COVID-19 hospitalizations have been on the rise for weeks as summer nears its end, but how concerned should you be? SARS-CoV-2, the virus behind COVID, continues to evolve and surprise us. So COVID transmission, hospitalization, and death rates can be difficult to predict. 

This news organization turned to the experts for their take on the current circulating virus, asking them to predict if we’ll be masking up again anytime soon, and what this fall and winter might look like, especially now that testing and vaccinations are no longer free of charge.
 

Question 1: Are you expecting an end-of-summer COVID wave to be substantial?

Eric Topol, MD: “This wave won’t likely be substantial and could be more of a ‘wavelet.’ I’m not thinking that physicians are too concerned,” said Dr. Topol, founder and director of Scripps Research Translational Institute in La Jolla, Calif. 

Thomas Gut, DO: “It’s always impossible to predict the severity of COVID waves. Although the virus has generally mutated in ways that favor easier transmission and milder illness, there have been a handful of surprising mutations that were more dangerous and deadly than the preceding strain,” said Dr. Gut, associate chair of medicine at Staten Island University Hospital/Northwell Health in New York.

Robert Atmar, MD: “I’ll start with the caveat that prognosticating for SARS-CoV-2 is a bit hazardous as we remain in unknown territory for some aspects of its epidemiology and evolution,” said Dr. Atmar, a professor of infectious diseases at Baylor College of Medicine in Houston. “It depends on your definition of substantial. We, at least in Houston, are already in the midst of a substantial surge in the burden of infection, at least as monitored through wastewater surveillance. The amount of virus in the wastewater already exceeds the peak level we saw last winter. That said, the increased infection burden has not translated into large increases in hospitalizations for COVID-19. Most persons hospitalized in our hospital are admitted with infection, not for the consequences of infection.”

Stuart Campbell Ray, MD: “It looks like there is a rise in infections, but the proportional rise in hospitalizations from severe cases is lower than in the past, suggesting that folks are protected by the immunity we’ve gained over the past few years through vaccination and prior infections. Of course, we should be thinking about how that applies to each of us – how recently we had a vaccine or COVID-19, and whether we might see more severe infections as immunity wanes,” said Dr. Ray, who is a professor of medicine in the division of infectious diseases at Johns Hopkins University in Baltimore. 

Question 2: Is a return to masks or mask mandates coming this fall or winter?

Dr. Topol: “Mandating masks doesn’t work very well, but we may see wide use again if a descendant of [variant] BA.2.86 takes off.”

Dr. Gut: “It’s difficult to predict if there are any mask mandates returning at any point. Ever since the Omicron strains emerged, COVID has been relatively mild, compared to previous strains, so there probably won’t be any plan to start masking in public unless a more deadly strain appears.”

Dr. Atmar: “I do not think we will see a return to mask mandates this fall or winter for a variety of reasons. The primary one is that I don’t think the public will accept mask mandates. However, I think masking can continue to be an adjunctive measure to enhance protection from infection, along with booster vaccination.”

Dr. Ray: “Some people will choose to wear masks during a surge, particularly in situations like commuting where they don’t interfere with what they’re doing. They will wear masks particularly if they want to avoid infection due to concerns about others they care about, disruption of work or travel plans, or concerns about long-term consequences of repeated COVID-19.”

Question 3: Now that COVID testing and vaccinations are no longer free of charge, how might that affect their use?

Dr. Topol: “It was already low, and this will undoubtedly further compromise their uptake.”

Dr. Gut: “I do expect that testing will become less common now that tests are no longer free. I’m sure there will be a lower amount of detection in patients with milder or asymptomatic disease compared to what we had previously.”

Dr. Atmar: “If there are out-of-pocket costs for the SARS-CoV-2 vaccine, or if the administrative paperwork attached to getting a vaccine is increased, the uptake of SARS-CoV-2 vaccines will likely decrease. It will be important to communicate to the populations targeted for vaccination the potential benefits of such vaccination.”

Dr. Ray: “A challenge with COVID-19, all along, has been disparities in access to care, and this will be worse without public support for prevention and testing. This applies to everyone but is especially burdensome for those who are often marginalized in our health care system and society in general. I hope that we’ll find ways to ensure that people who need tests and vaccinations are able to access them, as good health is in everyone’s interest.”

Question 4: Will the new vaccines against COVID work for the currently circulating variants?

Dr. Topol: “The XBB.1.5 boosters will be out Sept. 14. They should help versus EG.5.1 and FL.1.5.1. The FL.1.5.1 variant is gaining now.”

Dr. Gut: “In the next several weeks, we expect the newer monovalent XBB-based vaccines to be offered that offer good protection against current circulating COVID variants along with the new Eris variant.”

Dr. Atmar: “The vaccines are expected to induce immune responses to the currently circulating variants, most of which are strains that evolved from the vaccine strain. The vaccine is expected to be most effective in preventing severe illness and will likely be less effective in preventing infection and mild illness.”

Dr. Ray: “Yes, the updated vaccine design has a spike antigen (XBB.1.5) nearly identical to the current dominant variant (EG.5). Even as variants change, the boosters stimulate B cells and T cells to help protect in a way that is safer than getting COVID-19 infection.”

Question 5: Is there anything we should watch out for regarding the BA.2.86 variant in particular?

Dr. Topol: “The scenario could change if there are new functional mutations added to it.”

Dr. Gut: “BA.2.86 is still fairly uncommon and does not have much data to directly make any informed guesses. However, in general, people that have been exposed to more recent mutations of the COVID virus have been shown to have more protection from newer upcoming mutations. It’s fair to guess that people that have not had recent infection from COVID, or have not had a recent booster, are at higher risk for being infected by any XBB- or BA.2-based strains.”

Dr. Atmar: BA.2.86 has been designated as a variant under monitoring. We will want to see whether it becomes more common and if there are any unexpected characteristics associated with infection by this variant.”

Dr. Ray: “It’s still rare, but it’s been seen in geographically dispersed places, so it’s got legs. The question is how effectively it will bypass some of the immunity we’ve gained. T cells are likely to remain protective, because they target so many parts of the virus that change more slowly, but antibodies from B cells to spike protein may have more trouble recognizing BA.2.86, whether those antibodies were made to a vaccine or a prior variant.”

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

COVID-19 hospitalizations have been on the rise for weeks as summer nears its end, but how concerned should you be? SARS-CoV-2, the virus behind COVID, continues to evolve and surprise us. So COVID transmission, hospitalization, and death rates can be difficult to predict. 

This news organization turned to the experts for their take on the current circulating virus, asking them to predict if we’ll be masking up again anytime soon, and what this fall and winter might look like, especially now that testing and vaccinations are no longer free of charge.
 

Question 1: Are you expecting an end-of-summer COVID wave to be substantial?

Eric Topol, MD: “This wave won’t likely be substantial and could be more of a ‘wavelet.’ I’m not thinking that physicians are too concerned,” said Dr. Topol, founder and director of Scripps Research Translational Institute in La Jolla, Calif. 

Thomas Gut, DO: “It’s always impossible to predict the severity of COVID waves. Although the virus has generally mutated in ways that favor easier transmission and milder illness, there have been a handful of surprising mutations that were more dangerous and deadly than the preceding strain,” said Dr. Gut, associate chair of medicine at Staten Island University Hospital/Northwell Health in New York.

Robert Atmar, MD: “I’ll start with the caveat that prognosticating for SARS-CoV-2 is a bit hazardous as we remain in unknown territory for some aspects of its epidemiology and evolution,” said Dr. Atmar, a professor of infectious diseases at Baylor College of Medicine in Houston. “It depends on your definition of substantial. We, at least in Houston, are already in the midst of a substantial surge in the burden of infection, at least as monitored through wastewater surveillance. The amount of virus in the wastewater already exceeds the peak level we saw last winter. That said, the increased infection burden has not translated into large increases in hospitalizations for COVID-19. Most persons hospitalized in our hospital are admitted with infection, not for the consequences of infection.”

Stuart Campbell Ray, MD: “It looks like there is a rise in infections, but the proportional rise in hospitalizations from severe cases is lower than in the past, suggesting that folks are protected by the immunity we’ve gained over the past few years through vaccination and prior infections. Of course, we should be thinking about how that applies to each of us – how recently we had a vaccine or COVID-19, and whether we might see more severe infections as immunity wanes,” said Dr. Ray, who is a professor of medicine in the division of infectious diseases at Johns Hopkins University in Baltimore. 

Question 2: Is a return to masks or mask mandates coming this fall or winter?

Dr. Topol: “Mandating masks doesn’t work very well, but we may see wide use again if a descendant of [variant] BA.2.86 takes off.”

Dr. Gut: “It’s difficult to predict if there are any mask mandates returning at any point. Ever since the Omicron strains emerged, COVID has been relatively mild, compared to previous strains, so there probably won’t be any plan to start masking in public unless a more deadly strain appears.”

Dr. Atmar: “I do not think we will see a return to mask mandates this fall or winter for a variety of reasons. The primary one is that I don’t think the public will accept mask mandates. However, I think masking can continue to be an adjunctive measure to enhance protection from infection, along with booster vaccination.”

Dr. Ray: “Some people will choose to wear masks during a surge, particularly in situations like commuting where they don’t interfere with what they’re doing. They will wear masks particularly if they want to avoid infection due to concerns about others they care about, disruption of work or travel plans, or concerns about long-term consequences of repeated COVID-19.”

Question 3: Now that COVID testing and vaccinations are no longer free of charge, how might that affect their use?

Dr. Topol: “It was already low, and this will undoubtedly further compromise their uptake.”

Dr. Gut: “I do expect that testing will become less common now that tests are no longer free. I’m sure there will be a lower amount of detection in patients with milder or asymptomatic disease compared to what we had previously.”

Dr. Atmar: “If there are out-of-pocket costs for the SARS-CoV-2 vaccine, or if the administrative paperwork attached to getting a vaccine is increased, the uptake of SARS-CoV-2 vaccines will likely decrease. It will be important to communicate to the populations targeted for vaccination the potential benefits of such vaccination.”

Dr. Ray: “A challenge with COVID-19, all along, has been disparities in access to care, and this will be worse without public support for prevention and testing. This applies to everyone but is especially burdensome for those who are often marginalized in our health care system and society in general. I hope that we’ll find ways to ensure that people who need tests and vaccinations are able to access them, as good health is in everyone’s interest.”

Question 4: Will the new vaccines against COVID work for the currently circulating variants?

Dr. Topol: “The XBB.1.5 boosters will be out Sept. 14. They should help versus EG.5.1 and FL.1.5.1. The FL.1.5.1 variant is gaining now.”

Dr. Gut: “In the next several weeks, we expect the newer monovalent XBB-based vaccines to be offered that offer good protection against current circulating COVID variants along with the new Eris variant.”

Dr. Atmar: “The vaccines are expected to induce immune responses to the currently circulating variants, most of which are strains that evolved from the vaccine strain. The vaccine is expected to be most effective in preventing severe illness and will likely be less effective in preventing infection and mild illness.”

Dr. Ray: “Yes, the updated vaccine design has a spike antigen (XBB.1.5) nearly identical to the current dominant variant (EG.5). Even as variants change, the boosters stimulate B cells and T cells to help protect in a way that is safer than getting COVID-19 infection.”

Question 5: Is there anything we should watch out for regarding the BA.2.86 variant in particular?

Dr. Topol: “The scenario could change if there are new functional mutations added to it.”

Dr. Gut: “BA.2.86 is still fairly uncommon and does not have much data to directly make any informed guesses. However, in general, people that have been exposed to more recent mutations of the COVID virus have been shown to have more protection from newer upcoming mutations. It’s fair to guess that people that have not had recent infection from COVID, or have not had a recent booster, are at higher risk for being infected by any XBB- or BA.2-based strains.”

Dr. Atmar: BA.2.86 has been designated as a variant under monitoring. We will want to see whether it becomes more common and if there are any unexpected characteristics associated with infection by this variant.”

Dr. Ray: “It’s still rare, but it’s been seen in geographically dispersed places, so it’s got legs. The question is how effectively it will bypass some of the immunity we’ve gained. T cells are likely to remain protective, because they target so many parts of the virus that change more slowly, but antibodies from B cells to spike protein may have more trouble recognizing BA.2.86, whether those antibodies were made to a vaccine or a prior variant.”

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

COVID-19 hospitalizations have been on the rise for weeks as summer nears its end, but how concerned should you be? SARS-CoV-2, the virus behind COVID, continues to evolve and surprise us. So COVID transmission, hospitalization, and death rates can be difficult to predict. 

This news organization turned to the experts for their take on the current circulating virus, asking them to predict if we’ll be masking up again anytime soon, and what this fall and winter might look like, especially now that testing and vaccinations are no longer free of charge.
 

Question 1: Are you expecting an end-of-summer COVID wave to be substantial?

Eric Topol, MD: “This wave won’t likely be substantial and could be more of a ‘wavelet.’ I’m not thinking that physicians are too concerned,” said Dr. Topol, founder and director of Scripps Research Translational Institute in La Jolla, Calif. 

Thomas Gut, DO: “It’s always impossible to predict the severity of COVID waves. Although the virus has generally mutated in ways that favor easier transmission and milder illness, there have been a handful of surprising mutations that were more dangerous and deadly than the preceding strain,” said Dr. Gut, associate chair of medicine at Staten Island University Hospital/Northwell Health in New York.

Robert Atmar, MD: “I’ll start with the caveat that prognosticating for SARS-CoV-2 is a bit hazardous as we remain in unknown territory for some aspects of its epidemiology and evolution,” said Dr. Atmar, a professor of infectious diseases at Baylor College of Medicine in Houston. “It depends on your definition of substantial. We, at least in Houston, are already in the midst of a substantial surge in the burden of infection, at least as monitored through wastewater surveillance. The amount of virus in the wastewater already exceeds the peak level we saw last winter. That said, the increased infection burden has not translated into large increases in hospitalizations for COVID-19. Most persons hospitalized in our hospital are admitted with infection, not for the consequences of infection.”

Stuart Campbell Ray, MD: “It looks like there is a rise in infections, but the proportional rise in hospitalizations from severe cases is lower than in the past, suggesting that folks are protected by the immunity we’ve gained over the past few years through vaccination and prior infections. Of course, we should be thinking about how that applies to each of us – how recently we had a vaccine or COVID-19, and whether we might see more severe infections as immunity wanes,” said Dr. Ray, who is a professor of medicine in the division of infectious diseases at Johns Hopkins University in Baltimore. 

Question 2: Is a return to masks or mask mandates coming this fall or winter?

Dr. Topol: “Mandating masks doesn’t work very well, but we may see wide use again if a descendant of [variant] BA.2.86 takes off.”

Dr. Gut: “It’s difficult to predict if there are any mask mandates returning at any point. Ever since the Omicron strains emerged, COVID has been relatively mild, compared to previous strains, so there probably won’t be any plan to start masking in public unless a more deadly strain appears.”

