

Patients are opting for less care at the cheapest price based on incentives driven by cost and abetted by insurance companies and employers. The cost of medications has increased and provider services, coupled with medication and specialty costs have nearly priced many beyond their economic limits to pay. As a result, the patient is not always as committed as their provider to meeting the metrics of their insurance company, especially if that is increasing their out-of-pocket cost.

In addition to usual services, the primary care physician is required to demonstrate the adequacy of services provided through meeting certain practice quality metrics for nearly all insurance carriers, including Medicare and Medicaid. Because meeting these metrics carries a significant economic incentive many practices are retaining fewer noncompliant patients and have opted to bolster their bottom line with the more complaint. This adversely impacts the delivery of primary care to a significant portion of the population.

Patients that reside in poorer neighborhoods, rural areas, as well the marginalized compose a significant portion of many primary care provider’s practices and make up a significant percentage of noncompliant patients. Recognizing that the primary care physician’s overhead is high, coupled with the amount of financial and personal resources put into place to meet metrics, it costs much more to care for the marginalized, poor, and rural populations than easier-to-care for patient groups. This creates a disparity in health care.

A study that revisited the Folsom report concluded that “the 21st century primary care physician must be a true public health professional, forming partnerships and assisting data sharing with community organizations to facilitate healthy changes.” These observations have redefined primary care. This type of medicine is no longer tied to a physician; it is tied to a fairly expensive team of providers, which includes a nurse manager, physician, physician extender, social worker, and in some cases, a pharmacist. The days of mostly solo practitioners are waning and the days of the traditional family medicine residency training requires continuous nuancing, to accommodate the expanded list of practice-related responsibilities assigned to the family doctor.
 

Low reimbursements rates and high office overhead

The last change I have observed in the practice of family medicine over the past 50 years is a decline in the ratio of reimbursement rate for services to practice expenses. Many practitioners opt out of Medicaid or have certainly curtailed the number of Medicaid recipients on their panel because of its unacceptably low reimbursement rates combined with their high office overhead. The requirements for organizing community resources, including nursing agencies and church and community groups, carry no reimbursement for time invested. The primary care provider is responsible and evaluated on patient outcomes despite the noncompliant behavior of the patient.

What is the future of the primary care physician or provider?

The factors that determine this answer lie in what will be required of the provider and the role of the insurance company in assisting the provider of services. Insurance companies have a responsibility because they receive money to pay for metrics while remaining profitable. They must be brought into the success formula and assist the provider in order for the latter to survive. Currently the primary care provider, in an abundance of caution, is required to seek more specialty services, which drives up the cost of health care. Instead, the insurance company should allow the primary care provider to direct the health care and stop being the manager, approving or disapproving services. In summary, much has happened in family medicine over the past 50 years. The ongoing personal doctor-patient relationship has turned into a doctor-patient-insurance company relationship. The introduction of the third party has created an economic incentive for the physician to meet practice metrics, which sometimes, from the patient’s economic perspective, creates economic hardship.

Some patients enlist a primary care physician in name only but continue to drive their health care by the older model, thanks to the advent of the urgent care centers. These patients see participating in the crisis-care model as resulting in lower out-of-pocket costs. Insurance companies should enlist patient support by expanding their patient education to include the benefits of health, the benefits of meeting quality metrics by their physician, and the necessity of maintaining a compliant doctor-patient relationship. Just as they offer incentives to the primary care practitioner for meeting quality metrics incentives should be offered to those patients that meet quality metrics as well.

In the 21st century, a new model of health care emerged, which includes a primary care practitioner, nurse manager-educator, social worker, and a pharmacist. To deliver quality health care one person can’t be responsible for this burden and do it effectively. Many family practice residencies already use this model and most likely advise their graduates to seek employment where this model exists. Additionally, I am sure that family practice residencies are continually nuanced to achieve the teaching mantra required for successful postgraduate employment and good patient outcomes.
 

What is the future of family medicine?

The family medicine specialty is represented by a practice that looks at outcome metrics primarily without an incentive for helping the marginalized, poor, homeless, and displaced members of our society.

Urban family medicine, much like what I have practiced in this my 43rd year, is different. My practice community includes every segment of society and my approach lies in the improvement of outcomes from all that I serve. It is my impression that the future of family medicine education must include all members of our society and train residents to effectively care for all, irrespective of economic status, and evolve ways to improve the health outcomes for all.

The federal government, through reimbursement and incentive programs, needs to include such efforts in the model of care for these individuals to reduce the expense burden on the practitioner achieving better practice success and less burnout.

Dr. Betton practices family medicine in Little Rock, Ark. He also serves on the editorial advisory board of Family Practice News.

From my residency training graduation date, June 1978, many changes to the family medicine specialty have occurred. These are not due to certification requirements but to the dilution of physician control in health care.

The need to provide more affordable health care by insurance companies while maintaining quality prompted more changes. Additionally, employer-based decisions to change insurance plans, since they were the payer for employer-based health insurance, sometimes yearly, prompted mandatory changes in health insurance.

To achieve hospital-based goals and cost containment the advent and use of hospitalists and the expanded use of physician extenders emerged. While I have some support for these changes, they have redefined elements of the Folsom report^, which concluded that every American should have a personal physician to care for them and help integrate them into the health care system.

Changes in the health care delivery system and insurance companies’ need to contain costs, while expanding preventative medicine, coupled with a decreasing number of trained family medicine physicians, represents the background of some of the changes in family medicine over the past 50 years. Managed health care, I believe, was certainly part of the answer to implementing the following recommendation of the Folsom report: every American should have a physician-manager for their health care.

Despite the continual output of new family physicians, a shortage of physicians trained in this specialty remained. Advances in health care, which lengthened life expectancy and the fact that most health insurance companies required its members to name a primary care physician expanded the population requiring primary health care services. This only exacerbated the shortage of family physicians and lowered earning power for doctors practicing family medicine, and it created greater professional demands on family physicians, compared with those in other, more limited-scope specialties. The primary care physician shortage needed to be addressed, prompting a redefinition in the traditional nurse practitioner role.
 

The expansion of nurse practitioners and physician assistants’ roles

The nursing profession began training advanced-placement nurses and instituted a Doctor of Nurse Practitioner degree. At the same time physician assistants, a program that began while I was a resident, had a further role expansion, including training confined to a single specialty area of medicine. These roles were expanded by state legislators who added them to the list of primary care providers, in some locations, permitting independent practice and placing the physician assistant under the state medical boards and the nurse practitioner and Doctor of Nurse Practitioners under the nursing boards, for expanded regulations and the implementation of the new provider requirements for licensure.
 

The effects of insurance companies on primary care physicians and patients

When I started practicing medicine the physician was truly the manager of a person’s health care. With the advent of managed health care, that has changed. Physicians are no longer the managers; an uninvited marriage between physician, physician extender, insurance company, employer, and patient jointly controls health care.

Patients are opting for less care at the cheapest price based on incentives driven by cost and abetted by insurance companies and employers. The cost of medications has increased and provider services, coupled with medication and specialty costs have nearly priced many beyond their economic limits to pay. As a result, the patient is not always as committed as their provider to meeting the metrics of their insurance company, especially if that is increasing their out-of-pocket cost.

In addition to usual services, the primary care physician is required to demonstrate the adequacy of services provided through meeting certain practice quality metrics for nearly all insurance carriers, including Medicare and Medicaid. Because meeting these metrics carries a significant economic incentive many practices are retaining fewer noncompliant patients and have opted to bolster their bottom line with the more complaint. This adversely impacts the delivery of primary care to a significant portion of the population.