Dr. Atmar: “I do not think we will see a return to mask mandates this fall or winter for a variety of reasons. The primary one is that I don’t think the public will accept mask mandates. However, I think masking can continue to be an adjunctive measure to enhance protection from infection, along with booster vaccination.”

Dr. Ray: “Some people will choose to wear masks during a surge, particularly in situations like commuting where they don’t interfere with what they’re doing. They will wear masks particularly if they want to avoid infection due to concerns about others they care about, disruption of work or travel plans, or concerns about long-term consequences of repeated COVID-19.”

Question 3: Now that COVID testing and vaccinations are no longer free of charge, how might that affect their use?

Dr. Topol: “It was already low, and this will undoubtedly further compromise their uptake.”

Dr. Gut: “I do expect that testing will become less common now that tests are no longer free. I’m sure there will be a lower amount of detection in patients with milder or asymptomatic disease compared to what we had previously.”

Dr. Atmar: “If there are out-of-pocket costs for the SARS-CoV-2 vaccine, or if the administrative paperwork attached to getting a vaccine is increased, the uptake of SARS-CoV-2 vaccines will likely decrease. It will be important to communicate to the populations targeted for vaccination the potential benefits of such vaccination.”

Dr. Ray: “A challenge with COVID-19, all along, has been disparities in access to care, and this will be worse without public support for prevention and testing. This applies to everyone but is especially burdensome for those who are often marginalized in our health care system and society in general. I hope that we’ll find ways to ensure that people who need tests and vaccinations are able to access them, as good health is in everyone’s interest.”

Question 4: Will the new vaccines against COVID work for the currently circulating variants?

Dr. Topol: “The XBB.1.5 boosters will be out Sept. 14. They should help versus EG.5.1 and FL.1.5.1. The FL.1.5.1 variant is gaining now.”

Dr. Gut: “In the next several weeks, we expect the newer monovalent XBB-based vaccines to be offered that offer good protection against current circulating COVID variants along with the new Eris variant.”

Dr. Atmar: “The vaccines are expected to induce immune responses to the currently circulating variants, most of which are strains that evolved from the vaccine strain. The vaccine is expected to be most effective in preventing severe illness and will likely be less effective in preventing infection and mild illness.”

Dr. Ray: “Yes, the updated vaccine design has a spike antigen (XBB.1.5) nearly identical to the current dominant variant (EG.5). Even as variants change, the boosters stimulate B cells and T cells to help protect in a way that is safer than getting COVID-19 infection.”

Question 5: Is there anything we should watch out for regarding the BA.2.86 variant in particular?

Dr. Topol: “The scenario could change if there are new functional mutations added to it.”

Dr. Gut: “BA.2.86 is still fairly uncommon and does not have much data to directly make any informed guesses. However, in general, people that have been exposed to more recent mutations of the COVID virus have been shown to have more protection from newer upcoming mutations. It’s fair to guess that people that have not had recent infection from COVID, or have not had a recent booster, are at higher risk for being infected by any XBB- or BA.2-based strains.”

Dr. Atmar: BA.2.86 has been designated as a variant under monitoring. We will want to see whether it becomes more common and if there are any unexpected characteristics associated with infection by this variant.”

Dr. Ray: “It’s still rare, but it’s been seen in geographically dispersed places, so it’s got legs. The question is how effectively it will bypass some of the immunity we’ve gained. T cells are likely to remain protective, because they target so many parts of the virus that change more slowly, but antibodies from B cells to spike protein may have more trouble recognizing BA.2.86, whether those antibodies were made to a vaccine or a prior variant.”

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

Variability in antimicrobial prescribing among hospital-based physicians is not associated with patient characteristics or clinical outcomes, data suggest. The lowest level of such prescribing within each hospital could be considered a target for antimicrobial stewardship, according to the researchers.

In a multicenter study of 124 physicians responsible for more than 124,000 hospitalized patients, the difference in mean prescribing between the highest and lowest quartiles of prescription volume was 15.8 days of treatment per 100 patient-days.

Baseline patient characteristics were similar across the quartiles, and there were no differences in patient outcomes, including in-hospital deaths, hospital length of stay, intensive care unit transfer, and hospital readmission.

Although the investigators expected variation in prescribing, “what surprised us most was the limited association with any differences in clinical outcomes, particularly when it came to the amount of antimicrobials used,” study author Mark T. McIntyre, PharmD, pharmacotherapy specialist at the Sinai Health System in Toronto, told this news organization.

“Importantly, this is not a study that defines quality of care,” he said. “We looked at natural variation in practice and association with outcomes. So, I don’t want clinicians to think, ‘Well, I’m high, therefore I’m bad,’ or, ‘I’m low, therefore I’m good.’

“This is an early explanatory analysis that asks whether this is an opportunity to optimize prescribing in ways we hadn’t thought of before,” he said. “Now that we don’t have an association with higher or lower prescribing and outcomes, we can look at what else is driving that antimicrobial prescribing and what we can do about it. Comfort level, risk tolerance, and social, cultural, and contextual factors all likely play a role.”

The study was published online in the Canadian Medical Association Journal.
 

Antimicrobial reductions possible

The investigators conducted a retrospective cohort study using the General Medicine Inpatient Initiative database to assess physician-level volume and spectrum of antimicrobial prescribing in adult general medical wards. Four academic hospitals in Toronto were evaluated for the period 2010 to 2019.

The investigators stratified physicians into quartiles by hospital site on the basis of volume of antimicrobial prescribing (specifically, days of therapy per 100 patient-days and antimicrobial-free days) and antibacterial spectrum (modified spectrum score, which assigns a value to each antibacterial agent on the basis of its breadth of coverage).

They also examined potential differences between physician quartiles in patient characteristics, such as age, sex, the Laboratory-Based Acute Physiology Score, discharge diagnosis, and the Charlson Comorbidity Index.

Multilevel modeling allowed the investigators to evaluate the association between clinical outcomes and antimicrobial volume and spectrum.

The primary measure was days of therapy per 100 patient-days.

As noted, the cohort included 124 physicians who were responsible for 124,158 hospital admissions. The median physician-level volume of antimicrobial prescribing was 56.1 days of therapy per 100 patient-days. Patient characteristics were balanced across the quartiles of physician prescribing.

The difference in mean prescribing between physician quartile 4 and quartile 1 was 15.8 days of therapy per 100 patient-days, meaning the median physician in quartile 4 prescribed antimicrobials at a volume that was 30% higher than that of the median physician in quartile 1.

No significant differences were noted for any clinical outcome with regard to quartile of days of therapy, antimicrobial-free days, or modified spectrum score after adjustment for patient-level characteristics.

In addition, no significant differences in the case mix between quartile 4 and quartile 1 were found when the cohort was restricted to patients admitted and discharged by the same most responsible person, nor were differences found in an analysis that was restricted to those without a discharge diagnosis code of palliative care.

In-hospital mortality was higher among patients cared for by prescribers with higher modified spectrum scores (odds ratio, 1.13). “We still can’t fully explain this finding,” Dr. McIntyre acknowledged. “We only saw that in our primary analysis. When we did several sensitivity analyses, that finding didn’t appear.”

The authors concluded, “Ultimately, without discernible benefit in outcomes of patients of physicians who prescribe more frequently, less antimicrobial exposure may be possible, leading to lower risk of antimicrobial resistance.”
 

Decision-making support

Commenting on the study, Lawrence I. Kaplan, MD, section chief of general internal medicine and associate dean for interprofessional education at the Lewis Katz School of Medicine at Temple University in Philadelphia, said, “Trying to get to the lowest quartile would be a goal, and given that physician characteristics are involved, I think there needs to be much better training in clinical management decision-making: how you come about making a decision based on a diagnosis for a particular patient, in or out of the hospital.” Dr. Kaplan was not involved in the research.

“Clinical decision-making tools that can be plugged into the electronic health record can help,” he suggested. “The tools basically ask if a patient meets certain criteria and then might give a prompt that says, for example, ‘These symptoms are not consistent with bacterial sinusitis. The patient should be treated with decongestants, nasal steroids, et cetera, because antibiotics aren’t appropriate.’

“It’s a bit like checkbox medicine, which a lot of physicians bridle at,” he said. “But if it’s really based on evidence, I think that’s an appropriate use of evidence-based medicine.”

Dr. Kaplan said that more research is needed into the best way to get a physician or any provider to step back and say, “Is this the right decision?” or, “I’m doing this but I’m really on shaky ground. What am I missing?’” He noted that the Society for Medical Decision Making publishes research and resources in this area.

“I love the fact that the paper was authored by an interdisciplinary group,” Dr. Kaplan added. “A pharmacist embedded in the team can, for example, help with treatment decision-making and point out potential drug interactions that prescribers might not be aware of.

“We need to stop practicing medicine siloed, which is what we do a lot of ways, both in the hospital and out of the hospital, because it’s the path of least resistance,” Dr. Kaplan added. “But when we can say, ‘Hey, I have a question about this,’ be it to a computer or a colleague, I would argue that we come up with better care.”

No funding was provided for the study. Dr. McIntyre and Dr. Kaplan have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Variability in antimicrobial prescribing among hospital-based physicians is not associated with patient characteristics or clinical outcomes, data suggest. The lowest level of such prescribing within each hospital could be considered a target for antimicrobial stewardship, according to the researchers.

In a multicenter study of 124 physicians responsible for more than 124,000 hospitalized patients, the difference in mean prescribing between the highest and lowest quartiles of prescription volume was 15.8 days of treatment per 100 patient-days.

Baseline patient characteristics were similar across the quartiles, and there were no differences in patient outcomes, including in-hospital deaths, hospital length of stay, intensive care unit transfer, and hospital readmission.

Although the investigators expected variation in prescribing, “what surprised us most was the limited association with any differences in clinical outcomes, particularly when it came to the amount of antimicrobials used,” study author Mark T. McIntyre, PharmD, pharmacotherapy specialist at the Sinai Health System in Toronto, told this news organization.

“Importantly, this is not a study that defines quality of care,” he said. “We looked at natural variation in practice and association with outcomes. So, I don’t want clinicians to think, ‘Well, I’m high, therefore I’m bad,’ or, ‘I’m low, therefore I’m good.’

“This is an early explanatory analysis that asks whether this is an opportunity to optimize prescribing in ways we hadn’t thought of before,” he said. “Now that we don’t have an association with higher or lower prescribing and outcomes, we can look at what else is driving that antimicrobial prescribing and what we can do about it. Comfort level, risk tolerance, and social, cultural, and contextual factors all likely play a role.”

The study was published online in the Canadian Medical Association Journal.
 

Antimicrobial reductions possible

The investigators conducted a retrospective cohort study using the General Medicine Inpatient Initiative database to assess physician-level volume and spectrum of antimicrobial prescribing in adult general medical wards. Four academic hospitals in Toronto were evaluated for the period 2010 to 2019.

The investigators stratified physicians into quartiles by hospital site on the basis of volume of antimicrobial prescribing (specifically, days of therapy per 100 patient-days and antimicrobial-free days) and antibacterial spectrum (modified spectrum score, which assigns a value to each antibacterial agent on the basis of its breadth of coverage).

They also examined potential differences between physician quartiles in patient characteristics, such as age, sex, the Laboratory-Based Acute Physiology Score, discharge diagnosis, and the Charlson Comorbidity Index.

Multilevel modeling allowed the investigators to evaluate the association between clinical outcomes and antimicrobial volume and spectrum.

The primary measure was days of therapy per 100 patient-days.

As noted, the cohort included 124 physicians who were responsible for 124,158 hospital admissions. The median physician-level volume of antimicrobial prescribing was 56.1 days of therapy per 100 patient-days. Patient characteristics were balanced across the quartiles of physician prescribing.

The difference in mean prescribing between physician quartile 4 and quartile 1 was 15.8 days of therapy per 100 patient-days, meaning the median physician in quartile 4 prescribed antimicrobials at a volume that was 30% higher than that of the median physician in quartile 1.

No significant differences were noted for any clinical outcome with regard to quartile of days of therapy, antimicrobial-free days, or modified spectrum score after adjustment for patient-level characteristics.

In addition, no significant differences in the case mix between quartile 4 and quartile 1 were found when the cohort was restricted to patients admitted and discharged by the same most responsible person, nor were differences found in an analysis that was restricted to those without a discharge diagnosis code of palliative care.

In-hospital mortality was higher among patients cared for by prescribers with higher modified spectrum scores (odds ratio, 1.13). “We still can’t fully explain this finding,” Dr. McIntyre acknowledged. “We only saw that in our primary analysis. When we did several sensitivity analyses, that finding didn’t appear.”

The authors concluded, “Ultimately, without discernible benefit in outcomes of patients of physicians who prescribe more frequently, less antimicrobial exposure may be possible, leading to lower risk of antimicrobial resistance.”
 

Decision-making support

Commenting on the study, Lawrence I. Kaplan, MD, section chief of general internal medicine and associate dean for interprofessional education at the Lewis Katz School of Medicine at Temple University in Philadelphia, said, “Trying to get to the lowest quartile would be a goal, and given that physician characteristics are involved, I think there needs to be much better training in clinical management decision-making: how you come about making a decision based on a diagnosis for a particular patient, in or out of the hospital.” Dr. Kaplan was not involved in the research.

“Clinical decision-making tools that can be plugged into the electronic health record can help,” he suggested. “The tools basically ask if a patient meets certain criteria and then might give a prompt that says, for example, ‘These symptoms are not consistent with bacterial sinusitis. The patient should be treated with decongestants, nasal steroids, et cetera, because antibiotics aren’t appropriate.’

“It’s a bit like checkbox medicine, which a lot of physicians bridle at,” he said. “But if it’s really based on evidence, I think that’s an appropriate use of evidence-based medicine.”

Dr. Kaplan said that more research is needed into the best way to get a physician or any provider to step back and say, “Is this the right decision?” or, “I’m doing this but I’m really on shaky ground. What am I missing?’” He noted that the Society for Medical Decision Making publishes research and resources in this area.

“I love the fact that the paper was authored by an interdisciplinary group,” Dr. Kaplan added. “A pharmacist embedded in the team can, for example, help with treatment decision-making and point out potential drug interactions that prescribers might not be aware of.

“We need to stop practicing medicine siloed, which is what we do a lot of ways, both in the hospital and out of the hospital, because it’s the path of least resistance,” Dr. Kaplan added. “But when we can say, ‘Hey, I have a question about this,’ be it to a computer or a colleague, I would argue that we come up with better care.”

No funding was provided for the study. Dr. McIntyre and Dr. Kaplan have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Variability in antimicrobial prescribing among hospital-based physicians is not associated with patient characteristics or clinical outcomes, data suggest. The lowest level of such prescribing within each hospital could be considered a target for antimicrobial stewardship, according to the researchers.

In a multicenter study of 124 physicians responsible for more than 124,000 hospitalized patients, the difference in mean prescribing between the highest and lowest quartiles of prescription volume was 15.8 days of treatment per 100 patient-days.

Baseline patient characteristics were similar across the quartiles, and there were no differences in patient outcomes, including in-hospital deaths, hospital length of stay, intensive care unit transfer, and hospital readmission.

Although the investigators expected variation in prescribing, “what surprised us most was the limited association with any differences in clinical outcomes, particularly when it came to the amount of antimicrobials used,” study author Mark T. McIntyre, PharmD, pharmacotherapy specialist at the Sinai Health System in Toronto, told this news organization.

“Importantly, this is not a study that defines quality of care,” he said. “We looked at natural variation in practice and association with outcomes. So, I don’t want clinicians to think, ‘Well, I’m high, therefore I’m bad,’ or, ‘I’m low, therefore I’m good.’

“This is an early explanatory analysis that asks whether this is an opportunity to optimize prescribing in ways we hadn’t thought of before,” he said. “Now that we don’t have an association with higher or lower prescribing and outcomes, we can look at what else is driving that antimicrobial prescribing and what we can do about it. Comfort level, risk tolerance, and social, cultural, and contextual factors all likely play a role.”

The study was published online in the Canadian Medical Association Journal.
 

Antimicrobial reductions possible

The investigators conducted a retrospective cohort study using the General Medicine Inpatient Initiative database to assess physician-level volume and spectrum of antimicrobial prescribing in adult general medical wards. Four academic hospitals in Toronto were evaluated for the period 2010 to 2019.

The investigators stratified physicians into quartiles by hospital site on the basis of volume of antimicrobial prescribing (specifically, days of therapy per 100 patient-days and antimicrobial-free days) and antibacterial spectrum (modified spectrum score, which assigns a value to each antibacterial agent on the basis of its breadth of coverage).

They also examined potential differences between physician quartiles in patient characteristics, such as age, sex, the Laboratory-Based Acute Physiology Score, discharge diagnosis, and the Charlson Comorbidity Index.

Multilevel modeling allowed the investigators to evaluate the association between clinical outcomes and antimicrobial volume and spectrum.

The primary measure was days of therapy per 100 patient-days.

As noted, the cohort included 124 physicians who were responsible for 124,158 hospital admissions. The median physician-level volume of antimicrobial prescribing was 56.1 days of therapy per 100 patient-days. Patient characteristics were balanced across the quartiles of physician prescribing.

The difference in mean prescribing between physician quartile 4 and quartile 1 was 15.8 days of therapy per 100 patient-days, meaning the median physician in quartile 4 prescribed antimicrobials at a volume that was 30% higher than that of the median physician in quartile 1.

No significant differences were noted for any clinical outcome with regard to quartile of days of therapy, antimicrobial-free days, or modified spectrum score after adjustment for patient-level characteristics.

In addition, no significant differences in the case mix between quartile 4 and quartile 1 were found when the cohort was restricted to patients admitted and discharged by the same most responsible person, nor were differences found in an analysis that was restricted to those without a discharge diagnosis code of palliative care.

In-hospital mortality was higher among patients cared for by prescribers with higher modified spectrum scores (odds ratio, 1.13). “We still can’t fully explain this finding,” Dr. McIntyre acknowledged. “We only saw that in our primary analysis. When we did several sensitivity analyses, that finding didn’t appear.”

The authors concluded, “Ultimately, without discernible benefit in outcomes of patients of physicians who prescribe more frequently, less antimicrobial exposure may be possible, leading to lower risk of antimicrobial resistance.”
 

Decision-making support

Commenting on the study, Lawrence I. Kaplan, MD, section chief of general internal medicine and associate dean for interprofessional education at the Lewis Katz School of Medicine at Temple University in Philadelphia, said, “Trying to get to the lowest quartile would be a goal, and given that physician characteristics are involved, I think there needs to be much better training in clinical management decision-making: how you come about making a decision based on a diagnosis for a particular patient, in or out of the hospital.” Dr. Kaplan was not involved in the research.

“Clinical decision-making tools that can be plugged into the electronic health record can help,” he suggested. “The tools basically ask if a patient meets certain criteria and then might give a prompt that says, for example, ‘These symptoms are not consistent with bacterial sinusitis. The patient should be treated with decongestants, nasal steroids, et cetera, because antibiotics aren’t appropriate.’

“It’s a bit like checkbox medicine, which a lot of physicians bridle at,” he said. “But if it’s really based on evidence, I think that’s an appropriate use of evidence-based medicine.”

Dr. Kaplan said that more research is needed into the best way to get a physician or any provider to step back and say, “Is this the right decision?” or, “I’m doing this but I’m really on shaky ground. What am I missing?’” He noted that the Society for Medical Decision Making publishes research and resources in this area.

“I love the fact that the paper was authored by an interdisciplinary group,” Dr. Kaplan added. “A pharmacist embedded in the team can, for example, help with treatment decision-making and point out potential drug interactions that prescribers might not be aware of.

“We need to stop practicing medicine siloed, which is what we do a lot of ways, both in the hospital and out of the hospital, because it’s the path of least resistance,” Dr. Kaplan added. “But when we can say, ‘Hey, I have a question about this,’ be it to a computer or a colleague, I would argue that we come up with better care.”

No funding was provided for the study. Dr. McIntyre and Dr. Kaplan have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

U.S. regulators this year will begin to demand reports from cosmetics manufacturers about the ingredients used in their products. They are also preparing to assess potential risks of so-called forever chemicals in these products.

The Food and Drug Administration last year gained new authority over cosmetics when Congress passed the Modernization of Cosmetics Regulation Act of 2022 (MoCRA) by adding this bill to a December budget package.

Yulia Lisitsa/iStock/Getty Images Plus

“On average, consumers in the U.S. use six to 12 cosmetics products daily. But, until recently the FDA didn’t have the authority to require manufacturers to submit cosmetic product listings, including a list of ingredients used in these products, or register the facilities where they were produced,” Namandjé Bumpus, PhD, FDA’s chief scientist, said in a press release.

In the statement, the FDA announced the release of a draft guidance document that is intended to help companies comply with the transparency requirements slated to kick in this December. The agency is accepting comments on this draft guidance through Sept. 7.

“Later this year, registration and listing of cosmetic product facilities and products will become a requirement, making information about cosmetic products, including the ingredients used in products and the facilities where they are produced, readily available to the agency,” Dr. Bumpus said.

The products, according to the FDA statement, include makeup, nail polishes, shaving creams, other grooming products, perfumes, face and body cleansers, hair products, moisturizers, and other skin care items.

MoCRA “represents a sea change in how FDA regulates the cosmetics industry,” attorneys Frederick R. Ball, Alyson Walker Lotman, and Kelly A. Bonner, wrote in an article for the Food and Drug Law Institute published in spring 2023.

The FDA has called the MoCRA law “the most significant expansion” of its authority to regulate cosmetics since the Federal Food, Drug, and Cosmetic Act was passed in 1938.

The agency is in the process of expanding its staff to carry out newly authorized duties, including the tracking of adverse events. The FDA budget request for fiscal 2024, which begins Oct. 1, seeks $5 million for work needed to implement MoCRA.

PFAS, or ‘forever chemicals’

Some of the requested FDA funding is intended to prepare the agency to assess the use of per-and polyfluoroalkyl substances (PFAS) in cosmetics.

MoCRA sets a 3-year deadline for the FDA to issue an assessment of the use and potential risks of PFAS in cosmetics products. PFAS are sometimes added as ingredients in some cosmetic products, including lotions, cleansers, nail polish, shaving cream, foundation, lipstick, eyeliner, eyeshadow, and mascara, according to the FDA. Sometimes the presence of PFAS in cosmetics is unintentional and is the result of impurities in raw materials or is due to the breakdown of ingredients, the FDA said.

The FDA’s website says that so far, the available research doesn’t allow for “definitive conclusions about the potential health risks of PFAS in cosmetics.”

The Centers for Disease Control and Prevention has stated that research has suggested potential links between high levels of certain PFAS, in general, with increased cholesterol levels, changes in liver enzyme levels, increased risk of hypertension or preeclampsia in pregnant women, and increased risk of kidney or testicular cancer.

PFAS compounds often are used to resist grease, oil, water, and heat in industrial settings. They are used in thousands of products, from nonstick cookware to firefighting foams and protective gear, because they can reduce friction, according to a National Academies of Sciences, Engineering, and Medicine report on PFAS that was issued last year.

PFAS are known as “forever chemicals” because they contain a carbon-fluorine bond, which does not break naturally. Even when PFAS are transformed in the body, they can assume other forms of PFAS that preserve the troublesome carbon-fluorine bond. With PFAS, the human body is confronted with a substance it doesn’t have the tools to process.

This is in contrast to proteins and carbohydrates, which are in a sense prepackaged for relatively easy disassembly in the human body. Many of these compounds have weak links that enzymes and stomach acid can take apart, such as sulfur-to-sulfur (disulfide) bonds. That’s why protein-based biotech drugs are injected instead of administered as pills. The ultimate goal of this digestion is for the body to gain energy from these compounds.

But with PFAS, the body faces the challenge of carbon-fluorine bonds that are very hard to break down, and there is no payoff for these efforts, Graham F. Peaslee, PhD, professor of physics at the University of Notre Dame (Indiana), told this news organization.

“Nothing will naturally eat it because when you break the bond, it’s like eating celery,” he said. “You use more calories to eat the celery than you gain back from it.”
 

Interest from a U.S. senator

Dr. Peaslee was one of the authors of a 2021 article about PFAS in cosmetics that appeared in the journal Environmental Science and Technology Letters.

In the article, Dr. Peaslee and colleagues reported on their screening of 231 cosmetic products purchased in the United States and Canada using particle-induced gamma-ray emission spectroscopy. They found cases of undisclosed PFAS in cosmetic products. Foundations, mascaras, and lip products were noted as being especially problematic.

Sen. Susan Collins (R-ME) cited Dr. Peaslee’s article in a 2021 floor speech as she argued for having the FDA ban the intentional addition of PFAS to cosmetics.

“The findings of this study are particularly alarming, as many of these products are subject to direct human exposure,” Sen. Collins said. “For example, lipstick is often inadvertently ingested, and mascara is sometimes absorbed through tear ducts.”

In addition, workers at cosmetics plants may be exposed to PFAS and discarded cosmetics that have these compounds, which could potentially contaminate drinking water, Sen. Collins said. In 2021, she introduced legislation seeking a ban on PFAS that are intentionally added to cosmetics. That legislation did not advance through the Senate.

But the Senate Appropriations Committee, on which Sen. Collins is the ranking Republican, wants the FDA to keep a ban on PFAS in mind.

The Senate Agriculture Appropriations subcommittee, which oversees the FDA’s budget, raised the issue of PFAS and cosmetics in a June report. The FDA should develop a plan outlining research needed to inform “regulatory decision making, including potential development of a proposed rule to ban intentionally added PFAS substances in cosmetics,” the subcommittee said.
 

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

U.S. regulators this year will begin to demand reports from cosmetics manufacturers about the ingredients used in their products. They are also preparing to assess potential risks of so-called forever chemicals in these products.

The Food and Drug Administration last year gained new authority over cosmetics when Congress passed the Modernization of Cosmetics Regulation Act of 2022 (MoCRA) by adding this bill to a December budget package.

Yulia Lisitsa/iStock/Getty Images Plus

“On average, consumers in the U.S. use six to 12 cosmetics products daily. But, until recently the FDA didn’t have the authority to require manufacturers to submit cosmetic product listings, including a list of ingredients used in these products, or register the facilities where they were produced,” Namandjé Bumpus, PhD, FDA’s chief scientist, said in a press release.

In the statement, the FDA announced the release of a draft guidance document that is intended to help companies comply with the transparency requirements slated to kick in this December. The agency is accepting comments on this draft guidance through Sept. 7.

“Later this year, registration and listing of cosmetic product facilities and products will become a requirement, making information about cosmetic products, including the ingredients used in products and the facilities where they are produced, readily available to the agency,” Dr. Bumpus said.

The products, according to the FDA statement, include makeup, nail polishes, shaving creams, other grooming products, perfumes, face and body cleansers, hair products, moisturizers, and other skin care items.

MoCRA “represents a sea change in how FDA regulates the cosmetics industry,” attorneys Frederick R. Ball, Alyson Walker Lotman, and Kelly A. Bonner, wrote in an article for the Food and Drug Law Institute published in spring 2023.

The FDA has called the MoCRA law “the most significant expansion” of its authority to regulate cosmetics since the Federal Food, Drug, and Cosmetic Act was passed in 1938.

The agency is in the process of expanding its staff to carry out newly authorized duties, including the tracking of adverse events. The FDA budget request for fiscal 2024, which begins Oct. 1, seeks $5 million for work needed to implement MoCRA.

PFAS, or ‘forever chemicals’

Some of the requested FDA funding is intended to prepare the agency to assess the use of per-and polyfluoroalkyl substances (PFAS) in cosmetics.

MoCRA sets a 3-year deadline for the FDA to issue an assessment of the use and potential risks of PFAS in cosmetics products. PFAS are sometimes added as ingredients in some cosmetic products, including lotions, cleansers, nail polish, shaving cream, foundation, lipstick, eyeliner, eyeshadow, and mascara, according to the FDA. Sometimes the presence of PFAS in cosmetics is unintentional and is the result of impurities in raw materials or is due to the breakdown of ingredients, the FDA said.

The FDA’s website says that so far, the available research doesn’t allow for “definitive conclusions about the potential health risks of PFAS in cosmetics.”

The Centers for Disease Control and Prevention has stated that research has suggested potential links between high levels of certain PFAS, in general, with increased cholesterol levels, changes in liver enzyme levels, increased risk of hypertension or preeclampsia in pregnant women, and increased risk of kidney or testicular cancer.

PFAS compounds often are used to resist grease, oil, water, and heat in industrial settings. They are used in thousands of products, from nonstick cookware to firefighting foams and protective gear, because they can reduce friction, according to a National Academies of Sciences, Engineering, and Medicine report on PFAS that was issued last year.

PFAS are known as “forever chemicals” because they contain a carbon-fluorine bond, which does not break naturally. Even when PFAS are transformed in the body, they can assume other forms of PFAS that preserve the troublesome carbon-fluorine bond. With PFAS, the human body is confronted with a substance it doesn’t have the tools to process.

This is in contrast to proteins and carbohydrates, which are in a sense prepackaged for relatively easy disassembly in the human body. Many of these compounds have weak links that enzymes and stomach acid can take apart, such as sulfur-to-sulfur (disulfide) bonds. That’s why protein-based biotech drugs are injected instead of administered as pills. The ultimate goal of this digestion is for the body to gain energy from these compounds.