Patients that reside in poorer neighborhoods, rural areas, as well the marginalized compose a significant portion of many primary care provider’s practices and make up a significant percentage of noncompliant patients. Recognizing that the primary care physician’s overhead is high, coupled with the amount of financial and personal resources put into place to meet metrics, it costs much more to care for the marginalized, poor, and rural populations than easier-to-care for patient groups. This creates a disparity in health care.

A study that revisited the Folsom report concluded that “the 21st century primary care physician must be a true public health professional, forming partnerships and assisting data sharing with community organizations to facilitate healthy changes.” These observations have redefined primary care. This type of medicine is no longer tied to a physician; it is tied to a fairly expensive team of providers, which includes a nurse manager, physician, physician extender, social worker, and in some cases, a pharmacist. The days of mostly solo practitioners are waning and the days of the traditional family medicine residency training requires continuous nuancing, to accommodate the expanded list of practice-related responsibilities assigned to the family doctor.
 

Low reimbursements rates and high office overhead

The last change I have observed in the practice of family medicine over the past 50 years is a decline in the ratio of reimbursement rate for services to practice expenses. Many practitioners opt out of Medicaid or have certainly curtailed the number of Medicaid recipients on their panel because of its unacceptably low reimbursement rates combined with their high office overhead. The requirements for organizing community resources, including nursing agencies and church and community groups, carry no reimbursement for time invested. The primary care provider is responsible and evaluated on patient outcomes despite the noncompliant behavior of the patient.

What is the future of the primary care physician or provider?

The factors that determine this answer lie in what will be required of the provider and the role of the insurance company in assisting the provider of services. Insurance companies have a responsibility because they receive money to pay for metrics while remaining profitable. They must be brought into the success formula and assist the provider in order for the latter to survive. Currently the primary care provider, in an abundance of caution, is required to seek more specialty services, which drives up the cost of health care. Instead, the insurance company should allow the primary care provider to direct the health care and stop being the manager, approving or disapproving services. In summary, much has happened in family medicine over the past 50 years. The ongoing personal doctor-patient relationship has turned into a doctor-patient-insurance company relationship. The introduction of the third party has created an economic incentive for the physician to meet practice metrics, which sometimes, from the patient’s economic perspective, creates economic hardship.

Some patients enlist a primary care physician in name only but continue to drive their health care by the older model, thanks to the advent of the urgent care centers. These patients see participating in the crisis-care model as resulting in lower out-of-pocket costs. Insurance companies should enlist patient support by expanding their patient education to include the benefits of health, the benefits of meeting quality metrics by their physician, and the necessity of maintaining a compliant doctor-patient relationship. Just as they offer incentives to the primary care practitioner for meeting quality metrics incentives should be offered to those patients that meet quality metrics as well.

In the 21st century, a new model of health care emerged, which includes a primary care practitioner, nurse manager-educator, social worker, and a pharmacist. To deliver quality health care one person can’t be responsible for this burden and do it effectively. Many family practice residencies already use this model and most likely advise their graduates to seek employment where this model exists. Additionally, I am sure that family practice residencies are continually nuanced to achieve the teaching mantra required for successful postgraduate employment and good patient outcomes.
 

What is the future of family medicine?

The family medicine specialty is represented by a practice that looks at outcome metrics primarily without an incentive for helping the marginalized, poor, homeless, and displaced members of our society.

Urban family medicine, much like what I have practiced in this my 43rd year, is different. My practice community includes every segment of society and my approach lies in the improvement of outcomes from all that I serve. It is my impression that the future of family medicine education must include all members of our society and train residents to effectively care for all, irrespective of economic status, and evolve ways to improve the health outcomes for all.

The federal government, through reimbursement and incentive programs, needs to include such efforts in the model of care for these individuals to reduce the expense burden on the practitioner achieving better practice success and less burnout.

Dr. Betton practices family medicine in Little Rock, Ark. He also serves on the editorial advisory board of Family Practice News.

In a record year for the Match, psychiatry residencies filled 99.8% of their available positions in 2021, which were up 2.6% over last year, according to the National Resident Matching Program.

“Rather than faltering in these uncertain times, program fill rates increased across the board,” the NRMP said in a written statement. Overall, the 2021 Main Residency Match offered (35,194) and filled (33,353) more first-year (PGY-1) slots than ever before, for a fill rate of 94.8%, which was up from 94.6% the year before.

Psychiatry offered 1,907 positions in this year’s Match, up by 2.6% over 2020, and filled 1,904, for a 1-year increase of 3.6% and a fill rate of 99.8%. Almost 81% (1,537) of the available slots were given to U.S. seniors (MDs and DOs), while 16.2% went to international medical graduates. The corresponding PGY-1 numbers for the Match as a whole were 70.4% U.S. and 21.1% international medical graduates, based on NRMP data.

The number of positions offered in psychiatry residencies has increased by 412 (27.6%) since 2017, and such growth over time may “be a predictor of future physician workforce supply,” the NRMP suggested. Psychiatry also increased its share of all available residency positions from 5.1% in 2018 to 5.4% in 2021.

“Concerns about the impact of virtual recruitment on applicants’ matching into PGY-1 positions were not realized,” the NRMP noted, as “growth in registration was seen in every applicant group.” Compared with 2020, submissions of rank-order lists of programs were up by 2.8% for U.S. MD seniors, 7.9% for U.S. DO seniors, 2.5% among U.S.-citizen IMGs, and 15.0% for non–U.S.-citizen IMGs.

“The application and recruitment cycle was upended as a result of the pandemic, yet the results of the Match continue to demonstrate strong and consistent outcomes for participants,” said Donna L. Lamb, DHSc, MBA, BSN, president and CEO of the NRMP.

[email protected]

In a record year for the Match, psychiatry residencies filled 99.8% of their available positions in 2021, which were up 2.6% over last year, according to the National Resident Matching Program.

“Rather than faltering in these uncertain times, program fill rates increased across the board,” the NRMP said in a written statement. Overall, the 2021 Main Residency Match offered (35,194) and filled (33,353) more first-year (PGY-1) slots than ever before, for a fill rate of 94.8%, which was up from 94.6% the year before.

Psychiatry offered 1,907 positions in this year’s Match, up by 2.6% over 2020, and filled 1,904, for a 1-year increase of 3.6% and a fill rate of 99.8%. Almost 81% (1,537) of the available slots were given to U.S. seniors (MDs and DOs), while 16.2% went to international medical graduates. The corresponding PGY-1 numbers for the Match as a whole were 70.4% U.S. and 21.1% international medical graduates, based on NRMP data.

The number of positions offered in psychiatry residencies has increased by 412 (27.6%) since 2017, and such growth over time may “be a predictor of future physician workforce supply,” the NRMP suggested. Psychiatry also increased its share of all available residency positions from 5.1% in 2018 to 5.4% in 2021.

“Concerns about the impact of virtual recruitment on applicants’ matching into PGY-1 positions were not realized,” the NRMP noted, as “growth in registration was seen in every applicant group.” Compared with 2020, submissions of rank-order lists of programs were up by 2.8% for U.S. MD seniors, 7.9% for U.S. DO seniors, 2.5% among U.S.-citizen IMGs, and 15.0% for non–U.S.-citizen IMGs.

“The application and recruitment cycle was upended as a result of the pandemic, yet the results of the Match continue to demonstrate strong and consistent outcomes for participants,” said Donna L. Lamb, DHSc, MBA, BSN, president and CEO of the NRMP.

[email protected]

In a record year for the Match, psychiatry residencies filled 99.8% of their available positions in 2021, which were up 2.6% over last year, according to the National Resident Matching Program.