But with PFAS, the body faces the challenge of carbon-fluorine bonds that are very hard to break down, and there is no payoff for these efforts, Graham F. Peaslee, PhD, professor of physics at the University of Notre Dame (Indiana), told this news organization.

“Nothing will naturally eat it because when you break the bond, it’s like eating celery,” he said. “You use more calories to eat the celery than you gain back from it.”
 

Interest from a U.S. senator

Dr. Peaslee was one of the authors of a 2021 article about PFAS in cosmetics that appeared in the journal Environmental Science and Technology Letters.

In the article, Dr. Peaslee and colleagues reported on their screening of 231 cosmetic products purchased in the United States and Canada using particle-induced gamma-ray emission spectroscopy. They found cases of undisclosed PFAS in cosmetic products. Foundations, mascaras, and lip products were noted as being especially problematic.

Sen. Susan Collins (R-ME) cited Dr. Peaslee’s article in a 2021 floor speech as she argued for having the FDA ban the intentional addition of PFAS to cosmetics.

“The findings of this study are particularly alarming, as many of these products are subject to direct human exposure,” Sen. Collins said. “For example, lipstick is often inadvertently ingested, and mascara is sometimes absorbed through tear ducts.”

In addition, workers at cosmetics plants may be exposed to PFAS and discarded cosmetics that have these compounds, which could potentially contaminate drinking water, Sen. Collins said. In 2021, she introduced legislation seeking a ban on PFAS that are intentionally added to cosmetics. That legislation did not advance through the Senate.

But the Senate Appropriations Committee, on which Sen. Collins is the ranking Republican, wants the FDA to keep a ban on PFAS in mind.

The Senate Agriculture Appropriations subcommittee, which oversees the FDA’s budget, raised the issue of PFAS and cosmetics in a June report. The FDA should develop a plan outlining research needed to inform “regulatory decision making, including potential development of a proposed rule to ban intentionally added PFAS substances in cosmetics,” the subcommittee said.
 

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

U.S. regulators this year will begin to demand reports from cosmetics manufacturers about the ingredients used in their products. They are also preparing to assess potential risks of so-called forever chemicals in these products.

The Food and Drug Administration last year gained new authority over cosmetics when Congress passed the Modernization of Cosmetics Regulation Act of 2022 (MoCRA) by adding this bill to a December budget package.

Yulia Lisitsa/iStock/Getty Images Plus

“On average, consumers in the U.S. use six to 12 cosmetics products daily. But, until recently the FDA didn’t have the authority to require manufacturers to submit cosmetic product listings, including a list of ingredients used in these products, or register the facilities where they were produced,” Namandjé Bumpus, PhD, FDA’s chief scientist, said in a press release.

In the statement, the FDA announced the release of a draft guidance document that is intended to help companies comply with the transparency requirements slated to kick in this December. The agency is accepting comments on this draft guidance through Sept. 7.

“Later this year, registration and listing of cosmetic product facilities and products will become a requirement, making information about cosmetic products, including the ingredients used in products and the facilities where they are produced, readily available to the agency,” Dr. Bumpus said.

The products, according to the FDA statement, include makeup, nail polishes, shaving creams, other grooming products, perfumes, face and body cleansers, hair products, moisturizers, and other skin care items.

MoCRA “represents a sea change in how FDA regulates the cosmetics industry,” attorneys Frederick R. Ball, Alyson Walker Lotman, and Kelly A. Bonner, wrote in an article for the Food and Drug Law Institute published in spring 2023.

The FDA has called the MoCRA law “the most significant expansion” of its authority to regulate cosmetics since the Federal Food, Drug, and Cosmetic Act was passed in 1938.

The agency is in the process of expanding its staff to carry out newly authorized duties, including the tracking of adverse events. The FDA budget request for fiscal 2024, which begins Oct. 1, seeks $5 million for work needed to implement MoCRA.

PFAS, or ‘forever chemicals’

Some of the requested FDA funding is intended to prepare the agency to assess the use of per-and polyfluoroalkyl substances (PFAS) in cosmetics.

MoCRA sets a 3-year deadline for the FDA to issue an assessment of the use and potential risks of PFAS in cosmetics products. PFAS are sometimes added as ingredients in some cosmetic products, including lotions, cleansers, nail polish, shaving cream, foundation, lipstick, eyeliner, eyeshadow, and mascara, according to the FDA. Sometimes the presence of PFAS in cosmetics is unintentional and is the result of impurities in raw materials or is due to the breakdown of ingredients, the FDA said.

The FDA’s website says that so far, the available research doesn’t allow for “definitive conclusions about the potential health risks of PFAS in cosmetics.”

The Centers for Disease Control and Prevention has stated that research has suggested potential links between high levels of certain PFAS, in general, with increased cholesterol levels, changes in liver enzyme levels, increased risk of hypertension or preeclampsia in pregnant women, and increased risk of kidney or testicular cancer.

PFAS compounds often are used to resist grease, oil, water, and heat in industrial settings. They are used in thousands of products, from nonstick cookware to firefighting foams and protective gear, because they can reduce friction, according to a National Academies of Sciences, Engineering, and Medicine report on PFAS that was issued last year.

PFAS are known as “forever chemicals” because they contain a carbon-fluorine bond, which does not break naturally. Even when PFAS are transformed in the body, they can assume other forms of PFAS that preserve the troublesome carbon-fluorine bond. With PFAS, the human body is confronted with a substance it doesn’t have the tools to process.

This is in contrast to proteins and carbohydrates, which are in a sense prepackaged for relatively easy disassembly in the human body. Many of these compounds have weak links that enzymes and stomach acid can take apart, such as sulfur-to-sulfur (disulfide) bonds. That’s why protein-based biotech drugs are injected instead of administered as pills. The ultimate goal of this digestion is for the body to gain energy from these compounds.

But with PFAS, the body faces the challenge of carbon-fluorine bonds that are very hard to break down, and there is no payoff for these efforts, Graham F. Peaslee, PhD, professor of physics at the University of Notre Dame (Indiana), told this news organization.

“Nothing will naturally eat it because when you break the bond, it’s like eating celery,” he said. “You use more calories to eat the celery than you gain back from it.”
 

Interest from a U.S. senator

Dr. Peaslee was one of the authors of a 2021 article about PFAS in cosmetics that appeared in the journal Environmental Science and Technology Letters.

In the article, Dr. Peaslee and colleagues reported on their screening of 231 cosmetic products purchased in the United States and Canada using particle-induced gamma-ray emission spectroscopy. They found cases of undisclosed PFAS in cosmetic products. Foundations, mascaras, and lip products were noted as being especially problematic.

Sen. Susan Collins (R-ME) cited Dr. Peaslee’s article in a 2021 floor speech as she argued for having the FDA ban the intentional addition of PFAS to cosmetics.

“The findings of this study are particularly alarming, as many of these products are subject to direct human exposure,” Sen. Collins said. “For example, lipstick is often inadvertently ingested, and mascara is sometimes absorbed through tear ducts.”

In addition, workers at cosmetics plants may be exposed to PFAS and discarded cosmetics that have these compounds, which could potentially contaminate drinking water, Sen. Collins said. In 2021, she introduced legislation seeking a ban on PFAS that are intentionally added to cosmetics. That legislation did not advance through the Senate.

But the Senate Appropriations Committee, on which Sen. Collins is the ranking Republican, wants the FDA to keep a ban on PFAS in mind.

The Senate Agriculture Appropriations subcommittee, which oversees the FDA’s budget, raised the issue of PFAS and cosmetics in a June report. The FDA should develop a plan outlining research needed to inform “regulatory decision making, including potential development of a proposed rule to ban intentionally added PFAS substances in cosmetics,” the subcommittee said.
 

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

TOPLINE:

The Kettles Esophageal and Cardia Adenocarcinoma prediction (K-ECAN) tool predicts esophageal adenocarcinoma (EAC) and gastric cardia adenocarcinoma (GCA) using data from the electronic health record (EHR) and is more accurate than other tools, a large study suggests.

METHODOLOGY:

• Researchers performed a case-control study using data from the Veterans Affairs Central Cancer Registry.
• They identified 8,430 patients with EAC and 2,965 patients GCA; these patients were compared with more than 10 million control patients.
• K-ECAN uses basic information in the EHR to determine an individual’s future risk of developing EAC or GCA.

TAKEAWAY:

• With an area under the receiver operating characteristic of 0.77, K-ECAN demonstrated better discrimination than previously validated models and published guidelines.
• Using only data from 3 to 5 years prior to diagnosis only slightly diminished its accuracy (AUROC, 0.75).
• K-ECAN remained the most accurate tool when undersampling men to simulate a non-VHA population (AUROC, 0.85).
• Although gastroesophageal reflux disease (GERD) was strongly associated with EAC, it only contributed a small proportion of gain in information for prediction.

IN PRACTICE:

Because K-ECAN does not rely heavily on GERD symptoms to assess risk, it has the “potential to guide providers to increase appropriate uptake of screening. De-emphasizing GERD in decisions to offer screening could paradoxically increase appropriate uptake of screening for EAC and GCA,” the authors wrote.

SOURCE:

The study, with first author Joel H. Rubenstein, MD, with the LTC Charles S. Kettles VA Medical Center, Ann Arbor, Mich., was published online in Gastroenterology.

LIMITATIONS:

K-ECAN was developed and validated among U.S. veterans and needs to be validated in other populations.

DISCLOSURES:

Funding for the study was provided by the Department of Defense. Dr. Rubenstein has received research support from Lucid Diagnostics.

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

TOPLINE:

The Kettles Esophageal and Cardia Adenocarcinoma prediction (K-ECAN) tool predicts esophageal adenocarcinoma (EAC) and gastric cardia adenocarcinoma (GCA) using data from the electronic health record (EHR) and is more accurate than other tools, a large study suggests.

METHODOLOGY:

• Researchers performed a case-control study using data from the Veterans Affairs Central Cancer Registry.
• They identified 8,430 patients with EAC and 2,965 patients GCA; these patients were compared with more than 10 million control patients.
• K-ECAN uses basic information in the EHR to determine an individual’s future risk of developing EAC or GCA.

TAKEAWAY:

• With an area under the receiver operating characteristic of 0.77, K-ECAN demonstrated better discrimination than previously validated models and published guidelines.
• Using only data from 3 to 5 years prior to diagnosis only slightly diminished its accuracy (AUROC, 0.75).
• K-ECAN remained the most accurate tool when undersampling men to simulate a non-VHA population (AUROC, 0.85).
• Although gastroesophageal reflux disease (GERD) was strongly associated with EAC, it only contributed a small proportion of gain in information for prediction.

IN PRACTICE:

Because K-ECAN does not rely heavily on GERD symptoms to assess risk, it has the “potential to guide providers to increase appropriate uptake of screening. De-emphasizing GERD in decisions to offer screening could paradoxically increase appropriate uptake of screening for EAC and GCA,” the authors wrote.

SOURCE:

The study, with first author Joel H. Rubenstein, MD, with the LTC Charles S. Kettles VA Medical Center, Ann Arbor, Mich., was published online in Gastroenterology.

LIMITATIONS:

K-ECAN was developed and validated among U.S. veterans and needs to be validated in other populations.

DISCLOSURES:

Funding for the study was provided by the Department of Defense. Dr. Rubenstein has received research support from Lucid Diagnostics.

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

TOPLINE:

The Kettles Esophageal and Cardia Adenocarcinoma prediction (K-ECAN) tool predicts esophageal adenocarcinoma (EAC) and gastric cardia adenocarcinoma (GCA) using data from the electronic health record (EHR) and is more accurate than other tools, a large study suggests.

METHODOLOGY:

• Researchers performed a case-control study using data from the Veterans Affairs Central Cancer Registry.
• They identified 8,430 patients with EAC and 2,965 patients GCA; these patients were compared with more than 10 million control patients.
• K-ECAN uses basic information in the EHR to determine an individual’s future risk of developing EAC or GCA.

TAKEAWAY:

• With an area under the receiver operating characteristic of 0.77, K-ECAN demonstrated better discrimination than previously validated models and published guidelines.
• Using only data from 3 to 5 years prior to diagnosis only slightly diminished its accuracy (AUROC, 0.75).
• K-ECAN remained the most accurate tool when undersampling men to simulate a non-VHA population (AUROC, 0.85).
• Although gastroesophageal reflux disease (GERD) was strongly associated with EAC, it only contributed a small proportion of gain in information for prediction.

IN PRACTICE:

Because K-ECAN does not rely heavily on GERD symptoms to assess risk, it has the “potential to guide providers to increase appropriate uptake of screening. De-emphasizing GERD in decisions to offer screening could paradoxically increase appropriate uptake of screening for EAC and GCA,” the authors wrote.

SOURCE:

The study, with first author Joel H. Rubenstein, MD, with the LTC Charles S. Kettles VA Medical Center, Ann Arbor, Mich., was published online in Gastroenterology.

LIMITATIONS:

K-ECAN was developed and validated among U.S. veterans and needs to be validated in other populations.

DISCLOSURES:

Funding for the study was provided by the Department of Defense. Dr. Rubenstein has received research support from Lucid Diagnostics.

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

COPENHAGEN – Giving patients with Parkinson’s disease and constipation a probiotic for 3 months improved not only their gut microbiome but also nonmotor symptoms such as sleep, fatigue, and constipation, results of a new randomized trial show.

Participants taking the probiotic also saw a reduced delay in “time to on” of treatment with levodopa, thus reducing the delay until effectiveness of the treatment, said study presenter Valentina Leta, MD, PhD, department of neurosciences, King’s College London Institute of Psychiatry, Psychology and Neuroscience.

Dr. Leta presented the findings at the International Congress of Parkinson’s Disease and Movement Disorders.

“Virtually every person with Parkinson’s might have some degree of gastrointestinal dysfunction, and virtually the entire tract might be affected, from the mouth to the rectum,” Dr. Leta told attendees of the congress.

A number of different mechanisms have been associated with this gastrointestinal dysfunction, she noted, including proinflammatory changes in the gut microbiota, so a modulatory intervention “could be a therapeutic strategy for Parkinson’s disease.”

However, “despite numerous preclinical studies showing potential beneficial effects on a variety of pathological mechanisms involved in Parkinson’s disease, the clinical evidence is limited ... to the treatment of constipation,” she explained.

The team therefore conducted a multicenter, randomized, double-blind, placebo-controlled trial, in which patients with both Parkinson’s disease and constipation, based on the Rome IV criteria, were randomly assigned to receive a probiotic or placebo for 3 months.

The probiotic used was a liquid formulation (Symprove) and contained four strains: Lacticaseibacillus rhamnosus, Enterococcus faecium, Lactobacillus acidophilus, and Lactiplantibacillus plantarum.

A total of 74 patients were randomly assigned to the two study arms. The two groups were well matched for sociodemographics, Parkinson’s disease, and constipation-related characteristics, Dr. Leta reported, and only 3 patients in each arm discontinued the study. The probiotic intervention had a “good tolerability and safety profile, with a similar number of adverse events between the two groups, and no serious adverse events.”
 