“Rather than faltering in these uncertain times, program fill rates increased across the board,” the NRMP said in a written statement. Overall, the 2021 Main Residency Match offered (35,194) and filled (33,353) more first-year (PGY-1) slots than ever before, for a fill rate of 94.8%, which was up from 94.6% the year before.

Psychiatry offered 1,907 positions in this year’s Match, up by 2.6% over 2020, and filled 1,904, for a 1-year increase of 3.6% and a fill rate of 99.8%. Almost 81% (1,537) of the available slots were given to U.S. seniors (MDs and DOs), while 16.2% went to international medical graduates. The corresponding PGY-1 numbers for the Match as a whole were 70.4% U.S. and 21.1% international medical graduates, based on NRMP data.

The number of positions offered in psychiatry residencies has increased by 412 (27.6%) since 2017, and such growth over time may “be a predictor of future physician workforce supply,” the NRMP suggested. Psychiatry also increased its share of all available residency positions from 5.1% in 2018 to 5.4% in 2021.

“Concerns about the impact of virtual recruitment on applicants’ matching into PGY-1 positions were not realized,” the NRMP noted, as “growth in registration was seen in every applicant group.” Compared with 2020, submissions of rank-order lists of programs were up by 2.8% for U.S. MD seniors, 7.9% for U.S. DO seniors, 2.5% among U.S.-citizen IMGs, and 15.0% for non–U.S.-citizen IMGs.

“The application and recruitment cycle was upended as a result of the pandemic, yet the results of the Match continue to demonstrate strong and consistent outcomes for participants,” said Donna L. Lamb, DHSc, MBA, BSN, president and CEO of the NRMP.

[email protected]

Two newly published studies highlight recent success toward delaying the onset of type 1 diabetes in people at high risk and slowing progression in those with recent onset of the condition.

Both studies were initially presented in June 2020 at the annual scientific sessions of the American Diabetes Association and reported by this news organization at the time.  

As yet, neither of the two strategies – preserving insulin-producing pancreatic beta-cell function soon after diagnosis or delaying type 1 diabetes onset in those at high risk – represent a cure or certain disease prevention.

However, both can potentially lead to better long-term glycemic control with less hypoglycemia and a lower risk for diabetes-related complications.
 

Combination treatment prolongs beta-cell function in new-onset disease

The first study, entitled, “Anti–interleukin-21 antibody and liraglutide for the preservation of beta-cell function in adults with recent-onset type 1 diabetes,” was published online March 1, 2021, in The Lancet Diabetes & Endocrinology by Matthias von Herrath, MD, of Novo Nordisk, Søborg, Denmark, and colleagues.

The randomized, placebo-controlled, double-blind, phase 2 combination treatment trial involved 308 individuals aged 18-45 years who had been diagnosed with type 1 diabetes in the previous 20 weeks and still had residual beta-cell function.

Patients were randomized with 77 per group to receive monoclonal anti-IL-21 plus liraglutide, anti-IL-21 alone, liraglutide alone, or placebo. The antibody was given intravenously every 6 weeks and liraglutide or matching placebo were self-administered by daily injections.

Compared with placebo (ratio to baseline, 0.61; 39% decrease), the decrease in mixed meal tolerance test stimulated C-peptide concentration from baseline to week 54 – the primary outcome – was significantly smaller with combination treatment (0.90, 10% decrease; estimated treatment ratio, 1.48; P = .0017), but not with anti-IL-21 alone (1.23; P = .093) or liraglutide alone (1.12; P = .38).

Despite greater insulin use in the placebo group, the decrease in hemoglobin A1c (a key secondary outcome) at week 54 was greater with all active treatments (–0.50 percentage points) than with placebo (–0.10 percentage points), although the differences versus placebo were not significant.

“The combination of anti-IL-21 and liraglutide could preserve beta-cell function in recently diagnosed type 1 diabetes,” the researchers said.

“These results suggest that this combination has the potential to offer a novel and valuable disease-modifying therapy for patients with recently diagnosed type 1 diabetes. However, the efficacy and safety need to be further investigated in a phase 3 program,” Dr. von Herrath and colleagues concluded.
 

Teplizumab: 3-year data continue to show benefit

The other study looked at delaying the onset of type 1 diabetes. Entitled, “Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals,” the article was published online March 3, 2021, in Science Translational Medicine by Emily K. Sims, MD, of the department of pediatrics, Indiana University, Indianapolis, and colleagues.

This trial of the anti-CD3 monoclonal antibody adds an additional year of follow-up to the “game-changer” 2-year data reported in 2019.

Among the 76 individuals aged 8-49 years who were positive for two or more type 1 diabetes–related autoantibodies, 50% of those randomized to a single 14-day infusion course of teplizumab remained diabetes free at a median follow-up of 923 days, compared with only 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01).

The teplizumab group had a greater average C-peptide area under the curve, compared with placebo, reflecting improved beta-cell function (1.96 vs 1.68 pmol/mL; P = .006).

C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).

“It is very encouraging to see that a single course of teplizumab delayed insulin dependence in this high-risk population for approximately 3 years versus placebo,” said Frank Martin, PhD, JDRF director of research at Provention Bio, which is developing teplizumab.

“These exciting results have been made possible by the unwavering efforts of TrialNet and Provention Bio. Teplizumab, if approved by the FDA, could positively change the course of disease development for people at risk of developing T1D and their standard of care,” he concluded.

The teplizumab study was funded by TrialNet. Dr. von Herrath is an employee of Novo Nordisk, which funded the study involving its drug liraglutide. Dr. Sims reported no relevant financial relationships.

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

Two newly published studies highlight recent success toward delaying the onset of type 1 diabetes in people at high risk and slowing progression in those with recent onset of the condition.

Both studies were initially presented in June 2020 at the annual scientific sessions of the American Diabetes Association and reported by this news organization at the time.  

As yet, neither of the two strategies – preserving insulin-producing pancreatic beta-cell function soon after diagnosis or delaying type 1 diabetes onset in those at high risk – represent a cure or certain disease prevention.

However, both can potentially lead to better long-term glycemic control with less hypoglycemia and a lower risk for diabetes-related complications.
 

Combination treatment prolongs beta-cell function in new-onset disease

The first study, entitled, “Anti–interleukin-21 antibody and liraglutide for the preservation of beta-cell function in adults with recent-onset type 1 diabetes,” was published online March 1, 2021, in The Lancet Diabetes & Endocrinology by Matthias von Herrath, MD, of Novo Nordisk, Søborg, Denmark, and colleagues.

The randomized, placebo-controlled, double-blind, phase 2 combination treatment trial involved 308 individuals aged 18-45 years who had been diagnosed with type 1 diabetes in the previous 20 weeks and still had residual beta-cell function.

Patients were randomized with 77 per group to receive monoclonal anti-IL-21 plus liraglutide, anti-IL-21 alone, liraglutide alone, or placebo. The antibody was given intravenously every 6 weeks and liraglutide or matching placebo were self-administered by daily injections.

Compared with placebo (ratio to baseline, 0.61; 39% decrease), the decrease in mixed meal tolerance test stimulated C-peptide concentration from baseline to week 54 – the primary outcome – was significantly smaller with combination treatment (0.90, 10% decrease; estimated treatment ratio, 1.48; P = .0017), but not with anti-IL-21 alone (1.23; P = .093) or liraglutide alone (1.12; P = .38).

Despite greater insulin use in the placebo group, the decrease in hemoglobin A1c (a key secondary outcome) at week 54 was greater with all active treatments (–0.50 percentage points) than with placebo (–0.10 percentage points), although the differences versus placebo were not significant.

“The combination of anti-IL-21 and liraglutide could preserve beta-cell function in recently diagnosed type 1 diabetes,” the researchers said.

“These results suggest that this combination has the potential to offer a novel and valuable disease-modifying therapy for patients with recently diagnosed type 1 diabetes. However, the efficacy and safety need to be further investigated in a phase 3 program,” Dr. von Herrath and colleagues concluded.
 

Teplizumab: 3-year data continue to show benefit

The other study looked at delaying the onset of type 1 diabetes. Entitled, “Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals,” the article was published online March 3, 2021, in Science Translational Medicine by Emily K. Sims, MD, of the department of pediatrics, Indiana University, Indianapolis, and colleagues.

This trial of the anti-CD3 monoclonal antibody adds an additional year of follow-up to the “game-changer” 2-year data reported in 2019.

Among the 76 individuals aged 8-49 years who were positive for two or more type 1 diabetes–related autoantibodies, 50% of those randomized to a single 14-day infusion course of teplizumab remained diabetes free at a median follow-up of 923 days, compared with only 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01).

The teplizumab group had a greater average C-peptide area under the curve, compared with placebo, reflecting improved beta-cell function (1.96 vs 1.68 pmol/mL; P = .006).

C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).

“It is very encouraging to see that a single course of teplizumab delayed insulin dependence in this high-risk population for approximately 3 years versus placebo,” said Frank Martin, PhD, JDRF director of research at Provention Bio, which is developing teplizumab.

“These exciting results have been made possible by the unwavering efforts of TrialNet and Provention Bio. Teplizumab, if approved by the FDA, could positively change the course of disease development for people at risk of developing T1D and their standard of care,” he concluded.

The teplizumab study was funded by TrialNet. Dr. von Herrath is an employee of Novo Nordisk, which funded the study involving its drug liraglutide. Dr. Sims reported no relevant financial relationships.

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

Two newly published studies highlight recent success toward delaying the onset of type 1 diabetes in people at high risk and slowing progression in those with recent onset of the condition.

Both studies were initially presented in June 2020 at the annual scientific sessions of the American Diabetes Association and reported by this news organization at the time.  

As yet, neither of the two strategies – preserving insulin-producing pancreatic beta-cell function soon after diagnosis or delaying type 1 diabetes onset in those at high risk – represent a cure or certain disease prevention.

However, both can potentially lead to better long-term glycemic control with less hypoglycemia and a lower risk for diabetes-related complications.
 

Combination treatment prolongs beta-cell function in new-onset disease

The first study, entitled, “Anti–interleukin-21 antibody and liraglutide for the preservation of beta-cell function in adults with recent-onset type 1 diabetes,” was published online March 1, 2021, in The Lancet Diabetes & Endocrinology by Matthias von Herrath, MD, of Novo Nordisk, Søborg, Denmark, and colleagues.

The randomized, placebo-controlled, double-blind, phase 2 combination treatment trial involved 308 individuals aged 18-45 years who had been diagnosed with type 1 diabetes in the previous 20 weeks and still had residual beta-cell function.

Patients were randomized with 77 per group to receive monoclonal anti-IL-21 plus liraglutide, anti-IL-21 alone, liraglutide alone, or placebo. The antibody was given intravenously every 6 weeks and liraglutide or matching placebo were self-administered by daily injections.

Compared with placebo (ratio to baseline, 0.61; 39% decrease), the decrease in mixed meal tolerance test stimulated C-peptide concentration from baseline to week 54 – the primary outcome – was significantly smaller with combination treatment (0.90, 10% decrease; estimated treatment ratio, 1.48; P = .0017), but not with anti-IL-21 alone (1.23; P = .093) or liraglutide alone (1.12; P = .38).

Despite greater insulin use in the placebo group, the decrease in hemoglobin A1c (a key secondary outcome) at week 54 was greater with all active treatments (–0.50 percentage points) than with placebo (–0.10 percentage points), although the differences versus placebo were not significant.

“The combination of anti-IL-21 and liraglutide could preserve beta-cell function in recently diagnosed type 1 diabetes,” the researchers said.

“These results suggest that this combination has the potential to offer a novel and valuable disease-modifying therapy for patients with recently diagnosed type 1 diabetes. However, the efficacy and safety need to be further investigated in a phase 3 program,” Dr. von Herrath and colleagues concluded.
 

Teplizumab: 3-year data continue to show benefit

The other study looked at delaying the onset of type 1 diabetes. Entitled, “Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals,” the article was published online March 3, 2021, in Science Translational Medicine by Emily K. Sims, MD, of the department of pediatrics, Indiana University, Indianapolis, and colleagues.

This trial of the anti-CD3 monoclonal antibody adds an additional year of follow-up to the “game-changer” 2-year data reported in 2019.

Among the 76 individuals aged 8-49 years who were positive for two or more type 1 diabetes–related autoantibodies, 50% of those randomized to a single 14-day infusion course of teplizumab remained diabetes free at a median follow-up of 923 days, compared with only 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01).

The teplizumab group had a greater average C-peptide area under the curve, compared with placebo, reflecting improved beta-cell function (1.96 vs 1.68 pmol/mL; P = .006).

C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).

“It is very encouraging to see that a single course of teplizumab delayed insulin dependence in this high-risk population for approximately 3 years versus placebo,” said Frank Martin, PhD, JDRF director of research at Provention Bio, which is developing teplizumab.

“These exciting results have been made possible by the unwavering efforts of TrialNet and Provention Bio. Teplizumab, if approved by the FDA, could positively change the course of disease development for people at risk of developing T1D and their standard of care,” he concluded.

The teplizumab study was funded by TrialNet. Dr. von Herrath is an employee of Novo Nordisk, which funded the study involving its drug liraglutide. Dr. Sims reported no relevant financial relationships.

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

Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.

©Ingram Publishing/Thinkstock.com

Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.

“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.

“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
 

Ultraprocessed foods fly under the radar

“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”

The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”

The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m², and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.

During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.

In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)

The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.

Convenient, omnipresent, and affordable

The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.

“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”

The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.

[email protected]

Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.

©Ingram Publishing/Thinkstock.com

Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.

“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.

“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
 

Ultraprocessed foods fly under the radar

“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”

The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”

The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m², and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.

During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.

In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)

The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.

Convenient, omnipresent, and affordable

The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.

“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”

The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.

[email protected]

Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.

©Ingram Publishing/Thinkstock.com

Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.

“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.

“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
 

Ultraprocessed foods fly under the radar

“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”

The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”

The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m², and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.

During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.

In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)

The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.

Convenient, omnipresent, and affordable

The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.

“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”

The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.

[email protected]

Omidubicel, an investigational enriched umbilical cord blood product being developed by Gamida Cell for transplantation in patients with blood cancers, appears to have some advantages over standard umbilical cord blood.

The results come from a global phase 3 trial (NCT02730299) presented at the annual meeting of the European Society for Blood and Bone Marrow Transplantation.

“Transplantation with omidubicel, compared to standard cord blood transplantation, results in faster hematopoietic recovery, fewer infections, and fewer days in hospital,” said coinvestigator Guillermo F. Sanz, MD, PhD, from the Hospital Universitari i Politècnic la Fe in Valencia, Spain.

“Omidubicel should be considered as the new standard of care for patients eligible for umbilical cord blood transplantation,” Dr. Sanz concluded.

Zachariah DeFilipp, MD, from Mass General Cancer Center in Boston, a hematopoietic stem cell transplantation specialist who was not involved in the study, said in an interview that “omidubicel significantly improves the engraftment after transplant, as compared to standard cord blood transplant. For patients that lack an HLA-matched donor, this approach can help overcome the prolonged cytopenias that occur with standard cord blood transplants in adults.”