Increase in healthy bacteria

The study met its primary outcome of changes in gut microbiome at the end of the 12-week intervention, as measured on shallow shotgun sequencing.

The probiotic was associated with a “statistically significant increase of the abundance of bacteria which are known to have beneficial health related properties, such as Odoribacteraceae,” Dr. Leta said.

This bacterium is “known to be reduced in people with Parkinson’s disease,” she explained, “and is involved in the production of short-chain fatty acids, which are known to have beneficial health-related properties.”

The secondary endpoint of the study included changes in motor and nonmotor symptoms, and the probiotic was associated with a significant improvement in the “time to on” with levodopa treatment, shortening this period from an average of 31.43 minutes at baseline to 23.95 minutes at the postintervention assessment (P < .027).

There was also a significant improvement in the Non-Motor Symptoms Scale (NMSS) score between baseline and the postintervention assessment in patients given the probiotic, from 70.71 to 61.34 (P = .005).

This, Dr. Leta observed, was “driven by improvements in the sleep, fatigue, and gastrointestinal domains.”

No such significant improvements were observed in the placebo arm.
 

Probiotics ‘hot topic’ among patients

Claudia Trenkwalder, MD, full professor of neurology at University Medical Center Goettingen (Germany), said in an interview that the use of probiotics is a “hot topic in Parkinson’s disease research, especially among patients.”

Dr. Trenkwalder, who was not involved in the study, noted that Lactobacillus strains “are established in Parkinson’s disease constipation treatment, with randomized controlled trials showing a significant improvement in constipation.

“Therefore, this is a useful treatment. The question here is: Do we have additional effects that can be measured in the microbiome and in clinical symptomatology?”

The trial showed that the probiotic studied “did alter the microbiome and did improve the constipation,” said Dr. Trenkwalder; however, the current data cannot prove whether the probiotic influenced the symptoms of Parkinson’s disease because the improvement in NMSS scores “is driven by the improvement in constipation.”

This, she argued, could have resulted in better absorption of levodopa.

A dietitian in the audience agreed. She asked whether the probiotic was doing anything “besides improving constipation,” adding that the resulting increased ability to absorb levodopa is also “going to help your sleep.”
 

Beyond constipation?

Dr. Leta replied that “we can assume that there is a link between the reduction in the ‘time to on’ and the improvement in constipation. We are doing some analyses in terms of levodopa pharmacokinetics to really understand the mechanisms behind this result.”

Although the improvement in constipation is “one of the possible hypotheses for the improvement in ‘time to on,’” she continued, “there is a more speculative one” in which the probiotics are modulating inflammatory parameters that could contribute to the improvement in sleep.

Veronica Bruno, MD, MPH, assistant professor in the department of clinical neurosciences at the University of Calgary (Alta.), commented in a press release that there has been “increasing interest” in examining the relationship between gut dysbiosis and the “gut-brain axis” in Parkinson’s disease.

The current study “stands out as a significant contribution to this area of study,” she said.

“While the implications of the observed changes in gut microbiota remain a captivating realm for further investigation, a particularly noteworthy finding revolves around the reduction in the ‘time to on’ observed within the active treatment group.”

Dr. Bruno said that shortening of the time to on “holds promise for substantial enhancements in patients’ lives” by reducing “difficult ‘off’ intervals and enhancing overall well-being.”

The study was funded by the UK National Institute for Health Research Mental Health Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust, and King’s College London. No relevant financial relationships were declared.

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

COPENHAGEN – Giving patients with Parkinson’s disease and constipation a probiotic for 3 months improved not only their gut microbiome but also nonmotor symptoms such as sleep, fatigue, and constipation, results of a new randomized trial show.

Participants taking the probiotic also saw a reduced delay in “time to on” of treatment with levodopa, thus reducing the delay until effectiveness of the treatment, said study presenter Valentina Leta, MD, PhD, department of neurosciences, King’s College London Institute of Psychiatry, Psychology and Neuroscience.

Dr. Leta presented the findings at the International Congress of Parkinson’s Disease and Movement Disorders.

“Virtually every person with Parkinson’s might have some degree of gastrointestinal dysfunction, and virtually the entire tract might be affected, from the mouth to the rectum,” Dr. Leta told attendees of the congress.

A number of different mechanisms have been associated with this gastrointestinal dysfunction, she noted, including proinflammatory changes in the gut microbiota, so a modulatory intervention “could be a therapeutic strategy for Parkinson’s disease.”

However, “despite numerous preclinical studies showing potential beneficial effects on a variety of pathological mechanisms involved in Parkinson’s disease, the clinical evidence is limited ... to the treatment of constipation,” she explained.

The team therefore conducted a multicenter, randomized, double-blind, placebo-controlled trial, in which patients with both Parkinson’s disease and constipation, based on the Rome IV criteria, were randomly assigned to receive a probiotic or placebo for 3 months.

The probiotic used was a liquid formulation (Symprove) and contained four strains: Lacticaseibacillus rhamnosus, Enterococcus faecium, Lactobacillus acidophilus, and Lactiplantibacillus plantarum.

A total of 74 patients were randomly assigned to the two study arms. The two groups were well matched for sociodemographics, Parkinson’s disease, and constipation-related characteristics, Dr. Leta reported, and only 3 patients in each arm discontinued the study. The probiotic intervention had a “good tolerability and safety profile, with a similar number of adverse events between the two groups, and no serious adverse events.”
 

Increase in healthy bacteria

The study met its primary outcome of changes in gut microbiome at the end of the 12-week intervention, as measured on shallow shotgun sequencing.

The probiotic was associated with a “statistically significant increase of the abundance of bacteria which are known to have beneficial health related properties, such as Odoribacteraceae,” Dr. Leta said.

This bacterium is “known to be reduced in people with Parkinson’s disease,” she explained, “and is involved in the production of short-chain fatty acids, which are known to have beneficial health-related properties.”

The secondary endpoint of the study included changes in motor and nonmotor symptoms, and the probiotic was associated with a significant improvement in the “time to on” with levodopa treatment, shortening this period from an average of 31.43 minutes at baseline to 23.95 minutes at the postintervention assessment (P < .027).

There was also a significant improvement in the Non-Motor Symptoms Scale (NMSS) score between baseline and the postintervention assessment in patients given the probiotic, from 70.71 to 61.34 (P = .005).

This, Dr. Leta observed, was “driven by improvements in the sleep, fatigue, and gastrointestinal domains.”

No such significant improvements were observed in the placebo arm.
 

Probiotics ‘hot topic’ among patients

Claudia Trenkwalder, MD, full professor of neurology at University Medical Center Goettingen (Germany), said in an interview that the use of probiotics is a “hot topic in Parkinson’s disease research, especially among patients.”

Dr. Trenkwalder, who was not involved in the study, noted that Lactobacillus strains “are established in Parkinson’s disease constipation treatment, with randomized controlled trials showing a significant improvement in constipation.

“Therefore, this is a useful treatment. The question here is: Do we have additional effects that can be measured in the microbiome and in clinical symptomatology?”

The trial showed that the probiotic studied “did alter the microbiome and did improve the constipation,” said Dr. Trenkwalder; however, the current data cannot prove whether the probiotic influenced the symptoms of Parkinson’s disease because the improvement in NMSS scores “is driven by the improvement in constipation.”

This, she argued, could have resulted in better absorption of levodopa.

A dietitian in the audience agreed. She asked whether the probiotic was doing anything “besides improving constipation,” adding that the resulting increased ability to absorb levodopa is also “going to help your sleep.”
 

Beyond constipation?

Dr. Leta replied that “we can assume that there is a link between the reduction in the ‘time to on’ and the improvement in constipation. We are doing some analyses in terms of levodopa pharmacokinetics to really understand the mechanisms behind this result.”

Although the improvement in constipation is “one of the possible hypotheses for the improvement in ‘time to on,’” she continued, “there is a more speculative one” in which the probiotics are modulating inflammatory parameters that could contribute to the improvement in sleep.

Veronica Bruno, MD, MPH, assistant professor in the department of clinical neurosciences at the University of Calgary (Alta.), commented in a press release that there has been “increasing interest” in examining the relationship between gut dysbiosis and the “gut-brain axis” in Parkinson’s disease.

The current study “stands out as a significant contribution to this area of study,” she said.

“While the implications of the observed changes in gut microbiota remain a captivating realm for further investigation, a particularly noteworthy finding revolves around the reduction in the ‘time to on’ observed within the active treatment group.”

Dr. Bruno said that shortening of the time to on “holds promise for substantial enhancements in patients’ lives” by reducing “difficult ‘off’ intervals and enhancing overall well-being.”

The study was funded by the UK National Institute for Health Research Mental Health Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust, and King’s College London. No relevant financial relationships were declared.

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

COPENHAGEN – Giving patients with Parkinson’s disease and constipation a probiotic for 3 months improved not only their gut microbiome but also nonmotor symptoms such as sleep, fatigue, and constipation, results of a new randomized trial show.

Participants taking the probiotic also saw a reduced delay in “time to on” of treatment with levodopa, thus reducing the delay until effectiveness of the treatment, said study presenter Valentina Leta, MD, PhD, department of neurosciences, King’s College London Institute of Psychiatry, Psychology and Neuroscience.

Dr. Leta presented the findings at the International Congress of Parkinson’s Disease and Movement Disorders.

“Virtually every person with Parkinson’s might have some degree of gastrointestinal dysfunction, and virtually the entire tract might be affected, from the mouth to the rectum,” Dr. Leta told attendees of the congress.

A number of different mechanisms have been associated with this gastrointestinal dysfunction, she noted, including proinflammatory changes in the gut microbiota, so a modulatory intervention “could be a therapeutic strategy for Parkinson’s disease.”

However, “despite numerous preclinical studies showing potential beneficial effects on a variety of pathological mechanisms involved in Parkinson’s disease, the clinical evidence is limited ... to the treatment of constipation,” she explained.

The team therefore conducted a multicenter, randomized, double-blind, placebo-controlled trial, in which patients with both Parkinson’s disease and constipation, based on the Rome IV criteria, were randomly assigned to receive a probiotic or placebo for 3 months.

The probiotic used was a liquid formulation (Symprove) and contained four strains: Lacticaseibacillus rhamnosus, Enterococcus faecium, Lactobacillus acidophilus, and Lactiplantibacillus plantarum.

A total of 74 patients were randomly assigned to the two study arms. The two groups were well matched for sociodemographics, Parkinson’s disease, and constipation-related characteristics, Dr. Leta reported, and only 3 patients in each arm discontinued the study. The probiotic intervention had a “good tolerability and safety profile, with a similar number of adverse events between the two groups, and no serious adverse events.”
 

Increase in healthy bacteria

The study met its primary outcome of changes in gut microbiome at the end of the 12-week intervention, as measured on shallow shotgun sequencing.

The probiotic was associated with a “statistically significant increase of the abundance of bacteria which are known to have beneficial health related properties, such as Odoribacteraceae,” Dr. Leta said.

This bacterium is “known to be reduced in people with Parkinson’s disease,” she explained, “and is involved in the production of short-chain fatty acids, which are known to have beneficial health-related properties.”

The secondary endpoint of the study included changes in motor and nonmotor symptoms, and the probiotic was associated with a significant improvement in the “time to on” with levodopa treatment, shortening this period from an average of 31.43 minutes at baseline to 23.95 minutes at the postintervention assessment (P < .027).

There was also a significant improvement in the Non-Motor Symptoms Scale (NMSS) score between baseline and the postintervention assessment in patients given the probiotic, from 70.71 to 61.34 (P = .005).

This, Dr. Leta observed, was “driven by improvements in the sleep, fatigue, and gastrointestinal domains.”

No such significant improvements were observed in the placebo arm.
 

Probiotics ‘hot topic’ among patients

Claudia Trenkwalder, MD, full professor of neurology at University Medical Center Goettingen (Germany), said in an interview that the use of probiotics is a “hot topic in Parkinson’s disease research, especially among patients.”

Dr. Trenkwalder, who was not involved in the study, noted that Lactobacillus strains “are established in Parkinson’s disease constipation treatment, with randomized controlled trials showing a significant improvement in constipation.

“Therefore, this is a useful treatment. The question here is: Do we have additional effects that can be measured in the microbiome and in clinical symptomatology?”

The trial showed that the probiotic studied “did alter the microbiome and did improve the constipation,” said Dr. Trenkwalder; however, the current data cannot prove whether the probiotic influenced the symptoms of Parkinson’s disease because the improvement in NMSS scores “is driven by the improvement in constipation.”

This, she argued, could have resulted in better absorption of levodopa.

A dietitian in the audience agreed. She asked whether the probiotic was doing anything “besides improving constipation,” adding that the resulting increased ability to absorb levodopa is also “going to help your sleep.”
 

Beyond constipation?

Dr. Leta replied that “we can assume that there is a link between the reduction in the ‘time to on’ and the improvement in constipation. We are doing some analyses in terms of levodopa pharmacokinetics to really understand the mechanisms behind this result.”

Although the improvement in constipation is “one of the possible hypotheses for the improvement in ‘time to on,’” she continued, “there is a more speculative one” in which the probiotics are modulating inflammatory parameters that could contribute to the improvement in sleep.

Veronica Bruno, MD, MPH, assistant professor in the department of clinical neurosciences at the University of Calgary (Alta.), commented in a press release that there has been “increasing interest” in examining the relationship between gut dysbiosis and the “gut-brain axis” in Parkinson’s disease.

The current study “stands out as a significant contribution to this area of study,” she said.

“While the implications of the observed changes in gut microbiota remain a captivating realm for further investigation, a particularly noteworthy finding revolves around the reduction in the ‘time to on’ observed within the active treatment group.”

Dr. Bruno said that shortening of the time to on “holds promise for substantial enhancements in patients’ lives” by reducing “difficult ‘off’ intervals and enhancing overall well-being.”

The study was funded by the UK National Institute for Health Research Mental Health Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust, and King’s College London. No relevant financial relationships were declared.

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

TOPLINE:

Holding off on palliative chemotherapy until symptoms start appears to improve quality of life (QoL) without affecting survival for asymptomatic patients with advanced cancer.

METHODOLOGY:

• Traditionally, chemotherapy is started immediately when advanced cancer is diagnosed, but delaying chemotherapy until symptoms start could improve QoL.
• To find out, investigators performed a meta-analysis of five studies that explored the timing of palliative chemotherapy. The analysis included three randomized trials in advanced colorectal cancer (CRC), one in advanced ovarian cancer, and a review of patients with stage IV gastric cancer.
• Of the 919 patients, treatment was delayed for 467 patients (50.8%) until symptoms started in the colorectal trials. It was delayed until tumor recurrence in the ovarian cancer trial, and it was delayed until a month or more had passed in the gastric cancer study, regardless of symptoms.
• QoL was assessed largely by the EORTC-QLQ-C30 questionnaire. Median follow-up ranged from 11 to 60 months.

TAKEAWAY:

• The researchers found no significant differences in overall survival between patients for whom chemotherapy was delayed and those for whom chemotherapy began immediately (pooled hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.90-1.22; P = .52).
• Median overall survival was 11.9 to 25.7 months with immediate treatment, vs. 9 to 27.1 months with delayed treatment.
• In the three studies that evaluated QoL, the findings suggested that QoL was largely better among patients whose treatment was delayed. In the CRC studies that assessed QoL, for instance, global health status in the delayed treatment group was higher than that in the immediate treatment group at almost all time points, but not significantly so.
• Rates of grade 3/4 toxicities, evaluated in two studies, did not differ significantly between the groups.

IN PRACTICE:

There is limited evidence on the optimal timing for starting chemotherapy for asymptomatic patients with advanced cancer. In these studies, delaying chemotherapy until symptoms occurred did not result in worse overall survival compared with immediate treatment and may have resulted in better QoL, the researchers concluded. They noted that for asymptomatic patients, delaying the start of systemic therapy should be discussed with the patient.

SOURCE:

The study, led by Simone Augustinus of the University of Amsterdam, was published online Aug. 17 in The Oncologist.

LIMITATIONS:

• Only three types of cancer were included in the analysis, and the findings may not be generalizable to other types of cancer.
• Some of the studies were older and employed out-of-date treatment regimens.
• QoL was only evaluated in three of five studies and could not be evaluated overall in the meta-analysis because of the different time points measured in each trial.

DISCLOSURES:

The study received no external funding. Two investigators have advisory, speaker, and/or research ties to Celgene, Novartis, AstraZeneca, and other companies.

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

TOPLINE:

Holding off on palliative chemotherapy until symptoms start appears to improve quality of life (QoL) without affecting survival for asymptomatic patients with advanced cancer.

METHODOLOGY:

• Traditionally, chemotherapy is started immediately when advanced cancer is diagnosed, but delaying chemotherapy until symptoms start could improve QoL.
• To find out, investigators performed a meta-analysis of five studies that explored the timing of palliative chemotherapy. The analysis included three randomized trials in advanced colorectal cancer (CRC), one in advanced ovarian cancer, and a review of patients with stage IV gastric cancer.
• Of the 919 patients, treatment was delayed for 467 patients (50.8%) until symptoms started in the colorectal trials. It was delayed until tumor recurrence in the ovarian cancer trial, and it was delayed until a month or more had passed in the gastric cancer study, regardless of symptoms.
• QoL was assessed largely by the EORTC-QLQ-C30 questionnaire. Median follow-up ranged from 11 to 60 months.

TAKEAWAY:

• The researchers found no significant differences in overall survival between patients for whom chemotherapy was delayed and those for whom chemotherapy began immediately (pooled hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.90-1.22; P = .52).
• Median overall survival was 11.9 to 25.7 months with immediate treatment, vs. 9 to 27.1 months with delayed treatment.
• In the three studies that evaluated QoL, the findings suggested that QoL was largely better among patients whose treatment was delayed. In the CRC studies that assessed QoL, for instance, global health status in the delayed treatment group was higher than that in the immediate treatment group at almost all time points, but not significantly so.
• Rates of grade 3/4 toxicities, evaluated in two studies, did not differ significantly between the groups.

IN PRACTICE:

There is limited evidence on the optimal timing for starting chemotherapy for asymptomatic patients with advanced cancer. In these studies, delaying chemotherapy until symptoms occurred did not result in worse overall survival compared with immediate treatment and may have resulted in better QoL, the researchers concluded. They noted that for asymptomatic patients, delaying the start of systemic therapy should be discussed with the patient.

SOURCE:

The study, led by Simone Augustinus of the University of Amsterdam, was published online Aug. 17 in The Oncologist.

LIMITATIONS:

• Only three types of cancer were included in the analysis, and the findings may not be generalizable to other types of cancer.
• Some of the studies were older and employed out-of-date treatment regimens.
• QoL was only evaluated in three of five studies and could not be evaluated overall in the meta-analysis because of the different time points measured in each trial.

DISCLOSURES:

The study received no external funding. Two investigators have advisory, speaker, and/or research ties to Celgene, Novartis, AstraZeneca, and other companies.

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

TOPLINE:

Holding off on palliative chemotherapy until symptoms start appears to improve quality of life (QoL) without affecting survival for asymptomatic patients with advanced cancer.

METHODOLOGY:

• Traditionally, chemotherapy is started immediately when advanced cancer is diagnosed, but delaying chemotherapy until symptoms start could improve QoL.
• To find out, investigators performed a meta-analysis of five studies that explored the timing of palliative chemotherapy. The analysis included three randomized trials in advanced colorectal cancer (CRC), one in advanced ovarian cancer, and a review of patients with stage IV gastric cancer.
• Of the 919 patients, treatment was delayed for 467 patients (50.8%) until symptoms started in the colorectal trials. It was delayed until tumor recurrence in the ovarian cancer trial, and it was delayed until a month or more had passed in the gastric cancer study, regardless of symptoms.
• QoL was assessed largely by the EORTC-QLQ-C30 questionnaire. Median follow-up ranged from 11 to 60 months.

TAKEAWAY:

• The researchers found no significant differences in overall survival between patients for whom chemotherapy was delayed and those for whom chemotherapy began immediately (pooled hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.90-1.22; P = .52).
• Median overall survival was 11.9 to 25.7 months with immediate treatment, vs. 9 to 27.1 months with delayed treatment.
• In the three studies that evaluated QoL, the findings suggested that QoL was largely better among patients whose treatment was delayed. In the CRC studies that assessed QoL, for instance, global health status in the delayed treatment group was higher than that in the immediate treatment group at almost all time points, but not significantly so.
• Rates of grade 3/4 toxicities, evaluated in two studies, did not differ significantly between the groups.

IN PRACTICE:

There is limited evidence on the optimal timing for starting chemotherapy for asymptomatic patients with advanced cancer. In these studies, delaying chemotherapy until symptoms occurred did not result in worse overall survival compared with immediate treatment and may have resulted in better QoL, the researchers concluded. They noted that for asymptomatic patients, delaying the start of systemic therapy should be discussed with the patient.

SOURCE:

The study, led by Simone Augustinus of the University of Amsterdam, was published online Aug. 17 in The Oncologist.

LIMITATIONS:

• Only three types of cancer were included in the analysis, and the findings may not be generalizable to other types of cancer.
• Some of the studies were older and employed out-of-date treatment regimens.
• QoL was only evaluated in three of five studies and could not be evaluated overall in the meta-analysis because of the different time points measured in each trial.

DISCLOSURES:

The study received no external funding. Two investigators have advisory, speaker, and/or research ties to Celgene, Novartis, AstraZeneca, and other companies.

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

TOPLINE:

Patients undergoing systemic therapy for advanced cancer who received monthly screening for financial toxicity for up to 1 year were less likely to develop financial difficulties or have their financial issues get worse.

METHODOLOGY:

• About one in five cancer survivors report experiencing financial toxicity, but financial monitoring is not a routine part of clinical care.
• In the current analysis, researchers evaluated whether screening for financial toxicity during routine care could prevent patients with advanced cancer from developing financial difficulties.
• The study involved 1,191 patients undergoing systemic therapy for metastatic cancer at 52 community oncology practices in the United States. The practices were randomly assigned in a 1:1 ratio to use either digital symptom monitoring through patient-reported outcomes or usual care.
• With the digital monitoring, patients received online or automated telephone surveys between visits inquiring about symptoms, functioning, and financial toxicity for up to 1 year.
• The financial toxicity inquiry consisted of a single-item screening question, scored on a 0-5 scale, from the Functional Assessment of Chronic Illness Therapy COmprehensive Score for financial Toxicity (FACIT-COST): “In the last month, my illness has been a financial hardship to my family and me.” Scores higher than 2, indicating “quite a bit or very much,” triggered an automated alert to practice nurses.
• At different points, patients in both groups also received a question to assess a change in financial difficulties from baseline: “During the past week, has your physical condition or medical treatment caused you financial difficulties?”

TAKEAWAY:

• Among patients receiving financial toxicity screening, 30.2% developed or experienced worsening financial difficulties, compared with 39.0% of those treated at practices without the financial burden screening (P = .004).
• The results corresponded to a number needed to screen of 11.4, meaning that, on average, 11.4 patients would need to be screened for 1 additional patient to avoid developing financial difficulties or having their financial challenges get worse.
• Nurses and patients who were interviewed noted that financial screening helped them identify patients for financial counseling who otherwise may be reluctant to seek or were unaware of such assistance.
• The intervention had a similar positive impact among White patients, men, and women, compared with the overall study population, but appeared to have no effect among Black patients (38% for intervention vs. 39% for the control).

IN PRACTICE:

The findings suggest that “remote symptom monitoring, including [financial toxicity] screening, protected patients undergoing systemic therapy from experiencing worsening financial difficulties,” the authors concluded. Given the relatively low number needed to screen, “financial toxicity screening appears to be a high-yield intervention.”

SOURCE:

The analysis, by Victoria S. Binder, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues was published online in the Journal of Clinical Oncology.

LIMITATIONS:

• The use of a single-item measure could call the replicability of the findings into question.
• Given that the financial toxicity monitoring did not appear to be effective among Black patients, the screening intervention may not adequately address all racial and ethnic groups.

DISCLOSURES:

The trial was sponsored by the Foundation of the Alliance for Clinical Trials in Oncology and was supported in part by a Patient-Centered Outcomes Research Institute Award IHS-1511-33, 392. The authors’ disclosures are detailed in the published study.

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

TOPLINE:

Patients undergoing systemic therapy for advanced cancer who received monthly screening for financial toxicity for up to 1 year were less likely to develop financial difficulties or have their financial issues get worse.

METHODOLOGY:

• About one in five cancer survivors report experiencing financial toxicity, but financial monitoring is not a routine part of clinical care.
• In the current analysis, researchers evaluated whether screening for financial toxicity during routine care could prevent patients with advanced cancer from developing financial difficulties.
• The study involved 1,191 patients undergoing systemic therapy for metastatic cancer at 52 community oncology practices in the United States. The practices were randomly assigned in a 1:1 ratio to use either digital symptom monitoring through patient-reported outcomes or usual care.
• With the digital monitoring, patients received online or automated telephone surveys between visits inquiring about symptoms, functioning, and financial toxicity for up to 1 year.
• The financial toxicity inquiry consisted of a single-item screening question, scored on a 0-5 scale, from the Functional Assessment of Chronic Illness Therapy COmprehensive Score for financial Toxicity (FACIT-COST): “In the last month, my illness has been a financial hardship to my family and me.” Scores higher than 2, indicating “quite a bit or very much,” triggered an automated alert to practice nurses.
• At different points, patients in both groups also received a question to assess a change in financial difficulties from baseline: “During the past week, has your physical condition or medical treatment caused you financial difficulties?”

TAKEAWAY:

• Among patients receiving financial toxicity screening, 30.2% developed or experienced worsening financial difficulties, compared with 39.0% of those treated at practices without the financial burden screening (P = .004).
• The results corresponded to a number needed to screen of 11.4, meaning that, on average, 11.4 patients would need to be screened for 1 additional patient to avoid developing financial difficulties or having their financial challenges get worse.
• Nurses and patients who were interviewed noted that financial screening helped them identify patients for financial counseling who otherwise may be reluctant to seek or were unaware of such assistance.
• The intervention had a similar positive impact among White patients, men, and women, compared with the overall study population, but appeared to have no effect among Black patients (38% for intervention vs. 39% for the control).

IN PRACTICE:

The findings suggest that “remote symptom monitoring, including [financial toxicity] screening, protected patients undergoing systemic therapy from experiencing worsening financial difficulties,” the authors concluded. Given the relatively low number needed to screen, “financial toxicity screening appears to be a high-yield intervention.”

SOURCE:

The analysis, by Victoria S. Binder, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues was published online in the Journal of Clinical Oncology.

LIMITATIONS:

• The use of a single-item measure could call the replicability of the findings into question.
• Given that the financial toxicity monitoring did not appear to be effective among Black patients, the screening intervention may not adequately address all racial and ethnic groups.

DISCLOSURES:

The trial was sponsored by the Foundation of the Alliance for Clinical Trials in Oncology and was supported in part by a Patient-Centered Outcomes Research Institute Award IHS-1511-33, 392. The authors’ disclosures are detailed in the published study.

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

TOPLINE:

Patients undergoing systemic therapy for advanced cancer who received monthly screening for financial toxicity for up to 1 year were less likely to develop financial difficulties or have their financial issues get worse.

METHODOLOGY:

• About one in five cancer survivors report experiencing financial toxicity, but financial monitoring is not a routine part of clinical care.
• In the current analysis, researchers evaluated whether screening for financial toxicity during routine care could prevent patients with advanced cancer from developing financial difficulties.
• The study involved 1,191 patients undergoing systemic therapy for metastatic cancer at 52 community oncology practices in the United States. The practices were randomly assigned in a 1:1 ratio to use either digital symptom monitoring through patient-reported outcomes or usual care.
• With the digital monitoring, patients received online or automated telephone surveys between visits inquiring about symptoms, functioning, and financial toxicity for up to 1 year.
• The financial toxicity inquiry consisted of a single-item screening question, scored on a 0-5 scale, from the Functional Assessment of Chronic Illness Therapy COmprehensive Score for financial Toxicity (FACIT-COST): “In the last month, my illness has been a financial hardship to my family and me.” Scores higher than 2, indicating “quite a bit or very much,” triggered an automated alert to practice nurses.
• At different points, patients in both groups also received a question to assess a change in financial difficulties from baseline: “During the past week, has your physical condition or medical treatment caused you financial difficulties?”

TAKEAWAY:

• Among patients receiving financial toxicity screening, 30.2% developed or experienced worsening financial difficulties, compared with 39.0% of those treated at practices without the financial burden screening (P = .004).
• The results corresponded to a number needed to screen of 11.4, meaning that, on average, 11.4 patients would need to be screened for 1 additional patient to avoid developing financial difficulties or having their financial challenges get worse.
• Nurses and patients who were interviewed noted that financial screening helped them identify patients for financial counseling who otherwise may be reluctant to seek or were unaware of such assistance.
• The intervention had a similar positive impact among White patients, men, and women, compared with the overall study population, but appeared to have no effect among Black patients (38% for intervention vs. 39% for the control).

IN PRACTICE:

The findings suggest that “remote symptom monitoring, including [financial toxicity] screening, protected patients undergoing systemic therapy from experiencing worsening financial difficulties,” the authors concluded. Given the relatively low number needed to screen, “financial toxicity screening appears to be a high-yield intervention.”