Gamida Cell plans to submit these data for approval of omidubicel by the Food and Drug Administration in the fourth quarter of 2021.

Omidubicel is also being evaluated in a phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937).
 

Expanding possibilities

Although umbilical cord blood stem cell grafts come from a readily available source and show greater tolerance across HLA barriers than other sources (such as bone marrow), the relatively low dose of stem cells in each unit results in delayed hematopoietic recovery, increased transplant-related morbidity and mortality, and longer hospitalizations, Dr. Sanz said.

Omidubicel consists of two cryopreserved fractions from a single cord blood unit. The product contains both noncultured CD133-negative cells, including T cells, and CD133-positive cells that are then expanded ex vivo for 21 days in the presence of nicotinamide.

“Nicotinamide increases stem and progenitor cells, inhibits differentiation and increases migration, bone marrow homing, and engraftment efficiency while preserving cellular functionality and phenotype,” Dr. Sanz explained during his presentation.

In an earlier phase 1/2 trial in 36 patients with high-risk hematologic malignancies, omidubicel was associated with hematopoietic engraftment lasting at least 10 years.
 

Details of phase 3 trial results

The global phase 3 trial was conducted in 125 patients (aged 13-65 years) with high-risk malignancies, including acute myeloid and lymphoblastic leukemias, myelodysplastic syndrome, chronic myeloid leukemia, lymphomas, and rare leukemias. These patients were all eligible for allogeneic stem cell transplantation but did not have matched donors.

Patients were randomly assigned to receive hematopoietic reconstitution with either omidubicel (n = 52) or standard cord blood (n = 58).

At 42 days of follow-up, the median time to neutrophil engraftment in the intention-to-treat (ITT) population, the primary endpoint, was 12 days with omidubicel versus 22 days with standard cord blood (P < .001).

In the as-treated population – the 108 patients who actually received omidubicel or standard cord blood – median time to engraftment was 10.0 versus 20.5 days, respectively (P < .001).

Rates of neutrophil engraftment at 42 days were 96% with omidubicel versus 89% with standard cord blood.

The secondary endpoint of time-to-platelet engraftment in the ITT population also favored omidubicel, with a cumulative day 42 incidence rate of 55%, compared with 35% with standard cord blood (P = .028).

In the as-treated population, median times to platelet engraftment were 37 days and 50 days, respectively (P = .023). The cumulative rates of platelet engraftment at 100 days of follow-up were 83% and 73%, respectively.

The incidence of grade 2 or 3 bacterial or invasive fungal infections by day 100 in the ITT population was 37% among patients who received omidubicel, compared with 57% for patients who received standard cord blood (P = .027). Viral infections occurred in 10% versus 26% of patients, respectively.

The incidence of acute graft versus host disease at day 100 was similar between treatment groups, and there was no significant difference at 1 year.

Relapse and nonrelapse mortality rates, as well as disease-free and overall survival rates also did not differ between groups.

In the first 100 days post transplant, patients who received omidubicel were alive and out of the hospital for a median of 60.5 days, compared with 48 days for patients who received standard cord blood (P = .005).

The study was funded by Gamida Cell. Dr. Sanz reported receiving research funding from the company and several others, and consulting fees, honoraria, speakers bureau activity, and travel expenses from other companies. Dr. DeFilipp reported no relevant financial relationships.

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

Omidubicel, an investigational enriched umbilical cord blood product being developed by Gamida Cell for transplantation in patients with blood cancers, appears to have some advantages over standard umbilical cord blood.

The results come from a global phase 3 trial (NCT02730299) presented at the annual meeting of the European Society for Blood and Bone Marrow Transplantation.

“Transplantation with omidubicel, compared to standard cord blood transplantation, results in faster hematopoietic recovery, fewer infections, and fewer days in hospital,” said coinvestigator Guillermo F. Sanz, MD, PhD, from the Hospital Universitari i Politècnic la Fe in Valencia, Spain.

“Omidubicel should be considered as the new standard of care for patients eligible for umbilical cord blood transplantation,” Dr. Sanz concluded.

Zachariah DeFilipp, MD, from Mass General Cancer Center in Boston, a hematopoietic stem cell transplantation specialist who was not involved in the study, said in an interview that “omidubicel significantly improves the engraftment after transplant, as compared to standard cord blood transplant. For patients that lack an HLA-matched donor, this approach can help overcome the prolonged cytopenias that occur with standard cord blood transplants in adults.”

Gamida Cell plans to submit these data for approval of omidubicel by the Food and Drug Administration in the fourth quarter of 2021.

Omidubicel is also being evaluated in a phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937).
 

Expanding possibilities

Although umbilical cord blood stem cell grafts come from a readily available source and show greater tolerance across HLA barriers than other sources (such as bone marrow), the relatively low dose of stem cells in each unit results in delayed hematopoietic recovery, increased transplant-related morbidity and mortality, and longer hospitalizations, Dr. Sanz said.

Omidubicel consists of two cryopreserved fractions from a single cord blood unit. The product contains both noncultured CD133-negative cells, including T cells, and CD133-positive cells that are then expanded ex vivo for 21 days in the presence of nicotinamide.

“Nicotinamide increases stem and progenitor cells, inhibits differentiation and increases migration, bone marrow homing, and engraftment efficiency while preserving cellular functionality and phenotype,” Dr. Sanz explained during his presentation.

In an earlier phase 1/2 trial in 36 patients with high-risk hematologic malignancies, omidubicel was associated with hematopoietic engraftment lasting at least 10 years.
 

Details of phase 3 trial results

The global phase 3 trial was conducted in 125 patients (aged 13-65 years) with high-risk malignancies, including acute myeloid and lymphoblastic leukemias, myelodysplastic syndrome, chronic myeloid leukemia, lymphomas, and rare leukemias. These patients were all eligible for allogeneic stem cell transplantation but did not have matched donors.

Patients were randomly assigned to receive hematopoietic reconstitution with either omidubicel (n = 52) or standard cord blood (n = 58).

At 42 days of follow-up, the median time to neutrophil engraftment in the intention-to-treat (ITT) population, the primary endpoint, was 12 days with omidubicel versus 22 days with standard cord blood (P < .001).

In the as-treated population – the 108 patients who actually received omidubicel or standard cord blood – median time to engraftment was 10.0 versus 20.5 days, respectively (P < .001).

Rates of neutrophil engraftment at 42 days were 96% with omidubicel versus 89% with standard cord blood.

The secondary endpoint of time-to-platelet engraftment in the ITT population also favored omidubicel, with a cumulative day 42 incidence rate of 55%, compared with 35% with standard cord blood (P = .028).

In the as-treated population, median times to platelet engraftment were 37 days and 50 days, respectively (P = .023). The cumulative rates of platelet engraftment at 100 days of follow-up were 83% and 73%, respectively.

The incidence of grade 2 or 3 bacterial or invasive fungal infections by day 100 in the ITT population was 37% among patients who received omidubicel, compared with 57% for patients who received standard cord blood (P = .027). Viral infections occurred in 10% versus 26% of patients, respectively.

The incidence of acute graft versus host disease at day 100 was similar between treatment groups, and there was no significant difference at 1 year.

Relapse and nonrelapse mortality rates, as well as disease-free and overall survival rates also did not differ between groups.

In the first 100 days post transplant, patients who received omidubicel were alive and out of the hospital for a median of 60.5 days, compared with 48 days for patients who received standard cord blood (P = .005).