SOURCE:

The analysis, by Victoria S. Binder, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues was published online in the Journal of Clinical Oncology.

LIMITATIONS:

• The use of a single-item measure could call the replicability of the findings into question.
• Given that the financial toxicity monitoring did not appear to be effective among Black patients, the screening intervention may not adequately address all racial and ethnic groups.

DISCLOSURES:

The trial was sponsored by the Foundation of the Alliance for Clinical Trials in Oncology and was supported in part by a Patient-Centered Outcomes Research Institute Award IHS-1511-33, 392. The authors’ disclosures are detailed in the published study.

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

Concizumab (Novo Nordisk), a subcutaneous monoclonal antibody administered once daily, shows significant reductions in annualized bleeding rates in patients with hemophilia A or B with inhibitors, potentially representing the first subcutaneous treatment option for patients with hemophilia B with inhibitors.

“These results demonstrate the potential of concizumab as an efficacious treatment option for people living with hemophilia A or B with inhibitors – the latter a population with severely limited treatment options,” first author Tadashi Matsushita, MD, PhD, of the department of transfusion medicine, Nagoya (Japan) University Hospital, said in an interview regarding the study, published in the New England Journal of Medicine.

The results are from the prospective, multicenter, phase 3 explorer7 trial, involving 133 patients, including 80 with hemophilia A and 53 had hemophilia B, all with inhibitors, a complication of hemophilia therapy in which antibodies ‘inhibit’ clot formation and complicate standard treatment.

The patients, aged 12 or older and all receiving on-demand treatment with bypassing agents, were randomized to receive no prophylaxis for at least 24 weeks (n = 19) or concizumab prophylaxis for at least 32 weeks (n = 33), with the remaining patients nonrandomly assigned to two groups receiving concizumab prophylaxis for at least 24 weeks (n = 81).

For the primary endpoint of the estimated mean annualized bleeding rate, the rate in the no-prophylaxis group was 11.8 episodes versus just 1.7 episodes in the concizumab prophylaxis 32-week group (rate ratio, 0.14; P < .001).

The overall median annualized bleeding rate for patients in all three groups receiving concizumab was zero episodes.

Annualized rates of treated spontaneous, joint, and target joint bleeding episodes were also lower in the concizumab groups versus the no-prophylaxis group, with annualized rate ratios that were similar to the annualized rate ratio for the primary endpoint.

While similar annualized bleeding rates were observed in hemophilia subtypes, the study wasn’t powered to show superiority according the hemophilia A or B, the authors noted.

Plasma concentrations of concizumab remained stable over the course of the study.

There were no significant differences in terms of key secondary endpoints of change in bodily pain and physical functioning scores from the start of treatment to week 24.
 

Pause for safety

Treatment in the study was paused for 6 months from March 2020 to August 2020 following nonfatal thromboembolic events occurring in three patients receiving concizumab, including one in the explorer7 trial and two in the concurrent explorer8 trial, evaluating the drug in patients with hemophilia without inhibitors.

The authors wrote that the three patients had all received concomitant treatment for bleeding and had thrombotic risk factors including obesity and other comorbidities.

The trial resumed following mitigation measures that included revising the dosing regimen to include a 1–mg/kg concizumab loading dose, followed by a subcutaneous once-daily dose of 0.2 mg/kg concizumab. No further thromboembolic events were reported after the pause. Otherwise, adverse events were mainly low grade, with serious events being rare.
 

Option for hemophilia B important

Of the two disease types, hemophilia A is much more common, with an estimated prevalence in the United States of 12 cases per 100,000 males versus hemophilia B, which has a rate of only 3.7 cases per 100,000, according to the Centers for Disease Control and Prevention. Women make up only about 1% of cases with moderate to severe hemophilia.

A standard treatment of hemophilia A or B is prophylaxis with factor replacement therapies allow for improved clotting and reduced bleeding. However, one caveat is the need for intravenous injections, as often as once daily in some cases.

The development of inhibitors in response to replacement therapy may further necessitate the need for treatment with bypassing agents for breakthrough bleeding.

As an alternative, non–factor replacement therapies can promote coagulation, notably the factor VIII mimetic emicizumab, given by subcutaneous injection, and approved by the Food and Drug Administration in 2018 for patients with and without inhibitors.

Emicizumab is recommended by the World Federation on Hemophilia over bypassing agents as prophylaxis for patients with hemophilia A and persistent inhibitors.

Importantly, however, there are no effective prophylactic treatments or easily administered subcutaneous therapies available for hemophilia B with inhibitors, underscoring the potential importance of concizumab, which targets the tissue factor pathway inhibitor protein, linked to coagulation.

“Concizumab has the potential to become the first subcutaneous and first-in-class treatment for hemophilia B with inhibitors,” Dr. Matsushita said. “There are other therapies investigated for hemophilia B with and without inhibitors still in clinical development,” he noted.
 

FDA resubmission planned

In May, Novo Nordisk announced that the FDA had rejected its application for concizumab, requesting more information on the drug’s manufacturing process and its system for the monitoring and dosing of patients to ensure proper drug administration. In a statement, Novo Nordisk reported its plans to move ahead.

“Novo Nordisk has begun addressing the FDA’s feedback and is working closely with the FDA as plans for resubmission continue,” the company reported. “We are confident in the potential of concizumab to address a significant unmet need, particularly for people with hemophilia B with inhibitors who currently have limited prophylactic options and are committed to bringing this important treatment to people with hemophilia with inhibitors living in the U.S.A.”

Meanwhile in Canada, concizumab was approved in March 2023 for the treatment of adolescent and adult patients with hemophilia B with inhibitors and who require routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

The authors wrote that concizumab continues to be investigated across all hemophilia subtypes, including in the explorer10 study, which is evaluating the drug in children living with hemophilia A or B, with and without inhibitors.

The study was supported by Novo Nordisk. Dr. Matsushita reported speaking for and participating on a scientific advisory board of Novo Nordisk.

Concizumab (Novo Nordisk), a subcutaneous monoclonal antibody administered once daily, shows significant reductions in annualized bleeding rates in patients with hemophilia A or B with inhibitors, potentially representing the first subcutaneous treatment option for patients with hemophilia B with inhibitors.

“These results demonstrate the potential of concizumab as an efficacious treatment option for people living with hemophilia A or B with inhibitors – the latter a population with severely limited treatment options,” first author Tadashi Matsushita, MD, PhD, of the department of transfusion medicine, Nagoya (Japan) University Hospital, said in an interview regarding the study, published in the New England Journal of Medicine.

The results are from the prospective, multicenter, phase 3 explorer7 trial, involving 133 patients, including 80 with hemophilia A and 53 had hemophilia B, all with inhibitors, a complication of hemophilia therapy in which antibodies ‘inhibit’ clot formation and complicate standard treatment.

The patients, aged 12 or older and all receiving on-demand treatment with bypassing agents, were randomized to receive no prophylaxis for at least 24 weeks (n = 19) or concizumab prophylaxis for at least 32 weeks (n = 33), with the remaining patients nonrandomly assigned to two groups receiving concizumab prophylaxis for at least 24 weeks (n = 81).

For the primary endpoint of the estimated mean annualized bleeding rate, the rate in the no-prophylaxis group was 11.8 episodes versus just 1.7 episodes in the concizumab prophylaxis 32-week group (rate ratio, 0.14; P < .001).

The overall median annualized bleeding rate for patients in all three groups receiving concizumab was zero episodes.

Annualized rates of treated spontaneous, joint, and target joint bleeding episodes were also lower in the concizumab groups versus the no-prophylaxis group, with annualized rate ratios that were similar to the annualized rate ratio for the primary endpoint.

While similar annualized bleeding rates were observed in hemophilia subtypes, the study wasn’t powered to show superiority according the hemophilia A or B, the authors noted.

Plasma concentrations of concizumab remained stable over the course of the study.

There were no significant differences in terms of key secondary endpoints of change in bodily pain and physical functioning scores from the start of treatment to week 24.
 

Pause for safety

Treatment in the study was paused for 6 months from March 2020 to August 2020 following nonfatal thromboembolic events occurring in three patients receiving concizumab, including one in the explorer7 trial and two in the concurrent explorer8 trial, evaluating the drug in patients with hemophilia without inhibitors.

The authors wrote that the three patients had all received concomitant treatment for bleeding and had thrombotic risk factors including obesity and other comorbidities.

The trial resumed following mitigation measures that included revising the dosing regimen to include a 1–mg/kg concizumab loading dose, followed by a subcutaneous once-daily dose of 0.2 mg/kg concizumab. No further thromboembolic events were reported after the pause. Otherwise, adverse events were mainly low grade, with serious events being rare.
 

Option for hemophilia B important

Of the two disease types, hemophilia A is much more common, with an estimated prevalence in the United States of 12 cases per 100,000 males versus hemophilia B, which has a rate of only 3.7 cases per 100,000, according to the Centers for Disease Control and Prevention. Women make up only about 1% of cases with moderate to severe hemophilia.

A standard treatment of hemophilia A or B is prophylaxis with factor replacement therapies allow for improved clotting and reduced bleeding. However, one caveat is the need for intravenous injections, as often as once daily in some cases.

The development of inhibitors in response to replacement therapy may further necessitate the need for treatment with bypassing agents for breakthrough bleeding.

As an alternative, non–factor replacement therapies can promote coagulation, notably the factor VIII mimetic emicizumab, given by subcutaneous injection, and approved by the Food and Drug Administration in 2018 for patients with and without inhibitors.

Emicizumab is recommended by the World Federation on Hemophilia over bypassing agents as prophylaxis for patients with hemophilia A and persistent inhibitors.

Importantly, however, there are no effective prophylactic treatments or easily administered subcutaneous therapies available for hemophilia B with inhibitors, underscoring the potential importance of concizumab, which targets the tissue factor pathway inhibitor protein, linked to coagulation.

“Concizumab has the potential to become the first subcutaneous and first-in-class treatment for hemophilia B with inhibitors,” Dr. Matsushita said. “There are other therapies investigated for hemophilia B with and without inhibitors still in clinical development,” he noted.
 

FDA resubmission planned

In May, Novo Nordisk announced that the FDA had rejected its application for concizumab, requesting more information on the drug’s manufacturing process and its system for the monitoring and dosing of patients to ensure proper drug administration. In a statement, Novo Nordisk reported its plans to move ahead.

“Novo Nordisk has begun addressing the FDA’s feedback and is working closely with the FDA as plans for resubmission continue,” the company reported. “We are confident in the potential of concizumab to address a significant unmet need, particularly for people with hemophilia B with inhibitors who currently have limited prophylactic options and are committed to bringing this important treatment to people with hemophilia with inhibitors living in the U.S.A.”

Meanwhile in Canada, concizumab was approved in March 2023 for the treatment of adolescent and adult patients with hemophilia B with inhibitors and who require routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

The authors wrote that concizumab continues to be investigated across all hemophilia subtypes, including in the explorer10 study, which is evaluating the drug in children living with hemophilia A or B, with and without inhibitors.

The study was supported by Novo Nordisk. Dr. Matsushita reported speaking for and participating on a scientific advisory board of Novo Nordisk.

Concizumab (Novo Nordisk), a subcutaneous monoclonal antibody administered once daily, shows significant reductions in annualized bleeding rates in patients with hemophilia A or B with inhibitors, potentially representing the first subcutaneous treatment option for patients with hemophilia B with inhibitors.

“These results demonstrate the potential of concizumab as an efficacious treatment option for people living with hemophilia A or B with inhibitors – the latter a population with severely limited treatment options,” first author Tadashi Matsushita, MD, PhD, of the department of transfusion medicine, Nagoya (Japan) University Hospital, said in an interview regarding the study, published in the New England Journal of Medicine.

The results are from the prospective, multicenter, phase 3 explorer7 trial, involving 133 patients, including 80 with hemophilia A and 53 had hemophilia B, all with inhibitors, a complication of hemophilia therapy in which antibodies ‘inhibit’ clot formation and complicate standard treatment.

The patients, aged 12 or older and all receiving on-demand treatment with bypassing agents, were randomized to receive no prophylaxis for at least 24 weeks (n = 19) or concizumab prophylaxis for at least 32 weeks (n = 33), with the remaining patients nonrandomly assigned to two groups receiving concizumab prophylaxis for at least 24 weeks (n = 81).

For the primary endpoint of the estimated mean annualized bleeding rate, the rate in the no-prophylaxis group was 11.8 episodes versus just 1.7 episodes in the concizumab prophylaxis 32-week group (rate ratio, 0.14; P < .001).

The overall median annualized bleeding rate for patients in all three groups receiving concizumab was zero episodes.

Annualized rates of treated spontaneous, joint, and target joint bleeding episodes were also lower in the concizumab groups versus the no-prophylaxis group, with annualized rate ratios that were similar to the annualized rate ratio for the primary endpoint.

While similar annualized bleeding rates were observed in hemophilia subtypes, the study wasn’t powered to show superiority according the hemophilia A or B, the authors noted.

Plasma concentrations of concizumab remained stable over the course of the study.

There were no significant differences in terms of key secondary endpoints of change in bodily pain and physical functioning scores from the start of treatment to week 24.
 

Pause for safety

Treatment in the study was paused for 6 months from March 2020 to August 2020 following nonfatal thromboembolic events occurring in three patients receiving concizumab, including one in the explorer7 trial and two in the concurrent explorer8 trial, evaluating the drug in patients with hemophilia without inhibitors.

The authors wrote that the three patients had all received concomitant treatment for bleeding and had thrombotic risk factors including obesity and other comorbidities.

The trial resumed following mitigation measures that included revising the dosing regimen to include a 1–mg/kg concizumab loading dose, followed by a subcutaneous once-daily dose of 0.2 mg/kg concizumab. No further thromboembolic events were reported after the pause. Otherwise, adverse events were mainly low grade, with serious events being rare.
 

Option for hemophilia B important

Of the two disease types, hemophilia A is much more common, with an estimated prevalence in the United States of 12 cases per 100,000 males versus hemophilia B, which has a rate of only 3.7 cases per 100,000, according to the Centers for Disease Control and Prevention. Women make up only about 1% of cases with moderate to severe hemophilia.

A standard treatment of hemophilia A or B is prophylaxis with factor replacement therapies allow for improved clotting and reduced bleeding. However, one caveat is the need for intravenous injections, as often as once daily in some cases.

The development of inhibitors in response to replacement therapy may further necessitate the need for treatment with bypassing agents for breakthrough bleeding.

As an alternative, non–factor replacement therapies can promote coagulation, notably the factor VIII mimetic emicizumab, given by subcutaneous injection, and approved by the Food and Drug Administration in 2018 for patients with and without inhibitors.

Emicizumab is recommended by the World Federation on Hemophilia over bypassing agents as prophylaxis for patients with hemophilia A and persistent inhibitors.

Importantly, however, there are no effective prophylactic treatments or easily administered subcutaneous therapies available for hemophilia B with inhibitors, underscoring the potential importance of concizumab, which targets the tissue factor pathway inhibitor protein, linked to coagulation.

“Concizumab has the potential to become the first subcutaneous and first-in-class treatment for hemophilia B with inhibitors,” Dr. Matsushita said. “There are other therapies investigated for hemophilia B with and without inhibitors still in clinical development,” he noted.
 

FDA resubmission planned

In May, Novo Nordisk announced that the FDA had rejected its application for concizumab, requesting more information on the drug’s manufacturing process and its system for the monitoring and dosing of patients to ensure proper drug administration. In a statement, Novo Nordisk reported its plans to move ahead.

“Novo Nordisk has begun addressing the FDA’s feedback and is working closely with the FDA as plans for resubmission continue,” the company reported. “We are confident in the potential of concizumab to address a significant unmet need, particularly for people with hemophilia B with inhibitors who currently have limited prophylactic options and are committed to bringing this important treatment to people with hemophilia with inhibitors living in the U.S.A.”

Meanwhile in Canada, concizumab was approved in March 2023 for the treatment of adolescent and adult patients with hemophilia B with inhibitors and who require routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

The authors wrote that concizumab continues to be investigated across all hemophilia subtypes, including in the explorer10 study, which is evaluating the drug in children living with hemophilia A or B, with and without inhibitors.

The study was supported by Novo Nordisk. Dr. Matsushita reported speaking for and participating on a scientific advisory board of Novo Nordisk.

The understanding that human papillomavirus (HPV) causes oropharyngeal squamous cell carcinoma (OPSCC) has been linked with increased likelihood of adults having been vaccinated for HPV, new research indicates.

In a study published online in JAMA Otolaryngology–Head and Neck Surgery, most of the 288 adults surveyed with validated questions were not aware that HPV causes OPSCC and had not been told of the relationship by their health care provider.

Researchers found that when participants knew about the relationship between HPV infection and OPSCC they were more than three times as likely to be vaccinated (odds ratio, 3.7; 95% confidence interval, 1.8-7.6) as those without the knowledge.

The survey was paired with a novel point-of-care adult vaccination program within an otolaryngology clinic. 

“Targeted education aimed at unvaccinated adults establishing the relationship between HPV infection and OPSCC, paired with point-of-care vaccination, may be an innovative strategy for increasing HPV vaccination rates in adults,” write the authors, led by Jacob C. Bloom, MD, with the department of otolaryngology–head and neck surgery at Boston Medical Center.

Current HPV vaccination recommendations include three parts:

• Routine vaccination at age 11 or 12 years
• Catch-up vaccination at ages 13-26 years if not adequately vaccinated
• Shared clinical decision-making in adults aged 27-45 years if the vaccine series has not been completed.

Despite proven efficacy and safety of the HPV vaccine, vaccination rates are low for adults. Although 75% of adolescents aged 13-17 years have initiated the HPV vaccine, recent studies show only 16% of U.S. men aged 18-21 years have received at least 1 dose of the HPV vaccine, the authors write.

Christiana Zhang, MD, with the division of internal medicine at Johns Hopkins University in Baltimore, who was not part of the study, said she was not surprised by the lack of knowledge about the HPV-OPSCC link.

Patients are often counseled on the relationship between HPV and genital warts or anogenital cancers like cervical cancer, she says, but there is less patient education surrounding the relationship between HPV and oropharyngeal cancers.

She says she does counsel patients on the link with OPSCC, but not all providers do and provider knowledge in general surrounding HPV is low.

“Research has shown that knowledge and confidence among health care providers surrounding HPV vaccination is generally low, and this corresponds with a low vaccination recommendation rate,” she says.

She adds, “Patient education on HPV infection and its relationship with OPSCC, paired with point-of-care vaccination for qualifying patients, is a great approach.”

But the education needs to go beyond patients, she says.

“Given the important role that health care providers play in vaccine uptake, I think further efforts are needed to educate providers on HPV vaccination as well,” she says.

The study included patients aged 18-45 years who sought routine outpatient care at the otolaryngology clinic at Boston Medical Center from Sept. 1, 2020, to May 19, 2021.

Limitations of this study include studying a population from a single otolaryngology clinic in an urban, academic medical center. The population was more racially and ethnically diverse than the U.S. population with 60.3% identifying as racial and ethnic minorities. Gender and educational levels were also not reflective of U.S. demographics as half (50.8%) of the participants had a college degree or higher and 58.3% were women.

Dr. Bloom reports grants from the American Head and Neck Cancer Society during the conduct of the study. Coauthor Dr. Faden reports personal fees from Merck, Neotic, Focus, BMS, Chrystalis Biomedical Advisors, and Guidepoint; receiving nonfinancial support from BostonGene and Predicine; and receiving grants from Calico outside the submitted work. Dr. Zhang reports no relevant financial relationships.

The understanding that human papillomavirus (HPV) causes oropharyngeal squamous cell carcinoma (OPSCC) has been linked with increased likelihood of adults having been vaccinated for HPV, new research indicates.

In a study published online in JAMA Otolaryngology–Head and Neck Surgery, most of the 288 adults surveyed with validated questions were not aware that HPV causes OPSCC and had not been told of the relationship by their health care provider.

Researchers found that when participants knew about the relationship between HPV infection and OPSCC they were more than three times as likely to be vaccinated (odds ratio, 3.7; 95% confidence interval, 1.8-7.6) as those without the knowledge.

The survey was paired with a novel point-of-care adult vaccination program within an otolaryngology clinic. 

“Targeted education aimed at unvaccinated adults establishing the relationship between HPV infection and OPSCC, paired with point-of-care vaccination, may be an innovative strategy for increasing HPV vaccination rates in adults,” write the authors, led by Jacob C. Bloom, MD, with the department of otolaryngology–head and neck surgery at Boston Medical Center.

Current HPV vaccination recommendations include three parts:

• Routine vaccination at age 11 or 12 years
• Catch-up vaccination at ages 13-26 years if not adequately vaccinated
• Shared clinical decision-making in adults aged 27-45 years if the vaccine series has not been completed.

Despite proven efficacy and safety of the HPV vaccine, vaccination rates are low for adults. Although 75% of adolescents aged 13-17 years have initiated the HPV vaccine, recent studies show only 16% of U.S. men aged 18-21 years have received at least 1 dose of the HPV vaccine, the authors write.

Christiana Zhang, MD, with the division of internal medicine at Johns Hopkins University in Baltimore, who was not part of the study, said she was not surprised by the lack of knowledge about the HPV-OPSCC link.

Patients are often counseled on the relationship between HPV and genital warts or anogenital cancers like cervical cancer, she says, but there is less patient education surrounding the relationship between HPV and oropharyngeal cancers.

She says she does counsel patients on the link with OPSCC, but not all providers do and provider knowledge in general surrounding HPV is low.

“Research has shown that knowledge and confidence among health care providers surrounding HPV vaccination is generally low, and this corresponds with a low vaccination recommendation rate,” she says.

She adds, “Patient education on HPV infection and its relationship with OPSCC, paired with point-of-care vaccination for qualifying patients, is a great approach.”

But the education needs to go beyond patients, she says.

“Given the important role that health care providers play in vaccine uptake, I think further efforts are needed to educate providers on HPV vaccination as well,” she says.

The study included patients aged 18-45 years who sought routine outpatient care at the otolaryngology clinic at Boston Medical Center from Sept. 1, 2020, to May 19, 2021.

Limitations of this study include studying a population from a single otolaryngology clinic in an urban, academic medical center. The population was more racially and ethnically diverse than the U.S. population with 60.3% identifying as racial and ethnic minorities. Gender and educational levels were also not reflective of U.S. demographics as half (50.8%) of the participants had a college degree or higher and 58.3% were women.

Dr. Bloom reports grants from the American Head and Neck Cancer Society during the conduct of the study. Coauthor Dr. Faden reports personal fees from Merck, Neotic, Focus, BMS, Chrystalis Biomedical Advisors, and Guidepoint; receiving nonfinancial support from BostonGene and Predicine; and receiving grants from Calico outside the submitted work. Dr. Zhang reports no relevant financial relationships.

The understanding that human papillomavirus (HPV) causes oropharyngeal squamous cell carcinoma (OPSCC) has been linked with increased likelihood of adults having been vaccinated for HPV, new research indicates.

In a study published online in JAMA Otolaryngology–Head and Neck Surgery, most of the 288 adults surveyed with validated questions were not aware that HPV causes OPSCC and had not been told of the relationship by their health care provider.

Researchers found that when participants knew about the relationship between HPV infection and OPSCC they were more than three times as likely to be vaccinated (odds ratio, 3.7; 95% confidence interval, 1.8-7.6) as those without the knowledge.

The survey was paired with a novel point-of-care adult vaccination program within an otolaryngology clinic. 

“Targeted education aimed at unvaccinated adults establishing the relationship between HPV infection and OPSCC, paired with point-of-care vaccination, may be an innovative strategy for increasing HPV vaccination rates in adults,” write the authors, led by Jacob C. Bloom, MD, with the department of otolaryngology–head and neck surgery at Boston Medical Center.

Current HPV vaccination recommendations include three parts:

• Routine vaccination at age 11 or 12 years
• Catch-up vaccination at ages 13-26 years if not adequately vaccinated
• Shared clinical decision-making in adults aged 27-45 years if the vaccine series has not been completed.

Despite proven efficacy and safety of the HPV vaccine, vaccination rates are low for adults. Although 75% of adolescents aged 13-17 years have initiated the HPV vaccine, recent studies show only 16% of U.S. men aged 18-21 years have received at least 1 dose of the HPV vaccine, the authors write.

Christiana Zhang, MD, with the division of internal medicine at Johns Hopkins University in Baltimore, who was not part of the study, said she was not surprised by the lack of knowledge about the HPV-OPSCC link.

Patients are often counseled on the relationship between HPV and genital warts or anogenital cancers like cervical cancer, she says, but there is less patient education surrounding the relationship between HPV and oropharyngeal cancers.

She says she does counsel patients on the link with OPSCC, but not all providers do and provider knowledge in general surrounding HPV is low.

“Research has shown that knowledge and confidence among health care providers surrounding HPV vaccination is generally low, and this corresponds with a low vaccination recommendation rate,” she says.

She adds, “Patient education on HPV infection and its relationship with OPSCC, paired with point-of-care vaccination for qualifying patients, is a great approach.”

But the education needs to go beyond patients, she says.

“Given the important role that health care providers play in vaccine uptake, I think further efforts are needed to educate providers on HPV vaccination as well,” she says.

The study included patients aged 18-45 years who sought routine outpatient care at the otolaryngology clinic at Boston Medical Center from Sept. 1, 2020, to May 19, 2021.

Limitations of this study include studying a population from a single otolaryngology clinic in an urban, academic medical center. The population was more racially and ethnically diverse than the U.S. population with 60.3% identifying as racial and ethnic minorities. Gender and educational levels were also not reflective of U.S. demographics as half (50.8%) of the participants had a college degree or higher and 58.3% were women.

Dr. Bloom reports grants from the American Head and Neck Cancer Society during the conduct of the study. Coauthor Dr. Faden reports personal fees from Merck, Neotic, Focus, BMS, Chrystalis Biomedical Advisors, and Guidepoint; receiving nonfinancial support from BostonGene and Predicine; and receiving grants from Calico outside the submitted work. Dr. Zhang reports no relevant financial relationships.

Industry-sponsored research funding has fallen by more than 20% from 2014 to 2022, according to a new analysis.

“Despite the growing partnerships and networks between rheumatologists, the public sector, and the health care industry to optimize research funding allocations, the declining trend in industry-sponsored research payments is a concerning sign for all rheumatologists,” writes study author Anju Murayama, an undergraduate medical student at the Tohoku University School of Medicine in Sendai City, Japan. The data suggest that “more and more rheumatologists are facing difficulties in obtaining research funding from the health care industry.”

Dr. Murayama used the Open Payments Database, which contains records of payments made by drug and pharmaceutical companies to health care providers. The analysis included research payments provided directly to rheumatologists (direct-research payments) and payments given to clinicians or health care organizations related to research whose principal investigator was a rheumatologist (associated-research payments). These associated payments included costs for study enrollment and screening, safety monitoring committees, research publication, and more.

The research was published August 15 in The Journal of Rheumatology .

In 2014, the total direct payments to rheumatologists from industry were $1.4 million. These payments jumped to nearly $4.6 million in 2016 but have declined since. In 2022, there were $976,481 in total payments, a 31% drop from 9 years before.

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

Industry-sponsored research funding has fallen by more than 20% from 2014 to 2022, according to a new analysis.

“Despite the growing partnerships and networks between rheumatologists, the public sector, and the health care industry to optimize research funding allocations, the declining trend in industry-sponsored research payments is a concerning sign for all rheumatologists,” writes study author Anju Murayama, an undergraduate medical student at the Tohoku University School of Medicine in Sendai City, Japan. The data suggest that “more and more rheumatologists are facing difficulties in obtaining research funding from the health care industry.”

Dr. Murayama used the Open Payments Database, which contains records of payments made by drug and pharmaceutical companies to health care providers. The analysis included research payments provided directly to rheumatologists (direct-research payments) and payments given to clinicians or health care organizations related to research whose principal investigator was a rheumatologist (associated-research payments). These associated payments included costs for study enrollment and screening, safety monitoring committees, research publication, and more.

The research was published August 15 in The Journal of Rheumatology .

In 2014, the total direct payments to rheumatologists from industry were $1.4 million. These payments jumped to nearly $4.6 million in 2016 but have declined since. In 2022, there were $976,481 in total payments, a 31% drop from 9 years before.

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

Industry-sponsored research funding has fallen by more than 20% from 2014 to 2022, according to a new analysis.

“Despite the growing partnerships and networks between rheumatologists, the public sector, and the health care industry to optimize research funding allocations, the declining trend in industry-sponsored research payments is a concerning sign for all rheumatologists,” writes study author Anju Murayama, an undergraduate medical student at the Tohoku University School of Medicine in Sendai City, Japan. The data suggest that “more and more rheumatologists are facing difficulties in obtaining research funding from the health care industry.”

Dr. Murayama used the Open Payments Database, which contains records of payments made by drug and pharmaceutical companies to health care providers. The analysis included research payments provided directly to rheumatologists (direct-research payments) and payments given to clinicians or health care organizations related to research whose principal investigator was a rheumatologist (associated-research payments). These associated payments included costs for study enrollment and screening, safety monitoring committees, research publication, and more.

The research was published August 15 in The Journal of Rheumatology .

In 2014, the total direct payments to rheumatologists from industry were $1.4 million. These payments jumped to nearly $4.6 million in 2016 but have declined since. In 2022, there were $976,481 in total payments, a 31% drop from 9 years before.

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