The study was funded by Gamida Cell. Dr. Sanz reported receiving research funding from the company and several others, and consulting fees, honoraria, speakers bureau activity, and travel expenses from other companies. Dr. DeFilipp reported no relevant financial relationships.

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

Omidubicel, an investigational enriched umbilical cord blood product being developed by Gamida Cell for transplantation in patients with blood cancers, appears to have some advantages over standard umbilical cord blood.

The results come from a global phase 3 trial (NCT02730299) presented at the annual meeting of the European Society for Blood and Bone Marrow Transplantation.

“Transplantation with omidubicel, compared to standard cord blood transplantation, results in faster hematopoietic recovery, fewer infections, and fewer days in hospital,” said coinvestigator Guillermo F. Sanz, MD, PhD, from the Hospital Universitari i Politècnic la Fe in Valencia, Spain.

“Omidubicel should be considered as the new standard of care for patients eligible for umbilical cord blood transplantation,” Dr. Sanz concluded.

Zachariah DeFilipp, MD, from Mass General Cancer Center in Boston, a hematopoietic stem cell transplantation specialist who was not involved in the study, said in an interview that “omidubicel significantly improves the engraftment after transplant, as compared to standard cord blood transplant. For patients that lack an HLA-matched donor, this approach can help overcome the prolonged cytopenias that occur with standard cord blood transplants in adults.”

Gamida Cell plans to submit these data for approval of omidubicel by the Food and Drug Administration in the fourth quarter of 2021.

Omidubicel is also being evaluated in a phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937).
 

Expanding possibilities

Although umbilical cord blood stem cell grafts come from a readily available source and show greater tolerance across HLA barriers than other sources (such as bone marrow), the relatively low dose of stem cells in each unit results in delayed hematopoietic recovery, increased transplant-related morbidity and mortality, and longer hospitalizations, Dr. Sanz said.

Omidubicel consists of two cryopreserved fractions from a single cord blood unit. The product contains both noncultured CD133-negative cells, including T cells, and CD133-positive cells that are then expanded ex vivo for 21 days in the presence of nicotinamide.

“Nicotinamide increases stem and progenitor cells, inhibits differentiation and increases migration, bone marrow homing, and engraftment efficiency while preserving cellular functionality and phenotype,” Dr. Sanz explained during his presentation.

In an earlier phase 1/2 trial in 36 patients with high-risk hematologic malignancies, omidubicel was associated with hematopoietic engraftment lasting at least 10 years.
 

Details of phase 3 trial results

The global phase 3 trial was conducted in 125 patients (aged 13-65 years) with high-risk malignancies, including acute myeloid and lymphoblastic leukemias, myelodysplastic syndrome, chronic myeloid leukemia, lymphomas, and rare leukemias. These patients were all eligible for allogeneic stem cell transplantation but did not have matched donors.

Patients were randomly assigned to receive hematopoietic reconstitution with either omidubicel (n = 52) or standard cord blood (n = 58).

At 42 days of follow-up, the median time to neutrophil engraftment in the intention-to-treat (ITT) population, the primary endpoint, was 12 days with omidubicel versus 22 days with standard cord blood (P < .001).

In the as-treated population – the 108 patients who actually received omidubicel or standard cord blood – median time to engraftment was 10.0 versus 20.5 days, respectively (P < .001).

Rates of neutrophil engraftment at 42 days were 96% with omidubicel versus 89% with standard cord blood.

The secondary endpoint of time-to-platelet engraftment in the ITT population also favored omidubicel, with a cumulative day 42 incidence rate of 55%, compared with 35% with standard cord blood (P = .028).

In the as-treated population, median times to platelet engraftment were 37 days and 50 days, respectively (P = .023). The cumulative rates of platelet engraftment at 100 days of follow-up were 83% and 73%, respectively.

The incidence of grade 2 or 3 bacterial or invasive fungal infections by day 100 in the ITT population was 37% among patients who received omidubicel, compared with 57% for patients who received standard cord blood (P = .027). Viral infections occurred in 10% versus 26% of patients, respectively.

The incidence of acute graft versus host disease at day 100 was similar between treatment groups, and there was no significant difference at 1 year.

Relapse and nonrelapse mortality rates, as well as disease-free and overall survival rates also did not differ between groups.

In the first 100 days post transplant, patients who received omidubicel were alive and out of the hospital for a median of 60.5 days, compared with 48 days for patients who received standard cord blood (P = .005).

The study was funded by Gamida Cell. Dr. Sanz reported receiving research funding from the company and several others, and consulting fees, honoraria, speakers bureau activity, and travel expenses from other companies. Dr. DeFilipp reported no relevant financial relationships.

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

A new study has found that older men with high levels of abdominal aortic calcification (AAC) and a prevalent vertebral fracture – both of which can be assessed via lateral spine radiographs – are at increased risk of hip, clinical vertebral, and major osteoporotic fractures.

“The results of this study and others suggest that it may be appropriate to expand lateral spine imaging to include those with a significant pre-test probability of higher AAC being present,” wrote John T. Schousboe, MD, of the Park Nicollet Clinic and HealthPartners Institute in Bloomington, Minn. The study was published in the Journal of Bone and Mineral Research.

To determine the impact of prevalent vertebral fractures and AAC on fracture risk, the researchers assessed the lateral spine radiographs of 5,365 men who were enrolled in the Osteoporotic Fractures in Men (MrOS) study. All participants were 65 years or older, community dwelling, able to walk without assistance, and without bilateral hip arthroplasties. They split patients’ 24-point AAC (ACC-24) scores at the baseline visit into four levels: 0-1, 2-4, 5-8, and greater than 9. Self-reports of fractures were solicited from the cohort every 4 months.

Of all participants, 7.6% (n = 407) had a prevalent vertebral fracture at baseline. They were, on average, 1.5 years older than participants without a fracture; they were also more likely to be white and to have a prior nonspine fracture, along with having a lower femoral neck BMD (0.718 g/cm², compared with 0.787 g/cm²; P < .001). In addition, significantly more men with a prevalent vertebral fracture had an AAC score greater than 9 (27% vs. 21.2%).

After an average follow-up period of 12.4 years (standard deviation, 5.2), 634 men had a major osteoporotic fracture, 283 had a hip fracture, 206 had a clinical vertebral fracture, and 2,626 died without having any of the three. After adjustment for risk factors such as age, prior nonspine fracture, and prevalent vertebral fracture, men with higher AAC-24 scores had a higher risk of major osteoporotic fracture, compared with men who had scores of 0-1: a hazard ratio of 1.38 (95% confidence interval, 1.10-1.73; P < .001) for scores 2-4, a HR of 1.45 (95% CI, 1.14-1.84; P < .001) for scores 5-8, and a HR of 1.65 (95% CI, 1.29-2.10; P < .001) for scores greater than 9.

Similar findings were reported regarding risk of hip fractures: a HR of 1.54 (95% CI, 1.07-2.20; P < .001) for men with AAC-24 scores 2-4, a HR of 1.40 (95% CI, 0.96-2.06; P < .001) for scores 5-8, and a HR of 2.17 (95% CI, 1.50-3.13; P < .001) for scores greater than 9. AAC-24 score severity was not associated with a higher risk of clinical vertebral fractures.

After adjustment for risk factors and AAC-24 score, men with prevalent vertebral fractures had an increased risk of all three fracture outcomes, compared with men without any fractures at baseline: a HR of 1.56 (95% CI, 1.12-2.16; P < .001) for hip fracture, a HR of 1.85 (95% CI, 1.48-2.31; P < .001) for major osteoporotic fracture, and a HR of 2.76 (95% CI, 1.94-3.91; P < .001) for clinical vertebral fracture.

Adjusting for competing mortality produced similar results: men with higher levels of AAC had increased risk of major osteoporotic fracture and hip fracture, although AAC-24 score was not associated with higher risk of clinical vertebral fractures. Prevalent vertebral fractures were also still associated with higher risk of hip (subdistribution HR, 1.42; 95% CI, 1.01-2.00; P = .004), major osteoporotic fracture (SHR, 1.71; 95% CI, 1.36-2.14; P < .001), and clinical vertebral fracture (SHR, 2.46; 95% CI, 1.72-3.52; P < .001).

Fracture risk assessment proves to be “a nice proof of concept”

“It’s well known that prevalent fractures predict future fractures,” said Thomas M. Link, MD, PhD, chief of the musculoskeletal imaging section in the department of radiology and biomedical imaging at the University of California, San Francisco, in an interview. “The new finding is that aortic calcifications combined with prevalent fractures perform better in predicting major osteoporotic fractures. Traditionally on radiographs, we note that patients who have more calcifications in vessels have less density or calcium in the bone, so this is a nice proof of concept.”

“While the study shows excellent reproducibility, it is not clear how the AAC-24 score was validated,” he added. “Theoretically, abdominal CT could be used for this.”

Along with validation of the AAC-24 score on lateral spine radiographs, he expressed a desire that future research would be “clearer regarding how this would potentially impact patient management. Prevalent fractures already are an indication to treat patients with osteoporosis-specific drugs. How would the results of this study impact management beyond that?”

The authors acknowledged their study’s other potential limitations, including limits in their ability to estimate absolute and relative hip fracture risk in men with low AAC scores but a prevalent vertebral fracture. In addition, they noted that their cohort was “mostly white, healthy, community-dwelling older men” and therefore may not be generalizable to other populations.

The study was supported by the National Institutes of Health, including grants from the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences, and the NIH Roadmap for Medical Research. One author reported being supported by a National Heart Foundation of Australia Future Leader Fellowship. The others disclosed no potential conflicts of interest.

A new study has found that older men with high levels of abdominal aortic calcification (AAC) and a prevalent vertebral fracture – both of which can be assessed via lateral spine radiographs – are at increased risk of hip, clinical vertebral, and major osteoporotic fractures.

“The results of this study and others suggest that it may be appropriate to expand lateral spine imaging to include those with a significant pre-test probability of higher AAC being present,” wrote John T. Schousboe, MD, of the Park Nicollet Clinic and HealthPartners Institute in Bloomington, Minn. The study was published in the Journal of Bone and Mineral Research.

To determine the impact of prevalent vertebral fractures and AAC on fracture risk, the researchers assessed the lateral spine radiographs of 5,365 men who were enrolled in the Osteoporotic Fractures in Men (MrOS) study. All participants were 65 years or older, community dwelling, able to walk without assistance, and without bilateral hip arthroplasties. They split patients’ 24-point AAC (ACC-24) scores at the baseline visit into four levels: 0-1, 2-4, 5-8, and greater than 9. Self-reports of fractures were solicited from the cohort every 4 months.

Of all participants, 7.6% (n = 407) had a prevalent vertebral fracture at baseline. They were, on average, 1.5 years older than participants without a fracture; they were also more likely to be white and to have a prior nonspine fracture, along with having a lower femoral neck BMD (0.718 g/cm², compared with 0.787 g/cm²; P < .001). In addition, significantly more men with a prevalent vertebral fracture had an AAC score greater than 9 (27% vs. 21.2%).

After an average follow-up period of 12.4 years (standard deviation, 5.2), 634 men had a major osteoporotic fracture, 283 had a hip fracture, 206 had a clinical vertebral fracture, and 2,626 died without having any of the three. After adjustment for risk factors such as age, prior nonspine fracture, and prevalent vertebral fracture, men with higher AAC-24 scores had a higher risk of major osteoporotic fracture, compared with men who had scores of 0-1: a hazard ratio of 1.38 (95% confidence interval, 1.10-1.73; P < .001) for scores 2-4, a HR of 1.45 (95% CI, 1.14-1.84; P < .001) for scores 5-8, and a HR of 1.65 (95% CI, 1.29-2.10; P < .001) for scores greater than 9.

Similar findings were reported regarding risk of hip fractures: a HR of 1.54 (95% CI, 1.07-2.20; P < .001) for men with AAC-24 scores 2-4, a HR of 1.40 (95% CI, 0.96-2.06; P < .001) for scores 5-8, and a HR of 2.17 (95% CI, 1.50-3.13; P < .001) for scores greater than 9. AAC-24 score severity was not associated with a higher risk of clinical vertebral fractures.

After adjustment for risk factors and AAC-24 score, men with prevalent vertebral fractures had an increased risk of all three fracture outcomes, compared with men without any fractures at baseline: a HR of 1.56 (95% CI, 1.12-2.16; P < .001) for hip fracture, a HR of 1.85 (95% CI, 1.48-2.31; P < .001) for major osteoporotic fracture, and a HR of 2.76 (95% CI, 1.94-3.91; P < .001) for clinical vertebral fracture.

Adjusting for competing mortality produced similar results: men with higher levels of AAC had increased risk of major osteoporotic fracture and hip fracture, although AAC-24 score was not associated with higher risk of clinical vertebral fractures. Prevalent vertebral fractures were also still associated with higher risk of hip (subdistribution HR, 1.42; 95% CI, 1.01-2.00; P = .004), major osteoporotic fracture (SHR, 1.71; 95% CI, 1.36-2.14; P < .001), and clinical vertebral fracture (SHR, 2.46; 95% CI, 1.72-3.52; P < .001).

Fracture risk assessment proves to be “a nice proof of concept”

“It’s well known that prevalent fractures predict future fractures,” said Thomas M. Link, MD, PhD, chief of the musculoskeletal imaging section in the department of radiology and biomedical imaging at the University of California, San Francisco, in an interview. “The new finding is that aortic calcifications combined with prevalent fractures perform better in predicting major osteoporotic fractures. Traditionally on radiographs, we note that patients who have more calcifications in vessels have less density or calcium in the bone, so this is a nice proof of concept.”

“While the study shows excellent reproducibility, it is not clear how the AAC-24 score was validated,” he added. “Theoretically, abdominal CT could be used for this.”

Along with validation of the AAC-24 score on lateral spine radiographs, he expressed a desire that future research would be “clearer regarding how this would potentially impact patient management. Prevalent fractures already are an indication to treat patients with osteoporosis-specific drugs. How would the results of this study impact management beyond that?”

The authors acknowledged their study’s other potential limitations, including limits in their ability to estimate absolute and relative hip fracture risk in men with low AAC scores but a prevalent vertebral fracture. In addition, they noted that their cohort was “mostly white, healthy, community-dwelling older men” and therefore may not be generalizable to other populations.

The study was supported by the National Institutes of Health, including grants from the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences, and the NIH Roadmap for Medical Research. One author reported being supported by a National Heart Foundation of Australia Future Leader Fellowship. The others disclosed no potential conflicts of interest.

A new study has found that older men with high levels of abdominal aortic calcification (AAC) and a prevalent vertebral fracture – both of which can be assessed via lateral spine radiographs – are at increased risk of hip, clinical vertebral, and major osteoporotic fractures.

“The results of this study and others suggest that it may be appropriate to expand lateral spine imaging to include those with a significant pre-test probability of higher AAC being present,” wrote John T. Schousboe, MD, of the Park Nicollet Clinic and HealthPartners Institute in Bloomington, Minn. The study was published in the Journal of Bone and Mineral Research.

To determine the impact of prevalent vertebral fractures and AAC on fracture risk, the researchers assessed the lateral spine radiographs of 5,365 men who were enrolled in the Osteoporotic Fractures in Men (MrOS) study. All participants were 65 years or older, community dwelling, able to walk without assistance, and without bilateral hip arthroplasties. They split patients’ 24-point AAC (ACC-24) scores at the baseline visit into four levels: 0-1, 2-4, 5-8, and greater than 9. Self-reports of fractures were solicited from the cohort every 4 months.

Of all participants, 7.6% (n = 407) had a prevalent vertebral fracture at baseline. They were, on average, 1.5 years older than participants without a fracture; they were also more likely to be white and to have a prior nonspine fracture, along with having a lower femoral neck BMD (0.718 g/cm², compared with 0.787 g/cm²; P < .001). In addition, significantly more men with a prevalent vertebral fracture had an AAC score greater than 9 (27% vs. 21.2%).

After an average follow-up period of 12.4 years (standard deviation, 5.2), 634 men had a major osteoporotic fracture, 283 had a hip fracture, 206 had a clinical vertebral fracture, and 2,626 died without having any of the three. After adjustment for risk factors such as age, prior nonspine fracture, and prevalent vertebral fracture, men with higher AAC-24 scores had a higher risk of major osteoporotic fracture, compared with men who had scores of 0-1: a hazard ratio of 1.38 (95% confidence interval, 1.10-1.73; P < .001) for scores 2-4, a HR of 1.45 (95% CI, 1.14-1.84; P < .001) for scores 5-8, and a HR of 1.65 (95% CI, 1.29-2.10; P < .001) for scores greater than 9.

Similar findings were reported regarding risk of hip fractures: a HR of 1.54 (95% CI, 1.07-2.20; P < .001) for men with AAC-24 scores 2-4, a HR of 1.40 (95% CI, 0.96-2.06; P < .001) for scores 5-8, and a HR of 2.17 (95% CI, 1.50-3.13; P < .001) for scores greater than 9. AAC-24 score severity was not associated with a higher risk of clinical vertebral fractures.

After adjustment for risk factors and AAC-24 score, men with prevalent vertebral fractures had an increased risk of all three fracture outcomes, compared with men without any fractures at baseline: a HR of 1.56 (95% CI, 1.12-2.16; P < .001) for hip fracture, a HR of 1.85 (95% CI, 1.48-2.31; P < .001) for major osteoporotic fracture, and a HR of 2.76 (95% CI, 1.94-3.91; P < .001) for clinical vertebral fracture.

Adjusting for competing mortality produced similar results: men with higher levels of AAC had increased risk of major osteoporotic fracture and hip fracture, although AAC-24 score was not associated with higher risk of clinical vertebral fractures. Prevalent vertebral fractures were also still associated with higher risk of hip (subdistribution HR, 1.42; 95% CI, 1.01-2.00; P = .004), major osteoporotic fracture (SHR, 1.71; 95% CI, 1.36-2.14; P < .001), and clinical vertebral fracture (SHR, 2.46; 95% CI, 1.72-3.52; P < .001).

Fracture risk assessment proves to be “a nice proof of concept”

“It’s well known that prevalent fractures predict future fractures,” said Thomas M. Link, MD, PhD, chief of the musculoskeletal imaging section in the department of radiology and biomedical imaging at the University of California, San Francisco, in an interview. “The new finding is that aortic calcifications combined with prevalent fractures perform better in predicting major osteoporotic fractures. Traditionally on radiographs, we note that patients who have more calcifications in vessels have less density or calcium in the bone, so this is a nice proof of concept.”

“While the study shows excellent reproducibility, it is not clear how the AAC-24 score was validated,” he added. “Theoretically, abdominal CT could be used for this.”

Along with validation of the AAC-24 score on lateral spine radiographs, he expressed a desire that future research would be “clearer regarding how this would potentially impact patient management. Prevalent fractures already are an indication to treat patients with osteoporosis-specific drugs. How would the results of this study impact management beyond that?”

The authors acknowledged their study’s other potential limitations, including limits in their ability to estimate absolute and relative hip fracture risk in men with low AAC scores but a prevalent vertebral fracture. In addition, they noted that their cohort was “mostly white, healthy, community-dwelling older men” and therefore may not be generalizable to other populations.

The study was supported by the National Institutes of Health, including grants from the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences, and the NIH Roadmap for Medical Research. One author reported being supported by a National Heart Foundation of Australia Future Leader Fellowship. The others disclosed no potential conflicts of interest.

Background: Acute cholangitis (AC) in its most severe form is associated with a high mortality rate. Most patients respond to medical management involving intravenous hydration and antibiotics, though a sizable portion require biliary drainage. Current guidelines advocate for urgent drainage depending on the severity of AC, though do not specify optimal timing. Existing literature is conflicting on when ERCP should ideally be done for AC.

The studies included in the analysis were observational studies, so no causal relationship can be established. Only two of the nine studies reported outcome differences stratified by severity of presentation. Etiology of the AC was inconsistently reported amongst studies.

Bottom line: Emergent ERCP appears to be associated with reduced mortality and LOS in patients presenting with AC, though larger randomized controlled trials are needed to better delineate the optimal timing for biliary drainage in these patients.

Citation: Iqbal U et al. Emergent versus urgent ERCP in acute cholangitis: A systematic review and meta-analysis. Gastrointes Endosc. 2019 Oct 16. doi: 10.1016/j.gie.2019.09.040.

Dr. Babbel is a hospitalist and assistant professor of medicine at the University of Utah, Salt Lake City.

Background: Acute cholangitis (AC) in its most severe form is associated with a high mortality rate. Most patients respond to medical management involving intravenous hydration and antibiotics, though a sizable portion require biliary drainage. Current guidelines advocate for urgent drainage depending on the severity of AC, though do not specify optimal timing. Existing literature is conflicting on when ERCP should ideally be done for AC.

The studies included in the analysis were observational studies, so no causal relationship can be established. Only two of the nine studies reported outcome differences stratified by severity of presentation. Etiology of the AC was inconsistently reported amongst studies.

Bottom line: Emergent ERCP appears to be associated with reduced mortality and LOS in patients presenting with AC, though larger randomized controlled trials are needed to better delineate the optimal timing for biliary drainage in these patients.

Citation: Iqbal U et al. Emergent versus urgent ERCP in acute cholangitis: A systematic review and meta-analysis. Gastrointes Endosc. 2019 Oct 16. doi: 10.1016/j.gie.2019.09.040.

Dr. Babbel is a hospitalist and assistant professor of medicine at the University of Utah, Salt Lake City.

Background: Acute cholangitis (AC) in its most severe form is associated with a high mortality rate. Most patients respond to medical management involving intravenous hydration and antibiotics, though a sizable portion require biliary drainage. Current guidelines advocate for urgent drainage depending on the severity of AC, though do not specify optimal timing. Existing literature is conflicting on when ERCP should ideally be done for AC.

The studies included in the analysis were observational studies, so no causal relationship can be established. Only two of the nine studies reported outcome differences stratified by severity of presentation. Etiology of the AC was inconsistently reported amongst studies.

Bottom line: Emergent ERCP appears to be associated with reduced mortality and LOS in patients presenting with AC, though larger randomized controlled trials are needed to better delineate the optimal timing for biliary drainage in these patients.

Citation: Iqbal U et al. Emergent versus urgent ERCP in acute cholangitis: A systematic review and meta-analysis. Gastrointes Endosc. 2019 Oct 16. doi: 10.1016/j.gie.2019.09.040.

Dr. Babbel is a hospitalist and assistant professor of medicine at the University of Utah, Salt Lake City.